POLYPEPTIDE CONSTRUCTS BINDING TO CD3

The invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region and a VL region, wherein i) the VH region comprises: a CDR-H1 sequence of X₁YAX₂N, where X, is K, V, S, G, R, T, or I; and X₂is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX₁VKX₂, where X, is S or Q; and X₂is D, G, K, S, or E; and a CDR-H3 sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G, R, or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y; and ii) wherein the VL region comprises: a CDR-L1 sequence of X₁SSTGAVTX₂X₃X₄YX₅N, where X, is G, R, or A; X₂is S or T; X₃is G or S; X₄is N or Y; and X₅is P or A; a CDR-L2 sequence of X₁TX₂X₃X₄X₅X₆; where X, is G or A; X₂is K, D, or N; X₃is F, M or K; X₄is L or R; X₅is A, P, or V; and X₆is P or S; and a CDR-L3 sequence of X₁LWYSNX₂WV, where X, is V, A, or T; and X₂is R or L; and iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X₂4V and X₂4F in CDR-H1; D15, and X₁16A in CDR-H2; H1, X₁2E, F4, and N6 in CDR-H3; and X₁1L and W3 in CDR-L3. The invention also relates to a polynucleotide encoding the polypeptide or polypeptide construct of the invention, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or with said vector. Moreover, the invention also provides for a process for the production of said polypeptide or polypeptide construct and a pharmaceutical composition comprising said polypeptide or polypeptide construct of the invention. Furthermore, the invention relates to medical uses of said polypeptide or polypeptide construct and kits comprising said polypeptide or polypeptide construct.

T cell engagers (TCEs) make use of T cells' ability to recognize foreign peptides on mutated or infected cells through T cell receptors. T cell recognition is mediated by clonotypically distributed alpha beta and gamma delta T cell receptors (TcR) that interact with the peptide-loaded molecules of the peptide MHC (pMHC) at low affinities. The antigen-specific chains of the TcR do not possess signalling domains but instead are coupled to the conserved multisubunit signaling apparatus CD3. The mechanism by which TcR ligation is directly communicated to the signalling apparatus is a fundamental topic of interest in T cell biology. In brief, CD3 subunits that translate cell surface antigen binding into an intracellular phosphorylation signaling cascade. These phosphorylation events culminate in the activation of transcription factors such as NFAT and NFkB that lead to increased expression of cytokines and effector proteins such as granzymes and perforin. It is this characteristic that is used by TCEs which bind simultaneously a target antigen on a tumor cell and CD3 on T cells to form an artificial immune synapse eventually leading to the destruction of the cell expressing said target antigen.

From a clinical perspective, TCEs do not only have to show efficient cell killing activity, but at the same time other characteristics like, e.g., a manageable side effect profile are desired. However, these aspects are not the only considerations when it comes to the development of TCEs. Other areas of importance for drug development are pre-patient, i.e. concern characteristics of the TCE outside of the patient's body such as, e.g., shelf life, production scalability, solubility, stability, and ease of formulation. In other terms, an important feature from a pharmaceutical perspective is the developability of a given TCE or parts thereof to address certain needs such as for example in drug production or administration. Bringing together the requirements from clinical and pharmacological perspective is important for TCE platform advancement in relation to commercialization. In view of the biological complexities of having the TCE inducing the formation of the immune synapse, it can be challenging to manipulate the TCE in terms of its other characteristics such as for example shelf life, production scalability, solubility, stability, and ease of formulation while maintaining its effectiveness in mediating the killing of target cells.

Thermal stability of TCEs is an important feature within and outside of the patient's body. A higher thermal stability of TCEs reduces the formation of high molecular weight aggregates caused which in turn provides, e. g., for a TCE that is active for a prolonged time in the body but will also be more stable during storage. Moreover, the reduction of high molecular weight aggregates can also result in a more favourable immunogenetic profile of the TCE upon administration thereby reducing the risk of side effects.

Classically, the VH and VL domains making up the anti-target and anti-CD3 binding domains of TCEs are an area that has been the focus of improving stability. This is in particular true for Fvs that are part of TCEs. The hydrophobic interaction between the VH and the VL is believed to strongly determine the stability of a Fv. The interaction can in many Fvs not be strong enough to be stable for in vitro and/or in vivo applications. This has led to the coupling of the V-domains of an Fv by a linker resulting in single chain Fvs (scFvs). While the linker has shown to be effective in holding the V-domains (variable domains) together, it may not always be effective to keep a scFv active at all or active enough for a given application making it necessary to further improve stability. One approach to increase stability is that by increasing the interaction of the two V-domains, the stability of a biologically active Fv can be increased so that it remains a target binding monomer. Although approaches have been described in the art to improve stability of scFv, there is still a need in the art for improving stability of Fvs that are part of TCEs.

- i) the VH region comprises:
  - a CDR-H1 sequence of X₁YAX₂N, where X, is K, V, S, G, R, T, or I; and X₂is M or I;
  - a CDR-H2 sequence of RIRSKYNNYATYYADX₁VKX₂, where X, is S or Q; and X₂is D, G, K, S, or E; and
  - a CDR-H3 sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G, R, or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y; and
- ii) wherein the VL region comprises:
  - a CDR-L1 sequence of X₁SSTGAVTX₂X₃X₄YX₅N, where X, is G, R, or A; X₂is S or T; X₃is G or S; X₄is N or Y; and X₅is P or A;
  - a CDR-L2 sequence of X₁TX₂X₃X₄X₅X₆; where X, is G or A; X₂is K, D, or N; X₃is F, M or K; X₄is L or R; X₅is A, P, or V; and X₆is P or S; and
  - a CDR-L3 sequence of X₁LWYSNX₂WV, where X, is V, A, or T; and X₂is R or L; and
- iii) wherein one or more CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one or more amino acid substitutions selected from X₂4V and X₂4F in CDR-H1;
  - D15 (preferably E), and X₁16A in CDR-H2;
  - H1 (preferably A or N), X₁2E, F4 (preferably I), and N6 (preferably S or T) in CDR-H3; and
  - X₁1L and W3 (preferably Y) in CDR-L3.

The term “polypeptide construct” (alternatively referred to also as “compound” herein) refers to an antigen-binding (or epitope-binding) molecule comprising domains themselves comprising paratopes. In the context of the present invention, a polypeptide construct is understood as an organic polymer which comprises at least one continuous, unbranched amino acid chain that naturally is not existing, but was engineered. An example of a polypeptide construct that is a single polypeptide is a BiTE® molecule that comprises a core structure comprising at least one functional target binding domain together with at least one complete functional CD3 binding domain on a single polypeptide chain, wherein these domains are linked directly by flexible peptide (a “linker”) without any further inserted domain unlike, for example, Xmabs that comprise the target binder and the CD3 binder on different polypeptide chains. In the context of the present invention, such a polypeptide construct comprising more than one amino acid chain is likewise envisaged. It is preferred that the term “polypeptide” is used in connection with single chain forms of the compounds of the present invention, whereas “polypeptide construct” may preferably be more adequate to describe also polypeptides that comprise more than one polypeptide chain, for example two, three or four polypeptide chains. Additionally, the term “polypeptide construct” is also suitable to describe compounds of the invention that comprise one or more non-amino acid-based constituents, e.g. human serum albumin, etc. (HSA). An amino acid chain of a polypeptide typically comprises at least 50 amino acids, preferably at least 100, 200, 300, 400 or 500 amino acids. It is also envisaged in the context of the present invention that an amino acid chain of a polymer is linked to an entity which is not composed of amino acids.

The polypeptides comprise structural and/or functional features based on the structure and/or function of an antibody, e.g., of a full-length immunoglobulin molecule. A polypeptide construct, hence, specifically and, preferably, selectively or immunospecifically binds to its target or antigen, more precisely to an epitope of said target or target antigen, and/or it comprises the heavy chain variable region (VH) and/or the light chain variable region (VL) naturally found in an antibody, or comprises domains derived therefrom. Accordingly, the constructs may alternatively be regarded as comprising paratope-structured and epitope-binding structures, such as those found in natural antibodies or fragments thereof. A polypeptide construct according to the invention comprises the minimum structural requirements of an antibody which allow for immunospecific target binding, i.e., a paratope that recognizes immunospecifically or immunoselectively an epitope on a target antigen unless specified differently. This minimum requirement may e.g. be defined by the presence of at least three light chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VL region, also termed CDR-L1, CDRL2, and CDR-L3) and/or three heavy chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VH region, also termed CDR-H1, CDR-H2 and CDR-H3), preferably of all six CDRs. A polypeptide construct may hence be characterized by the presence of three or six CDRs in a binding domain, and the skilled person knows where (in which order) those CDRs are located within the paratopic binding structures. In in the context of the CD3 binding domain of the polypeptide or polypeptide construct, said paratopic binding structure is specified to be a binding domain characterized by the presence of a VH and VL region comprising CDRs. Hence, a polypeptide/polypeptide construct according to the invention comprises at least a paratopic binding structure being a binding domain binding selectively, immunospecifically and/or immunoselectively to an extracellular epitope of the human CD3ε (also termed CD3epsilon or “CD3 epsilon” herein) chain comprising VH and VL regions with CDRs. Accordingly, a polypeptide/polypeptide construct according to the invention comprises a paratope selectively, immunospecifically and/or immunoselectively binding to an epitope of human CD3 epsilon. The terms “CDR”, and its plural “CDRs”, refer to the complementarity determining region of which three make up the binding character of a light chain variable region (CDR-L1, CDR-L2 and CDR-L3) and three make up the binding character of a heavy chain variable region (CDR-H1, CDR-H2 and CDR-H3). CDRs contain most of the residues responsible for specific interactions of antibodies (or constructs or binding domain) with an antigen and hence contribute to the functional activity of an antibody molecule: they are the main determinants of antigen specificity. The exact definition of CDR boundaries and lengths is subject to different classification and numbering systems. CDRs may therefore be referred to by Kabat, Chothia, contact or any other boundary definitions, including the numbering system described herein. Despite differing boundaries, each of these systems has some degree of overlap in what constitutes the so called “hypervariable regions” within the variable sequences. CDR definitions according to these systems may therefore differ in length and boundary areas with respect to the adjacent framework region. See for example Kabat (an approach based on cross-species sequence variability), Chothia (an approach based on crystallographic studies of antigen-antibody complexes), and/or MacCallum (Kabat et al., loc. cit.; Chothia et al., J. Mol. Biol, 1987, 196: 901-917; and MacCallum et al., J. Mol. Biol, 1996, 262: 732). Still another standard for characterizing the antigen binding site is the AbM definition used by Oxford Molecular's AbM antibody modeling software. See, e.g., Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Antibody Engineering Lab Manual (Ed.: Duebel, S. and Kontermann, R., Springer-Verlag, Heidelberg). To the extent that two residue identification techniques define regions of overlapping, but not identical regions, they can be combined to define a hybrid CDR. However, the numbering in accordance with the so-called Kabat system is preferred The term “antigen-binding structure”, as used herein, refers to any polypeptide/polypeptide construct that comprises an antigen-binding structure or any molecule that has binding activity to a specified antigen. Said antigen-binding structures or molecules are not limited to those derived from a living organism, and for example, they may be a polypeptide produced from an artificially designed sequence. They may also be any of a naturally occurring polypeptide, synthetic polypeptide, recombinant polypeptide, and such. As the antigen-binding structure in accordance with the present invention bind specifically to parts of an antigen, i.e., they bind specifically to an epitope of CD3epsilon, the antigen (epitope)-binding structure may also be broadly defined as “paratopic structure” herein. Accordingly, the polypeptides/polypeptide constructs according to the invention may also be defined as a domain comprising a paratope that are preferably immunospecifically or immunoselectively binding to a target antigen/target epitope; and in certain embodiments comprising at least a further paratope, preferably immunospecifically or immunoselectively, binding to a further, different or same, target antigen/target epitope. Therefore, whenever the present description refers to a domain of a construct or molecule of the present invention, the construct comprises at least one paratopic structure (or paratope) binding human CD3epsilon as specified herein, particularly according to any one of the appended claims. In certain embodiments, said construct comprises at least a further paratope binding also to human CD3epsilon or a different target antigen as defined herein.

The term “antibody” as used in accordance with the invention comprises full-length antibodies, also including camelid antibodies and other immunoglobulins generated by biotechnological or protein engineering methods or processes. These full-length antibodies may be for example monoclonal, recombinant, chimeric, deimmunized, humanized and human antibodies, as well as antibodies from other species such as mouse, hamster, rabbit, rat, goat, or non-human primates.

“Polypeptides/polypeptide constructs” of the present invention may also comprise the structure of a full-length immunoglobulin as it occurs naturally. For example, they may comprise (at least) two full-length antibody heavy chains and two full-length antibody light chains. However, given that the polypeptides/polypeptide constructs according to the invention preferably comprise a linker linking the VH and VL region of the CD3 binding domain, preferably resulting in a scFv, and/or, in other embodiments, comprise at least one further binding domain comprising a paratope, they do not occur naturally, and they are markedly different in their function from naturally occurring products. A polypeptide or polypeptide construct of the invention is hence an artificial “hybrid” molecule comprising, preferably, an scFv and/or, in some embodiments, distinct paratopes/binding domains with different specificities and/or selectivities.

As indicated above, the polypeptides of the invention may comprise more than one polypeptide chain, i.e. polypeptides comprising two or more polypeptide chains are also subject to the present invention, particularly polypeptides forming a three-dimensional protein-like structure that allows for the immunospecific binding to CD3epsilon. Therefore, the definition of the term “polypeptide construct” includes molecules consisting of only one polypeptide chain as well as molecules consisting of two, three, four or more polypeptide chains, which chains can be either identical (homodimers, homotrimers or homo oligomers) or different (heterodimer, heterotrimer or heterooligomer). Examples for the above identified antibodies and their fragments, variants, derivatives and constructs derived therefrom are described inter alia in Harlow and Lane, Antibodies: A laboratory manual, CSHL Press (1988); Kontermann and Dübel, Antibody Engineering, Springer, 2nd ed. 2010; and Little, Recombinant Antibodies for Immunotherapy, Cambridge University Press 2009.

“Polypeptides/polypeptide constructs” of the present invention may also comprise fragments of full-length antibodies, such as VH, VHH, VL, (s)dAb, Fv, light chain (VL-CL), Fd (VH-CH1), heavy chain, Fab, Fab′, F(ab′)2 or “rIgG” (“half antibody” consisting of a heavy chain and a light chain), whereas not all of the foregoing fragments are applicable for the CD3epsilon binding domain since it is defined to comprise a VH and a VL region, but to the embodiments regarding the at least one further binding domain. Polypeptides/polypeptide constructs according to the invention may also comprise modified fragments of antibodies, also called antibody variants or antibody derivatives. Examples include, but are not limited to, scFv, di-scFv or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabodies, single chain diabodies, tandem diabodies (Tandab's), tandem di-scFv, tandem tri-scFv “minibodies” exemplified by a structure which is as follows: (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3), ((scFv)2-CH3) or (scFv-CH3-scFv)2, multibodies such as triabodies or tetrabodies, and single domain antibodies such as nanobodies or single variable domain antibodies comprising merely one variable region, which might be VHH, VH or VL, that selectively and, preferably, specifically binds to an antigen or target independently of other variable regions or domains, whereas not all of the foregoing fragments are applicable for the CD3epsilon binding domain since it is defined to comprise a VH and a VL region, but to the embodiments regarding the at least one further binding domain. Further possible formats of the polypeptides/polypeptide constructs according to the invention are cross bodies, maxi bodies, hetero Fc constructs, mono Fc constructs and scFc constructs. Examples for those formats will be described herein below.

Furthermore, the definition of the term “polypeptide construct” includes bivalent and polyvalent/multivalent polypeptides/polypeptide constructs as well as bispecific and polyspecific/multispecific polypeptides/polypeptide constructs, which selectively and, preferably, specifically bind to two, three or more antigenic structures (epitopes), through distinct binding domains. A polypeptide construct can have more binding valences than specificities, e.g. in a case where it has two binding domains for one target (CD3epsilon) and one binding domain for another target, for example those described herein below, or vice versa, in which case the polypeptide construct is trivalent and bispecific. In general, the term “bispecific” includes the meaning that a polypeptide construct binds to at least two different antigens, such as said CD3epsilon and a further target, for example those specified herein below.

The terms “paratope”, “antigen-binding domain”, “epitope-binding domain”, “binding domain” or “domain which binds to . . . ” characterize, in connection with the present invention, a domain of the construct which selectively and, preferably, specifically or immunospecifically binds to/interacts with/recognizes an epitope on the target or antigen (here: CD3). The terms “binding domain” or “domain which binds to . . . ” or “domain” as far as it relates to the herein described “constructs” characterizes in connection with the present invention a domain of the construct which immunospecifically binds to/interacts with/recognizes an epitope on the target or antigen. The structure and function of the CD3epsilon binding domain (also termed as first binding domain in the case of a polypeptide/polypeptide construct comprising a further, consequently second, third, and so on, binding domain), and preferably also the structure and/or function of any further binding domain (binding to for example to a cell surface antigen such as a tumor antigen), is/are based on the structure and/or function of an antibody, e.g. of a full-length immunoglobulin polypeptide. The “binding domain” or “domain which binds to . . . ” may hence comprise the minimum structural requirements of an antibody which allow for immunospecific target binding. While the structural requirements of the CD3epsilon binding domain is specified to comprise a VH and VL region with corresponding three CDRs per region, said minimum structural requirement in any further binding domain may e.g. be defined by the presence of at least three light chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VL region) and/or of three heavy chain CDRs (i.e. CDR1, CDR2 and CDR3 of the VH region), preferably of all six CDRs. A “domain which binds to” (or a “binding domain”) may typically comprise an antibody light chain variable region (VL) and an antibody heavy chain variable region (VH); however, it does not have to comprise both, but may comprise only one of VH or VL. Fd fragments, for example, often retain some antigen-binding function of the intact antigen-binding domain. The terms “paratope”, “antigen-binding structure” and “epitope-binding structure, as used herein, refer also to a portion of an antibody (or a molecule according to the invention), which comprises a region that specifically binds and is complementary to the whole or a portion of an antigen or a part thereof, i.e. an antibody can only bind to a particular portion of the antigen. The particular portion is called “epitope”. An antigen-binding domain can be provided from one or more antibody variable domains. Preferably, the antigen-binding domains contain antibody variable region that comprising both the antibody light chain variable region (VL) and antibody heavy chain variable region (VH). Such preferable antigen-binding domains include, for example, “single-chain Fv (scFv)”, “single-chain antibody”, “Fv”, “single-chain Fv2 (scFv2)”, “Fab”, and “F (ab”)2 “. For the CD3epsilon binding domain it is preferred that it takes the form of an scFv.

Examples for the format of a “domain which binds to”, “domain comprising a paratope” (or “binding domain”, “antigen-binding structure”, “epitope-binding structure”) include unless otherwise defined, but are not limited to, full-length antibodies, fragments of full-length antibodies (such as VH, VHH, VL), (s)dAb, Fv, light chain (VL-CL), Fd (VH-CH1), heavy chain, Fab, Fab′, F(ab′)2 or “r IgG” (“half antibody”)), antibody variants or derivatives such as scFv, di-scFv or bi(s)-scFv, scFv-Fc, scFv-zipper, scFab, Fab2, Fab3, diabodies, single chain diabodies, tandem diabodies (Tandab's), tandem di-scFv, tandem tri-scFv, “minibodies” (selected from formats such as (VH-VL-CH3)2, (scFv-CH3)2, ((scFv)2-CH3+CH3)), ((scFv)2-CH3) or (scFv-CH3-scFv)2, multibodies such as triabodies or tetrabodies, and single domain antibodies such as nanobodies or single variable domain antibodies comprising merely one variable region, which might be VHH, VH or VL. Further examples for the format of a “domain which binds to” (or a “binding domain”) include (1) an antibody fragment or variant comprising VL, VH, CL and CH1 (such as Fab); (2) an antibody fragment or variant comprising two linked Fab fragments (such as a F(ab′)2); (3) an antibody fragment or variant comprising VH and CH1 (such as Fd); (4) an antibody fragment or variant comprising VL and CL (such as the light chain); (5) an antibody fragment or variant comprising VL and VH (such as Fv); (5) a dAb fragment (Ward et al., (1989) Nature 341:544-546), which has a VH domain; (6) an antibody variant comprising at least three isolated CDRs of the heavy and/or the light chain; and (7) a single chain Fv (scFv). Examples for embodiments of constructs or binding domains according to the invention are e.g. described in WO 00/006605, WO 2005/040220, WO 2008/119567, WO 2010/037838, WO 2013/026837, WO 2013/026833, US 2014/0308285, US 2014/0302037, W O2014/144722, WO 2014/151910, and WO 2015/048272. In the context of the present invention, a paratope is understood as an antigen-binding site which is a part of a polypeptide as described herein and which recognizes and binds to an antigen. A paratope is typically a small region of about at least 5 amino acids. A paratope as understood herein typically comprises parts of antibody-derived heavy (VH) and light chain (VL) sequences. Each binding domain of a polypeptide according to the present invention is provided with a paratope comprising a set of 6 complementarity-determining regions (CDR loops) with three of each being comprised within the antibody-derived VH and VL sequence, respectively.

It is envisaged for the compounds, particularly for the constructs of the present invention that a) the construct is a single chain polypeptide or a single chain construct, b) the CD3epsilon binding domain is in the format of an scFv, c) any further, such as a second binding and/or third domain is in the format of an scFv, d) the first and said further, such as said second and/or third domain are connected via a linker, preferably a peptide linker, more preferably a glycine/serine or glycine/glutamine linker, and/or e) the construct comprises a domain providing an extended serum half-life, such as an Fc-based domain, or human serum albumin (HSA). In the latter case, it is a preferred embodiment, wherein the term “polypeptide construct” makes clear that it comprises more than a single peptide chain. A preferred Fc-based domain which extends the serum half-life (also termed “HLE” domain) comprises two polypeptide monomers, each comprising a hinge, a CH2 domain and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker (see, e.g., SEQ ID NO: 18 and 19); the format is in N-terminal to C-terminal order: hinge-CH2-CH3-linker-hinge-CH2-CH3.

The constructs of the present invention are preferably “in vitro generated constructs” and/or “recombinant constructs”. In the context of the present invention, the term “in vitro generated” refers to a construct according to the above definition where all or part of the binding domain or of a variable region (e.g., at least one CDR) is generated in a non-immune cell selection, e.g., in an in vitro phage display, on a protein chip or in any other method in which candidate amino acid sequences can be tested for their ability to bind to an antigen. This term thus preferably excludes sequences generated solely by genomic rearrangement in an immune cell in an animal. It is envisaged that the first and/or second domain of the construct is produced by or obtainable by phage display or library screening methods rather than by grafting CDR sequences from a pre-existing (monoclonal) antibody into a scaffold. A “recombinant construct” is a construct generated or produced using (inter alia) recombinant DNA technology or genetic engineering.

The constructs of the present invention are envisaged to be monoclonal. As used herein, polypeptides or constructs that are denominated “monoclonal” (mAb) are obtained from a population of substantially homogeneous antibodies/constructs, i.e., the individual antibodies/constructs comprised in the population are identical (in particular with respect to their amino acid sequence) except for possible naturally occurring mutations and/or post-translational modifications (e.g., isomerizations, amidations) that may be present in minor amounts. Monoclonal antibodies/constructs are highly specific, being directed against a single epitope within the antigen, in contrast to polyclonal antibody preparations which typically include different antibodies directed against different determinants (or epitopes). In addition to their specificity, monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, hence uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody/construct as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any specific method.

For the preparation of monoclonal antibodies, any technique providing antibodies produced by continuous cell line cultures can be used. For example, monoclonal antibodies to be used may be made by the hybridoma method first described by Koehler et al., Nature, 256: 495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567). Examples for further techniques to produce human monoclonal antibodies include the trioma technique, the human B-cell hybridoma technique (Kozbor, Immunology Today 4 (1983), 72) and the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), 77-96).

Hybridomas can then be screened using standard methods, such as enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (BIACORE™) analysis, to identify one or more hybridomas that produce an antibody that selectively and, preferably, specifically or immunospecifically binds to a specified antigen. Any form of the relevant antigen may be used as the immunogen, e.g., recombinant antigen, naturally occurring forms, any variants or fragments thereof, as well as an antigenic peptide thereof. Surface plasmon resonance as employed in the BIAcore™ system can be used to increase the efficiency of phage antibodies/constructs which bind to an epitope of a target antigen (Schier, Human Antibodies Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol. Methods 183 (1995), 7-13).

Another exemplary method of making constructs or binding domains includes screening protein expression libraries, e.g., phage display or ribosome display libraries. Phage display is described, for example, in Ladner et al., U.S. Pat. No. 5,223,409; Smith (1985) Science 228:1315-1317, Clackson et al., Nature, 352: 624-628 (1991) and Marks et al., J. Mol. Biol., 222: 581-597 (1991).

In addition to the use of display libraries, the relevant antigen can be used to immunize a non-human animal, e.g., a rodent (such as a mouse, hamster, rabbit or rat). In one embodiment, the non-human animal includes at least a part of a human immunoglobulin gene. For example, it is possible to engineer mouse strains deficient in mouse antibody production with large fragments of the human Ig (immunoglobulin) loci. Using the hybridoma technology, antigen-specific monoclonal antibodies derived from the genes with the desired specificity may be produced and selected. See, e.g., Xenomouse™ mouse, Green et al. (1994) Nature Genetics 7:13-21, US 2003-0070185, WO 96/34096, and WO 96/33735.

A monoclonal antibody can also be obtained from a non-human animal, and then modified, e.g., humanized, deimmunized, rendered chimeric etc., using recombinant DNA techniques known in the art. Examples of modified constructs or binding domains include humanized variants of non-human antibodies/constructs, “affinity matured” constructs or binding domains (see, e.g. Hawkins et al. J. Mol. Biol. 254, 889-896 (1992) and Lowman et al., Biochemistry 30, 10832-10837 (1991)) and antibody variants or mutants with altered effector function(s) (see, e.g., U.S. Pat. No. 5,648,260, Kontermann and Dubel (2010), loc. cit. and Little (2009), loc. cit.).

In immunology, affinity maturation is the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. Like the natural prototype, the in vitro affinity maturation is based on the principles of mutation and selection. The in vitro affinity maturation has successfully been used to optimize antibodies, antibody fragments, antibody variants, constructs or binding domains. Random mutations inside the CDRs are introduced using radiation, chemical mutagens or error-prone PCR. In addition, the genetic diversity can be increased by chain shuffling. Two or three rounds of mutation and selection using display methods like phage display usually results in antibodies, antibody fragments, antibody variants, constructs or binding domains with affinities in the low nanomolar range.

A preferred type of an amino acid substitutional variation of the constructs or binding domains of the invention involves substituting one or more residues within the hypervariable region of a parent antibody structure (e.g. a humanized or human antibody structure). Generally, the resulting variant(s) selected for further development will have improved biological properties relative to the parent antibody structure from which they are generated. A convenient way for generating such substitutional variants involves affinity maturation using phage display. Briefly, several sites of the hypervariable region (e. g. 6-7 sites) are mutated to generate all possible amino acid substitutions at each site. The variants thus generated are displayed in a monovalent fashion from filamentous phage particles as fusions to the gene Ill product of M13 packaged within each particle. The phage-displayed variants are then screened for their biological activity (e.g. binding affinity) as disclosed herein. To identify candidate hypervariable region sites contributing significantly to antigen binding (candidates for modification), alanine scanning mutagenesis can also be performed. Alternatively, or additionally, it may be beneficial to analyze a crystal structure of the complex between the antigen and the construct or the binding domain to identify contact points between the binding domain and its specific antigen. Such contact residues and neighbouring residues are candidates for substitution according to the techniques elaborated herein. Once such variants are generated, the panel of variants is subjected to screening as described herein and antibodies, their antigen-binding fragments, constructs or binding domains with superior properties in one or more relevant assays may be selected for further development.

The constructs and binding domains of the present invention specifically include “chimeric” versions in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is/are identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments or variants of such antibodies, so long as they exhibit the desired biological activity (U.S. Pat. No. 4,816,567; Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)). Chimeric constructs or binding domains of interest herein include “primitized” constructs comprising variable domain antigen-binding sequences derived from a non-human primate (e.g., Old World Monkey, Ape etc.) and human constant region sequences. A variety of approaches for making chimeric antibodies or constructs have been described. See e.g., Morrison et al., Proc. Natl. Acad. ScL U.S.A. 81:6851, 1985; Takeda et al., Nature 314:452, 1985, Cabilly et al., U.S. Pat. No. 4,816,567; Boss et al., U.S. Pat. No. 4,816,397; Tanaguchi et al., EP 0171496; EP 0173494; and GB 2177096.

An antibody, polypeptide construct, antibody fragment, antibody variant or binding domain may also be modified by specific deletion of human T cell epitopes (a method called “deimmunization”) using methods disclosed for example in WO 98/52976 or WO 00/34317. Briefly, the heavy and light chain variable regions of an antibody, construct or binding domain can be analyzed for peptides that bind to MHC class II; these peptides represent potential T cell epitopes (as defined e.g. in WO 98/52976 and WO 00/34317). For detection of potential T cell epitopes, a computer modeling approach termed “peptide threading” can be applied, and in addition a database of human MHC class II binding peptides can be searched for motifs present in the VH and VL sequences, as described in WO 98/52976 and WO 00/34317. These motifs bind to any of the 18 major MHC class II DR allotypes, and thus constitute potential T cell epitopes. Potential T cell epitopes detected can be eliminated by substituting small numbers of amino acid residues in the variable domains or variable regions, or preferably, by single amino acid substitutions. Typically, conservative substitutions are made. Often, but not exclusively, an amino acid common to a position in human germline antibody sequences may be used. Human germline sequences are disclosed e.g. in Tomlinson, et al. (1992) J. Mol. Biol. 227:776-798; Cook, G. P. et al. (1995) Immunol. Today Vol. 16 (5): 237-242; and Tomlinson et al. (1995) EMBO J. 14: 14:4628-4638. The V BASE directory (www2.mrc-Imb.cam.ac.uk/vbase/list2.php) provides a comprehensive directory of human immunoglobulin variable region sequences (compiled by Tomlinson, L A. et al. MRC Centre for Protein Engineering, Cambridge, UK). These sequences can be used as a source of human sequence, e.g., for framework regions and CDRs. Consensus human framework regions can also be used, for example as described in U.S. Pat. No. 6,300,064.

“Humanized” antibodies, variants or fragments thereof, constructs and binding domains are based on immunoglobulins of mostly human sequences, which contain (a) minimal sequence(s) derived from non-human immunoglobulin. For the most part, humanized antibodies, variants or fragments thereof, constructs and binding domains are based on human immunoglobulins (recipient antibodies) in which residues from a hypervariable region or CDR are replaced by residues from a hypervariable region or CDR of a non-human species (donor antibody) such as a rodent (e.g. mouse, hamster, rat or rabbit) having the desired specificity, affinity, capacity and/or biological activity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, “humanized” antibodies, variants or fragments thereof, constructs and binding domains as used herein may also comprise residues which are found neither in the recipient antibody nor the donor antibody. These modifications are made to further refine and optimize antibody performance. The humanized antibodies, variants or fragments thereof, constructs and binding domains may also comprise at least a portion of an immunoglobulin constant region (such as Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature, 321: 522-525 (1986); Reichmann et al., Nature, 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992).

Humanized antibodies, variants or fragments thereof, constructs and binding domains can be generated by replacing sequences of the (Fv) variable region that are not directly involved in antigen binding with equivalent sequences from human (Fv) variable regions. Exemplary methods for generating such molecules are provided by Morrison (1985) Science 229:1202-1207; by Oi et al. (1986) BioTechniques 4:214; and by U.S. Pat. Nos. 5,585,089; 5,693,761; 5,693,762; 5,859,205; and 6,407,213. These methods include isolating, manipulating, and expressing the nucleic acid sequences that encode all or part of immunoglobulin (Fv) variable regions from at least one of a heavy or light chain. Such nucleic acids may be obtained from a hybridoma producing an antibody against a predetermined target, as described above, as well as from other sources. The recombinant DNA encoding the humanized antibody, variant or fragment thereof, construct or binding domain can then be cloned into an appropriate expression vector.

Humanized antibodies, variants or fragments thereof, constructs and binding domains may also be produced using transgenic animals such as mice that express human heavy and light chain genes but are incapable of expressing the endogenous mouse immunoglobulin heavy and light chain genes. Winter describes an exemplary CDR grafting method that may be used to prepare the humanized molecules described herein (U.S. Pat. No. 5,225,539). All the CDRs of a given human sequence may be replaced with at least a portion of a non-human CDR, or only some of the CDRs may be replaced with non-human CDRs. It is only necessary to replace the number of CDRs required for binding of the humanized molecule to a predetermined antigen.

A humanized antibody, variant or fragment thereof, construct or binding domain can be optimized by the introduction of conservative substitutions, consensus sequence substitutions, germline substitutions and/or back mutations. Such altered immunoglobulin molecules can be made by any of several techniques known in the art, (e.g., Teng et al., Proc. Natl. Acad. Sci. U.S.A., 80: 7308-7312, 1983; Kozbor et al., Immunology Today, 4: 7279, 1983; Olsson et al., Meth. Enzymol., 92: 3-16, 1982, and EP 239 400).

Human anti-mouse antibody (HAMA) responses have led the industry to prepare chimeric or otherwise humanized antibodies/constructs. It is however expected that certain human anti-chimeric antibody (HACA) responses will be observed, particularly in chronic or multi-dose utilizations of an antibody or construct. Thus, it would be desirable to provide constructs comprising a human binding domain against a target, to vitiate concerns and/or effects of HAMA or HACA response.

Therefore, according to one embodiment, the polypeptide construct having at least one further binding domain, said binding domain(s) are “human”. The term “human antibody”, “human construct” and “human binding domain” includes antibodies, constructs and binding domains, respectively, having antibody-derived regions such as variable and constant regions or domains which correspond substantially to human germline immunoglobulin sequences known in the art, including, for example, those described by Kabat et al. (1991) (loc. cit.). The human constructs or binding domains of the invention may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs, and particularly in CDR3. The human constructs or binding domains can have at least one, two, three, four, five, or more positions replaced with an amino acid residue that is not encoded by the human germline immunoglobulin sequence. The definition of human antibodies, constructs and binding domains as used herein also contemplates fully human antibodies, constructs and binding domains which include only non-artificially and/or genetically altered human sequences of antibodies as those can be derived by using technologies or systems such as the XenomouseT mouse.

Polypeptides/polypeptide constructs comprising at least one human binding domain may avoid some of the problems associated with antibodies or constructs that possess non-human such as rodent (e.g. murine, rat, hamster or rabbit) variable and/or constant regions. The presence of such rodent derived proteins can lead to the rapid clearance of the antibodies or constructs or can lead to the generation of an immune response against the antibody or construct by a patient. To avoid the use of rodent-derived constructs, humanized or fully human constructs can be generated through the introduction of human antibody function into a rodent so that the rodent produces fully human antibodies.

The ability to clone and reconstruct megabase-sized human loci in YACs and to introduce them into the mouse germline provides a powerful approach to elucidating the functional components of very large or crudely mapped loci as well as generating useful models of human disease. Furthermore, the use of such technology for substitution of mouse loci with their human equivalents could provide unique insights into the expression and regulation of human gene products during development, their communication with other systems, and their involvement in disease induction and progression.

An important practical application of such a strategy is the “humanization” of the mouse humoral immune system. Introduction of human immunoglobulin (Ig) loci into mice in which the endogenous Ig genes have been inactivated offers the opportunity to study the mechanisms underlying programmed expression and assembly of antibodies as well as their role in B-cell development. Furthermore, such a strategy could provide an ideal source for production of fully human monoclonal antibodies (mAbs)—an important milestone towards fulfilling the promise of antibody therapy in human disease. Fully human antibodies or constructs derived therefrom are expected to minimize the immunogenic and allergic responses intrinsic to mouse or mouse-derivatized mAbs and thus to increase the efficacy and safety of the administered antibodies/constructs. The use of fully human antibodies or constructs can be expected to provide a substantial advantage in the treatment of chronic and recurring human diseases, such as inflammation, autoimmunity, and cancer, which require repeated compound administrations.

One approach towards this goal was to engineer mouse strains deficient in mouse antibody production with large fragments of the human Ig loci in anticipation that such mice would produce a large repertoire of human antibodies in the absence of mouse antibodies. Large human Ig fragments would preserve the large variable gene diversity as well as the proper regulation of antibody production and expression. By exploiting the mouse machinery for antibody diversification and selection and the lack of immunological tolerance to human proteins, the reproduced human antibody repertoire in these mouse strains should yield high affinity antibodies against any antigen of interest, including human antigens. Using the hybridoma technology, antigen-specific human mAbs with the desired specificity could be readily produced and selected. This general strategy was demonstrated in connection with the generation of the first XenoMouse™ mouse strains (see Green et al. Nature Genetics 7:13-21 (1994)). The XenoMouse strains were engineered with yeast artificial chromosomes (YACs) containing 245 kb and 190 kb-sized germline configuration fragments of the human heavy chain locus and kappa light chain locus, respectively, which contained core variable and constant region sequences. The human Ig containing YACs proved to be compatible with the mouse system for both rearrangement and expression of antibodies and were capable of substituting for the inactivated mouse Ig genes. This was demonstrated by their ability to induce B cell development, to produce an adult-like human repertoire of fully human antibodies, and to generate antigen-specific human mAbs. These results also suggested that introduction of larger portions of the human Ig loci containing greater numbers of V genes, additional regulatory elements, and human Ig constant regions might recapitulate substantially the full repertoire that is characteristic of the human humoral response to infection and immunization. The work of Green et al. was extended to the introduction of greater than approximately 80% of the human antibody repertoire through introduction of megabase sized, germline configuration YAC fragments of the human heavy chain loci and kappa light chain loci, respectively. See Mendez et al. Nature Genetics 15:146-156 (1997) and U.S. patent application Ser. No. 08/759,620.

The production of the XenoMouse™ model is further discussed and delineated in U.S. patent application Ser. No. 07/466,008, Ser. No. 07/610,515, Ser. No. 07/919,297, Ser. No. 07/922,649, Ser. No. 08/031,801, Ser. No. 08/112,848, Ser. No. 08/234,145, Ser. No. 08/376,279, Ser. No. 08/430,938, Ser. No. 08/464,584, Ser. No. 08/464,582, Ser. No. 08/463,191, Ser. No. 08/462,837, Ser. No. 08/486,853, Ser. No. 08/486,857, Ser. No. 08/486,859, Ser. No. 08/462,513, Ser. No. 08/724,752, Ser. No. 08/759,620; and U.S. Pat. Nos. 6,162,963; 6,150,584; 6,114,598; 6,075,181, and 5,939,598 and Japanese Patent Nos. 3 068 180 B2, 3 068 506 B2, and 3 068 507 B2. See also Mendez et al. Nature Genetics 15:146-156 (1997) and Green and Jakobovits J. Exp. Med. 188:483-495 (1998), EP 0 463 151 B1, WO94/02602, WO96/34096, WO98/24893, WO 00/76310, and WO 03/47336.

In an alternative approach, others, including GenPharm International, Inc., have utilized a “minilocus” approach. In the minilocus approach, an exogenous Ig locus is mimicked through the inclusion of pieces (individual genes) from the Ig locus. Thus, one or more VH genes, one or more DH genes, one or more JH genes, a mu constant region, and a second constant region (preferably a gamma constant region) are formed into a construct for insertion into an animal. This approach is described in U.S. Pat. No. 5,545,807 to Surani et al. and U.S. Pat. Nos. 5,545,806; 5,625,825; 5,625,126; 5,633,425; 5,661,016; 5,770,429; 5,789,650; 5,814,318; 5,877,397; 5,874,299; and 6,255,458 each to Lonberg and Kay, U.S. Pat. Nos. 5,591,669 and 6,023,010 to Krimpenfort and Berns, U.S. Pat. Nos. 5,612,205; 5,721,367; and U.S. Pat. No. 5,789,215 to Berns et al., and U.S. Pat. No. 5,643,763 to Choi and Dunn, and GenPharm International U.S. patent application Ser. No. 07/574,748, Ser. No. 07/575,962, Ser. No. 07/810,279, Ser. No. 07/853,408, Ser. No. 07/904,068, Ser. No. 07/990,860, Ser. No. 08/053,131, Ser. No. 08/096,762, Ser. No. 08/155,301, Ser. No. 08/161,739, Ser. No. 08/165,699, Ser. No. 08/209,741. See also EP 0 546 073 B1, WO 92/03918, WO 92/22645, WO 92/22647, WO 92/22670, WO 93/12227, WO 94/00569, WO 94/25585, WO 96/14436, WO 97/13852, and WO 98/24884 and U.S. Pat. No. 5,981,175. See further Taylor et al. (1992), Chen et al. (1993), Tuaillon et al. (1993), Choi et al. (1993), Lonberg et al. (1994), Taylor et al. (1994), and Tuaillon et al. (1995), Fishwild et al. (1996).

Kirin has also demonstrated the generation of human antibodies from mice in which, through microcell fusion, large pieces of chromosomes, or entire chromosomes, have been introduced. See European Patent Application Nos. 773 288 and 843 961. Xenerex Biosciences is developing a technology for the potential generation of human antibodies. In this technology, SCID mice are reconstituted with human lymphatic cells, e.g., B and/or T cells. Mice are then immunized with an antigen and can generate an immune response against the antigen. See U.S. Pat. Nos. 5,476,996; 5,698,767; and 5,958,765.

In some embodiments, the constructs of the invention are “isolated” or “substantially pure” constructs. “Isolated” or “substantially pure”, when used to describe the constructs disclosed herein, means a construct that has been identified, separated and/or recovered from a component of its production environment. Preferably, the construct is free or substantially free of association with all other components from its production environment. Contaminant components of its production environment, such as that resulting from recombinant transfected cells, are materials that could interfere with diagnostic or therapeutic uses for the construct, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous compounds. It is understood that the isolated or substantially pure construct may constitute from 5% to 99.9% by weight of the total protein/polypeptide content in a given sample, depending on the circumstances. The desired construct may be produced at a significantly higher concentration using an inducible promoter or high expression promoter. The definition includes the production of a construct in a wide variety of organisms and/or host cells that are known in the art. In certain embodiments, the construct will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie Blue or, preferably, silver staining. Usually, however, an isolated construct will be prepared by at least one purification step.

According to one embodiment, the entire construct and/or the binding domains are in the form of one or more polypeptides or in the form of proteins. In addition to proteinaceous parts, such polypeptides or proteins may include non-proteinaceous parts (e.g. chemical linkers or chemical cross-linking agents such as glutaraldehyde).

Peptides are short chains of amino acid monomers linked by covalent peptide (amide) bonds. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers. Amino acids that are part of a peptide or polypeptide chain are termed “residues” and can be consecutively numbered. All peptides except cyclic peptides have an N-terminal residue at one end and a C-terminal residue at the other end of the peptide. An oligopeptide consists of only a few amino acids (usually between two and twenty). A polypeptide is a longer, continuous, and unbranched peptide chain. Peptides are distinguished from proteins based on size, and as an arbitrary benchmark can be understood to contain approximately 50 or fewer amino acids. Proteins consist of one or more polypeptides, usually arranged in a biologically functional way. While aspects of the lab techniques applied to peptides versus polypeptides and proteins differ (e.g., the specifics of electrophoresis, chromatography, etc.), the size boundaries that distinguish peptides from polypeptides and proteins are not absolute. Therefore, in the context of the present invention, the terms “peptide”, “polypeptide” and “protein” may be used interchangeably, and the term “polypeptide” is often preferred.

Polypeptides may further form multimers such as dimers, trimers and higher oligomers, which consist of more than one polypeptide molecule, as mentioned above. Polypeptide molecules forming such dimers, trimers etc. may be identical or non-identical. The corresponding structures of higher order of such multimers are, consequently, termed homo- or heterodimers, homo- or heterotrimers etc. An example for a hereteromultimer is an antibody or immunoglobulin molecule, which, in its naturally occurring form, consists of two identical light polypeptide chains and two identical heavy polypeptide chains. The terms “peptide”, “polypeptide” and “protein” also refer to naturally modified peptides/polypeptides/proteins wherein the modification is accomplished e.g. by post-translational modifications like glycosylation, acetylation, phosphorylation and the like. A “peptide”, “polypeptide” or “protein” when referred to herein may also be chemically modified such as pegylated. Such modifications are well known in the art and described herein below.

The terms “selectively” and, “preferably, selectively”, “(specifically or immunospecifically) binds to”, “(specifically or immunospecifically) recognizes”, or “(specifically or immunospecifically) reacts with” mean in accordance with this invention that a construct or a binding domain selectively interacts or (immuno-)specifically interacts with a given epitope on the target molecule (antigen), here: CD3, respectively. This selective interaction or association occurs more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of these parameters, to an epitope on the specific target (here: CD3epsilon) than to alternative substances (non-target molecules, e.g., here CD3gamma, etc.). Because of the sequence similarity between homologous proteins in different species, a construct or a binding domain that selectively and/or immunspecifically binds to its target (such as a human target) may, however, cross-react with homologous target molecules from different species (such as, from non-human primates). The terms “selectively binds to”, “specific/immunospecific binding”, etc. can hence include the binding of a construct or binding domain to epitopes or structurally related epitopes in more than one species. In the context of the present invention, a polypeptide of the present invention binds to its respective target structure in a particular manner. Preferably, a polypeptide according to the present invention comprises one paratope per binding domain which specifically or immunospecifically binds to”, “(specifically or immunospecifically) recognizes”, or “(specifically or immunospecifically) reacts with” its respective target structure. This means in accordance with this invention that a polypeptide or a binding domain thereof interacts or (immuno-)specifically interacts with a given epitope on the target molecule (antigen), namely CD3epsilon, and in certain embodiments with a given epitope on at least one further, such as a second and/or a third target molecule. This interaction or association occurs more frequently, more rapidly, with greater duration, with greater affinity, or with some combination of these parameters, to an epitope on the specific target than to alternative substances (non-target molecules). Because of the sequence similarity between homologous proteins in different species, an antibody construct or a binding domain that immunspecifically binds to its target (such as a human target) may, however, cross-react with homologous target molecules from different species (such as, from non-human primates). The term “specific/immunospecific binding” can hence include the binding of an antibody construct or binding domain to epitopes and/or structurally related epitopes in more than one species. The term “(immuno-) selectively binds does exclude the binding to structurally related epitopes.

In the context of the present invention, the term “epitope” refers to the part or region of the antigen that is selectively recognized/immunospecifically recognized by the binding structure, i.e. the paratope. An “epitope” is antigenic, and thus the term epitope is sometimes also referred to as “antigenic structure” or “antigenic determinant”. The part of the binding domain that binds to the epitope is called a paratope. Specific binding is believed to be accomplished by specific motifs in the amino acid sequence of the binding domain and the antigen. Thus, binding is achieved because of their primary, secondary and/or tertiary structure as well as the result of potential secondary modifications of said structures. The specific interaction of the paratope with its antigenic determinant may result in a simple binding of said site to the antigen. In some cases, the specific interaction may alternatively or additionally result in the initiation of a signal, e.g. due to the induction of a change of the conformation of the antigen, an oligomerization of the antigen, etc.

The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope. A conformational epitope is composed of discontinuous sections of the antigen's amino acid sequence. These epitopes interact with the paratope based on the three-dimensional surface features and shape or tertiary structure (folding) of the antigen. Methods of determining the conformation of epitopes include, but are not limited to, x-ray crystallography, two-dimensional nuclear magnetic resonance (2D-NMR) spectroscopy and site-directed spin labelling and electron paramagnetic resonance (EPR) spectroscopy. By contrast, linear epitopes interact with the paratope based on their primary structure. A linear epitope is formed by a continuous sequence of amino acids from the antigen and typically includes at least 3 or at least 4, and more usually, at least 5 or at least 6 or at least 7, for example, about 8 to about 10 amino acids in a unique sequence.

A method for epitope mapping for a given human target protein is described in the following: A pre-defined region (a contiguous amino acid stretch) within said given human target protein is exchanged/replaced with a corresponding region of a target protein paralogue (so long as the binding domain is not cross-reactive with the paralogue used). These human target/paralogue chimeras are expressed on the surface of host cells (such as CHO cells). Binding of the antibody or construct can be tested via FACS analysis. When the binding of the antibody or construct to the chimeric molecule is entirely abolished, or when a significant binding decrease is observed, it can be concluded that the region of human target which was removed from this chimeric molecule is relevant for the immunospecific epitope-paratope recognition. Said decrease in binding is preferably at least 10%, 20%, 30%, 40%, or 50%; more preferably at least 60%, 70%, or 80%, and most preferably 90%, 95% or even 100% in comparison to the binding to human (wild-type) target, whereby binding to the human target is set to be 100%. Alternatively, the above described epitope mapping analysis can be modified by introducing one or several point mutations into the sequence of the human target. These point mutations can e.g. reflect the differences between the human target and its paralogue.

A further method to determine the contribution of a specific residue of a target antigen to the recognition by a construct or binding domain is alanine scanning (see e.g. Morrison KL & Weiss G A. Curr Opin Chem Biol. 2001 June; 5(3):302-7), where each residue to be analyzed is replaced by alanine, e.g. via site-directed mutagenesis. Alanine is used because of its non-bulky, chemically inert, methyl functional group that nevertheless mimics the secondary structure references that many of the other amino acids possess. Sometimes bulky amino acids such as valine or leucine can be used in cases where conservation of the size of mutated residues is desired.

The interaction between the binding domain and the epitope of the target antigen implies that a binding domain exhibits appreciable or significant affinity for the epitope/the target antigen (here: CD3) and, generally, does not exhibit significant affinity for proteins or antigens other than the target antigen—notwithstanding the above discussed cross-reactivity with homologous targets e.g. from other species. “Significant affinity” includes binding with an affinity (dissociation constant, KD) of ≤10⁻⁶M. Preferably, binding is considered specific when the binding affinity is ≤10⁻⁷M, ≤10⁻⁸M, ≤10⁻⁹M, ≤10⁻¹⁰M, or even ≤10¹¹M, or ≤10⁻¹²M. Whether a binding domain (immuno-)specifically reacts with or binds to a target can be tested readily e.g. by comparing the affinity of said binding domain to its desired target protein or antigen with the affinity of said binding domain to non-target proteins or antigens (here: proteins other than CD3). Preferably, a construct of the invention does not significantly bind to proteins or antigens other than CD3 (i.e., the CD3 binding domain does not bind to proteins other than CD3)—unless any further binding domain(s) directed against a further target is/are deliberately introduced into the construct of the invention, in which case the binding of that binding domain to its specific target is also provided by the present invention.

It is envisaged that the affinity of the first domain for human CD3epsilon is ≤100 nM, ≤90 nM, ≤80 nM, ≤70 nM, ≤60 nM, ≤50 nM, ≤40 nM, ≤30 nM or ≤20 nM. These values are preferably measured in a cell-based assay, such as a Scatchard assay. Other methods of determining the affinity are also well-known. These values are preferably measured in a surface plasmon resonance assay, such as a Biacore assay.

The term “does not significantly bind” and “does not selectively bind” mean that a construct or binding domain of the present invention does not bind to a protein or antigen other than said CD3, when said protein or antigen is expressed on the surface of a cell. The construct hence shows reactivity of ≤30%, preferably ≤20%, more preferably ≤10%, particularly preferably ≤9%, ≤8%, ≤7%, ≤6%, ≤5%, ≤4%, ≤3%, ≤2%, or ≤1% with proteins or antigens other than CD3 (when said proteins or antigens are expressed on the surface of a cell), whereby binding to CD3, respectively, is set to be 100%. The “reactivity” can e.g. be expressed in an affinity value (see above).

It is envisaged that the construct of the invention (and more specifically the domain comprising a paratope/binding domain that binds to human CD3epsilon) does not bind or does not significantly bind to CD3epsilon paralogues, more specifically to human CD3epsilon paralogues and/or to macaque/cyno CD3epsilon paralogues. It is also envisaged that the construct does not bind or does not significantly bind to (human or macaque/cyno) CD3epsilon paralogues on the surface of a target cell.

The VH region as part of the binding domain binding to an extracellular epitope of the human CD3ε chain comprises a CDR-H1, a CDR-H2 and CDR-H3 sequence as set out herein above. The CDR sequences contain placeholders denoted as “X” for a given amino acid residue that can take the place of the placeholder as is common practice in the art. The placeholders are consecutively numbered in the format X₁, X₂, X₃, and so forth, per given CDR sequence. The amino acid residues that can take place of the placeholder in the recited CDR sequences are listed according to preference, wherein the first listed amino acid is the most preferred, the second listed is the second most preferred, and so forth, if not otherwise specified, e.g. in other embodiments. If a sequence contains more than one placeholder, the same applies in relation to the preference of the amino acids; namely, it is the combination of the first listed amino acid residue for each of the placeholders that is most preferred, the combination of the second listed amino acid residue for each of the placeholders that is second most preferred, and so forth. This hierarchy of preference does not exclude the combination of amino acid residues for each of the placeholders independent of said preference hierarchy so that amino acid residues of different preference are combined. The same hierarchy is true for all amino acid residues that are listed herein below to take the place of a place holder in an amino acid sequence described herein below. Accordingly, the above also applies for the placeholders denoted as “X” in the sequences of the VH and VL sequences and any other sequences recited throughout the specification.

The CDR-H1 sequence comprises the amino acid sequence of X₁YAX₂N, where X, is K, V, S, G, R, T, or I; and X₂is M or I. Following the above-explained hierarchy as regards the placeholder amino acids, the amino acids for the placeholders X₁and X₂are listed according to their preference, wherein the first listed amino acid is the most preferred, the second listed is the second-most preferred, and so forth. For X₁, the amino acid K is most preferred, and for X₂, the amino acid M is most preferred. A preferred combination is M for X₂in combination with any of the amino acid residues of X₁, such as the combinations for X₁and X₂, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₁and X₂, respectively. Preferred examples of the CDR-H1 sequence are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, TYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is most preferred.

The CDR-H2 sequence comprises the amino acid sequence of RIRSKYNNYATYYADX₁VK X₂, where X, is S or Q; and X₂is D, G, K, S, or E. For X₁, the amino acid S is most preferred, and for X₂, the amino acid D is most preferred. A preferred combination is S for X₁in combination with any of the amino acid residues of X₂, such as the combinations for X₁and X₂, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of the CDR-H2 sequence are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD is most preferred.

The CDR-H3 sequence comprises the amino acid sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G, R, or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y. For X₁, the amino acid G is most preferred; for X₂, the amino acid I is most preferred; for X₃, the amino acid Y is most preferred; and for X₄, the amino acid W is most preferred. Preferred examples of the CDR-H3 sequence are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred.

The CDR-L1 sequence comprises the amino acid sequence of X₁SSTGAVTX₂X₃X₄YX₅N, where X, is G, R, or A; X₂is S or T; X₃is G or S; X₄is N or Y; and X₅is P or A. For X₁, the amino acid G is most preferred; for X₂, the amino acid S is most preferred; for X₃, the amino acid G is most preferred; for X₄, the amino acid N is most preferred; and for X₅, the amino acid P is most preferred. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred.

The CDR-L2 sequence comprises the amino acid sequence of X₁TX₂X₃X₄X₅X₆; where X, is G or A; X₂is K, D, or N; X₃is F, M or K; X₄is L or R; X₅is A, P, or V; and X₆is P or S. For X₁, the amino acid G is most preferred; for X₂, the amino acid K is most preferred; for X₃, the amino acid F is most preferred; for X₄, the amino acid L is most preferred; for X₅, the amino acid A is most preferred and for X₆, the amino acid P is most preferred. Preferred examples of the CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred.

The CDR-L3 sequence comprises the amino acid sequence of X₁LWYSNX₂WV, where X, is V, A, or T; and X₂is R or L. For X₁, the amino acid V is most preferred, and for X₂, the amino acid R is most preferred. Preferred combinations are R for X₂in combination with any of the amino acid residues of X₁, such as the combinations for X₁and X₂, respectively, selected from V and R, A and R, T and R, most preferred the combination V and R. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

In a preferred embodiment, said VH region of i) comprises: a CDR-H1 sequence comprising or consisting of the amino acid sequence of X₁YAX₂N, where X, is K, V, S, G, R, or I; and X₂is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX₁VKX₂, where X, is S or Q; and X₂is D, G, K, S, or E; and a CDR-H3 sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G, R, or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y; and said VL region of ii) comprises: a CDR-L1 sequence of X₁SSTGAVTSGX₂YPN, where X, is G, R, or A; and X₂is N or Y; a CDR-L2 sequence of X₁TX₂X₃X₄X₅X₆; where X, is G or A; X₂is K or D; X₃is F or M; X₄is L or R; X₅is A, P, or V; and X₆is P or S; and a CDR-L3 sequence of X₁LWYSNRWV, where X, is V, A, or T; and wherein said one or more CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one or more amino acid substitutions selected from X₂4V or X₂4F in CDR-H1; D15 (preferably E), X₁16A in CDR-H2; H1 (preferably A or N), X₁2E, F4 (preferably I), and/or N6 (preferably S or T) in CDR-H3; and W93 (preferably Y) in CDR-L3.

Said CDR-H1 sequence comprises or consists of the amino acid sequence of X₁YAX₂N, where X, is K, V, S, G, R, or I; and X₂is M or I. For X₁, the amino acid K is most preferred, and for X₂, the amino acid M is most preferred. A preferred combination is M for X₂in combination with any of the amino acid residues of X₁, such as the combinations for X₁and X₂, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₁and X₂, respectively. Preferred examples of the CDR-H1 sequence are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is preferred, wherein KYAMN is most preferred.

Said CDR-H2 sequence comprises or consist of the amino acid sequence of RIRSKYNNYATYYADX₁VK X₂, where X, is S or Q; and X₂is D, G, K, S, or E. For X₁, the amino acid S is most preferred, and for X₂, the amino acid D is most preferred. A preferred combination is S for X₁in combination with any of the amino acid residues of X₂, such as the combinations for X₁and X₂, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of the CDR-H2 sequence are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD is most preferred.

The CDR-L1 sequence comprises the amino acid sequence of X₁SSTGAVTSGX₂YPN, where X, is G, R, or A; and X₂is N or Y. For X₁, the amino acid G is most preferred; and for X₂, the amino acid N is preferred. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, and ASSTGAVTSGNYPN, wherein GSSTGAVTSGNYPN or ASSTGAVTSGNYPN is preferred, wherein GSSTGAVTSGNYPN is most preferred.

The CDR-L2 sequence comprises the amino acid sequence of X₁TX₂X₃X₄X₅X₆; where X, is G or A; X₂is K or D; X₃is F or M; X₄is L or R; X₅is A, P, or V; and X₆is P or S. For X₁, the amino acid G is most preferred; for X₂, the amino acid K is most preferred; for X₃, the amino acid F is most preferred; for X₄, the amino acid L is most preferred; for X₅, the amino acid A is most preferred and for X₆, the amino acid P is most preferred. Preferred examples of the CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, and GTKFLVP, wherein GTKFLAP or GTKFLVP is preferred, wherein GTKFLAP is most preferred.

The CDR-L3 sequence comprises the amino acid sequence of X₁LWYSNRWV, where X, is V, A, or T, wherein the amino acid V is most preferred. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, and TLWYSNRWV, wherein VLWYSNRWV or TLWYSNRWV is more preferred, wherein VLWYSNRWV is most preferred.

In a further preferred embodiment, said VH region of i) comprises: a CDR-H1 sequence comprising or consisting of the amino acid sequence of X₁YAX₂N, where X, is K, V, S, R, or I; and X₂is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX₁VKX₂, where X, is S or Q; and X₂is D, G, K, or S; and a CDR-H3 sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y; and said VL region of ii) comprises: a CDR-L1 sequence of X₁SSTGAVTSGX₂YPN, where X, is G or A; and X₂is N or Y; a CDR-L2 sequence of GTKFLX₁P; where X, is A or V; and a CDR-L3 sequence of X₁LWYSNRWV, where X, is V, A, or T; and wherein said one or more CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one or more amino acid substitutions selected from X₂4V or X₂4F in CDR-H1; D15 (preferably E), X₁16A in CDR-H2; H1 (preferably A or N), X₁2E, F4 (preferably I), and/or N6 (preferably S or T) in CDR-H3; and W93 (preferably Y) in CDR-L3.

Said CDR-H1 sequence comprises or consists of the amino acid sequence of X₁YAX₂N, where X, is K, V, S, R, or I; and X₂is M or I. For X₁, the amino acid K is most preferred, and for X₂, the amino acid M is most preferred. A preferred combination is M for X₂in combination with any of the amino acid residues of X₁, such as the combinations for X₁and X₂, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₁and X₂, respectively. Preferred examples of the CDR-H1 sequence are selected from KYAMN, VYAMN, SYAMN, RYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is preferred, wherein KYAMN is most preferred.

Said CDR-H2 sequence comprises or consist of the amino acid sequence of RIRSKYNNYATYYADX₁VKX₂, where X, is S or Q; and X₂is D, G, K, or S. For X₁, the amino acid S is most preferred, and for X₂, the amino acid D is most preferred. A preferred combination is S for X₁in combination with any of the amino acid residues of X₂, such as the combinations for X₁and X₂, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of the CDR-H2 sequence are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADQVKD is preferred, wherein RIRSKYNNYATYYADSVKD is most preferred.

Said CDR-H3 sequence comprises or consist of the amino acid sequence of HX₁NFGNSYX₂SX₃X₄AY, where X, is G or A; X₂is I, L, V, or T; X₃is Y, W or F; and X₄is W, F or Y. For X₁, the amino acid G is most preferred; for X₂, the amino acid I is most preferred; for X₃, the amino acid Y is most preferred; and for X₄, the amino acid W is most preferred. Preferred examples of the CDR-H3 sequence are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, and HANFGNSYISYWAY, wherein HGNFGNSYISYWAY or HANFGNSYISYWAY is preferred, wherein HGNFGNSYISYWAY is most preferred.

Said CDR-L1 sequence comprises or consists the amino acid sequence of X₁SSTGAVTSGX₂YPN, where X, is G or A; and X₂is N or Y. For X₁, the amino acid G is most preferred; and for X₂, the amino acid N is preferred. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, GSSTGAVTSGYYPN, and ASSTGAVTSGNYPN, wherein GSSTGAVTSGNYPN or ASSTGAVTSGNYPN is preferred, wherein GSSTGAVTSGNYPN is most preferred.

Said CDR-L2 sequence comprises or consists of the amino acid sequence of GTKFLX₁P; where X, is A or V. For X₁, the amino acid A is preferred. Said CDR-L2 sequence is GTKFLAP or GTKFLVP, wherein GTKFLAP is preferred.

The CDR-L3 sequence comprises or consists of the amino acid sequence of X₁LWYSNRWV, where X, is V, A, or T, wherein the amino acid V is most preferred. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, and TLWYSNRWV, wherein VLWYSNRWV or TLWYSNRWV is more preferred, wherein VLWYSNRWV is most preferred.

In an even more preferred embodiment, said VH region of i) comprises: a CDR-H1 sequence comprising or consisting of the amino acid sequence of X₁YAMN, where X, is K or S; a CDR-H2 sequence of RIRSKYNNYATYYADSVKX₁, where X, is D or G; and a CDR-H3 sequence of HGNFGNSYX₁SX₂WAY, where X, is I or V; and X₂is Y or W; and said VL region of ii) comprises: a CDR-L1 sequence of GSSTGAVTSGX₁YPN, where X, is N or Y; a CDR-L2 sequence of GTKFLAP; and a CDR-L3 sequence of X₁LWYSNRWV, where X, is V or A; and wherein said one or more CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one or more amino acid substitutions selected from M4V or M4F in CDR-H1; D15 (preferably E), S16A in CDR-H2; H1 (preferably A or N), G2E, F4 (preferably I), and/or N6 (preferably S or T) in CDR-H3; and W93 (preferably Y) in CDR-L3.

Said CDR-H1 sequence comprises or consists of the amino acid sequence of X₁YAMN, where X, is K or S, wherein the amino acid K is preferred. Said CDR-H1 sequence is KYAMN or SYAMN, wherein KYAMN is most preferred.

Said CDR-H2 sequence comprises or consist of the amino acid sequence of RIRSKYNNYATYYADSVKX₁, where X, is D or G. For X₁, the amino acid D is preferred. Said CDR-H2 sequence is RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADSVKG, wherein RIRSKYNNYATYYADSVKD is preferred.

Said CDR-H3 sequence comprises or consist of the amino acid sequence of HGNFGNSYX₁SX₂WAY, where X, is I or V; and X₂is Y or W. For X₁, the amino acid I is preferred; for X₂, the amino acid Y is preferred. Said CDR-H3 sequence is HGNFGNSYISYWAY or HGNFGNSYVSWWAY, wherein HGNFGNSYISYWAY is preferred.

Said CDR-L1 sequence comprises or consists the amino acid sequence of GSSTGAVTSGX₁YPN, where X, is N or Y. For X₁, the amino acid N is preferred. Said CDR-L1 sequence is GSSTGAVTSGNYPN or GSSTGAVTSGYYPN, wherein GSSTGAVTSGNYPN is preferred.

Said CDR-L2 sequence comprises or consists of the amino acid sequence of GTKFLAP.

The CDR-L3 sequence comprises or consists of the amino acid sequence of X₁LWYSNRWV, where X, is V or A, wherein V is preferred. Said CDR-L3 sequence VLWYSNRWV or ALWYSNRWV, wherein VLWYSNRWV is preferred.

Each of the CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 sequences be freely combined in the format CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3 (this is the preferred orientation of the VH and the VL region) or CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, CDR-H3 and exhibiting the recited binding to an extracellular epitope of the human CD3ε chain.

Preferred combinations of CDR-L1 to L3 sequences of the VL region and preferred combinations of CDR-H1 to H3 sequences of the VH region are listed in the below Table 1.

TABLE 1

CDR-L1
CDR-L2
CDR-L3

GSSTGAVTSGYYP
GTKFLAP
ALWYSNRWV

N

RSSTGAVTSGYYP
ATDMRPS
ALWYSNRWV

N

GSSTGAVTSGNYP
GTKFLAP
VLWYSNRWV

N

ASSTGAVTSGNYP
GTKFLVP
TLWYSNRWV

N

RSSTGAVTTSNYA
GTNKRAP
ALWYSNLWV

N

CDR-H1
CDR-H2
CDR-H3

IYAMN
RIRSKYNNYATYYADSVKS
HGNFGNSYVSFFAY

KYAMN
RIRSKYNNYATYYADSVKD
HGNFGNSYISYWAY

SYAMN
RIRSKYNNYATYYADSVKG
HGNFGNSYLSFWAY

RYAMN
RIRSKYNNYATYYADSVKG
HGNFGNSYLSYFAY

VYAMN
RIRSKYNNYATYYADSVKK
HGNFGNSYLSWWAY

KYAMN
RIRSKYNNYATYYADSVKS
HGNFGNSYTSYYAY

GYAMN
RIRSKYNNYATYYADSVKE
HRNFGNSYLSWFAY

VYAMN
RIRSKYNNYATYYADSVKK
HGNFGNSYISWWAY

SYAMN
RIRSKYNNYATYYADSVKG
HGNFGNSYVSWWAY

KYAIN
RIRSKYNNYATYYADQVKD
HANFGNSYISYWAY

TYAMN
RIRSKYNNYATYYADSVKD
HGNFGNSYVSWFAY

Preferably, any of the above listed combinations of CDR-L1 to L3 combinations is combined with any of the above-listed combinations CDR-H1 to H3 as part of the binding domain binding to an extracellular of the human CD3ε chain. In other words, the VL region comprises or consists of as CDR-L1, CDR-L2, CDR-L3 sequence, in this order,

GSSTGAVTSGYYPN, GTKFLAP, ALWYSNRWV;

RSSTGAVTSGYYPN, ATDMRPS, ALWYSNRWV;

GSSTGAVTSGNYPN, GTKFLAP, VLWYSNRWV;

ASSTGAVTSGNYPN, GTKFLVP, TLWYSNRWV;

or

RSSTGAVTTSNYAN, GTNKRAP, ALWYSNLWV;

the VL region comprises or consists of as CDR-H1, CDR-H2, CDR-H3 sequence, in this order,

IYAMN, RIRSKYNNYATYYADSVKS, HGNFGNSYVSFFAY;

KYAMN, RIRSKYNNYATYYADSVKD, HGNFGNSYISYWAY;

SYAMN, RIRSKYNNYATYYADSVKG, HGNFGNSYLSFWAY;

RYAMN, RIRSKYNNYATYYADSVKG, HGNFGNSYLSYFAY;

VYAMN, RIRSKYNNYATYYADSVKK, HGNFGNSYLSWWAY;

KYAMN, RIRSKYNNYATYYADSVKS, HGNFGNSYTSYYAY;

GYAMN, RIRSKYNNYATYYADSVKE, HRNFGNSYLSWFAY;

VYAMN, RIRSKYNNYATYYADSVKK, HGNFGNSYISWWAY;

SYAMN, RIRSKYNNYATYYADSVKG, HGNFGNSYVSWWAY;

KYAIN, RIRSKYNNYATYYADQVKD, HANFGNSYISYWAY;

or

TYAMN, RIRSKYNNYATYYADSVKD, HGNFGNSYVSWFAY.

In accordance with the invention, preferred CDR sequence combinations of the VH and the VL regions, listed in the order CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3, are as defined in SEQ ID NOs: 118 to 123, 166 to 171, 356 to 361, 546 to 551, 724 to 729, 922 to 927, 1100 to 1105, 1290 to 1295, 1468 to 1473, 1658 to 1663, 1848 to 1853.

Most preferred is that the VL region comprises as CDR-L1, CDR-L2, CDR-L3 sequence, listed in this order,

GSSTGAVTSGNYPN, GTKFLAP, VLWYSNRWV; and

the VL region comprises as CDR-H1, CDR-H2, CDR-H3 sequence, listed in this order, KYAMN, RIRSKYNNYATYYADSVKD, HGNFGNSYISYWAY; as depicted in SEQ ID NOs: 1848 to 1853. Preferably the orientation of the CDRs is VH to VL, i.e. the orientation of the variable regions is from N- to C-terminus VH to VL.

In accordance with the invention, said CDR sequences of the VH and/or the VL region comprise one or more amino acid substitutions. As is common in the art, the position and nature of amino acid substitutions are denoted herein by indicating the original amino acid residue at the position to be substituted and the amino acid used for substitution in the format of, e.g., F41, wherein “F” denotes the original amino acid residue occurring at position “4” of the given amino acid sequence and “I” denotes the amino acid residue which substituted “F” at position 4. In case substitution is by any amino acid residue (other than the original amino acid residue), no amino acid residue is indicated, but only the originally occurring amino acid residue and its position in the given amino acid sequence, so that the previous example would be denoted as “F4” only. Preferably, only naturally occurring amino acids are used for substitution.

The VH region of i) and/or VL region of ii) comprise one or more amino acid substitutions as specified herein in one or more CDR sequences as recited herein above. Accordingly, at least one of the recited amino acid substitutions of the variable regions is comprised in said binding domain binding to an extracellular epitope of the human CD3ε chain. Said at least one or one or more amino acid substitution, in the case that only one amino acid substation is present, can be present in a CDR sequence in said VH or said VL region or, in case more than one amino acid substitution is present, in CDRs in both the VH and the VL region or restricted to CDR sequences in only the VH or the VL region. In certain embodiments where there are more than one amino acid substitutions, the substitutions are in the VH and the VL region or, alternatively, only in one variable region. Preferably, the substitutions are in the CDRs of the VH and the VL region.

In case the CDR-H1 is to comprise an amino acid substitution at position 4 it is, preferably, the substitution of the original amino acid with the amino acid V. Preferably, the CDR-H1 sequence is KYAIN or KYAMN, i.e. comprising none of said recited amino acid substitutions.

In CDR-H2, the amino acid substitution at position 15 is, preferably, D15E, or the amino acid substitution at position 16 with amino acid A. Preferably, CDR-H1 comprises the amino acid residue substitution at position 16 with amino acid A; in this case, a preferred amino acid for the last amino acid of CDR-H2 is D or G, most preferred D. Hence, a preferred CDR-H2 sequence is RIRSKYNNYATYYADAVKD or RIRSKYNNYATYYADAVKG, with RIRSKYNNYATYYADAVKD more preferred. In case CDR-H2 contains two amino acid substitutions, the combination of the amino acid E at position 15 and amino acid A at position 16 are preferred; in this case, a preferred amino acid for the last amino acid of CDR-H2 is G. Hence, a preferred CDR-H2 sequence for the combination of the amino acid E at position 15 and amino acid A at position 16 is RIRSKYNNYATYYAEAVKG.

In CDR-H3, the amino acid substitutions are at position 1, preferably a substitution with amino acid A or N, at position 2 with amino acid E, at position 4, preferably with amino acid I, and at position 6, preferably with amino acid S or T. Preferably, CDR-H3 comprises the amino acid A or N at position 1, the amino acid S or T at position 6; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, preferred amino acids for X₁are G or A, most preferred G; for X₂is I; for X₃is Y; and for X₄are W or Y. In case CDR-H3 comprises two amino acid substitutions, preferred combinations are the amino acid A at position 1 and the amino acid S at position 6; and the amino acid N at position 1 and the amino acid T at position 6; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₁is G or A, most preferred G; for X₂is I, for X₃is Y, and for X₄are W and F. In case CDR-H3 comprises three amino acid substitutions, preferred combinations are the amino acid A at position 1, the amino acid I at position 4, and the amino acid S at position 6; and the amino acid N at position 1, the amino acid I at position 4 and the amino acid T at position 6, in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₂is I, for X₃is Y, and for X₄are W and F. In case CDR-H3 comprises four amino acid substitutions, a preferred combination is the amino acid N at position 1, the amino acid E at position 2, the amino acid I at position 4, and the amino acid T at position 6; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₂is I, for X₃is Y, and for X₄is W. Hence, preferred CDR-H3 sequences are selected from AGNFGSSYISYWAY, NENIGTSYISYWAY, AGNFGTSYISYWAY, NANFGTSYISYFAY, and AGNFGSSYISYFAY, with AGNFGSSYISYWAY and AGNFGSSYISYFAY most preferred.

In CDR-L3, the amino acid substitution at position 1 is with amino acid L or the amino acid substitution is W93, preferably W93Y (which may also be referred to as X₁93Y), in the sequence of X₁LWYSNX₂WV, where X, is V, A, or T; and X₂is R or L. Preferably, the CDR-L3 sequence is VLYYSNRWV when CDR-L3 comprises only one amino acid substitution. It is preferred, however, that CDR-L3 does not comprise said X₁1L and W93 amino acid substitution, in which case a preferred CDR-L3 sequence is VLYYSNRWV.

Without wishing to be bound by a specific scientific theory, each of the above recited amino acid substitution(s) lead(s) to an increase in thermal stability of the binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region linked to a VL region as described herein as compared to the binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region linked to a VL region sequence that is unmodified, i.e. does not contain said amino acid residue substitution(s). Said increase of the temperature stability is, preferably, measured by the well know and also herein described method of Differential Scanning Fluorimetry (DSF). Said method is, e.g., described in Wen et al., “Nano differential scanning fluorimetry for comparability studies of therapeutic proteins”, Analytical Biochemistry, Volume 593, 2020, 113581, ISSN 0003-2697; or Dart, M. L., et al. (2018). “Homogeneous Assay for Target Engagement Utilizing Bioluminescent Thermal Shift”. ACS medicinal chemistry letters, 9(6), 546-551). As evident from the example section, it was shown that the amino acid substitutions or combinations thereof as defined herein result in an increased thermal stability (see Example 1, Table 2 and 3) as compared to the unmodified CD3 binding domain defined herein (“I2C”) while the cytotoxic activity was maintained which was not the case with a prior art method to improve thermal stability, namely the CC44/100 cys clamp, in which an additional disulfide bond was engineered for stabilizing (Reiter, Y. et al., 1994) by replacing the amino acid residues with cysteine residues at position 44 in the heavy chain variable region and at position 100 in the light chain variable region (numbering scheme according to Kabat et al., 1991) of the unmodified CD3 binding domain defined herein (VH and VL SEQ ID NOs: 1854 and 1855, respectively; see Example 2, Table 5). The VH and VL region combinations of the CD3epsilon binding domain described herein are therefore temperature stabilized as compared to the VH and VL region sequence that does not contain the given substitution(s) that are introduced at the positions defined herein.

In a preferred embodiment of the polypeptide or polypeptide construct of claim 1 of the invention, in addition to said one amino acid substitution or a combination thereof as defined in iii) X₂is I in said CDR-H1 sequence; X₂is G in said CDR-H2 sequence; X₁is A, X₄is F in said CDR-H3 sequence; and/or X₁is A in said CDR-L3 sequence. The one amino acid substitution or combination thereof as defined herein is/are in addition combined with specific amino acids at specific positions in the CDRs. Hence, at least one of the recited amino acid substitutions in accordance with iii) is present and at least one of X₂is G in said CDR-H2 sequence; X₁is A, X₄is F in said CDR-H3; and/or X₁is A in said CDR-L3 sequence is additionally present in the CDRs. As previously stated herein above, a preferred amino acid for X₂is I in said CDR-H1 sequence or X₂is G in said CDR-H2 sequence, if only one additional amino acid is present in the CDRs, wherein it is most preferred that X₂is I in said CDR-H1 sequence. A preferred combination of two of said additional amino acids is X₂is I in said CDR-H1 sequence and X₄is F in said CDR-H3 sequence; or X₂is G in said CDR-H2 sequence and X₄is F in said CDR-H3 sequence. A preferred combination of three of said additional amino acids is X₂is I in said CDR-H1 sequence, X, is A, and X₄is F in said CDR-H3 sequence; or X₂is I in said CDR-H1 sequence, X₄is F in said CDR-H3 sequence, and X, is A in said CDR-L3 sequence. Since the latter amino acids are to be present additionally, it is understood that those recited additional amino acids that overlap in position with the amino acid substitution of iii) cannot replace the overlapping amino acid substitution. For example, if the only amino acid substitution in accordance with iii) is either X₂4V or X₂4F in CDR-H1, said amino acid cannot be replaced by amino acid I in said CDR-H1 sequence, since there would be no amino acid substitution as defined in iii) remaining in the binding domain. In other terms, there must always be at least one of the amino acid substitutions as defined in iii) comprised in the polypeptide or polypeptide construct of the invention.

It is also understood that depending on the actual sequence of the CDRs, one or more of said additional amino acids may already be part of the CDRs as defined herein above or, if this is not the case, those CDRs will be changed to exhibit said additional amino acid(s) in combination with one amino acid substitution or a combination thereof as recited in iii).

In another preferred embodiment, the polypeptide or polypeptide construct of the invention comprises or consists of combinations of said amino acid substitutions as defined in iii) of two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more amino acid substitutions, or of up to two, three, four, five, six, seven, eight, nine, ten, eleven, twelve amino acid substitutions. Preferably, only the substitution(s) defined herein are introduced in the VH and the VL region sequence. This applies to all embodiments recited herein so that the VH and the VL region sequence consists of the unmodified amino acid sequence with the substitution(s) as defined herein.

More specifically, it is preferred that i) said one amino acid substitution is selected from: a. X₂4V or X₂4F in CDR-H1; H1A in CDR-H3; and b. X₁1L and W3Y in CDR-L3; ii) said combination of two or more amino acid substitutions are selected from X₁16A in CDR-H2 and N6S in CDR-H3; and X₁16A in CDR-H2 and N6T in CDR-H3; iii) said combination of three or more amino acid substitutions are selected from X₁16A in CDR-H2, H1A and N6S in CDR-H3; X₁16A in CDR-H2, H1A and N6T in CDR-H3; X₁16A in CDR-H2, H1N and N6T in CDR-H3; iv) said combination of four or more amino acid substitutions are selected from X₁16A in CDR-H2, H1A, N6S in CDR-H3, and W3Y in CDR-L3; D15E, X₁16A in CDR-H2, H1A, and N6T in CDR-H3; D15E, X₁16A in CDR-H2, H1A, and N6S in CDR-H3; X₁16A in CDR-H2, H1A, F41 and N6S in CDR-H3; v) said combination of five or six amino acid substitutions are selected from X₁16A in CDR-H2, H1A, X₁2E, F41, and N6T in CDR-H3; X₁16A in CDR-H2, H1N, X₁2E, F41, and N6S in CDR-H3; D15E, X₁16A in CDR-H2, H1A, N6S in CDR-H3; and W3Y in CDR-L3; D15E, X₁16A in CDR-H2, H1N, X₁2E, F41 and N6T in CDR-H3; D15E, X₁16A in CDR-H2, H1A, X₁2E, F41 and N6T in CDR-H3; D15E, X₁16A in CDR-H2, X₁2E, F41 and N6T in CDR-H3.

In accordance with the foregoing, the amino acid substitution H1A in CDR-H3 is preferably the amino acid substitution, in case there is only one amino acid substitution in the CD3epsilon binding domain, within the CDR sequences or the VH region sequences as defined herein. Furthermore, in case of combinations of amino acid substitutions as defined in iii) preferably H1A in CDR-H3 is one of the amino acid substitutions of said combination.

In an embodiment, the invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region and a VL region, wherein

- i) the VH region comprises the sequence of EVX₁LX₂ESGGGLX₃QPX₄GSLKLSCAASGFTFNX₅YAX₆NWVRQAPGKGLEWVA RIRSKYNNYATYYADX₇VKX₃RFTISRDDSXX₁₀X₁₁X₁₂YLQMNNLKTEDTAX₁₃YYC VRHX₁₄NFGNSYX₁₅SX₁₆X₁₇AYWGQGTLVTVSX₁₈, where X₁is Q or K; X₂is V or L; X₃is V or E; X₄is G or K; X₅is K, V, S, G, R, T, or I; X₆is M or I; X₇is S or Q; X₈is D, G, K, S, or E; X₉is K or Q; X₁₀is N or S; X₁₁is T or 1; X₁₂is A or L; X₁₃is V or M; X₁₄is G, R or A; X₁₅is I, L, V, or T; X₁₆is Y, W or F; X₁₇is W, F or Y; and X₁₈is S or A; and
- ii) the VL region comprises the sequence of QX₁VVTQEX₂X₃LTX₄SPGX₅TVTLTCX₆SSTGAVTX₇X₈X₉YX₁₀NWVQX₁KPX₁₂X₁₃X₁₄X₁₅X₁₆GLIGX₁₇TX₁₈X₁₉X₂₀X₂₁X₂₂GX₂₃PARFSGSLX₂₄GX₂₅KAALTX₂₆X₂₇GX₂₈QX₂₉EDEAX₃₀YX₃₁CX₃₂LWYSNX₃₃WVFGGGTKLTVL, where X₁is T or A; X₂is P or S; X₃is S or A; X₄is V or T; X₅is G or E; X₆is G, R, or A; X₇is S or T; X₈is G or S; X₉is N or Y; X₁₀is P or A; X₁₁is Q or E; X₁₂is G or D; X₁₃is Q or H; X₁₄is A or L; X₁₅is P or F; X₁is R or T; X₁₇is G or A; X₁₈is K or D; X₁₉is F or M; X₂₀is L or R; X₂₁is A, P or V; X₂₂is P or S; X₂₃is Tor V; X₂₄is L or 1; X₂₅is G or D; X₂₆is L or 1; X₂₇is S or T; X₂₈is V or A; X₂₉is P or T; X₃₀is E or I; X₃₁is Y or F; X₃₂is V, A, or T; X₃₃is R or L; and
- iii) wherein the VH and/or VL region sequence comprises one or more amino acid substitutions selected from
  - a. N30 (preferably S), X₆34V, X₆34F, Q39 (E, K, R, D, preferably E), L45 (M or V, preferably M), D64 (preferably E), X₇65A, X₁₂81V, X₁₂81T, X₁₂811, V99 (A or L, preferably A), H101 (preferably A or N), X₁₄102E, F104 (preferably I), and N106 (preferably S or T) in the VH region sequence in i); and
  - b. L20 (preferably I or M), V38 (preferably I), X₁₁40R, X₁₁40K, X₂₄69 (S or E, preferably S), X₃₂91L, X₃₃93 (preferably Y), and G102 (preferably S) in the VL region sequence in ii).

In this embodiment, preferred VH and VL region sequences comprised in the binding domain and mediating the binding to the human CD3ε chain are described. As evident from the above, the VH and VL region sequences of i) and ii) comprise various placeholders, wherein the same hierarchy and nomenclature applies for the placeholders as recited herein above in the context of the CDRs comprised in said VH and VL region of i) and ii). As is evident from the sequences for the VH and VL region, said CDRs described herein above are part of said VH and VL region sequence. Accordingly, the preferred embodiments of said CDRs of i) and ii) as described herein above also apply to this preferred embodiment.

The VH region of i) comprises or consists of the sequence of EVX₁LX₂ESGGGLX₃QPX₄GSLKLSCAASGFTFNX₅YAX₆NWVRQAPGKGLEWVARIRSKYNN YATYYADX₇VKX₈RFTISRDDSX₉X₁₀X₁₁X₁₂YLQMNNLKTEDTAX₁₃YYCVRHX₁₄NFGNSYX₁₅S X₁₆X₁₇AYWGQGTLVTVSX₁₈, where X₁is Q or K; X₂is V or L; X₃is V or E; X₄is G or K; X₅is K, V, S, G, R, T, or I; X₆is M or I; X₇is S or Q; X₈is D, G, K, S, or E; X₉is K or Q; X₁₀is N or S; X₁₁is T or 1; X₁₂is A or L; X₁₃is V or M; X₁₄is G, R or A; X₁₅is 1, L, V, or T; X₁₆is Y, W or F; X₁₇is W, F or Y; and X₁₈is S or A.

The CDR sequences within said VH region are as follows: a CDR-H1 sequence comprising or consisting of X₅YAX₆N; a CDR-H2 sequence comprising or consisting of RIRSKYNNYATYYADX₇VKX₈; and a CDR-H3 sequence comprising or consisting of HX₁₄NFGNSYX₁₅SX₁₆X₁₇AY. Preferred examples of said CDR-H1 sequence X₅YAX₆N are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, TYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is most preferred. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₇VKX₈are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD is most preferred. Preferred examples of said CDR-H3 sequence HX₁₄NFGNSYX₁₅SX₁₆X₁₇AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred.

For X₁, the amino acid Q is preferred. For X₂, the amino acid V is preferred. For X₃, the amino acid V is preferred. For X₄, the amino acid G is preferred. For X₅, the amino acid K is most preferred, and for X₆, the amino acid M is most preferred. A preferred combination for X₅and X₆is M for X₆in combination with any of the amino acid residues of X₅, such as the combinations for X₅and X₆, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₅and X₆, respectively. Preferred examples of said CDR-H1 sequence X₅YAX₆N are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, TYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is most preferred. For X₇, the amino acid S is most preferred, and for X₈, the amino acid D is most preferred. A preferred combination is S for X₇in combination with any of the amino acid residues of X₈, such as the combinations for X₇and X₈, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₇VKX₈are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD is most preferred. For X₉, the amino acid K is preferred. For X₁₀, the amino acid N is preferred. For X₁₁, the amino acid T is preferred. For X₁₂, the amino acid A is preferred. For X₁₃, the amino acid V is preferred. For X₁₄, the amino acid G is most preferred; for X₁₅, the amino acid I is most preferred; for X₁₆, the amino acid Y is most preferred; and for X₁₇, the amino acid W is most preferred. Preferred examples of said CDR-H3 sequence HX₁₄NFGNSYX₁₅SX₁₆X₁₇AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred. For X₁₈, the amino acid sequence S is preferred.

The VL region of ii) comprises or consists of the sequence of QX₁VVTQEX₂X₃LTX₄SPGX₅TVTLTCX₆SSTGAVTX₇X₈X₉YX₁₀NWVQX₁KPX₁₂X₁₃X₁₄X₁₅X₁₆GL IGX₁₇TX₁₈X₁₉X₂₀X₂₁X₂₂GX₂₃PARFSGSLX₂₄GX₂₅KAALTX₂₆X₂₇GX₂₈QX₂₉EDEAX₃₀YX₃₁CX₃₂LW YSNX₃₃WVFGGGTKLTVL, where X₁is T or A; X₂is P or S; X₃is S or A; X₄is V or T; X₅is G or E; X₆is G, R, or A; X₇is S or T; X₈is G or S; X₉is N or Y; X₁₀is P or A; X₁₁is Q or E; X₁₂is G or D; X₁₃is Q or H; X₁₄is A or L; X₁₅is P or F; X₁₆is R or T; X₁₇is G or A; X₁₈is K or D; X₁₉is F or M; X₂₀is L or R; X₂₁is A, P or V; X₂₂is P or S; X₂₃is T or V; X₂₄is L or I; X₂₅is G or D; X₂₆is L or I; X₂₇is S or T; X₂₈is V or A; X₂₉is P or T; X₃₀is E or I; X₃₁is Y or F; X₃₂is V, A, or T; and X₃₃is R or L.

The CDR sequences within said VL region are as follows: a CDR-L1 sequence comprising or consisting of X₆SSTGAVTX₇X₈X₉YX₁₀N; a CDR-L2 sequence comprising or consisting of X₁₇TX₁₈X₁₉X₂₀X₂₁X₂₂; and a CDR-L3 sequence comprising or consisting of X₃₂LWYSNX₃₃WV. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. Preferred examples of the CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

For X₁, the amino acid T is preferred. For X₂, the amino acid P is preferred. For X₃, the amino acid S is preferred. For X₄, the amino acid V is preferred. For X₅, the amino acid G is preferred. For X₆, the amino acid G is most preferred. For X₇, the amino acid S is most preferred. For X₈, the amino acid G is most preferred. For X₉, the amino acid N is most preferred. For X₁₀, the amino acid P is most preferred. X₆to X₁₀are part of the CDR-L1 sequence within the VL region. Preferred examples of said CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. For X₁₁, the amino acid Q is preferred. For X₁₂, the amino acid G is preferred. For X₁₃, the amino acid Q is preferred. For X₁₄, the amino acid A is preferred. For X₁₅, the amino acid P is preferred. For X₁₆, the amino acid R is preferred. For X₁₇, the amino acid G is preferred. For X₁₈, the amino acid K is preferred. For X₁₉, the amino acid F is preferred. For X₂₀, the amino acid L is preferred. For X₂₁, the amino acid A is preferred. For X₂₂, the amino acid P is preferred. X₁₇to X₂₂are part of the CDR-L2 sequence of the VL region. Preferred examples of said CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred. For X₂₃, the amino acid T is preferred. For X₂₄, the amino acid L is preferred. For X₂₅, the amino acid G is preferred. For X₂₆, the amino acid L is preferred. For X₂₇, the amino acid S is preferred. For X₂₈, the amino acid V is preferred. For X₂₉, the amino acid P is preferred. For X₃₀, the amino acid E is preferred. For X₃₁, the amino acid Y is preferred. For X₃₂, the amino acid V is preferred. For X₃₃, the amino acid R is preferred. X₃₂and X₃₃are part of the CDR-L3 sequence of the VL region. Preferred examples of said CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

In a more preferred embodiment, the VH region of i) comprises or consists of the sequence of EVQLVESGGGLX₁QPGGSLKLSCAASGFTFNX₂YAX₃NWVRQAPGKGLEWVARIRSKYNNY ATYYADX₄VKX₅RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHX₆NFGNSYX₇SX₈X₉AYW GQGTLVTVSS, where X₁is V or E; X₂is K, V, S, G, R, or I; X₃is M or I; X₄is S or Q; X₅is D, G, K, S, or E; X₆is G, R or A; X₇is I, L, V, or T; X₈is Y, W or F; and X₉is W or F; and the VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCX₁SSTGAVTSGX₂YPNWVQQKPGQAPRGLIGX₃TX₄X₅X₆X₇X₃GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCX₉LWYSNRWVFGGGTKLTVL, where X, is G, R, or A; X₂is N or Y; X₃is G or A; X₄is K or D; X₅is F or M; X₆is L or R; X₇is A, P or V; X₈is P or S; and X₉is V, A, or T.

The VH region of i) comprises or consists of the sequence of EVQLVESGGGLX₁QPGGSLKLSCAASGFTFNX₂YAX₃NWVRQAPGKGLEWVARIRSKYNNY ATYYADX₄VKX₅RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHX₆NFGNSYX₇SX₈X₉AYW GQGTLVTVSS, where X, is V or E; X₂is K, V, S, G, R, or I; X₃is M or I; X₄is S or Q; X₅is D, G, K, S, or E; X₆is G, R or A; X₇is I, L, V, or T; X₈is Y, W or F; and X₉is W or F.

The CDR sequences within said VH region are as follows: a CDR-H1 sequence comprising or consisting of X₂YAX₃N; a CDR-H2 sequence comprising or consisting of RIRSKYNNYATYYADX₄VKX₅; and a CDR-H3 sequence comprising or consisting of HX₆NFGNSYX₇SX₃X₉AY. Preferred examples of said CDR-H1 sequence X₂YAX₃N are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, TYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is more preferred, wherein KYAMN is most preferred. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₄VKX₅are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADQVKD is more preferred, wherein RIRSKYNNYATYYADSVKD is most preferred. Preferred examples of said CDR-H3 sequence HX₆NFGNSYX₇SX₃X₉AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred.

For X₁, the amino acid V is preferred. For X₂, the amino acid K is most preferred, and for X₃, the amino acid M is most preferred. A preferred combination for X₂and X₃is M for X₃in combination with any of the amino acid residues of X₂, such as the combinations for X₂and X₃, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₂and X₃, respectively. Preferred examples of said CDR-H1 sequence X₂YAX₃N are selected from KYAMN, VYAMN, SYAMN, GYAMN, RYAMN, TYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN is more preferred, wherein KYAMN is most preferred. For X₄, the amino acid S is preferred. For X₅, the amino acid D is most preferred. A preferred combination is S for X₄in combination with any of the amino acid residues of X₅, such as the combinations for X₄and X₅, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₄VKX₅are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADQVKD is more preferred, wherein RIRSKYNNYATYYADSVKD is most preferred. For X₆, the amino acid G is most preferred; for X₇, the amino acid I is most preferred; for X₈, the amino acid Y is most preferred; and for X₉, the amino acid W is most preferred. Preferred examples of said CDR-H3 sequence HX₆NFGNSYX₇SX₈X₉AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred.

The VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCX₁SSTGAVTSGX₂YPNWVQQKPGQAPRGLIGX₃TX₄X₅X₆X₇X₈GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCX₉LWYSNRWVFGGGTKLTVL, where X, is G, R, or A; X₂is N or Y; X₃is G or A; X₄is K or D; X₅is F or M; X₆is L or R; X₇is A, P or V; X₈is P or S; and X₉is V, A, or T.

The CDR sequences within said VL region are as follows: a CDR-L1 sequence comprising or consisting of X₁SSTGAVTSGX₂YPN; a CDR-L2 sequence comprising or consisting of X₃TX₄X₅X₆X₇X₈; and a CDR-L3 sequence comprising or consisting of X₉LWYSNRWV. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. Preferred examples of the CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

For X₁, the amino acid G is most preferred. For X₂, the amino acid N is preferred. X₁and X₂are part of the CDR-L1 sequence X₁SSTGAVTSGX₂YPN within the VL region. Preferred examples of said CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. For X₃, the amino acid G is preferred. For X₄, the amino acid K is preferred. For X₅, the amino acid F is preferred. For X₆, the amino acid L is preferred. For X₇, the amino acid A is most preferred. For X₈, the amino acid P is preferred. X₃to X₈are part of the CDR-L2 sequence X₃TX₄X₅X₆X₇X₈of the VL region. Preferred examples of said CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred. For X₉, the amino acid V is most preferred. X₉is part of the CDR-L3 sequence X_LLWYSNRWV of the VL region. Preferred examples of said CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

In another preferred embodiment, the VH region of ii) comprises or consists of the sequence of EVQLVESGGGLX₁QPGGSLKLSCAASGFTFNX₂YAX₃NWVRQAPGKGLEWVARIRSKYNNY ATYYADX₄VKX₅RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHX₆NFGNSYX₇SX₃X₉AYW GQGTLVTVSS, where X, is V or E; X₂is K, V, S, R, or I; X₃is M or I; X₄is S or Q; X₅is D, G, K or S; X₆is G or A; X₇is I, L, V, or T; X₈is Y, W or F; and X₉is W or F; and the VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCX₁SSTGAVTSGX₂YPNWVQQKPGQAPRGLIGGTKFLX₃PG TPARFSGSLLGGKAALTLSGVQPEDEAEYYCX₄LWYSNRWVFGGGTKLTVL, where X, is G or A; X₂is N or Y; X₃is A or V; and X₄is V, A, or T.

The VH region of ii) comprises or consists of the sequence of EVQLVESGGGLX₁QPGGSLKLSCAASGFTFNX₂YAX₃NWVRQAPGKGLEWVARIRSKYNNY ATYYADX₄VKX₅RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHX₆NFGNSYX₇SX₃X₉AYW GQGTLVTVSS, where X, is V or E; X₂is K, V, S, R, or I; X₃is M or I; X₄is S or Q; X₅is D, G, K or S; X₆is G or A; X₇is I, L, V, or T; X₈is Y, W or F; and X₉is W or F.

The CDR sequences within said VH region are as follows: a CDR-H1 sequence comprising or consisting of X₂YAX₃N; a CDR-H2 sequence comprising or consisting of RIRSKYNNYATYYADX₄VKX₅; and a CDR-H3 sequence comprising or consisting of HX₆NFGNSYX₇SX₃X₉AY. Preferred examples of said CDR-H1 sequence X₂YAX₃N are selected from KYAMN, VYAMN, SYAMN, RYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN are more preferred, wherein KYAMN is most preferred. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₄VKX₅are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADQVKD are more preferred, wherein RIRSKYNNYATYYADSVKD is most preferred. Preferred examples of said CDR-H3 sequence HX₆NFGNSYX₇SX₃X₉AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY or HANFGNSYISYWAY are more preferred, wherein HGNFGNSYISYWAY is most preferred.

For X₁, the amino acid V is preferred. For X₂, the amino acid K is most preferred, and for X₃, the amino acid M is most preferred. A preferred combination for X₂and X₃is M for X₃in combination with any of the amino acid residues of X₂, such as the combinations for X₂and X₃, respectively, selected from K and M, V and M, S and M, most preferred the combination K and M. Another preferred combination is K and I, for X₂and X₃, respectively. Preferred examples of said CDR-H1 sequence X₂YAX₃N are selected from KYAMN, VYAMN, SYAMN, RYAMN, IYAMN, and KYAIN, wherein KYAMN or KYAIN are more preferred, wherein KYAMN is most preferred. For X₄, the amino acid S is preferred. For X₅, the amino acid D is most preferred. A preferred combination is S for X₄in combination with any of the amino acid residues of X₅, such as the combinations for X₄and X₅, respectively, selected from S and D, S and G, S and K, S and S, most preferred the combination S and D. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADX₄VKX₅are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD or RIRSKYNNYATYYADQVKD are more preferred, wherein RIRSKYNNYATYYADSVKD is most preferred are selected from RIRSKYNNYATYYADSVKD, RIRSKYNNYATYYADSVKK, RIRSKYNNYATYYADSVKS, RIRSKYNNYATYYADSVKE, RIRSKYNNYATYYADSVKG, and RIRSKYNNYATYYADQVKD, wherein RIRSKYNNYATYYADSVKD is most preferred. For X₈, the amino acid G is most preferred; for X₇, the amino acid I is most preferred; for X₈, the amino acid Y is most preferred; and for X₉, the amino acid W is most preferred. Preferred examples of said CDR-H3 sequence HX₆NFGNSYX₇SX₈X₉AY are selected from HGNFGNSYISYWAY, HGNFGNSYLSWWAY, HGNFGNSYTSYYAY, HRNFGNSYLSWFAY, HGNFGNSYVSFFAY, HGNFGNSYISWWAY, HGNFGNSYVSWWAY, HGNFGNSYLSYFAY, HGNFGNSYLSFWAY, HANFGNSYISYWAY, and HGNFGNSYVSWFAY, wherein HGNFGNSYISYWAY is most preferred.

The VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCX₁SSTGAVTSGX₂YPNWVQQKPGQAPRGLIGGTKFLX₃PG TPARFSGSLLGGKAALTLSGVQPEDEAEYYCX₄LWYSNRWVFGGGTKLTVL, where X, is G or A; X₂is N or Y; X₃is A or V; and X₄is V, A, or T.

The CDR sequences within said VL region are as follows: a CDR-L1 sequence comprising or consisting of X₁SSTGAVTSGX₂YPN; a CDR-L2 sequence comprising or consisting of GTKFLX₃P; and a CDR-L3 sequence comprising or consisting of X₄LWYSNRWV. Preferred examples of the CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. Preferred examples of the CDR-L2 sequence are selected from GTKFLAP, ATDMRPS, GTKFLVP, and GTNKRAP, wherein GTKFLAP is most preferred. Preferred examples of the CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, TLWYSNRWV, and ALWYSNLWV, wherein VLWYSNRWV is most preferred.

For X₁, the amino acid G is preferred. For X₂, the amino acid N is preferred. X₁and X₂are part of the CDR-L1 sequence X₁SSTGAVTSGX₂YPN within the VL region. Preferred examples of said CDR-L1 sequence are selected from GSSTGAVTSGNYPN, RSSTGAVTSGYYPN, GSSTGAVTSGYYPN, ASSTGAVTSGNYPN, and RSSTGAVTTSNYAN, wherein GSSTGAVTSGNYPN is most preferred. X₃is part of the CDR-L2 sequence GTKFLX₃P of the VL region. Said CDR-L2 sequence can either be GTKFLAP or GTKFLVP, wherein GTKFLAP is preferred. For X₃, the amino acid A is preferred. X₄is part of the CDR-L3 sequence X₄LWYSNRWV of the VL region. Preferred examples of said CDR-L3 sequence are selected from VLWYSNRWV, ALWYSNRWV, and TLWYSNRWV, wherein VLWYSNRWV is most preferred. For X₄, the amino acid V is most preferred.

In a further preferred embodiment, the VH region of i) comprises or consists of the sequence of EVQLVESGGGLVQPGGSLKLSCAASGFTFNX₁YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKX₂RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYX₃SX₄WAYWGQ GTLVTVSS, where X, is K or S; X₂is D or G; X₃is I or V; and X₄is Y or W; and the VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGX₁YPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEYYCX₂LWYSNRWVFGGGTKLTVL, where X, is N or Y; and X₂is V or A.

The VH region of i) comprises or consists of the sequence of EVQLVESGGGLVQPGGSLKLSCAASGFTFNX₁YAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKX₂RFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYX₃SX₄WAYWGQ GTLVTVSS, where X, is K or S, wherein K is preferred; X₂is D or G, wherein D is preferred; X₃is I or V, wherein I is preferred; and X₄is Y or W, wherein Y is preferred.

The CDR sequences within said VH region are as follows: a CDR-H1 sequence comprising or consisting of X₁YAMN; a CDR-H2 sequence comprising or consisting of RIRSKYNNYATYYADSVKX₂; and a CDR-H3 sequence comprising or consisting of HGNFGNSYX₃SX₄WAY. Said CDR-H1 sequence X₁YAMN is selected from KYAMN or SYAMN, wherein KYAMN is preferred. Preferred examples of said CDR-H2 sequence RIRSKYNNYATYYADSVKX₂are selected from RIRSKYNNYATYYADSVKD and RIRSKYNNYATYYADSVKG, wherein RIRSKYNNYATYYADSVKD is preferred. Said CDR-H3 sequence HGNFGNSYX₃SX₄WAY is HGNFGNSYISYWAY or HGNFGNSYVSWWAY, wherein HGNFGNSYISYWAY is preferred.

The VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGX₁YPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEYYCX₂LWYSNRWVFGGGTKLTVL, where X, is N or Y, wherein N preferred; and X₂is V or A, wherein V preferred.

The CDR sequences within said VL region are as follows: a CDR-L1 sequence comprising or consisting of GSSTGAVTSGX₁YPN; a CDR-L2 sequence comprising or consisting of GTKFLAP; and a CDR-L3 sequence comprising or consisting of X₂LWYSNRWV. The CDR-L1 sequence is GSSTGAVTSGNYPN or GSSTGAVTSGYYPN, wherein GSSTGAVTSGNYPN is preferred. The CDR-L3 sequence is VLWYSNRWV or ALWYSNRWV, wherein VLWYSNRWV is preferred.

In a preferred embodiment, the VH region of i) comprises or consists of the sequence as defined in SEQ ID NOs: 124, 172, 362, 552, 730, 928, 1106, 1296, 1474, 1664 or 1854; and the VL region of ii) comprises or consists of the sequence of as defined in SEQ ID NOs: 125, 173, 363, 553, 731, 929, 1107, 1297, 1475, 1665, or 1855. Preferred combinations of VH and VL regions of i) and ii) are defined in SEQ ID NOs: 124 and 125 (combination of binder termed “2B2”), 172 and 173 (“A2J”), 362 and 363 (“E1L”), 552 and 553 (“E2M”), 730 and 731 (“F12Q”), 928 and 929 (“F6A”), 1106 and 1107 (“F70”), 1296 and 1297 (“G4H”), 1474 and 1475 (“H1E”), 1664 and 1665 (“H2C”), or 1854 and 1855 (“I2C”). Preferred is that the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 124 and 125, 172 and 173, 362 and 363, 552 and 553, 730 and 731, 928 and 929, 1106 and 1107, 1296 and 1297, 1474 and 1475, 1664 and 1665, and 1854 and 1855. More preferred is that the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 124 and 125, 362 and 363, 730 and 731, 928 and 929, 1106 and 1107, 1296 and 1297, 1474 and 1475, 1664 and 1665, and 1854 and 1855. Even more preferred is that the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 124 and 125, 730 and 731, 1664 and 1665, and 1854 and 1855. In a yet even more preferred embodiment, the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 730 and 731, 1664 and 1665, and 1854 and 1855.

In the most preferred embodiment, the VH region of i) comprises or consists of the sequence of EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYA TYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGT LVTVSS (SEQ ID NO: 1854); and the VL region of ii) comprises or consists of the sequence of QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGT PARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL (SEQ ID NO: 1855).

As outlined herein above in relation to amino acid substitutions in the CDR sequences and also applying to this embodiment, the VH region of i) and/or VL region of ii) comprise one or more amino acid substitutions as specified herein above. Accordingly, at least one of the recited amino acid substitutions of the variable regions is comprised in said binding domain binding to an extracellular epitope of the human CD3ε chain. Said at least one or one or more amino acid substitution, in the case that only one amino acid substation is present, can be present in a CDR sequence in said VH or said VL region or, in case more than one amino acid substitution is present, in CDRs in both the VH and the VL region or restricted to CDR sequences in only the VH or the VL region. In certain embodiments where there are more than one amino acid substitutions, the substitutions are in the VH and the VL region or, alternatively, only in one variable region. Preferably, the substitutions are in the VH and the VL region.

Specifically, the VH of i) and/or VL region sequence of ii) comprises one or more amino acid substitutions selected from a. N30 (preferably S), X₆34V, X₆34F, Q39 (E, K, R, D, preferably E), L45 (M or V, preferably M), D64 (preferably E), X₇65A, X₁₂81V, X₁₂81T, X₁₂811, V99 (A or L, preferably A), H101 (preferably A or N), X₁₄102E, F104 (preferably I), N106 (preferably S or T) in the VH region sequence in i); and b. L20 (preferably I or M), V38 (1, L, M, F or Y, preferably I), X₁₁40R, X₁₁40K, X₂₄69 (S or E, preferably S), X₃₂91L, X₃₃93 (preferably Y), G102 (preferably S) in the VL region sequence in ii).

In the VH region sequence, the amino acid substitution at position 30 is, preferably, S (hence, can be written as N30S; same is true for the subsequent substitutions given according to their position number). The amino acid substitution at position 34 is V or F. Preferably, position 34 of the VH region sequence comprises an I or M, most preferred an 1. The amino acid substitution at position 39 is E, K, R, D, preferably E. The amino acid substitution at position 45 is preferably M or V, more preferred M. The amino acid substitution at position 64 is preferably E. The amino acid substitution at position 65 is A. The amino acid substitution at position 81 is V, T or I, preferably V. The amino acid substitution at position 99 is preferably A or L, more preferred A. The amino acid substitution at position 101 is preferably A or N, more preferred A (H1A). The amino acid substitution at position 102 is E. The amino acid substitution at position 104 is preferably 1. The amino acid substitution at position 106 is preferably S or T, more preferred S.

Notwithstanding the above, in the CDR-H2 sequence within the VH region sequence, the amino acid substitution at position 64 is, preferably, D15E, or the amino acid substitution at position 65 with amino acid A. Preferably, said CDR-H2 comprises the amino acid residue substitution at position 65 with amino acid A; in this case, a preferred amino acid for the last amino acid of CDR-H2 is D or G, preferred D. Hence, a preferred CDR-H2 sequence is RIRSKYNNYATYYADAVKD or RIRSKYNNYATYYADAVKG, with RIRSKYNNYATYYADAVKD more preferred. In case CDR-H2 contains two amino acid substitutions, the combination of the amino acid E at position 64 and amino acid A at position 64 are preferred; in this case, a preferred amino acid for the last amino acid of CDR-H2 is G. Hence, a preferred CDR-H2 sequence for the combination of the amino acid E at position 64 and amino acid A at position 65 is RIRSKYNNYATYYAEAVKG.

In the CDR-H3 sequence of the VH sequence, the amino acid substitutions are at position 101, preferably a substitution with amino acid A or N, more preferably A, at position 102 with amino acid E, at position 104, preferably with amino acid I, and at position 106, preferably with amino acid S or T. Preferably, CDR-H3 comprises the amino acid A or N at position 101, the amino acid S or T at position 106; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, preferred amino acids for X₁₄are G or A, most preferred G; for X₁₅is I; for X₁₆is Y; and for X₁₇are W or Y. In case CDR-H3 comprises two amino acid substitutions, preferred combinations are the amino acid A at position 101 and the amino acid S at position 106; and the amino acid N at position 101 and the amino acid T at position 106; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₁₄is G or A, most preferred G; for X₁₅is I, for X₁₆is Y, and for X₁₇are W and F. In case CDR-H3 comprises three amino acid substitutions, preferred combinations are the amino acid A at position 101, the amino acid I at position 104, and the amino acid S at position 106; and the amino acid N at position 101, the amino acid I at position 104 and the amino acid T at position 106, in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₁₅is I, for X₁₆is Y, and for X₁₇are Wand F. In case CDR-H3 comprises four amino acid substitutions, a preferred combination is the amino acid N at position 101, the amino acid E at position 102, the amino acid I at position 104, and the amino acid T at position 106; in this case and if placeholders are present in the CDR-H3 sequence at the indicated positions, a preferred amino acid for X₁₅is I, for X₁₆is Y, and for X₁₇is W. Hence, preferred CDR-H3 sequences are selected from AGNFGSSYISYWAY, NENIGTSYISYWAY, AGNFGTSYISYWAY, NANFGTSYISYFAY, and AGNFGSSYISYFAY, with AGNFGSSYISYWAY and AGNFGSSYISYFAY most preferred.

In the VL region sequence, the amino acid substitution at position 20 is preferably I or M, more preferred I. The amino acid substitution at position 38 is preferably I, L, M, F or Y, more preferred with I. The amino acid substitution at position 40 is preferably K or R, more preferred K. The amino acid substitution at position 69 is preferably S or E, more preferred S. The amino acid substitution at position 91 is L. The amino acid substitution at position 93 is preferably Y. The amino acid substitution at position 102 is preferably S.

Notwithstanding the above, in the CDR-L3 sequence within the VL region sequence, the amino acid substitution at position 1 is with amino acid L or the amino acid substitution is W93, preferably W93Y. Preferably, the CDR-L3 sequence is VLYYSNRWV when CDR-L3 comprises an amino acid substitution. It is preferred, however, that CDR-L3 does not comprise said X₁1L and W93 amino acid substitution, in which case a preferred CDR-L3 sequence is VLYYSNRWV.

In accordance with the foregoing, the amino acid substitution H101A in the VH region (part of CDR-H3) is preferably the amino acid substitution, in case there is only one amino acid substitution present in the CD3epsilon binding domain, within the VH and/or VL region sequences as defined herein. Furthermore, in case of combinations of amino acid substitutions as defined in iii) preferably H101A in the VH region sequence is one of the amino acid substitutions of said combination.

In a preferred embodiment of the polypeptide or polypeptide construct of the invention, wherein in addition to said one amino acid substitution or a combination thereof as defined in iii) X₆is I; X₃is G; X₁₂is L, X₁₄is A, X₁₇is F in said VH region sequence; and/or X₃₂is A in said VL region sequence. In a preferred embodiment of the polypeptide or polypeptide construct of claim 1 of the invention, in addition to said one amino acid substitution or a combination thereof as defined in iii) X₆is I; X₃is G; X₁₄is A, X₁₇is F in said VH region sequence; and/or X₃₂is A in said VL region sequence. The one amino acid substitution or combination thereof as defined herein is/are in addition combined with specific amino acids at specific positions in the CDRs. Hence, at least one of the recited amino acid substitutions in accordance with iii) is present and at least one of X₃is G; X₁₄is A, X₁₇is F in said VH region sequence; and/or X₃₂is A in said VL region sequence is additionally present in the CDRs. As previously stated herein above, a preferred amino acid for X₆is I or X₃is G in said VH region sequence, if only one additional amino acid is present in the CDRs, wherein it is most preferred that X₅is I in said VH region sequence. A preferred combination of two of said additional amino acids is X₆is I and X₁₇is F in said VH region sequence; or X₃is G and X₁₇is F in said VH region sequence. A preferred combination of three of said additional amino acids is X₆is I, X₁₄is A, and X₁₇is F in said VH region sequence; or X₆is I, X₁₇is F in said VH region sequence, and X₃₂is A in said VL region sequence. Since the latter amino acids are to be present additionally, it is understood that those recited additional amino acids that overlap in position with the amino acid substitution of iii) cannot replace the overlapping amino acid substitution. For example, if the only amino acid substitution in accordance with iii) is either X₆34V or X₆34F in CDR-H1, said amino acid cannot be replaced by amino acid I in said CDR-H1 sequence, since there would be no amino acid substitution as defined in iii) remaining in the binding domain. In other terms, there must always be at least one of the amino acid substitutions as defined in iii) comprised in the polypeptide or polypeptide construct of the invention.

It is also understood that depending on the actual sequence of the VH and/or VL region sequences, one or more of said additional amino acids may already be part of the given variable sequence as defined herein above or, if this is not the case, said given variable region will be changed to exhibit said additional amino acid(s) in combination with one amino acid substitution or a combination thereof as recited in iii).

In a preferred embodiment of the polypeptide or polypeptide construct of the invention, it comprises combinations of said amino acid substitutions as defined in iii) of two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more amino acid substitutions.

In a preferred embodiment of the polypeptide or polypeptide construct of the invention, i) said one acid substitution is selected from a. X₆34V, Q39E, Q39K, Q39R, Q39D, L45M, L45V, X₁₂81V, X₁₂81T, X₁₂811, V99A, V99L, H101A, H101N in the VH region; and b. V381, V38L, V38M, V38F, V38Y, X₁₁40R, X₁₁40K, X₂₄69S, X₂₄69E, X₃₂91L, X₃₃93Y; ii) said combination of two or more amino acid substitutions are selected from X₆34F and A81V (which may also be referred to as X₁₂81V) in the VH region; Q39E in the VH region and X₁₁40K in the VL region; Q39E in the VH region and X₁₁40R in the VL region; Q39D in the VH region and X₁₁40K in the VL region; Q39D in the VH region and X₁₁40R in the VL region; L45V in the VH region and V38F in the VL region; L45V in the VH region and V38Y in the VL region; L45M in the VH region and X₁₁40K in the VL region; L20I and G102S in the VL region; A81V in the VH region and X₁₁40K in the VL region; iii) said combination of three or more amino acid substitutions are selected from Q39E in the VH region, X₁₁40K and G102S in the VL region; Q39E in the VH region, X₁₁40R and G102S in the VL region; Q39D in the VH region, X₁₁40K and G102S in the VL region; Q39D in the VH region, X₁₁40R and G102S in the VL region; L45M in the VH region, X₁₁40K and G102S in the VL region; X₇65A, H101A, and N106S in the VH region; L20I, X₁₁40K, and G102S in the VL region; iv) said combination of four or more amino acid substitutions are selected from Q39E in the VH region, L20I, X₁₁40K and G102S in the VL region; Q39E in the VH region, L20I, X₁₁40R and G102S in the VL region; Q39D in the VH region, L20I, X₁₁40K and G102S in the VL region; Q39D in the VH region, L20I, X₁₁40R and G102S in the VL region; L45M in the VH region, L20I, X₁₁40K and G102S in the VL region; L20I, X₁₁40K, X₂₄69S, and G102S in the VL region; A81V in the VH region, L20I, X₁₁40K, and G102S in the VL region; and/or v) said combination of five, six, seven, eight, nine, ten, or more amino acid substitutions are selected from X₇65A, A81V, V99A, N106S in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region; D64E, X₇65A, A81V, X₁₄102E, F104I, N106T in the VH region, L20I, X₂₄69S, and G102S in the VL region; L45M, X₇65A, N106T in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region; X₇65A, A81V, V99A, H101A, F104I, N106S in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region; X₇65A, A81V, V99A, H101A, N106S in the VH region; A81V, V99A in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region; Q39E, A81V in the VH region, L20I, X₁₁40K, and G102S in the VL region; L45V in the VH region, L20I, V38F, X₁₁40K and G102S in the VL region.

In a more preferred embodiment of the polypeptide or polypeptide construct of the invention, said combination of amino acid substitutions is selected from:

- i) in the VH region
  - a. X₇65A, A81V, V99A, H101A and N106S;
  - b. D64E, X₇65A, A81V, H101N, X₁₄102E, F104I, and N106S;
  - c. L45M, X₇65A, H101A, and N106T;
  - d. L45M, X₇65A, H101A, and N106S;
  - e. Q39E, X₇65A, H101N, and N106T;
  - f. D64E, X₇65A, V99A, H101A, and N106T;
  - g. X₇65A, A81V, V99A, H101A, X₁₄102E, F104I, and N106T;
  - h. X₇65A, A81V, H101N, X₁₄102E, F104I, and N106S;
  - i. D64E, X₇65A, A81V, H101A, and N106S;
  - j. D64E, X₇65A, H101A, and N106T;
  - k. X₇65A, V99A, H101A, and N106T;
  - l. D64E, X₇65A, H101A, and N106S;
  - m. D64E, X₇65A, A81V, V99A, H101A, and N106S;
  - n. X₇65A, H101A and N106S;
  - o. N30S, Q39E, D64E, X₇65A, A81V, H101A, X₁₄102E, F104I, and N106T;
  - p. L45M, D64E, X₇65A, H101A, and N106T;
  - q. N30S, L45M, X₇65A, A81V, H101A, and N106T;
  - r. N30S, L45M, D64E, X₇65A, A81V, H101A, and N106S;
- ii) in the VL region
  - a. L20I, X₁₁40K, X₂₄69S, and G102S;
  - b. L20I, X₂₄69S, and G102S;
  - c. L20I, V381, X₁₁40K, X₂₄69E, G102S and W93Y;
  - d. X₁₁40K and G102S;
  - e. L20I, X₁₁40K, X₂₄69S, G102S and W93Y;
  - f. L20M, X₁₁40K and X₂₄69E;
  - g. L20I, V381, X₁₁40K, X₂₄69E and G102S;
  - h. X₁₁40K, X₂₄69S and W93Y;
  - i. X₁₁40K and X₂₄69S; and
- iii) a combination of one amino acid substitution combination of i) and ii).

In yet another preferred embodiment of the polypeptide or polypeptide construct of the invention, said combination of amino acid substitution combinations of iii) is selected from:

- a. X₇65A, A81V, V99A, H101A, N106S in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region;
- b. D64E, X₇65A, A81V, H101N, X₁₄102E, F104I, N106S in the VH region, L20I, X₂₄69S, and G102S in the VL region:
- c. L45M, X₇65A, H101A, N106T in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region;
- d. L45M, X₇65A, H101A, N106S in the VH region, L20I, V381, X₁₁40K, X₂₄69E, G102S and W93Y in the VL region;
- e. Q39E, X₇65A, H101N, N106T in the VH region, X₁₁40K and G102S in the VL region;
- f. D64E, X₇65A, V99A, H101A, N106T in the VH region, X₁₁40K and G102S in the VL region;
- g. X₇65A, A81V, V99A, H101A, X₁₄102E, F104I, N106T in the VH region, L20I, X₁₁40K, X₂₄69S, and G102S in the VL region;
- h. X₇65A, A81V, H101N, X₁₄102E, F104I, N106S in the VH region, L20I, X₂₄69S, and G102S in the VL region;
- i. D64E, X₇65A, A81V, H101A, N106S in the VH region, L20I, X₂₄69S, and G102S in the VL region;
- j. D64E, X₇65A, H101A, N106T in the VH region, X₁₁40K and G102S in the VL region;
- k. X₇65A, V99A, H101A, N106T in the VH region, X₁₁40K and G102S in the VL region;
- l. D64E, X₇65A, H101A, N106S in the VH region, X₁₁40K and G102S in the VL region;
- m. D64E, X₇65A, A81V, V99A, H101A, N106S in the VH region, L20I, X₁₁40K, X₂₄69S, G102S and W93Y in the VL region;
- n. X₇65A, H101A N106S in the VH region, X₁₁40K and G102S in the VL region;
- o. N30S, Q39E, D64E, X₇65A, A81V, H101A, X₁₄102E, F104I, N106T in the VH region, L20M, X₁₁40K and X₂₄69E in the VL region;
- p. L45M, D64E, X₇65A, H101A, N106T in the VH region, L20I, V381, X₁₁40K, X₂₄69E and G102S in the VL region;
- q. N30S, L45M, X₇65A, A81V, H101A, N106T in the VH region, X₁₁40K and X₂₄69S in the VL region; and
- r. N30S, L45M, D64E, X₇65A, A81V, H101A, N106S in the VH region, X₁₁40K and X₂₄69S in the VL region.

In another preferred embodiment of the polypeptide or polypeptide construct of the invention, in said combination of amino acid substitution combinations defined in:

- a. and m. X₆is I in said VH region sequence;
- b. and r. X₃is G in said VH region sequence;
- c. X₁₂is L in said VH region;
- d. X₁₂is L and X₁₇is F in said VH region;
- e. X₆is I, X₁₄is A and X₁₇is F in said VH region sequence;
- f. X₆is I in said VH region sequence; and X₃₂is A in said VL region sequence;
- g. X₆is I in said VH region sequence;
- h. and i. X₃is G in said VH region sequence;
- j., l. and n. X₆is I and X₁₇is F in said VH region sequence; and X₃₂is A in said VL region sequence;
- k. X₆is I said VH region sequence; and X₃₂is A in said VL region sequence;
- p. X₁₂is L in said VH region; or
- q. X₃is G and X₁₇is F in said VH region sequence.

Examples of VH and VL region sequences as defined in this embodiment are defined by SEQ ID NOs: 2012 and 2013; 2020 and 2021; 2028 and 2029; 2036 and 2037; 2044 and 2045; 26 and 27; 34 and 35; 42 and 43; 50 and 51; 58 and 59; 66 and 67; 74 and 75; 82 and 83; 90 and 91; 98 and 99; 100 and 101; 108 and 109; 116 and 117. Table 2 evidences the increase of the aforementioned VH and VL region sequence combinations of the CD3epsilon binding domain in temperature stability over the CD3epsilon binding domain comprising a VH and VL combination defined as “I2C” (SEQ ID NOs: 1854 and 1855, respectively).

In accordance with the invention, the binding domain of the polypeptide or polypeptide construct of the invention that binds to an extracellular epitope of the human CD3ε chain and comprising or consisting of a VH region and a VL region as defined herein comprises at least one of the following CDR sequences or a combination thereof as defined in SEQ ID NOs: 1878, 1908, 1989, and 2003. Said sequences contain one amino acid substitution or a combination thereof as defined in iii), and in some instances also said additional amino acids as defined herein above. Preferred combinations of said CDR sequences are listed in the following in the order of CDR-H1, CDR-H2, CDR-H3, CDR-11, CDR-L2, CDR-L3: 1878 to 1883; 1908 to 1913; 1984 to 1989; 1998 to 2003.

Also in accordance with the invention are CDR sequence combinations in the order of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3 as defined in SEQ ID NOs: 126 to 131; 134 to 139; 142 to 147; 150 to 155; 158 to 163.

Also in accordance with the invention and more preferred are CDR sequence combinations as defined in SEQ ID NOs (listed in the order of CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3): 2006 to 2011; 2014 to 2019; 2022 to 2027; 2030 to 2035; 2038 to 2043; 20 to 25; 36 to 41; 44 to 49; 52 to 57; 60 to 65; 68 to 73; 76 to 81; 84 to 89; 92 to 97; 102 to 107; 110 to 115. Further examples are SEQ ID NOs: 282 to 287; 290 to 295; 298 to 303; 306 to 311; 314 to 319; 472 to 477; 480 to 485; 488 to 493; 496 to 501; 504 to 509; 650 to 655; 658 to 663; 666 to 671; 674 to 679; 682 to 687; 840 to 845; 848 to 853; 856 to 861; 864 to 869; 872 to 877; 1026 to 1031; 1034 to 1039; 1042 to 1047; 1050 to 1055; 1058 to 1063; 1216 to 1221; 1224 to 1229; 1232 to 1237; 1240 to 1245; 1248 to 1253; 1394 to 1399; 1402 to 1407; 1410 to 1415; 1418 to 1423; 1426 to 1431; 1584 to 1589; 1592 to 1597; 1600 to 1605; 1608 to 1613; 1616 to 1621; 1774 to 1779; 1782 to 1787; 1790 to 1795; 1798 to 1803; 1806 to 1811;

In accordance with the invention, the binding domain of the polypeptide or polypeptide construct of the invention that binds to an extracellular epitope of the human CD3ε chain comprises or consists of a VH region sequence as defined in the following SEQ ID NOs: 1856, 1860, 1862, 1864, 1872, 1884, 1894, 1896, 1898, 1900, 1902, 1904, 1906, 1914, 1916, 1918, 1920, 1922, 1924, 1926, 1928, 1930, 1932, 1934, 1936, 1938, 1940, 1942, 1944, 1946, 1948, 1950. Said sequences contain one amino acid substitution or a combination thereof as defined herein above, and in some instances also said additional amino acids as defined herein above. This is also true for the below embodiments characterizing by sequence ID number CD3epsilon binding domains that result from amino acid residue exchanges as specified herein.

Preferred combinations of VH and VL region sequences of said binding domain of the polypeptide or polypeptide construct of the invention that binds to an extracellular epitope of the human CD3ε chain are defined in the following SEQ ID NOs: 1856 and 1857; 1860 and 1861; 1862 and 1863; 1864 and 1865; 1866 and 1867; 1868 and 1869; 1870 and 1871; 1872 and 1873; 1874 and 1875; 1876 and 1877; 1884 and 1885; 1894 and 1895; 1896 and 1897; 1898 and 1899; 1900 and 1901; 1902 and 1903; 1904 and 1905; 1906 and 1907; 1914 and 1915; 1916and 1917; 1918 and 1919; 1920and 1921; 1922 and 1923; 1924 and 1925; 1926 and 1927; 1928 and 1929; 1930 and 1931; 1932 and 1933; 1934 and 1935; 1936 and 1937; 1938 and 1939; 1940 and 1941; 1942 and 1943; 1944 and 1945; 1946 and 1947; 1948 and 1949; 1950 and 1951; 1960 and 1961; 1962 and 1963; 1964 and 1965; 1966 and 1967; 1968 and 1969; 1970 and 1971; 1974 and 1975; 1990 and 1991; 1992 and 1993; 1994 and 1995; 1996 and 1997; or 2004 and 2005.

Also in accordance with the invention are VH region sequences as defined in SEQ ID NO: 132, 140, 148, 156, and 164.

Also in accordance with the invention are VL region sequences as defined in SEQ ID NO: 133, 141, 149, 157, and 165.

Also in accordance with the invention are any combinations of the foregoing particularly preferred VH and VL region sequences. Preferred are the following VH and VL combinations as defined by SEQ ID NOs: 132 and 133; 140 and 141; 148 and 149; 156 and 157; and 164 and 165.

Also in accordance with the invention and more preferred are VH region sequences as defined in SEQ ID NO: 2012, 2020, 2028, 2036, 2044, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 100, 108, and 116. Further examples are SEQ ID NOs: 288, 296, 304, 312, 320, 478, 486, 494, 502, 510, 656, 664, 672, 680, 688, 846, 854, 862, 870, 878, 1032, 1040, 1048, 1056, 1064, 1222, 1230, 1238, 1246, 1254, 1400, 1408, 1416, 1424, 1432, 1590, 1598, 1606, 1614, 1622, 1780, 1788, 1796, 1804, and 1812.

Also in accordance with the invention and more preferred are VL region sequences as defined in SEQ ID NO: 2013, 2021, 2029, 2037, 2045, 27, 35, 43, 51, 59, 67, 75, 83, 91, 99, 101, 109, and 117. Further examples are SEQ ID NOs: 289, 297, 305, 313, 321, 479, 487, 495, 503, 511, 657, 665, 673, 681, 689, 847, 855, 863, 871, 879, 1033, 1041, 1049, 1057, 1065, 1223, 1231, 1239, 1247, 1255, 1401, 1409, 1417, 1425, 1433, 1591, 1599, 1607, 1615, 1623, 1781, 1789, 1797, 1805, and 1813.

Also in accordance with the invention and preferred are any combinations of the foregoing particularly preferred VH and VL region sequences. Preferred are the following VH and VL combinations as defined by SEQ ID NOs: 2012 and 2013; 2020 and 2021; 2028 and 2029; 2036 and 2037; 2044 and 2045; 26 and 27; 34 and 35; 42 and 43; 50 and 51; 58 and 59; 66 and 67; 74 and 75; 82 and 83; 90 and 91; 98 and 99; 100 and 101; 108 and 109; and 116 and 117. Further examples are SEQ ID NOs: 288 and 289; 296 and 297; 304 and 305; 312 and 313; 320 and 321; 478 and 479; 486 and 487; 494 and 495; 502 and 503; 510 and 511; 656 and 657; 664 and 665; 672 and 673; 680 and 681; 688 and 689; 846 and 847; 854 855; 862 and 863; 870 and 871; 878 and 879; 1032 and 1033; 1040 and 1041; 1048 and 1049; 1056 and 1057; 1064 and 1065; 1222 and 1223; 1230 and 1231; 1238 and 1239; 1246 and 1247; 1254 and 1255; 1400 and 1401; 1408 and 1409; 1416 and 1417; 1424 and 1425; 1432 and 1433; 1590 and 1591; 1598 and 1599; 1606 and 1607; 1614 and 1615; 1622 and 1623; 1780 and 1781; 1788 and 1789; 1796 and 1797; 1804 and 1805; and 1812 and 1813.

In accordance with the invention, said binding domain of the polypeptide or polypeptide construct of the invention that binds to an extracellular epitope of the human CD3ε chain comprises or consists of a VH region sequence selected from SEQ ID NOs: 2012, 2020, 2028, 2036, 2044, 26, 34, 42, 50, 58, 66, 74, 82, 90, 98, 100, 108, 116, 288, 296, 304, 312, 320, 478, 486, 494, 502, 510, 656, 664, 672, 680, 688, 846, 854, 862, 870, 878, 1032, 1040, 1048, 1056, 1064, 1222, 1230, 1238, 1246, 1254, 1400, 1408, 1416, 1424, 1432, 1590, 1598, 1606, 1614, 1622, 1780, 1788, 1796, 1804, 1812, 1856, 1860, 1862, 1864, 1872, 1884, 1894, 1896, 1898, 1900, 1902, 1904, 1906, 1914, 1916, 1918, 1920, 1922, 1924, 1926, 1928, 1930, 1932, 1934, 1936, 1938, 1940, 1942, 1944, 1946, 1948, 1950, 132, 140, 148, 156, and 164; and/or a VL region sequence selected from SEQ ID NOs: 2013, 2021, 2029, 2037, 2045, 27, 35, 43, 51, 59, 67, 75, 83, 91, 99, 101, 109, and 117, 289, 297, 305, 313, 321, 479, 487, 495, 503, 511, 657, 665, 673, 681, 689, 847, 855, 863, 871, 879, 1033, 1041, 1049, 1057, 1065, 1223, 1231, 1239, 1247, 1255, 1401, 1409, 1417, 1425, 1433, 1591, 1599, 1607, 1615, 1623, 1781, 1789, 1797, 1805, 1813, 1867, 1869, 1871, 1875, 1877, 1899, 1901, 1903, 1905, 1907, 1919, 1921, 1923, 1925, 1927, 1929, 1931, 1933, 1935, 1937, 1939, 1941, 1943, 1961, 1963, 1965, 1967, 1969, 1971, 1975, 1991, 1993, 1995, 1997, 2005, 133, 141, 149, 157, and 165.

According to the invention, it is preferred that the polypeptide or polypeptide construct comprises: a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of i) a VH region and ii) a VL region, wherein said VH and VL region of i) and ii) is selected from the VH and VL region combination as defined in SEQ ID NOs: 124 and 125, 172 and 173, 362 and 363, 552 and 553, 730 and 731, 928 and 929, 1106 and 1107, 1296 and 1297, 1474 and 1475, 1664 and 1665, and 1854 and 1855, wherein said one amino acid substitution or a combination thereof in said VH and/or VL region sequence results in a VH and/or a VL region sequence having the amino acid residue:

- i. I at position 34, A at position 65, V at position 81, A at position 99, A at position 101, S at position 106 in the VH region sequence, I at position 20, K at position 40, S at position 69, and S at position 102 in the VL region sequence;
  - M at position 45, A at position 65, L at position 81, A at position 101, T at position 106 in the VH region sequence, I at position 20, K at position 40, S at position 69 and S at position 102 in the VL region sequence;
  - M at position 45, A at position 65, L at position 81, A at position 101, S at position 106, F at position 112 in the VH region sequence, I at position 20, I at position 38, K at position 40, E at position 69, S at position 102 and Y at position 93 in the VL region sequence;
  - I at position 34, E at position 39, A at position 65, N at position 101, A at position 102,
  - T at position 106, F at position 112 in the VH region sequence, K at position 40 and S at position 102 in the VL region sequence;
  - I at position 34, E at position 64, A at position 65, A at position 99, A at position 101, T at position 106 in the VH region sequence, K at position 40, A at position 91 and S at position 102 in the VL region sequence;
  - I at position 34, A at position 65, V at position 81, A at position 99, A at position 101, E at position 102, I at position 104, T at position 106 in the VH region sequence, I at position 20, K at position 40, S at position 69 and S at position 102 in the VL region sequence;
  - E at position 64, A at position 65, G at position 68, V at position 81, A at position 101, S at position 106 in the VH region sequence, I at position 20, S at position 69 and S at position 102 in the VL region sequence;
  - I at position 34, E at position 64, A at position 65, A at position 101, T at position 106, F at position 112 in the VH region sequence, K at position 40, A at position 91 and S at position 102 in the VL region sequence;
  - I at position 34, E at position 64, A at position 65, A at position 101, S at position 106, F at position 112 in the VH region sequence, K at position 40, A at position 91 and S at position 102 in the VL region sequence;
  - I at position 34, E at position 64, A at position 65, V at position 81, A at position 99, A at position 101, S at position 106 in the VH region sequence, I at position 20, K at position 40, S at position 69, S at position 102 and Y at position 93 in the VL region sequence;
  - I at position 34, A at position 65, A at position 101, S at position 106, F at position 112 in the VH region sequence, K at position 40, A at position 91 and S at position 102 in the VL region sequence;
  - M at position 45, E at position 64, A at position 65, L at position 81, A at position 101, T at position 106 in the VH region sequence, I at position 20, I at position 38, K at position 40, E at position 69 and S at position 102 in the VL region sequence;
  - S at position 30, M at position 45, A at position 65, G at position 68, V at position 81, A at position 101, T at position 106, F at position 112 in the VH region sequence, K at position 40, S at position 69 and Y at position 93 in the VL region sequence; and
  - S at position 30, M at position 45, E at position 64, A at position 65, G at position 68, V at position 81, A at position 101, S at position 106 in the VH region sequence, K at position 40 and S at position 69 in the VL region sequence;
- ii. E at position 64, A at position 65, G at position 68, V at position 81, N at position 101, E at position 102, I at position 104, T at position 106 in the VH region sequence, I at position 20, S at position 69 and S at position 102 in the VL region sequence;
  - A at position 65, G at position 68, V at position 81, N at position 101, E at position 102, I at position 104, S at position 106 in the VH region sequence, I at position 20, S at position 69 and S at position 102 in the VL region sequence;
  - I at position 34, A at position 65, A at position 99, A at position 101, T at position 106 in the VH region sequence, K at position 40, A at position 91 and S at position 102 in the VL region sequence; and
  - S at position 30, E at position 39, E at position 64, A at position 65, V at position 81, A at position 101, E at position 102, 1 at position 104, T at position 106 in the VH region sequence, M at position 20, K at position 40 and E at position 69 in the VL region sequence;
- iii. A at position 101 in the VH region sequence;
- iv. V at position 81, A at position 99_in the VH region sequence, I at position 20, K at position 40, S at position 69 and S at position 102 in the VL region sequence;
  - I at position 34,_V at position 81 in the VH region sequence, I at position 20,_K at position 40 and S at position 102 in the VL region sequence;
  - I at position 34 in the VH region sequence, I at position 20,_K at position 40_and S at position 102 in the VL region sequence;
  - I at position 34,_E at position 39,_V at position 81 in the VH region sequence, I at position 20,_K at position 40 and S at position 102 in the VL region sequence;
- v. I at position 34,_V at position 81 in the VH region sequence, and K at position 40 in the VL region sequence;
  - M at position 45 in the VH region sequence, I at position 20,_K at position 40 and S at position 102 in the VH region sequence;
  - I at position 34,_A at position 65,_A at position 101 and_S at position 106S in the VH region sequence;
  - I at position 20,_K at position 40,_S at position 69 and_S at position 102 in the VL region sequence;
  - F at position 34_and V at position 81 in the VH region sequence;
  - M at position 45 in the VH region sequence, K at position 40 and_S at position 102 in the VL region sequence;
  - D at position 39 in the VH region sequence, I at position 20,_K at position 40 and S at position 102 in the VL region sequence;
  - I at position 34_and V at position 81 in the VH region sequence;
  - E at position 39 in the VH region sequence, I at position 20,_K at position 40 and S at position 102 in the VL region sequence;
  - M at position 45 in the VH region sequence and K at position 40 in the VL region sequence;
  - I at position 34,_A at position 65,_V at position 81,_A at position 99,_A at position 101_and S at position 106 in the VH region sequence; or
- vi. D at position 39 in the VH region sequence,_I at position 20,_R at position 40 and_S at position 102 in the VL region sequence;
  - I at position 34 in the VH region sequence;
  - K at position 40 in the VL region sequence;
  - D at position 39_in the VH region sequence, K at position 40 and S at position 102 in the VL region sequence;
  - I at position 20 and S at position 102 in the VH region sequence; K at position 39 in the VH region sequence;
  - E at position 39 in the VH region sequence,_K at position 40_and S at position 102 in the VL region sequence;
  - E at position 39 in the VH region sequence,_I at position 20,_R at position 40_and S at position 102 in the VL region sequence;
  - D at position 39_in the VH region sequence,_R at position 40_and S at position 102 in the VL region sequence;
  - V at position 81 in the VH region sequence;
  - D at position 39 in the VH region sequence and_K at position 40 in the VL region sequence;
  - F at position 112 in the VH region sequence;
  - F at position 112 in the VH region sequence and_I at position 38 in the VL region sequence;
  - E at position 39 in the VH region sequence and K at position 40 in the VL region sequence;
  - V at position 34 in the VH region sequence.

The above recited amino acid residues are present at the given position(s) in the CD3epsilon binding domain according to the invention. In case one of the VH and/or VL region sequences that are to be changed (the VH region of i) and the VL region of ii)), i.e. the base VH and/or VL region sequence, already contain one of the above recited amino acid residues at a given position, it follows that these cannot changed since the respective amino acid residue is already present in the VH region and/or VL region of i) and/or ii).

More preferred is that the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 124 and 125, 362 and 363, 730 and 731, 928 and 929, 1106 and 1107, 1296 and 1297, 1474 and 1475, 1664 and 1665, and 1854 and 1855. Even more preferred is that the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 124 and 125, 730 and 731, 1664 and 1665, and 1854 and 1855. In a yet even more preferred embodiment, the CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) selected from the group consisting of SEQ ID NOs: 730 and 731, 1664 and 1665, and 1854 and 1855. Most preferred is that said CD3epsilon binding domain comprises or consists of a combination of VH and VL region of i) and ii) of SEQ ID NOs: 1854 and 1855, respectively.

As evident from the example section, the above recited amino acid residues at the given position(s) have a favorable effect on an increase of the temperature stability that is measured by the well know and also herein described method of DSF (Differential Scanning Fluorimetry; cf. e.g., Wen et al., “Nano differential scanning fluorimetry for comparability studies of therapeutic proteins”, Analytical Biochemistry, Volume 593, 2020, 113581, ISSN 0003-2697; Dart, M. L., et al. (2018). “Homogeneous Assay for Target Engagement Utilizing Bioluminescent Thermal Shift”. ACS medicinal chemistry letters, 9(6), 546-551) when introduced in the above recited VH and VL sequences of i) and ii). More specifically, the amino acid residues at the given positions recited in sections i. and iv. exhibit an increase in temperature stability of 6° C. or more as compared to the value measured for the unmodified sequence, i.e. the respective base VH and VL sequence. Section ii. and v. exhibit an increase in temperature stability of 3° C. or more as compared to the value measured for the unmodified sequence, i.e. the respective base VH and VL sequence, whereas sections iii. and vi. exhibit an increase in temperature stability of 1° C. or more as compared to the value measured for the unmodified sequence, i.e. the respective base VH and VL sequence. Preferably, the amino acid residues at the given position(s) in section i. ii., iv., and/or v. are present in the CD3epsilon binding domain according to this embodiment. More preferred is that the amino acid residues at the given position(s) in section i. and/or iv. are present in the CD3epsilon binding domain according to the invention. This preference also applies to the preferred embodiments recited in the following. As outlined herein, it is also preferred that the VH and VL region is linked by a linker, preferably a peptide linker most preferred a G₄S or a G₄Q linker, preferably said G₄S or a G₄Q linker is repeated three times, i.e. it is a (G₄S)₃or a (G₄Q)₃linker.

According to the invention, it relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3ε chain comprising or consisting of a VH region and a VL region, wherein

- a) the VH region comprises or consist of the sequence as defined in SEQ ID NO: 1854 and the VL region comprises or consists of the sequence as defined in SEQ ID NO: 1855; and wherein the VH and/or VL region sequence comprise the amino acid substitution(s) selected from:
  - i. M34I, S65A, A81V, V99A, H101A, N106S in the VH region sequence (resulting VH sequence as defined in SEQ ID NO: 2012), L20I, Q40K, L69S, and G102S in the VL region sequence (resulting VL sequence as defined in SEQ ID NO: 2013);
    - L45M, S65A, A81L, H101A, N106T in the VH region sequence (SEQ ID NO: 2036), L20I, Q40K, L69S, and G102S in the VL region sequence (SEQ ID NO: 2037);
    - L45M, S65A, A81L, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 2028), L20I, V381, Q40K, L69E, G102S and W93Y in the VL region sequence (SEQ ID NO: 2029);
    - M34I, Q39E, S65A, H101N, G102A, N106T, W112F in the VH region sequence (SEQ ID NO: 2044), Q40K and G102S in the VL region sequence (SEQ ID NO: 2045);
    - M34I, D64E, S65A, V99A, H101A, N106T in the VH region sequence (SEQ ID NO: 34), Q40K, V91A and G102S in the VL region sequence (SEQ ID NO: 35);
    - M34I, S65A, A81V, V99A, H101A, G102E, F104I, N106T in the VH region sequence (SEQ ID NO: 90), L20I, Q40K, L69S, and G102S in the VL region sequence (SEQ ID NO: 91);
    - D64E, S65A, D68G, A81V, H101A, N106S in the VH region sequence (SEQ ID NO: 100), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 101);
    - M34I, D64E, S65A, H101A, N106T, W112F in the VH region sequence (SEQ ID NO: 58), Q40K, V91A and G102S in the VL region sequence (SEQ ID NO: 59);
    - M34I, D64E, S65A, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 50), Q40K, V91A and G102S in the VL region sequence (SEQ ID NO: 51);
    - M34I, D64E, S65A, A81V, V99A, H101A, N106S in the VH region sequence (SEQ ID NO: 98), L20I, Q40K, L69S, G102S and W93Y in the VL region sequence (SEQ ID NO: 99);
    - M34I, S65A, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 42), Q40K, V91A and G102S in the VL region sequence (SEQ ID NO: 43);
    - L45M, D64E, S65A, A81L, H101A, N106T in the VH region sequence (SEQ ID NO: 116), L20I, V381, Q40K, L69E and G102S in the VL region sequence (SEQ ID NO: 117);
    - N30S, L45M, S65A, D68G, A81V, H101A, N106T, W112F in the VH region sequence (SEQ ID NO: 82), Q40K, L69S and W93Y in the VL region sequence (SEQ ID NO: 83); and
    - N30S, L45M, D64E, S65A, D68G, A81V, H101A, N106S in the VH region sequence (SEQ ID NO: 74), Q40K and L69S in the VL region sequence (SEQ ID NO: 75);
  - ii. D64E, S65A, D68G, A81V, H101N, G102E, F104I, N106T in the VH region sequence (SEQ ID NO: 2020), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 2021);
    - S65A, D68G, A81V, H101N, G102E, F104I, N106S in the VH region sequence (SEQ ID NO: 108), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 109);
    - M34I, S65A, V99A, H101A, N106T in the VH region sequence (SEQ ID NO: 26), Q40K, V91A and G102S in the VL region sequence (SEQ ID NO: 27); and
    - N30S, Q39E, D64E, S65A, A81V, H101A, G102E, F104I, N106T in the VH region sequence (SEQ ID NO: 66), L20M, Q40K and L69E in the VL region sequence (SEQ ID NO: 67);
  - iii. H101A in the VH region sequence (SEQ ID NO: 2560);
  - iv. A81V, V99A_in the VH region sequence, L20I, Q40K, L69S and G102S in the VL region sequence;
    - M34I,_A81V in the VH region sequence (SEQ ID NO: 1898),_L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1899);
    - M34I in the VH region sequence (SEQ ID NO: 1904), L20I,_Q40K_and G102S in the VL region sequence (1905);
    - M34I,_Q39E,_A81V in the VH region sequence (SEQ ID NO: 1906), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1907);
  - v. M34I,_A81V in the VH region sequence (SEQ ID NO: 1900), and Q40K in the VL region sequence (SEQ ID NO: 1901);
    - L45M in the VH region sequence (SEQ ID NO: 1866),_L20I,_Q40K and_G102S in the VH region sequence (SEQ ID NO: 1867);
    - M34I,_S65A,_H101A and_N106S in the VH region sequence; L20I,_Q40K,_L69S and_G102S in the VL region sequence; M34F_and A81V in the VH region sequence (SEQ ID NO: 1884);
    - L45M in the VH region sequence (SEQ ID NO: 1870), Q40K and_G102S in the VL region sequence (SEQ ID NO: 1871); Q39D in the VH region sequence (SEQ ID NO: 1918), L20I,_Q40K and G102S in the VL region sequence (SEQ ID NO: 1919);
    - M34I_and A81V in the VH region sequence (SEQ ID NO: 1869); Q39E in the VH region sequence (SEQ ID NO:_1932), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1933);
    - L45M in the VH region sequence (SEQ ID NO:_1868)_and_Q40K in the VI region sequence (SEQ ID NO: 1869);
    - M34I,_S65A,_A81V,_V99A,_H101A_and N106S in the VH region sequence; or
  - vi. Q39D in the VH region sequence (SEQ ID NO: 1928),_L20I,_Q40R and_G102S in the VL region sequence (SEQ ID NO: 1929);
    - M34I in the VH region sequence (SEQ ID NO: 1892); Q40K in the VL region sequence (SEQ ID NO: 1974); Q39D_in the VH region sequence (SEQ ID NO: 1922), Q40K and_G102S in the VL region sequence (SEQ ID NO: 1923);
    - L20I and_G102S in the VH region sequence;
    - Q39K in the VH region sequence (SEQ ID NO: 1944);
    - Q39E in the VH regions sequence (SEQ ID NO: 1938),_Q40K_and G102S in the VL region sequence (SEQ ID NO: 1939);
    - Q39E in the VH region sequence (SEQ ID NO: 1934),_L20I,_Q40R_and G102S in the VL region sequence (SEQ ID NO: 1935);
    - Q39D_in the VH region sequence (SEQ ID NO: 1926),_Q40R_and G102S in the VL region sequence (SEQ ID NO: 1926);
    - A81V in the VH region sequence (SEQ ID NO: 1862);
    - Q39D in the VH region sequence (SEQ ID NO: 1920) and_Q40K in the VL region sequence (SEQ ID NO: 1921);
    - W112F in the VH region sequence (SEQ ID NO: 1958);
    - W112F in the VH region sequence (SEQ ID NO: 1960) and_V381 in the VL region sequence (SEQ ID NO: 1961);
    - Q39E in the VH region sequence (SEQ ID NO: 1936)_and_Q40K in the VL region sequence (SEQ ID NO: 1937);
    - M34V in the VH region sequence (SEQ ID NO: 1914);
- b) the VH region comprises or consist of the sequence as defined in SEQ ID NO: 730 and the VL region comprises or consists of the sequence as defined in SEQ ID NO: 731; and wherein the VH and/or VL region sequence comprise the amino acid substitution(s) selected from:
  - i. M34I, S65A, A81V, V99A, H101A, N106S in the VH region sequence (resulting VH sequence as defined in SEQ ID NO: 846), L20I, Q40K, L69S, and G102S in the VL region sequence (resulting VL sequence as defined in SEQ ID NO: 847);
    - L45M, S65A, A81L, H101A, N106T in the VH region sequence (SEQ ID NO: 870), L20I, Q40K, L69S, and G102S in the VL region sequence (SEQ ID NO: 871);
    - L45M, S65A, A81L, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 862), L20I, V381, Q40K, L69E, G102S and W93Y in the VL region sequence (SEQ ID NO: 863);
    - M34I, Q39E, S65A, H101N, G102A, N106T, W112F in the VH region sequence (SEQ ID NO: 878), Q40K and G102S in the VL region sequence (SEQ ID NO: 879);
    - M34I, D64E, S65A, V99A, H101A, N106T in the VH region sequence, Q40K, V91A and G102S in the VL region sequence;
    - M34I, S65A, A81V, V99A, H101A, G102E, F104I, N106T in the VH region sequence, L20I, Q40K, L69S, and G102S in the VL region sequence; D64E, S65A, A81V, H101A, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - M34I, D64E, S65A, H101A, N106T, W112F in the VH region sequence, Q40K, V91A and G102S in the VL region sequence;
    - M34I, D64E, S65A, H101A, N106S, W112F in the VH region sequence, Q40K, V91A and G102S in the VL region sequence;
    - M34I, D64E, S65A, A81V, V99A, H101A, N106S in the VH region sequence, L20I, Q40K, L69S, G102S and W93Y in the VL region sequence;
    - M34I, S65A, H101A, N106S, W112F in the VH region sequence, Q40K, V91A and G102S in the VL region sequence;
    - L45M, D64E, S65A, A81L, H101A, N106T in the VH region sequence, L20I, V381, Q40K, L69E and G102S in the VL region sequence;
    - N30S, L45M, S65A, A81V, H101A, N106T, W112F in the VH region sequence, Q40K, L69S and W93Y in the VL region sequence; and
    - N30S, L45M, D64E, S65A, A81V, H101A, N106S in the VH region sequence, Q40K and L69S in the VL region sequence;
  - ii. D64E, S65A, A81V, H101N, G102E, F104I, N106T in the VH region sequence (SEQ ID NO: 854), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 855);
    - S65A, A81V, H101N, G102E, F104I, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - M34I, S65A, V99A, H101A, N106T in the VH region sequence, Q40K, V91A and G102S in the VL region sequence; and
    - N30S, Q39E, D64E, S65A, A81V, H101A, G102E, F104I, N106T in the VH region sequence, L20M, Q40K and L69E in the VL region sequence;
  - iii. H101A in the VH region sequence;
  - iv. A81V, V99A_in the VH region sequence, L20I, Q40K, L69S and G102S in the VL region sequence;
    - M34I,_A81V in the VH region sequence (SEQ ID NO: 774),_L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 775);
    - M34I in the VH region sequence (SEQ ID NO: 780), L20I,_Q40K_and G102S in the VL region sequence (781);
    - M34I,_Q39E,_A81V in the VH region sequence (SEQ ID NO: 782), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 783);
  - v. M34I,_A81V in the VH region sequence (SEQ ID NO: 776), and Q40K in the VL region sequence (SEQ ID NO: 777);
    - L45M in the VH region sequence (SEQ ID NO: 742),_L20I,_Q40K and_G102S in the VH region sequence (SEQ ID NO: 743);
    - M34I,_S65A,_H101A and_N106S in the VH region sequence;
    - L20I,_Q40K,_L69S and_G102S in the VL region sequence;
    - M34F_and A81V in the VH region sequence (SEQ ID NO: 760);
    - L45M in the VH region sequence (SEQ ID NO: 746), Q40K and_G102S in the VL region sequence (SEQ ID NO: 747);
    - Q39D in the VH region sequence (SEQ ID NO: 794), L20I,_Q40K and G102S in the VL region sequence (SEQ ID NO: 795);
    - M34I_and A81V in the VH region sequence (SEQ ID NO: 772);
    - Q39E in the VH region sequence (SEQ ID NO:_808), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 809);
    - L45M in the VH region sequence (SEQ ID NO:_744)_and_Q40K in the VI region sequence (SEQ ID NO: 745);
    - M34I,_S65A,_A81V,_V99A,_H101A_and N106S in the VH region sequence; or
  - vi. Q39D in the VH region sequence (SEQ ID NO: 796),_L20I,_Q40R and_G102S in the VL region sequence (SEQ ID NO: 797);
    - M34I in the VH region sequence (SEQ ID NO: 768);
    - Q40K in the VL region sequence (SEQ ID NO: 891);
    - Q39D_in the VH region sequence (SEQ ID NO: 800), Q40K and_G102S in the VL region sequence (SEQ ID NO: 801);
    - L20I and_G102S in the VH region sequence;
    - Q39K in the VH region sequence (SEQ ID NO: 820);
    - Q39E in the VH region sequence (SEQ ID NO: 814),_Q40K_and G102S in the VL region sequence (SEQ ID NO: 815);
    - Q39E in the VH region sequence (SEQ ID NO: 810),_L20I,_Q40R_and G102S in the VL region sequence (SEQ ID NO: 811);
    - Q39D_in the VH region sequence (SEQ ID NO: 804),_Q40R_and G102S in the VL region sequence (SEQ ID NO: 805);
    - A81V in the VH region sequence (SEQ ID NO: 738);
    - Q39D in the VH region sequence (SEQ ID NO: 798) and_Q40K in the VL region sequence (SEQ ID NO: 799);
    - W112F in the VH region sequence (SEQ ID NO: 834);
    - W112F in the VH region sequence (SEQ ID NO: 836) and_V381 in the VL region sequence (SEQ ID NO: 837);
    - Q39E in the VH region sequence (SEQ ID NO: 812)_and_Q40K in the VL region sequence (SEQ ID NO: 813);
    - M34V in the VH region sequence (SEQ ID NO: 790)
- c) the VH region comprises or consist of the sequence as defined in SEQ ID NO: 1664 and the VL region comprises or consists of the sequence as defined in SEQ ID NO: 1665; and wherein the VH and/or VL region sequence comprise the amino acid substitution(s) selected from:
  - i. M34I, S65A, A81V, V99A, H101A, N106S in the VH region sequence (resulting VH sequence as defined in SEQ ID NO: 1780), L20I, Q40K, L69S, and G102S in the VL region sequence (resulting VL sequence as defined in SEQ ID NO: 1781);
    - L45M, S65A, A81L, H101A, N106T in the VH region sequence (SEQ ID NO: 1804), L20I, Q40K, L69S, and G102S in the VL region sequence (SEQ ID NO: 1805);
    - L45M, S65A, A81L, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 1796), L20I, V381, Q40K, L69E, G102S and W93Y in the VL region sequence (SEQ ID NO: 1797);
    - M34I, Q39E, S65A, H101N, G102A, N106T, W112F in the VH region sequence (SEQ ID NO: 1812), Q40K and G102S in the VL region sequence (SEQ ID NO: 1813);
    - M34I, D64E, S65A, V99A, H101A, N106T in the VH region sequence, Q40K and G102S in the VL region sequence;
    - M34I, S65A, A81V, V99A, H101A, G102E, F104I, N106T in the VH region sequence, L20I, Q40K, L69S, and G102S in the VL region sequence; D64E, S65A, D68G, A81V, H101A, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - M34I, D64E, S65A, H101A, N106T, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - M34I, D64E, S65A, H101A, N106S, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - M34I, D64E, S65A, A81V, V99A, H101A, N106S in the VH region sequence, L20I, Q40K, L69S, G102S and W93Y in the VL region sequence;
    - M34I, S65A, H101A, N106S, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - L45M, D64E, S65A, A81L, H101A, N106T in the VH region sequence, L20I, V381, Q40K, L69E and G102S in the VL region sequence;
    - N30S, L45M, S65A, D68G, A81V, H101A, N106T, W112F in the VH region sequence, Q40K, L69S and W93Y in the VL region sequence; and
    - N30S, L45M, D64E, S65A, D68G, A81V, H101A, N106S in the VH region sequence, Q40K and L69S in the VL region sequence;
  - ii. D64E, S65A, D68G, A81V, H101N, G102E, F104I, N106T in the VH region sequence (SEQ ID NO: 1788), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 1789);
    - S65A, D68G, A81V, H101N, G102E, F104I, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - M34I, S65A, V99A, H101A, N106T in the VH region sequence, Q40K and G102S in the VL region sequence; and
    - N30S, Q39E, D64E, S65A, A81V, H101A, G102E, F104I, N106T in the VH region sequence, L20M, Q40K and L69E in the VL region sequence;
  - iii. H101A in the VH region sequence;
  - iv. A81V, V99A_in the VH region sequence, L20I, Q40K, L69S and G102S in the VL region sequence;
    - M34I,_A81V in the VH region sequence (SEQ ID NO: 1708),_L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1709);
    - M34I in the VH region sequence (SEQ ID NO: 1714), L20I,_Q40K_and G102S in the VL region sequence (1715);
    - M34I,_Q39E,_A81V in the VH region sequence (SEQ ID NO: 1716), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1717);
  - v. M34I,_A81V in the VH region sequence (SEQ ID NO: 1710), and Q40K in the VL region sequence (SEQ ID NO: 1711);
    - L45M in the VH region sequence (SEQ ID NO: 1676),_L20I,_Q40K and_G102S in the VH region sequence (SEQ ID NO: 1677);
    - M34I,_S65A,_H101A and_N106S in the VH region sequence;
    - L20I,_Q40K,_L69S and_G102S in the VL region sequence;
    - M34F_and A81V in the VH region sequence (SEQ ID NO: 1694);
    - L45M in the VH region sequence (SEQ ID NO: 1680), Q40K and_G102S in the VL region sequence (SEQ ID NO: 1681);
    - Q39D in the VH region sequence (SEQ ID NO: 1728), L20I,_Q40K and G102S in the VL region sequence (SEQ ID NO: 1729);
    - M34I_and A81V in the VH region sequence (SEQ ID NO: 1706);
    - Q39E in the VH region sequence (SEQ ID NO:_1742), L20I,_Q40K and_G102S in the VL region sequence (SEQ ID NO: 1743);
    - L45M in the VH region sequence (SEQ ID NO:_1678)_and_Q40K in the VI region sequence (SEQ ID NO: 1679);
    - M34I,_S65A,_A81V,_V99A,_H101A_and N106S in the VH region sequence; or
  - vi. Q39D in the VH region sequence (SEQ ID NO: 1730),_L20I,_Q40R and_G102S in the VL region sequence (SEQ ID NO: 1731);
    - M34I in the VH region sequence (SEQ ID NO: 1702);
    - Q40K in the VL region sequence (SEQ ID NO: 1755);
    - Q39D_in the VH region sequence (SEQ ID NO: 1734), Q40K and_G102S in the VL region sequence (SEQ ID NO: 1735);
    - L20I and_G102S in the VH region sequence;
    - Q39K in the VH region sequence (SEQ ID NO: 1754);
    - Q39E in the VH regions sequence (SEQ ID NO: 1748),_Q40K_and G102S in the VL region sequence (SEQ ID NO: 1749);
    - Q39E in the VH region sequence (SEQ ID NO: 1744),_L20I,_Q40R_and G102S in the VL region sequence (SEQ ID NO: 1745);
    - Q39D_in the VH region sequence (SEQ ID NO: 1738),_Q40R_and G102S in the VL region sequence (SEQ ID NO: 1739);
    - A81V in the VH region sequence (SEQ ID NO: 1672);
    - Q39D in the VH region sequence (SEQ ID NO: 1732) and_Q40K in the VL region sequence (SEQ ID NO: 1733);
    - W112F in the VH region sequence (SEQ ID NO: 1768);
    - W112F in the VH region sequence (SEQ ID NO: 1770) and_V381 in the VL region sequence (SEQ ID NO: 1771);
    - Q39E in the VH region sequence (SEQ ID NO: 1746)_and_Q40K in the VL region sequence (SEQ ID NO: 1747);
    - M34V in the VH region sequence (SEQ ID NO: 1724); or
- d) the VH region comprises or consist of the sequence as defined in SEQ ID NO: 124 and the VL region comprises or consists of the sequence as defined in SEQ ID NO: 125; and wherein the VH and/or VL region sequence comprise the amino acid substitution(s) selected from:
  - i. Q65A, A81V, V99A, H101A, N106S in the VH region sequence (resulting VH sequence as defined in SEQ ID NO: 132), L20I, Q40K, L69S, and G102S in the VL region sequence (resulting VL sequence as defined in SEQ ID NO: 133);
    - L45M, Q65A, A81L, H101A, N106T in the VH region sequence (SEQ ID NO: 156), L20I, Q40K, L69S, and G102S in the VL region sequence (SEQ ID NO: 157);
    - L45M, Q65A, A81L, H101A, N106S, W112F in the VH region sequence (SEQ ID NO: 148), L20I, V381, Q40K, L69E, G102S and W93Y in the VL region sequence (SEQ ID NO: 149);
    - Q39E, Q65A, H101N, N106T, W112F in the VH region sequence (SEQ ID NO: 164), Q40K and G102S in the VL region sequence (SEQ ID NO: 165);
    - D64E, Q65A, V99A, H101A, N106T in the VH region sequence, Q40K, T91A and G102S in the VL region sequence;
    - Q65A, A81V, V99A, H101A, A102E, F104I, N106T in the VH region sequence, L20I, Q40K, L69S, and G102S in the VL region sequence;
    - D64E, Q65A, D68G, A81V, H101A, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - D64E, Q65A, H101A, N106T, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - D64E, Q65A, H101A, N106S, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - D64E, Q65A, A81V, V99A, H101A, N106S in the VH region sequence, L20I, Q40K, L69S, G102S and W93Y in the VL region sequence;
    - Q65A, H101A, N106S, W112F in the VH region sequence, Q40K and G102S in the VL region sequence;
    - L45M, D64E, Q65A, A81L, H101A, N106T in the VH region sequence, L20I, V381, Q40K, L69E and G102S in the VL region sequence;
    - N30S, L45M, Q65A, D68G, A81V, H101A, N106T, W112F in the VH region sequence, Q40K, L69S and W93Y in the VL region sequence; and
    - N30S, L45M, D64E, Q65A, D68G, A81V, H101A, N106S in the VH region sequence, Q40K and L69S in the VL region sequence;
  - ii. D64E, Q65A, D68G, A81V, H101N, A102E, F104I, N106T in the VH region sequence (SEQ ID NO: 140), L20I, L69S, and G102S in the VL region sequence (SEQ ID NO: 141);
    - Q65A, D68G, A81V, H101N, A102E, F104I, N106S in the VH region sequence, L20I, L69S, and G102S in the VL region sequence;
    - Q65A, V99A, H101A, N106T in the VH region sequence, Q40K and G102S in the VL region sequence; and
    - N30S, Q39E, D64E, Q65A, A81V, H101A, A102E, F104I, N106T in the VH region sequence, L20M, Q40K and L69E in the VL region sequence;
  - iii. H101A in the VH region sequence;
  - iv. A81V, V99A_in the VH region sequence, L20I, Q40K, L69S and G102S in the VL region sequence;
    - A81V in the VH region sequence,_L20I,_Q40K and_G102S in the VL region sequence;
    - L20I,_Q40K_and G102S in the VL region sequence;
    - Q39E,_A81V in the VH region sequence, L20I,_Q40K and_G102S in the VL region sequence;
  - v. A81V in the VH region sequence, and Q40K in the VL region sequence;
    - L45M in the VH region sequence,_L20I,_Q40K and_G102S in the VH region sequence;
    - Q65A,_H101A and_N106S in the VH region sequence;
    - L20I,_Q40K,_L69S and_G102S in the VL region sequence; 134F_and A81V in the VH region sequence;
    - L45M in the VH region sequence, Q40K and_G102S in the VL region sequence;
    - Q39D in the VH region sequence, L20I,_Q40K and G102S in the VL region sequence;
    - Q39E in the VH region sequence, L20I,_Q40K and_G102S in the VL region sequence;
    - L45M in the VH region sequence_and_Q40K in the VL region sequence; Q65A,_A81V,_V99A,_H101A_and N106S in the VH region sequence; or
  - vi. Q39D in the VH region sequence,_L20I,_Q40R and_G102S in the VL region sequence;
    - Q40K in the VL region sequence;
    - Q39D_in the VH region sequence, Q40K and_G102S in the VL region sequence;
    - L20I and_G102S in the VH region sequence;
    - Q39K in the VH region sequence;
    - Q39E in the VH region sequence,_Q40K_and G102S in the VL region sequence;
    - Q39E in the VH region sequence,_L20I,_Q40R_and G102S in the VL region sequence;
    - Q39D_in the VH region sequence,_Q40R_and G102S in the VL region sequence);
    - A81V in the VH region sequence;
    - Q39D in the VH region sequence and_Q40K in the VL region sequence;
    - W112F in the VH region sequence;
    - W112F in the VH region sequence and_V381 in the VL region sequence;
    - Q39E in the VH region sequence_and_Q40K in the VL region sequence;
    - M34V in the VH region sequence.
      
      The alternatives a) to c) are preferred, more preferred is the alternative a) as recited above as CD3epsilon binding domain of the polypeptide or polypeptide construct of the invention. The above recited preferred linkers are also preferred for this embodiment, i.e (G₄S)₃or G₄Q)3.

In accordance with the invention, the polypeptide or polypeptide construct the invention may have linkers, half-life extending peptides, and other structural moieties as disclosed in SEQ ID NOs: 1 to 19 and 2551. Details on nature and functions of these structures are found in the sequence table disclosed herein.

The invention provides an embodiment wherein the polypeptide construct is in a format selected from the group consisting of scFv, and to the extent that a further binding domain is present (scFv)2, diabodies and oligomers of any of the aforementioned formats. The term “is in a format” does not exclude that the construct can be further modified, e.g. by attachment or fusion to other moieties, as described herein. According to one embodiment of the polypeptide construct of the present invention, the domains comprising the herein described paratopes are in the format of an scFv. In an scFv, the VH region and the and VL region are arranged in the order VH-VL or VL-VH (from N- to C-terminus). It is envisaged that the VH and the VL regions of the domain(s) are connected via a linker, preferably a peptide linker. In a preferred embodiment, the peptide linker is a G₄S, or G₄Q linker or repetitions thereof, such as preferably (G₄S)3 (i.e. three repetitions of G₄S), or (G₄Q)3 (i.e. three repetitions of G₄Q). According to one embodiment of the binding domain(s) comprising the herein described VH and the VL regions, the VH-region is positioned N-terminally of the linker, and the VL-region is positioned C-terminally of the linker. In other words, in one embodiment of the domains comprising the herein described paratopes, the scFv comprises from the N-terminus to the C-terminus: VH-linker-VL. It is furthermore envisaged that binding domain(s) (comprising the herein described paratopes) of the construct, in case the polypeptide or polypeptide construct comprises at least one further binding domain in addition to said CD3 epsilon binding domain, are connected via a linker, preferably a peptide linker. The construct may e.g. comprise the domains in the order (from N-terminus to C-terminus) CD3 binding domain-linker-further binding domain. The inverse order (further binding domain(s)-linker-CD3 binding domain) is also possible and is the preferred orientation.

The linkers are preferably peptide linkers, more preferably short peptide linkers. In accordance with the present invention, a “peptide linker” comprises an amino acid sequence which connects the amino acid sequences of one domain with another (variable and/or binding) domain (e.g. a variable domain or a binding domain) of the construct. An essential technical feature of such peptide linker is that it does not comprise any polymerization activity. Among the suitable peptide linkers are those described in U.S. Pat. Nos. 4,751,180 and 4,935,233 or WO 88/09344. The peptide linkers can also be used to attach other domains or modules or regions (such as half-life extending domains) to the construct of the invention. Examples of useful peptide linkers are shown in SEQ ID NOs: 1 to 11 and 2551. In the present context, a “short” linker has between 2 and 50 amino acids, preferably between 3 and 35, between 4 and 30, between 5 and 25, between 6 and 20, or between 6 and 17 amino acids. The linker between two variable regions of one binding domain may have a different length (e.g. may be longer) than the linker between the two binding domains. For example, the linker between two variable regions of one binding domain may have a length between 7 and 15 amino acids, preferably between 9 and 13, and the linker between the two binding domains may have a length between 3 and 10 amino acids, preferably between 4 and 8. It is further envisaged that the peptide linkers are glycine/serine linkers, such as those depicted in SEQ ID NOs: 1 to 11 and 2551. Most of the amino acids in glycine/serine linkers are selected from glycine and serine.

If a linker is used, this linker is preferably of a length and sequence to ensure that each of the first and second domains can, independently from one another, retain their differential binding specificities. For peptide linkers which connect the at least two binding domains (or the two variable regions forming one binding domain) in the construct, those peptide linkers are envisaged which comprise only a few amino acid residues, e.g. 12 amino acid residues or less. Thus, peptide linkers of 12, 11, 10, 9, 8, 7, 6 or 5 amino acid residues are preferred. An envisaged peptide linker with less than 5 amino acids comprises 4, 3, 2 or one amino acid(s), wherein Gly-rich linkers are preferred. A “single amino acid” linker in the context of said “peptide linker” is Gly. Another embodiment of a peptide linker is characterized by the amino acid sequence Gly-Gly-Gly-Gly-Ser, i.e. Gly4Ser (SEQ ID NO: 15), or polymers thereof, i.e. (Gly4Ser)x, where x is an integer of 1 or greater (e.g. 2 or 3), for example SEQ ID NOs: 1 and 2. Preferred linkers are depicted in SEQ ID NOs: 2, 4, 5, 6, 8, 10, 11, and 2551. Another preferred linker comprises or consists of (Gly4Ser)6. The characteristics of said peptide linkers are known in the art and are described e.g. in Dall'Acqua et al. (Biochem. (1998) 37, 9266-9273), Cheadle et al. (Mol Immunol (1992) 29, 21-30) and Raag and Whitlow (FASEB (1995) 9(1), 73-80). Peptide linkers which do not promote any secondary structures are preferred. The linkage of said domains to each other can be provided, e.g., by genetic engineering. Methods for preparing fused and operatively linked bispecific single chain constructs and expressing them in mammalian cells or bacteria are well-known in the art (e.g. WO 99/54440 or Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2001). More preferred, said peptide linker is a G₄S, or G₄Q linker or repetitions thereof, such as (G₄S)3 or (G₄Q)3.

According to one embodiment of the invention, the polypeptide construct of the invention is a “single chain construct” or “single chain polypeptide”. In the case of a further binding domain, it is also envisaged that either the CD3 binding or the further (also termed “second”) or both binding domains may be in the format of a “single chain Fv” (scFv). Although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by an artificial linker—as described hereinbefore—that enables them to be made as a single protein chain in which the VL and VH regions pair to form a monovalent molecule; see e.g., Huston et al. (1988) Proc. Natl. Acad. Sci USA 85:5879-5883). These antibody fragments are obtained using conventional techniques known to those with skill in the art, and the fragments are evaluated for function in the same manner as are full-length antibodies or IgGs. A single-chain variable fragment (scFv) is hence a fusion protein of the variable region of the heavy chain (VH) and of the light chain (VL) of immunoglobulins, usually connected with a short linker peptide. The linker is usually rich in glycine for flexibility, as well as serine or also threonine for solubility, and can either connect the N-terminus of the VH with the C-terminus of the VL, or vice versa. This protein retains the specificity of the original immunoglobulin, despite removal of the constant regions and introduction of the linker.

Bispecific single chain molecules are known in the art and are described in WO 99/54440, Mack, J. Immunol. (1997), 158, 3965-3970, Mack, PNAS, (1995), 92, 7021-7025, Kufer, Cancer Immunol. Immunother., (1997), 45, 193-197, Löffler, Blood, (2000), 95, 6, 2098-2103, Brühl, Immunol., (2001), 166, 2420-2426, Kipriyanov, J. Mol. Biol., (1999), 293, 41-56. Techniques described for producing single chain constructs (see, inter alia, U.S. Pat. No. 4,946,778, Kontermann and Dübel (2010), loc. cit. and Little (2009), loc. cit.) can be adapted to produce single chain constructs selectively and, preferably, specifically recognizing (an) elected target(s).

Bivalent (also called divalent) or bispecific single-chain variable fragments (bi-scFvs or di-scFvs) having the format (scFv)2 can be engineered by linking two scFv molecules (e.g. with linkers as described hereinbefore). The linking can be done by producing a single polypeptide chain with two VH regions and two VL regions, yielding tandem scFvs (see e.g. Kufer, P. et al., (2004) Trends in Biotechnology 22(5):238-244). Another possibility is the creation of scFv molecules with linker peptides that are too short for the two variable regions to fold together (e.g. about five amino acids), forcing the scFvs to dimerize. In this case, the VH and the VL of a binding domain (binding either to CD3epsilon or the further target antigen) are not directly connected via a peptide linker. Thus, the VH of the CD3 binding domain may e.g. be fused to the VL of the further target antigen binding domain via a peptide linker, and the VH of the further target antigen binding domain is fused to the VL of the CD3 binding domain via such peptide linker. This type is known as diabodies (see e.g. Hollinger, Philipp et al., (July 1993) Proceedings of the National Academy of Sciences of the United States of America 90 (14): 6444-8.).

In accordance with the invention, the polypeptide or polypeptide construct the invention comprises at least one further binding domain. In other words, the polypeptide or polypeptide construct comprises the CD3epsilon binding domain defined herein above and at least one further binding domain. Said further binding domain can be a further CD3 binding domain, preferably one as defined herein. As such, the polypeptide can comprise two of the same CD3 binding domains as defined herein. Alternatively or additionally (in a construct comprising at least three binding domains), the at least one further binding domain binds to a different target, such as a cell surface antigen.

Preferably, said at least one further binding domain binds to a cell surface antigen. The term “cell surface antigen” as used herein denotes a molecule, which is displayed on the surface of a cell. In most cases, this molecule will be located in or on the plasma membrane of the cell such that at least part of this molecule remains accessible from outside the cell in tertiary form. A non-limiting example of a cell surface molecule, which is located in the plasma membrane is a transmembrane protein comprising, in its tertiary conformation, regions of hydrophilicity and hydrophobicity. Here, at least one hydrophobic region allows the cell surface molecule to be embedded, or inserted in the hydrophobic plasma membrane of the cell while the hydrophilic regions extend on either side of the plasma membrane into the cytoplasm and extracellular space, respectively. It will be appreciated that an extracellular epitope refers to an epitope comprised by a portion of a protein that is disposed in the extracellular space, for example a portion of a cell surface molecule that extends into the extracellular space when that cell surface molecule is a native configuration disposed, embedded, or inserted in the plasma membrane. Non-limiting examples of cell surface molecules which are located on the plasma membrane are proteins which have been modified at a cysteine residue to bear a palmitoyl group, proteins modified at a C-terminal cysteine residue to bear a farnesyl group or proteins which have been modified at the C-terminus to bear a glycosyl phosphatidyl inositol (“GPI”) anchor.

Said cell surface antigen is preferably a tumor antigen. The term “tumor antigen” as used herein may be understood as those antigens that are presented on tumor cells. These antigens can be presented on the cell surface with an extracellular part, which is often combined with a transmembrane and cytoplasmic part of the molecule. These antigens can sometimes be presented only by tumor cells and never by the normal ones. Tumor antigens can be exclusively expressed on tumor cells or might represent a tumor specific mutation compared to normal cells. In this case, they are called tumor-specific antigens. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens. These tumor-associated antigens can be overexpressed compared to normal cells or are accessible for antibody binding in tumor cells due to the less compact structure of the tumor tissue compared to normal tissue.

In a preferred embodiment, the tumor antigen is selected from the group consisting of BCMA (B-cell maturation antigen), CD123 (interleukin-3 receptor alpha chain (IL-3R)), CD19 (B-lymphocyte antigen CD19), CD20 (B-lymphocyte antigen CD20), CD22 (cluster of differentiation-22), CD33 (Siglec-3), CD70 (Cluster of Differentiation 70), CDH19 (Cadherin 19), CDH3 (Cadherin 3), CLL1 (C-type lectin domain family 12 member A), CS1 (CCND3 subset 1), CLDN6 (Claudin-6), CLDN18.2 (Claudin 18.2), DLL3 (Delta-like ligand 3), EGFRvII (Epidermal growth factor receptor vIII), FLT3 (fms like tyrosine kinase 3), MAGEB2 (Melanoma-associated antigen B2), MART1 (Melanoma Antigen Recognized By T-Cells 1), MSLN (Mesothelin), MUC17 (Mucin-17), PSMA (prostate-specific membrane antigen), and STEAP1 (Metalloreductase STEAP1). These tumor antigens are well known in the art due to their expression on tumor cells.

Preferred CDR sequences and VH/VL region sequences for BCMA binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a BCMA binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2072 to 2095.

Preferred CDR sequences and VH/VL region sequences for CD123 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD123 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2096 to 2110.

Preferred CDR sequences and VH/VL region sequences for CD19 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD19 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2111 to 2125.

Preferred CDR sequences and VH/VL region sequences for CD20 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD20 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2126 to 2140.

Preferred CDR sequences and VH/VL region sequences for CD22 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD22 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2141 to 2154.

Preferred CDR sequences and VH/VL region sequences for CD33 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD33 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2155 to 2178.

Preferred CDR sequences and VH/VL region sequences for CD70 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CD70 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2179 to 2192.

Preferred CDR sequences and VH/VL region sequences for CDH19 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CDH19 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2193 to 2212.

Preferred CDR sequences and VH/VL region sequences for CDH3 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CDH3 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2213 to 2256.

Preferred CDR sequences and VH/VL region sequences for CLL1 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CLL1 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2257 to 2271.

Preferred CDR sequences and VH/VL region sequences for CS1 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CS1 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2272 to 2285.

Preferred CDR sequences and VH/VL region sequences for CLDN6 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CLDN6 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2286 to 2299.

Preferred CDR sequences and VH/VL region sequences for CLDN18.2 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a CLDN18.2 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2300 to 2314.

Preferred CDR sequences and VH/VL region sequences for DLL3 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a DLL3 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2315 to 2328.

Preferred CDR sequences and VH/VL region sequences for EGFRvIII binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a EGFRvIII binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2329 to 2342.

Preferred CDR sequences and VH/VL region sequences for FLT3 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a FLT3 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2343 to 2357.

Preferred CDR sequences and VH/VL region sequences for MAGEB2 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a MAGEB2 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2358 to 2378.

Preferred CDR sequences and VH/VL region sequences for MART1 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention are defined in SEQ ID NOs: 2379 to 2387.

Preferred CDR sequences and VH/VL region sequences for MSLN binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a MSLN binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2388 to 2431.

Preferred CDR sequences and VH/VL region sequences for MUC17 binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a MUC17 binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2432 to 2445.

Preferred CDR sequences and VH/VL region sequences for PSMA binding domains as further binding domains of the polypeptide or polypeptide construct of the invention, and bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having a PSMA binding domain as further binding domain (with and without half-life extending domain) are defined in SEQ ID NOs: 2446 to 2475.

Preferred bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having CD20 and CD22 binding domains as further binding domains (with and without a further CD3 binding domain as defined herein) and a half-life extending domain are defined in SEQ ID NOs: 2505 to 2516.

Preferred bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having CS1 and BCMA binding domains as further binding domains and a half-life extending domain are defined in SEQ ID NOs: 2517 to 2522.

Preferred bispecific single chain molecule sequences of a polypeptide or polypeptide construct in accordance with the invention having MSLN and CDH3 binding domains as further binding domains and a half-life extending domain are defined in SEQ ID NOs: 2529 to 2536.

As laid out herein above, the polypeptide construct of the invention comprises a binding domain which binds to CD3 on the surface of a T cell. “CD3” (cluster of differentiation 3) is a T cell co-receptor composed of four chains. In mammals, the CD3 protein complex contains a CD3γ (gamma) chain, a CD3δ (delta) chain, and two CD3ε (epsilon) chains. These four chains associate with the T cell receptor (TCR) and the so-called ((zeta) chain to for the “T cell receptor complex” and to generate an activation signal in T lymphocytes. The CD3γ (gamma), CD3δ (delta), and CD3ε (epsilon) chains are highly related cell-surface proteins of the immunoglobulin superfamily and each contain a single extracellular immunoglobulin domain. The intracellular tails of the CD3 molecules contain a single conserved motif known as an immunoreceptor tyrosine-based activation motif (ITAM), which is essential for the signaling capacity of the TCR. The CD3 epsilon molecule is a polypeptide which in humans is encoded by the CD3 epsilon gene which resides on chromosome 11. In the context of the present invention, CD3 is understood as a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell (CD8+ naive T cells) and T helper cells (CD4+ naive T cells). It is typically composed of four distinct chains. Especially in mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor (TCR) and the ζ-chain (zeta-chain) to generate an activation signal in T lymphocytes. The TCR, ζ-chain, and CD3 molecules together constitute the TCR complex.

The redirected lysis of target cells via the recruitment of T cells by a construct which binds to CD3 on the T cell and to a target protein on the target cell generally involves cytolytic synapse formation and delivery of perforin and granzymes. The engaged T cells are capable of serial target cell lysis and are not affected by immune escape mechanisms interfering with peptide antigen processing and presentation, or clonal T cell differentiation; see e.g. WO 2007/042261.

Cytotoxicity mediated by given tumor antigen×CD3 constructs can be measured in various ways. The “half maximal effective concentration” (EC50) is commonly used as a measure of potency of a biologically active molecule such as a construct of the present invention. It may be expressed in molar units. In the present case of measuring cytotoxicity, the EC50 value refers to the concentration of a construct inducing a cytotoxic response (lysis of target cells) halfway between the baseline and the maximum. Effector cells in a cytotoxicity assay can e.g. be stimulated enriched (human) CD8 positive T cells or unstimulated (human) peripheral blood mononuclear cells (PBMC). An EC50 value may typically be expected to be lower when stimulated/enriched CD8+ T cells are used as effector cells, compared with unstimulated PBMC. If the target cells are of macaque origin or express or are transfected with a given macaque tumor antigen, the effector cells should also be of macaque origin, such as a macaque T cell line, e.g. 4119LnPx. The target cells should express said tumor antigen on the cell surface. Target cells can be a cell line (such as CHO) which is stably or transiently transfected with said tumor antigen. Alternatively, the target cells can be a tumor antigen positive natural expresser cell line, such as the human cancer lines. Usually EC50 values are expected to be lower when using target cells that express higher levels of said tumor antigen on the cell surface compared with target cells having a lower target expression rate.

The effector to target cell (E:T) ratio in a cytotoxicity assay is usually about 10:1, but can also vary. Cytotoxic activity of tumor antigen×CD3 constructs can be measured in a 51-chromium release assay (e.g. with an incubation time of about 18 hours) or in a in a FACS-based cytotoxicity assay (e.g. with an incubation time of about 48 hours). Modifications of the incubation time (cytotoxic reaction) are also envisaged. Other methods of measuring cytotoxicity are well-known and comprise MTT or MTS assays, ATP-based assays including bioluminescent assays, the sulforhodamine B (SRB) assay, WST assay, clonogenic assay and the ECIS technology.

According to one embodiment, the cytotoxic activity mediated by tumor antigen×CD3 constructs of the present invention is measured in a cell-based cytotoxicity assay. It may also be measured in a 51-chromium release assay. It is envisaged that the EC50 value of the constructs of the invention is ≤300 pM, ≤280 pM, ≤260 pM, ≤250 pM, ≤240 pM, ≤220 pM, ≤200 pM, ≤180 pM, ≤160 pM, ≤150 pM, ≤140 pM, ≤120 pM, ≤100 pM, ≤90 pM, ≤80 pM, ≤70 pM, ≤60 pM, ≤50 pM, ≤40 pM, ≤30 pM, ≤20 pM, ≤15 pM, ≤10 pM, or ≤5 pM.

The above given EC50 values can be measured in different assays and under different conditions. For example, when human PBMCs are used as effector cells and tumor antigen transfected cells such as CHO cells are used as target cells, it is envisaged that the EC50 value of the tumor antigen×CD3 construct is ≤500 pM, ≤400 pM, ≤300 pM, ≤280 pM, ≤260 pM, ≤250 pM, ≤240 pM, ≤220 pM, ≤200 pM, ≤180 pM, ≤160 pM, ≤150 pM, ≤140 pM, ≤120 pM, ≤100 pM, ≤90 pM, ≤80 pM, ≤70 pM, ≤60 pM, ≤50 pM, ≤40 pM, ≤30 pM, ≤20 pM, ≤15 pM, ≤10 pM, or 55 pM. When human PBMCs are used as effector cells and when the target cells are a CLDN6 positive cell line such as, it is envisaged that the EC50 value of the CLDN6×CD3 construct is ≤300 pM, ≤280 pM, ≤260 pM, ≤250 pM, ≤240 pM, ≤220 pM, ≤200 pM, ≤180 pM, ≤160 pM, ≤150 pM, ≤140 pM, ≤120 pM, ≤100 pM, ≤90 pM, ≤80 pM, ≤70 pM, ≤60 pM, ≤50 pM, ≤40 pM, ≤30 pM, ≤20 pM, ≤15 pM, ≤10 pM, or ≤5 pM.

According to one embodiment, the tumor antigen×CD3 polypeptides/polypeptide constructs of the present invention do not induce/mediate lysis or do not essentially induce/mediate lysis of cells that do not express said given tumor antigen on their surface (tumor antigen negative cells), such as CHO cells. The term “do not induce lysis”, “do not essentially induce lysis”, “do not mediate lysis” or “do not essentially mediate lysis” means that a construct of the present invention does not induce or mediate lysis of more than 30%, preferably not more than 20%, more preferably not more than 10%, particularly preferably not more than 9%, 8%, 7%, 6% or 5% of tumor antigen negative cells, whereby lysis of tumor antigen expressing target cells (such as cells transformed or transfected with said tumor antigen or a natural expresser cell line such as the human cancer lines) is set to be 100%. This usually applies for concentrations of the construct of up to 500 nM. Cell lysis measurement is a routine technique. Moreover, the present specification teaches specific instructions how to measure cell lysis.

The difference in cytotoxic activity between the monomeric and the dimeric isoform of individual tumor antigen×CD3 polypeptides/polypeptide constructs is referred to as “potency gap”. This potency gap can e.g. be calculated as ratio between EC50 values of the molecule's monomeric and dimeric form. In one method to determine this gap, an 18 hour 51-chromium release assay or a 48h FACS-based cytotoxicity assay is carried out as described hereinbelow with purified construct monomer and dimer. Effector cells are stimulated enriched human CD8+ T cells or unstimulated human PBMC. Target cells are hu tumor antigen transfected CHO cells. Effector to target cell (E:T) ratio is 10:1. Potency gaps of the tumor antigen×CD3 constructs of the present invention are preferably ≤5, more preferably s 4, even more preferably s 3, even more preferably s 2 and most preferably s 1.

The binding domain(s) of the polypeptide construct of the invention is/are preferably cross-species specific for members of the mammalian order of primates, such as macaques. According to one embodiment, the further binding domain(s), in addition to binding to a human tumor antigen, will also bind to said tumor antigen of primates including (but not limited to) new world primates (such as Callithrix jacchus, Saguinus Oedipus or Saimiri sciureus), old world primates (such as baboons and macaques), gibbons, orangutans and non-human hominidae. It is envisaged that the domain which binds to human CD3 on the surface of a T cell of the invention also binds at least to macaque CD3. A preferred macaque is Macaca fascicularis. Macaca mulatta (Rhesus) is also envisaged. The polypeptide or polypeptide construct of the invention comprises a domain which binds to human CD3epsilon on the surface of a T cell and at least macaque CD3.

In one embodiment, the affinity gap of the constructs according to the invention for binding macaque CD3 versus human CD3 [KD ma CD3: KD hu CD3] (as determined e.g. by BiaCore or by Scatchard analysis) is between 0.01 and 100, preferably between 0.1 and 10, more preferably between 0.2 and 5, more preferably between 0.3 and 4, even more preferably between 0.5 and 3 or between 0.5 and 2.5, and most preferably between 0.5 and 1.

As detailed herein above, said binding domain of the polypeptide or polypeptide construct of the invention binds to human CD3 epsilon (or human CD3 epsilon on the surface of a T cell) and, preferably, to Callithrix jacchus or Saimiri sciureus CD3 epsilon. More specifically, said domain binds to an extracellular epitope of human CD3 epsilon. It is also envisaged that said domain binds to an extracellular epitope of the human and the Macaca CD3 epsilon chain. Said extracellular epitope of CD3 epsilon is comprised within amino acid residues 1-27 of the human CD3 epsilon extracellular domain (see SEQ ID NO: 2552; amino acid residues 1-27 in SEQ ID NO: 2553). Even more particularly, the epitope comprises at least the amino acid sequence Gln-Asp-Gly-Asn-Glu. Callithrix jacchus is a new world primate belonging to the family of Callitrichidae, while Saimiri sciureus is a new world primate belonging to the family of Cebidae.

In a preferred embodiment, the polypeptide or polypeptide construct of the invention is a single chain polypeptide that is at least bispecific. It is preferred for this embodiment that the CD3 binding domain according to the invention is present as a scFv in the polypeptide or polypeptide construct.

It is also envisaged that the polypeptide construct of the invention has, in addition to its function to bind to CD3 and, in certain embodiments to bind to at least a further binding domain, a further function. In this format, the construct may be a trifunctional or multifunctional construct by targeting target cells through, preferably, tumor antigen binding, mediating cytotoxic T cell activity through CD3 binding and providing a further function such as means or domains to enhance or extend serum half-life, a fully functional or modified Fc constant domain mediating cytotoxicity through recruitment of effector cells, a label (fluorescent etc.), a therapeutic agent such as a toxin or radionuclide, etc.

Examples for means or domains to extend serum half-life of the polypeptides/polypeptide constructs of the invention include peptides, proteins or domains of proteins, which are fused or otherwise attached to the polypeptides/polypeptide constructs. The group of peptides, proteins or protein domains includes peptides binding to other proteins with preferred pharmacokinetic profile in the human body such as serum albumin (see WO 2009/127691). An alternative concept of such half-life extending peptides includes peptides binding to the neonatal Fc receptor (FcRn, see WO 2007/098420), which can also be used in the constructs of the present invention. The concept of attaching larger domains of proteins or complete proteins includes the fusion of human serum albumin, variants or mutants of human serum albumin (see WO 2011/051489, WO 2012/059486, WO 2012/150319, WO 2013/135896, WO 2014/072481, WO 2013/075066) or domains thereof, as well as the fusion of an immunoglobulin constant region (Fc domain) and variants thereof. Such variants of Fc domains are called Fc-based domains and may e.g. be optimized/modified to allow the desired pairing of dimers or multimers, to abolish Fc receptor binding (e.g. to avoid ADCC or CDC) or for other reasons. A further concept known in the art to extend the half-life of substances or molecules in the human body is the pegylation of those molecules (such as the constructs of the present invention).

In one embodiment, the polypeptides/polypeptide constructs according to the invention are linked (e.g. via peptide bond) with a fusion partner (such as a protein, polypeptide or peptide), e.g. for extending the construct's serum half-life. These fusion partners can be selected from human serum albumin (“HSA” or “HALB”) as wells as sequence variants thereof, peptides binding to HSA, peptides binding to FcRn (“FcRn BP”), or constructs comprising an (antibody derived) Fc region. Exemplary sequences of these fusion partners are depicted in SEQ ID NOs: 16, 18 and 19. In general, the fusion partners may be linked to the N-terminus or to the C-terminus of the constructs according to the invention, either directly (e.g. via peptide bond) or through a peptide linker such as (GGGGS)n or (GGGGQ)n (wherein “n” is an integer of 2 or greater, e.g. 2 or 3 or 4). Suitable peptide linkers are discussed above and are shown in SEQ ID NOs: 2 and 2551.

It is envisaged that a polypeptide construct according to the present invention comprises a single chain polypeptide that is at least bispecific, wherein said polypeptide comprises or consists of in the following order from N-terminus to C-terminus:

- a) VL (comprising part of a cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope);
- b) VH (comprising part of a cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope);
- c) VL (comprising part of a cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain);
- d) VH (comprising part of a cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain);
- e) VH (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a first cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VL (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a second cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain);
- f) VH (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a first cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a second cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain);
- g) VL (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a first cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VL (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a second cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain)
- h) VL (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a first cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a second cell surface antigen binding domain/paratope)-Peptide linker (SG4S) or (SG4Q)-VH (comprising part of the CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of the CD3epsilon binding domain/paratope)-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6 or -Fc monomer (part of the HLE domain); or
- i) Binding domain 1 ((VL (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a first cell surface antigen binding domain/paratope)) or (VH (comprising part of a first cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a first cell surface antigen binding domain/paratope)))-Peptide linker (G4S) or (G4Q)-CD3 binding domain 1 (VH (comprising part of a first CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a first CD3epsilon binding domain/paratope))-Peptide linker (G4)-Fc monomer (part of the HLE domain)-(G4S)6 or (G4Q)6-Fc monomer (part of the HLE domain)-Peptide linker (G4)-Binding domain 2 ((VL (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VH (comprising part of a first cell surface antigen binding domain/paratope)) or (VH (comprising part of a second cell surface antigen binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a second cell surface antigen binding domain/paratope)))—Peptide linker (G4S) or (G4Q)-CD3 binding domain 2 (VH (comprising part of a second CD3epsilon binding domain/paratope)-(G4S)3 or (G4Q)3-VL (comprising part of a second CD3epsilon binding domain/paratope)).

As is evident from the above, the VH and VL region sequence orientation of the binding domain(s) of the cell surface antigen can be VH-VL or VL-VH. Preferably, the cell surface antigen is a tumor antigen as detailed herein above. The HLE domain sequences made up of the Fc monomers and connecting linkers as detailed are preferably selected from the sequences as defined in SEQ ID NOs: 18 and 19. The two CD3 binding domains of the polypeptide construct of item i) are preferably the same CD3 binding domains, such as, preferably, the CD3 binding domain with VH and VL region sequences of SEQ ID NOs: 2028 and 2029. While peptide linkers (SG4S) or (SG4Q) are preferred at the indicated positions, they can also be replaced by (G4S) or (G4Q) linkers.

Covalent modifications of the polypeptides/polypeptide constructs are also included within the scope of this invention, and are generally, but not always, done post-translationally. For example, several types of covalent modifications of the construct are introduced into the molecule by reacting specific amino acid residues of the construct with an organic derivatizing agent that can react with selected side chains or with the N- or C-terminal residues. Derivatization with bifunctional agents is useful for crosslinking the constructs of the present invention to a water-insoluble support matrix or surface for use in a variety of methods. Glutaminyl and asparaginyl residues are frequently deamidated to the corresponding glutamyl and aspartyl residues, respectively. Alternatively, these residues are deamidated under mildly acidic conditions. Either form of these residues falls within the scope of this invention. Other modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the α-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, 1983, pp. 79-86), acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.

Another type of covalent modification of the constructs included within the scope of this invention comprises altering the glycosylation pattern of the protein. As is known in the art, glycosylation patterns can depend on both the sequence of the protein (e.g., the presence or absence of specific glycosylation amino acid residues, discussed below), or the host cell or organism in which the protein is produced. Specific expression systems are discussed below. Glycosylation of polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tri-peptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tri-peptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose, to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used.

Addition of glycosylation sites to the construct is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tri-peptide sequences (for N-linked glycosylation sites). The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the starting sequence (for O-linked glycosylation sites). For ease, the amino acid sequence of a construct may be altered through changes at the DNA level, particularly by mutating the DNA encoding the polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.

Another means of increasing the number of carbohydrate moieties on the construct is by chemical or enzymatic coupling of glycosides to the protein. These procedures are advantageous in that they do not require production of the protein in a host cell that has glycosylation capabilities for N- and O-linked glycosylation. Depending on the coupling mode used, the sugar(s) may be attached to (a) arginine and histidine, (b) free carboxyl groups, (c) free sulfhydryl groups such as those of cysteine, (d) free hydroxyl groups such as those of serine, threonine, or hydroxyproline, (e) aromatic residues such as those of phenylalanine, tyrosine, or tryptophan, or (f) the amide group of glutamine. These methods are described in WO 87/05330, and in Aplin and Wriston, 1981, CRC Crit. Rev. Biochem., pp. 259-306.

Removal of carbohydrate moieties present on the starting construct may be accomplished chemically or enzymatically. Chemical deglycosylation requires exposure of the protein to the compound trifluoromethanesulfonic acid, or an equivalent compound. This treatment results in the cleavage of most or all sugars except the linking sugar (N-acetylglucosamine or N-acetylgalactosamine), while leaving the polypeptide intact. Chemical deglycosylation is described by Hakimuddin et al., 1987, Arch. Biochem. Biophys. 259:52 and by Edge et al., 1981, Anal. Biochem. 118:131. Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved using a variety of endo- and exo-glycosidases as described by Thotakura et al., 1987, Meth. Enzymol. 138:350. Glycosylation at potential glycosylation sites may be prevented using the compound tunicamycin as described by Duskin et al., 1982, J. Biol. Chem. 257:3105. Tunicamycin blocks the formation of protein-N-glycoside linkages.

Other modifications of the construct are also contemplated herein. For example, another type of covalent modification of the construct comprises linking the construct to various non-proteinaceous polymers, including polyols, in the manner set forth in U.S. Pat. Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337. In addition, as is known in the art, amino acid substitutions may be made in various positions within the construct, e.g. to facilitate the addition of polymers such as polyethylene glycol (PEG).

In some embodiments, the covalent modification of the constructs of the invention comprises the addition of one or more labels. The labelling group may be coupled to the construct via spacer arms of various lengths to reduce potential steric hindrance. Various methods for labelling proteins are known in the art and can be used in performing the present invention. The term “label” or “labelling group” refers to any detectable label. In general, labels fall into a variety of classes, depending on the assay in which they are to be detected—the following examples include, but are not limited to:

- a) isotopic labels, which may be radioactive or heavy isotopes, such as radioisotopes or radionuclides (e.g., ³H, ¹⁴C ¹⁵N, S, ⁸⁹Zr, ⁹⁰, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I)
- b) magnetic labels (e.g., magnetic particles)
- c) redox active moieties
- d) optical dyes (including, but not limited to, chromophores, phosphors and fluorophores) such as fluorescent groups (e.g., FITC, rhodamine, lanthanide phosphors), chemiluminescent groups, and fluorescent labels or fluorophores which can be either “small molecule” fluores or proteinaceous fluores
- e) enzymatic groups (e.g. horseradish peroxidase, β-galactosidase, luciferase, alkaline phosphatase)
- f) biotinylated groups
- g) predetermined polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags, etc.).

By “fluorescent label” is meant any molecule that may be detected via its inherent fluorescent properties. Suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosin, coumarin, methyl-coumarins, pyrene, Malacite green, stilbene, Lucifer Yellow, Cascade BlueJ, Texas Red, IAEDANS, EDANS, BODIPY FL, LC Red 640, Cy 5, Cy 5.5, LC Red 705, Oregon green, the Alexa-Fluor dyes (Alexa Fluor 350, Alexa Fluor 430, Alexa Fluor 488, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 633, Alexa Fluor 660, Alexa Fluor 680), Cascade Blue, Cascade Yellow and R-phycoerythrin (PE) (Molecular Probes, Eugene, OR), FITC, Rhodamine, and Texas Red (Pierce, Rockford, IL), Cy5, Cy5.5, Cy7 (Amersham Life Science, Pittsburgh, PA). Suitable optical dyes, including fluorophores, are described in Molecular Probes Handbook by Richard P. Haugland.

Suitable proteinaceous fluorescent labels also include, but are not limited to, green fluorescent protein, including a Renilla, Ptilosarcus, or Aequorea species of GFP (Chalfie et al., 1994, Science 263:802-805), EGFP (Clontech Laboratories, Inc., Genbank® Accession Number U55762), blue fluorescent protein (BFP, Quantum Biotechnologies, Inc. 1801 de Maisonneuve Blvd. West, 8th Floor, Montreal, Quebec, Canada H3H 1J9; Stauber, 1998, Biotechniques 24:462-471; Heim et al., 1996, Curr. Biol. 6:178-182), enhanced yellow fluorescent protein (EYFP, Clontech Laboratories, Inc.), luciferase (Ichiki et al., 1993, J. Immunol. 150:5408-5417), p galactosidase (Nolan et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:2603-2607) and Renilla (WO92/15673, WO95/07463, WO98/14605, WO98/26277, WO99/49019, U.S. Pat. Nos. 5,292,658; 5,418,155; 5,683,888; 5,741,668; 5,777,079; 5,804,387; 5,874,304; 5,876,995; 5,925,558).

Leucine zipper domains are peptides that promote oligomerization of the proteins in which they are found. Leucine zippers were originally identified in several DNA-binding proteins (Landschulz et al., 1988, Science 240:1759), and have since been found in a variety of different proteins. Among the known leucine zippers are naturally occurring peptides and derivatives thereof that dimerize or trimerize. Examples of leucine zipper domains suitable for producing soluble oligomeric proteins are described in PCT application WO 94/10308, and the leucine zipper derived from lung surfactant protein D (SPD) described in Hoppe et al., 1994, FEBS Letters 344:191. The use of a modified leucine zipper that allows for stable trimerization of a heterologous protein fused thereto is described in Fanslow et al., 1994, Semin. Immunol. 6:267-78.

The polypeptide construct of the invention may also comprise additional domains, which are e.g. helpful in the isolation of the molecule or relate to an adapted pharmacokinetic profile of the molecule. Domains helpful for the isolation of a construct may be selected from peptide motives or secondarily introduced moieties, which can be captured in an isolation method, e.g. an isolation column. Non-limiting embodiments of such additional domains comprise peptide motives known as Myc-tag, HAT-tag, HA-tag, TAP-tag, GST-tag, chitin binding domain (CBD-tag), maltose binding protein (MBP-tag), Flag-tag, Strep-tag and variants thereof (e.g. StrepII-tag) and His-tag. All herein disclosed constructs characterized by the identified CDRs may comprise a His-tag domain, which is generally known as a repeat of consecutive His residues in the amino acid sequence of a molecule, e.g. of five His residues, or of six His residues (hexa-histidine). The His-tag may be located e.g. at the N- or C-terminus of the construct. In one embodiment, a hexa-histidine tag (HHHHHH) is linked via peptide bond to the C-terminus of the construct according to the invention. A histidine tag is preferred, especially a 6×His tag.

The invention also relates to a polynucleotide encoding a polypeptide or polypeptide construct of the invention. Nucleic acid molecules are biopolymers composed of nucleotides. A polynucleotide is a biopolymer composed of 13 or more nucleotide monomers covalently bonded in a chain. DNA (such as cDNA) and RNA (such as mRNA) are examples of polynucleotides/nucleic acid molecules with distinct biological function. Nucleotides are organic molecules that serve as the monomers or subunits of nucleic acid molecules like DNA or RNA. The nucleic acid molecule or polynucleotide of the present invention can be double stranded or single stranded, linear or circular. It is envisaged that the nucleic acid molecule or polynucleotide is comprised in a vector. It is furthermore envisaged that such vector is comprised in a host cell. Said host cell is, e.g. after transformation or transfection with the vector or the polynucleotide/nucleic acid molecule of the invention, capable of expressing the construct. For this purpose, the polynucleotide or nucleic acid molecule is operatively linked with control sequences.

The genetic code is the set of rules by which information encoded within genetic material (nucleic acids) is translated into proteins. Biological decoding in living cells is accomplished by the ribosome which links amino acids in an order specified by mRNA, using tRNA molecules to carry amino acids and to read the mRNA three nucleotides at a time. The code defines how sequences of these nucleotide triplets, called codons, specify which amino acid will be added next during protein synthesis. With some exceptions, a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. Because the vast majority of genes are encoded with exactly the same code, this particular code is often referred to as the canonical or standard genetic code.

Degeneracy of codons is the redundancy of the genetic code, exhibited as the multiplicity of three-base pair codon combinations that specify an amino acid. Degeneracy results because there are more codons than encodable amino acids. The codons encoding one amino acid may differ in any of their three positions; however, often this difference is in the second or third position. For instance, codons GAA and GAG both specify glutamic acid and exhibit redundancy; but, neither specifies any other amino acid nor thus demonstrate ambiguity. The genetic codes of different organisms can be biased towards using one of the several codons that encode the same amino acid over the others—that is, a greater frequency of one will be found than expected by chance. For example, leucine is specified by six distinct codons, some of which are rarely used. Codon usage tables detailing genomic codon usage frequencies for most organisms are available. Recombinant gene technologies commonly take advantage of this effect by implementing a technique termed codon optimization, in which those codons are used to design a polynucleotide which are preferred by the respective host cell (such as a cell of human hamster origin, an Escherichia coli cell, or a Saccharomyces cerevisiae cell), e.g. to increase protein expression. It is hence envisaged that the polynucleotides/nucleic acid molecules of the present disclosure are codon optimized. Nevertheless, the polynucleotide/nucleic acid molecule encoding a construct of the invention may be designed using any codon that encodes the desired amino acid.

According to one embodiment, the polynucleotide/nucleic acid molecule of the present invention encoding the polypeptide construct of the invention is in the form of one single molecule or in the form of two or more separate molecules. If the construct of the present invention is a single chain construct, the polynucleotide/nucleic acid molecule encoding such construct will most likely also be in the form of one single molecule. However, it is also envisaged that different components of the polypeptide construct (such as the different domains, e.g. the paratope (antigen-binding (epitope-binding) structure)-comprising domain which binds to a cell surface antigen, the paratope (antigen-binding (epitope-binding) structure)-comprising domain which binds to CD3, and/or further domains such as antibody constant domains) are located on separate polypeptide chains, in which case the polynucleotide/nucleic acid molecule is most likely in the form of two or more separate molecules.

The same applies for the vector comprising a polynucleotide/nucleic acid molecule of the present invention. If the construct of the present invention is a single chain construct, one vector may comprise the polynucleotide which encodes the construct in one single location (as one single open reading frame, ORF). One vector may also comprise two or more polynucleotides/nucleic acid molecules at separate locations (with individual ORFs), each one of them encoding a different component of the construct of the invention. It is envisaged that the vector comprising the polynucleotide/nucleic acid molecule of the present invention is in the form of one single vector or two or more separate vectors. In one embodiment, and for the purpose of expressing the construct in a host cell, the host cell of the invention should comprise the polynucleotide/nucleic acid molecule encoding the construct or the vector comprising such polynucleotide/nucleic acid molecule in their entirety, meaning that all components of the construct—whether encoded as one single molecule or in separate molecules/locations—will assemble after translation and form together the biologically active construct of the invention.

The invention further relates to a vector comprising a polynucleotide/nucleic acid molecule of the invention. A vector is a nucleic acid molecule used as a vehicle to transfer (foreign) genetic material into a cell, usually to ensure the replication and/or expression of the genetic material. The term “vector” encompasses—but is not restricted to—plasmids, viruses, cosmids, and artificial chromosomes. Some vectors are designed specifically for cloning (cloning vectors), others for protein expression (expression vectors). So-called transcription vectors are mainly used to amplify their insert. The manipulation of DNA is normally conducted on E. coli vectors, which contain elements necessary for their maintenance in E. coli. However, vectors may also have elements that allow them to be maintained in another organism such as yeast, plant or mammalian cells, and these vectors are called shuttle vectors. Insertion of a vector into the target or host cell is usually called transformation for bacterial cells and transfection for eukaryotic cells, while insertion of a viral vector is often called transduction.

In general, engineered vectors comprise an origin of replication, a multicloning site and a selectable marker. The vector itself is generally a nucleotide sequence, commonly a DNA sequence, that comprises an insert (transgene) and a larger sequence that serves as the “backbone” of the vector. While the genetic code determines the polypeptide sequence for a given coding region, other genomic regions can influence when and where these polypeptides are produced. Modern vectors may therefore encompass additional features besides the transgene insert and a backbone: promoter, genetic marker, antibiotic resistance, reporter gene, targeting sequence, protein purification tag. Vectors called expression vectors (expression constructs) specifically are for the expression of the transgene in the target cell, and generally have control sequences.

The term “control sequences” refers to DNA sequences necessary for the expression of an operably linked coding sequence in a specific host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, a Kozak sequence and enhancers.

A nucleic acid is “operably linked” when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned to facilitate translation. Generally, “operably linked” means that the nucleotide sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.

“Transfection” is the process of deliberately introducing nucleic acid molecules or polynucleotides (including vectors) into target cells. The term is mostly used for non-viral methods in eukaryotic cells. Transduction is often used to describe virus-mediated transfer of nucleic acid molecules or polynucleotides. Transfection of animal cells typically involves opening transient pores or “holes” in the cell membrane, to allow the uptake of material. Transfection can be carried out using biological particles (such as viral transfection, also called viral transduction), chemical-based methods (such as using calcium phosphate, lipofection, Fugene, cationic polymers, nanoparticles) or physical treatment (such as electroporation, microinjection, gene gun, cell squeezing, magnetofection, hydrostatic pressure, impalefection, sonication, optical transfection, heat shock).

The term “transformation” is used to describe non-viral transfer of nucleic acid molecules or polynucleotides (including vectors) into bacteria, and into non-animal eukaryotic cells, including plant cells. Transformation is hence the genetic alteration of a bacterial or non-animal eukaryotic cell resulting from the direct uptake through the cell membrane(s) from its surroundings and subsequent incorporation of exogenous genetic material (nucleic acid molecules). Transformation can be achieved by artificial means. For transformation to happen, cells or bacteria must be in a state of competence, which might occur as a time-limited response to environmental conditions such as starvation and cell density and can also be artificially induced.

Moreover, the invention provides a host cell transformed or transfected with the polynucleotide/nucleic acid molecule of the invention or with the vector of the invention.

As used herein, the terms “host cell” or “recipient cell” are intended to include any individual cell or cell culture that can be or has been recipient of vectors, exogenous nucleic acid molecules and/or polynucleotides encoding the construct of the present invention; and/or recipients of the construct itself. The introduction of the respective material into the cell is carried out by way of transformation, transfection and the like (vide supra). The term “host cell” is also intended to include progeny or potential progeny of a single cell. Because certain modifications may occur in succeeding generations due to either natural, accidental, or deliberate mutation or due to environmental influences, such progeny may not, in fact, be completely identical (in morphology or in genomic or total DNA complement) to the parent cell but is still included within the scope of the term as used herein. Suitable host cells include prokaryotic or eukaryotic cells and include—but are not limited to—bacteria (such as E. coli), yeast cells, fungi cells, plant cells, and animal cells such as insect cells and mammalian cells, e.g., hamster, murine, rat, macaque or human.

In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for the construct of the invention. Saccharomyces cerevisiae, or common baker's yeast, is the most commonly used among lower eukaryotic host microorganisms. However, a number of other genera, species, and strains are commonly available and useful herein, such as Schizosaccharomyces pombe, Kluyveromyces hosts such as K. lactis, K. fragilis (ATCC 12424), K. bulgaricus (ATCC 16045), K. wickeramii (ATCC 24178), K. waltii (ATCC 56500), K. drosophilarum (ATCC 36906), K. thermotolerans, and K. marxianus; yarrowia (EP 402 226); Pichia pastoris (EP 183 070); Candida; Trichoderma reesia (EP 244 234); Neurospora crassa; Schwanniomyces such as Schwanniomyces occidentalis; and filamentous fungi such as Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts such as A. nidulans and A. niger.

Suitable host cells for the expression of a glycosylated construct are derived from multicellular organisms. Examples of invertebrate cells include plant and insect cells. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruit fly), and Bombyx mori (silkmoth) have been identified. A variety of viral strains for transfection are publicly available, e.g., the L-1 variant of Autographa californica NPV and the Bm-5 strain of Bombyx mori NPV, and such viruses may be used as the virus herein according to the present invention, particularly for transfection of Spodoptera frugiperda cells.

Plant cell cultures of cotton, corn, potato, soybean, petunia, tomato, Arabidopsis and tobacco can also be used as hosts. Cloning and expression vectors useful in the production of proteins in plant cell culture are known to those of skill in the art. See e.g. Hiatt et al., Nature (1989) 342: 76-78, Owen et al. (1992) Bio/Technology 10: 790-794, Artsaenko et al. (1995) The Plant J 8: 745-750, and Fecker et al. (1996) Plant Mol Biol 32: 979-986.

However, interest has been greatest in vertebrate cells, and propagation of vertebrate cells in culture (cell culture) has become a routine procedure. Examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (such as COS-7, ATCC CRL 1651); human embryonic kidney line (such as 293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol. 36: 59 (1977)); baby hamster kidney cells (such as BHK, ATCC CCL 10); Chinese hamster ovary cells/-DHFR (such as CHO, Urlaub et al., Proc. Natl. Acad. Sci. USA 77: 4216 (1980)); mouse sertoli cells (such as TM4, Mather, Biol. Reprod. 23: 243-251 (1980)); monkey kidney cells (such as CVI ATCC CCL 70); African green monkey kidney cells (such as VERO-76, ATCC CRL1587); human cervical carcinoma cells (such as HELA, ATCC CCL 2); canine kidney cells (such as MDCK, ATCC CCL 34); buffalo rat liver cells (such as BRL 3A, ATCC CRL 1442); human lung cells (such as W138, ATCC CCL 75); human liver cells (such as Hep G2,1413 8065); mouse mammary tumor (such as MMT 060562, ATCC CCL-51); TRI cells (Mather et al., Annals N. Y Acad. Sci. (1982) 383: 44-68); MRC 5 cells; FS4 cells; and a human hepatoma line (such as Hep G2).

In a further embodiment, the invention provides a process for the production of a polypeptide or polypeptide construct of the invention, said process comprising culturing a host cell of the invention under conditions allowing the expression of the construct of the invention and recovering the produced construct from the culture.

As used herein, the term “culturing” refers to the in vitro maintenance, differentiation, growth, proliferation and/or propagation of cells under suitable conditions in a medium. Cells are grown and maintained in a cell growth medium at an appropriate temperature and gas mixture. Culture conditions vary widely for each cell type. Typical growth conditions are a temperature of about 37° C., a C02 concentration of about 5% and a humidity of about 95%. Recipes for growth media can vary e.g. in pH, concentration of the carbon source (such as glucose), nature and concentration of growth factors, and the presence of other nutrients (such as amino acids or vitamins). The growth factors used to supplement media are often derived from the serum of animal blood, such as fetal bovine serum (FBS), bovine calf serum (FCS), equine serum, and porcine serum. Cells can be grown either in suspension or as adherent cultures. There are also cell lines that have been modified to be able to survive in suspension cultures, so they can be grown to a higher density than adherent conditions would allow.

The term “expression” includes any step involved in the production of a construct of the invention including, but not limited to, transcription, post-transcriptional modification, translation, folding, post-translational modification, targeting to specific subcellular or extracellular locations, and secretion. The term “recovering” refers to a series of processes intended to isolate the construct from the cell culture. The “recovering” or “purification” process may separate the protein and non-protein parts of the cell culture, and finally separate the desired construct from all other polypeptides and proteins. Separation steps usually exploit differences in protein size, physico-chemical properties, binding affinity and biological activity. Preparative purifications aim to produce a relatively large quantity of purified proteins for subsequent use, while analytical purification produces a relatively small amount of a protein for a variety of research or analytical purposes.

When using recombinant techniques, the construct can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the construct is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, are removed, for example, by centrifugation or ultrafiltration. The construct of the invention may e.g. be produced in bacteria such as E. coli. After expression, the construct is isolated from the bacterial cell paste in a soluble fraction and can be purified e.g. via affinity chromatography and/or size exclusion. Final purification can be carried out in a manner that is like the process for purifying a construct expressed in mammalian cells and secreted into the medium. Carteret al. (Biotechnology (NY) 1992 February; 10(2):163-7) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli.

Where the antibody is secreted into the medium, supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an ultrafiltration unit.

The construct of the invention prepared from the host cells can be recovered or purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography. Other techniques for protein purification such as fractionation on an ion-exchange column, mixed mode ion exchange, HIC, ethanol precipitation, size exclusion chromatography, reverse phase HPLC, chromatography on silica, chromatography on heparin sepharose, chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), immunoaffinity (such as Protein A/G/L) chromatography, chromato-focusing, SDS-PAGE, ultracentrifugation, and ammonium sulfate precipitation are also available depending on the construct to be recovered.

A protease inhibitor may be included in any of the foregoing steps to inhibit proteolysis, and antibiotics may be included to prevent the growth of contaminants.

Moreover, the invention provides a pharmaceutical composition or formulation comprising a polypeptide or polypeptide construct of the invention or a polypeptide or polypeptide construct produced according to the process of the invention.

As used herein, the term “pharmaceutical composition” relates to a composition which is suitable for administration to a patient, preferably a human patient. The particularly preferred pharmaceutical composition of this invention comprises one or a plurality of the construct(s) of the invention, preferably in a therapeutically effective amount. Preferably, the pharmaceutical composition further comprises suitable formulations of one or more (pharmaceutically effective) carriers, stabilizers, excipients, diluents, solubilizers, surfactants, emulsifiers, preservatives and/or adjuvants. Acceptable constituents of the composition are preferably nontoxic to recipients at the dosages and concentrations employed. Pharmaceutical compositions of the invention include, but are not limited to, liquid, frozen, and lyophilized compositions.

The compositions may comprise a pharmaceutically acceptable carrier. In general, as used herein, “pharmaceutically acceptable carrier” means all aqueous and non-aqueous solutions, sterile solutions, solvents, buffers, e.g. phosphate buffered saline (PBS) solutions, water, suspensions, emulsions, such as oil/water emulsions, various types of wetting agents, liposomes, dispersion media and coatings, which are compatible with pharmaceutical administration, in particular with parenteral administration. The use of such media and agents in pharmaceutical compositions is well known in the art, and the compositions comprising such carriers can be formulated by well-known conventional methods.

Certain embodiments provide pharmaceutical compositions comprising the construct of the invention and further one or more excipients such as those illustratively described in this section and elsewhere herein. Excipients can be used in the invention for a wide variety of purposes, such as adjusting physical, chemical, or biological properties of formulations, such as adjustment of viscosity, and or processes of the invention to improve effectiveness and/or to stabilize such formulations and processes against degradation and spoilage e.g. due to stresses that occur during manufacturing, shipping, storage, pre-use preparation, administration, and thereafter. Excipients should in general be used in their lowest effective concentrations.

In certain embodiments, the pharmaceutical composition may contain formulation materials for modifying, maintaining or preserving certain characteristics of the composition such as the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration (see, Remington's Pharmaceutical Sciences, 18” Edition, 1990, Mack Publishing Company). In such embodiments, suitable formulation materials may include, but are not limited to:

- amino acids
- antimicrobials such as antibacterial and antifungal agents
- antioxidants
- buffers, buffer systems and buffering agents that are used to maintain the composition at physiological pH or at a slightly lower pH, typically within a range of from about 5 to about 8 or 9
- non-aqueous solvents, vegetable oils, and injectable organic esters
- aqueous carriers including water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media
- biodegradable polymers such as polyesters
- bulking agents
- chelating agents
- isotonic and absorption delaying agents
- complexing agents
- fillers
- carbohydrates
- (low molecular weight) proteins, polypeptides or proteinaceous carriers, preferably of human origin
- coloring and flavouring agents
- sulfur containing reducing agents
- diluting agents
- emulsifying agents
- hydrophilic polymers
- salt-forming counter-ions
- preservatives
- metal complexes
- solvents and co-solvents
- sugars and sugar alcohols
- suspending agents
- surfactants or wetting agents
- stability enhancing agents
- tonicity enhancing agents
- parenteral delivery vehicles
- intravenous delivery vehicles

It is common knowledge that the different constituents of the pharmaceutical composition can have different effects, for example, and amino acid can act as a buffer, a stabilizer and/or an antioxidant; mannitol can act as a bulking agent and/or a tonicity enhancing agent; sodium chloride can act as delivery vehicle and/or tonicity enhancing agent; etc.

In the context of the present invention, a pharmaceutical composition may comprise:

- (a) a polypeptide or polypeptide construct as described herein,
- (b) at least one buffer agent,
- (c) at least one saccharide, and
- (d) at least one surfactant;
- wherein the pH of the pharmaceutical composition is in the range of 3.5 to 6.

In the composition described above, the first domain preferably has an isoelectric point (pI) in the range of 4 to 9.5; the second domain has a pI in the range of 8 to 10, preferably 8.5 to 9.0; and the construct optionally comprises a third domain comprising two polypeptide monomers, each comprising a hinge, a CH2 domain and a CH3 domain, wherein said two polypeptide monomers are fused to each other via a peptide linker.

In the composition described above, it is further envisaged that the at least one buffer agent is present at a concentration range of 5 to 200 mM, more preferably at a concentration range of 10 to 50 mM. It is also envisaged that the at least one saccharide is selected from the group consisting of monosaccharide, disaccharide, cyclic polysaccharide, sugar alcohol, linear branched dextran or linear non-branched dextran. It is also envisaged that the disaccharide is selected from the group consisting of sucrose, trehalose and mannitol, sorbitol, and combinations thereof. It is further envisaged that the sugar alcohol is sorbitol. It is also envisaged that the at least one saccharide is present at a concentration in the range of 1 to 15% (m/V), preferably in a concentration range of 9 to 12% (m/V). It is further envisaged that the construct is present in a concentration range of 0.1 to 8 mg/ml, preferably of 0.2-2.5 mg/ml, more preferably of 0.25-1.0 mg/ml.

According to one embodiment of the composition described above, the at least one surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, poloxamer 188, pluronic F68, triton X-100, polyoxyethylen, PEG 3350, PEG 4000 and combinations thereof. It is further envisaged that the at least one surfactant is present at a concentration in the range of 0.004 to 0.5% (m/V), preferably in the range of 0.001 to 0.01% (m/V). It is envisaged that the pH of the composition is in the range of 4.0 to 5.0, preferably 4.2. It is also envisaged that the pharmaceutical composition has an osmolarity in the range of 150 to 500 mOsm. It is further envisaged that the pharmaceutical composition further comprises an excipient selected from the group consisting of one or more polyol(s) and one or more amino acid(s). It is envisaged in the context of the present invention that said one or more excipient is present in the concentration range of 0.1 to 15% (w/V).

The present invention also provides a pharmaceutical composition comprising (a) the construct as described herein, preferably in a concentration range of 0.1 to 8 mg/ml, preferably of 0.2-2.5 mg/ml, more preferably of 0.25-1.0 mg/ml; (b) 10 mM glutamate or acetate; (c) 9% (m/V) sucrose or 6% (m/V) sucrose and 6% (m/V) hydroxypropyl-β-cyclodextrin; (d) 0.01% (m/V) polysorbate 80; wherein the pH of the liquid pharmaceutical composition is 4.2.

It is envisaged that the composition of the invention might comprise, in addition to the construct of the invention defined herein, further biologically active agents, depending on the intended use of the composition. Such agents might be drugs acting on the gastro-intestinal system, drugs acting as cytostatica, drugs preventing hyperurikemia, drugs inhibiting immunoreactions, drugs modulating the inflammatory response, drugs acting on the circulatory system and/or agents such as cytokines known in the art. It is also envisaged that the polypeptide construct of the present invention is applied in a co-therapy, i.e., in combination with another anti-cancer medicament.

In this context, it is envisaged that the pharmaceutical composition of the invention (which comprises a construct comprising a CD3 binding domain and at least a further binding domain which binds to a cell surface target antigen, preferably a tumor antigen on the surface of a target cell, as described in more detail herein above) furthermore comprises an agent, preferably an antibody or construct, which binds to a protein of the immune checkpoint pathway (such as PD-1 or CTLA-4) or to a co-stimulatory immune checkpoint receptor (such as 4-11BE). The present invention also refers to a combination of a polypeptide construct according to the invention (which comprises a construct comprising a CD3 binding domain and at least a further binding domain which binds to a cell surface target antigen, preferably a tumor antigen on the surface of a target cell, as described in more detail herein above) and an agent, preferably an antibody or polypeptide construct, which binds to a protein of the immune checkpoint pathway (such as PD-1 or CTLA-4) or to a co-stimulatory immune checkpoint receptor (such as 4-11BE). Due to the nature of the at least two ingredients of the combination, namely their pharmaceutical activity, the combination can also be referred to as a therapeutic combination. In some embodiments, the combination can be in the form of a pharmaceutical composition or of a kit. According to one embodiment, the pharmaceutical composition or the combination comprises a construct of the invention and an antibody or construct which binds to PD-1. Anti-PD-1 binding proteins useful for this purpose are e.g. described in detail in PCT/US2019/013205 incorporated herein by reference.

In certain embodiments, the optimal pharmaceutical composition is determined depending upon, for example, the intended route of administration, delivery format and desired dosage. See, for example, Remington's Pharmaceutical Sciences, supra. In certain embodiments, such compositions may influence the physical state, stability, rate of in vivo release and rate of in vivo clearance of the construct of the invention. In certain embodiments, the primary vehicle or carrier in a pharmaceutical composition may be either aqueous or non-aqueous in nature. For example, a suitable vehicle or carrier may be water for injection or physiological saline solution, possibly supplemented with other materials common in compositions for parenteral administration. In certain embodiments, the compositions comprising the construct of the invention may be prepared for storage by mixing the selected composition having the desired degree of purity with optional formulation agents (Remington's Pharmaceutical Sciences, supra) in the form of a lyophilized cake or an aqueous solution. Further, in certain embodiments, the construct of the invention may be formulated as a lyophilizate using appropriate excipients.

When parenteral administration is contemplated, the therapeutic compositions for use in this invention may be provided in the form of a pyrogen-free, parenterally acceptable aqueous solution comprising the desired construct of the invention in a pharmaceutically acceptable vehicle. A particularly suitable vehicle for parenteral injection is sterile distilled water in which the construct of the invention is formulated as a sterile, isotonic solution, properly preserved. In certain embodiments, the preparation can involve the formulation of the desired molecule with an agent that may provide controlled or sustained release of the product which can be delivered via depot injection, or that may promote sustained duration in the circulation. In certain embodiments, implantable drug delivery devices may be used to introduce the desired construct.

Additional pharmaceutical compositions will be evident to those skilled in the art, including formulations involving the construct of the invention in sustained or controlled delivery formulations. Techniques for formulating a variety of sustained- or controlled-delivery means are known to those skilled in the art. The construct may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, in colloidal drug delivery systems, or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences, supra.

Pharmaceutical compositions used for in vivo administration are typically provided as sterile preparations. Sterilization can be accomplished by filtration through sterile filtration membranes. When the composition is lyophilized, sterilization using this method may be conducted either prior to or following lyophilization and reconstitution. Compositions for parenteral administration can be stored in lyophilized form or in a solution. Parenteral compositions are generally placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.

Another aspect of the invention includes self-buffering formulations comprising the construct of the invention, which can be used as pharmaceutical compositions, as described in international patent application WO 2006/138181. A variety of publications are available on protein stabilization and formulation materials and methods useful in this regard, such as Arawaka T. et al., Pharm Res. 1991 March; 8(3):285-91; Kendrick et al., “Physical stabilization of proteins in aqueous solution” in: Rational Design of Stable Protein Formulations: Theory and Practice, Carpenter and Manning, eds. Pharmaceutical Biotechnology. 13: 61-84 (2002), and Randolph and Jones, Pharm Biotechnol. 2002; 13:159-75, see particularly the parts pertinent to excipients and processes for self-buffering protein formulations, especially as to protein pharmaceutical products and processes for veterinary and/or human medical uses.

Salts may be used in accordance with certain embodiments of the invention, e.g. to adjust the ionic strength and/or the isotonicity of a composition or formulation and/or to improve the solubility and/or physical stability of a construct or other ingredient of a composition in accordance with the invention. Ions can stabilize the native state of proteins by binding to charged residues on the protein's surface and by shielding charged and polar groups in the protein and reducing the strength of their electrostatic interactions, attractive, and repulsive interactions. Ions also can stabilize the denatured state of a protein by binding to, particularly the denatured peptide linkages (—CONH) of the protein. Furthermore, ionic interaction with charged and polar groups in a protein also can reduce intermolecular electrostatic interactions and, thereby, prevent or reduce protein aggregation and insolubility.

Ionic species differ significantly in their effects on proteins. Several categorical rankings of ions and their effects on proteins have been developed that can be used in formulating pharmaceutical compositions in accordance with the invention. One example is the Hofmeister series, which ranks ionic and polar non-ionic solutes by their effect on the conformational stability of proteins in solution. Stabilizing solutes are referred to as “kosmotropic”. Destabilizing solutes are referred to as “chaotropic”. Kosmotropes are commonly used at high concentrations to precipitate proteins from solution (“salting-out”). Chaotropes are commonly used to denature and/or to solubilize proteins (“salting-in”). The relative effectiveness of ions to “salt-in” and “salt-out” defines their position in the Hofmeister series.

Free amino acids can be used in formulations or compositions comprising the construct of the invention in accordance with various embodiments of the invention as bulking agents, stabilizers, and antioxidants, as well as for other standard uses. Certain amino acids can be used for stabilizing proteins in a formulation, others are useful during lyophilization to ensure correct cake structure and properties of the active ingredient. Some amino acids may be useful to inhibit protein aggregation in both liquid and lyophilized formulations, and others are useful as antioxidants.

Polyols are kosmotropic and are useful as stabilizing agents in both liquid and lyophilized formulations to protect proteins from physical and chemical degradation processes. Polyols are also useful for adjusting the tonicity of formulations and for protecting against freeze-thaw stresses during transport or the preparation of bulks during the manufacturing process. Polyols can also serve as cryoprotectants in the context of the present invention.

Certain embodiments of the formulation or composition comprising the construct of the invention can comprise surfactants. Proteins may be susceptible to adsorption on surfaces and to denaturation and resulting aggregation at air-liquid, solid-liquid, and liquid-liquid interfaces. These deleterious interactions generally scale inversely with protein concentration and are typically exacerbated by physical agitation, such as that generated during the shipping and handling of a product. Surfactants are routinely used to prevent, minimize, or reduce surface adsorption. Surfactants also are commonly used to control protein conformational stability. The use of surfactants in this regard is protein specific, since one specific surfactant will typically stabilize some proteins and destabilize others.

Certain embodiments of the formulation or composition comprising the construct of the invention can comprise one or more antioxidants. To some extent deleterious oxidation of proteins can be prevented in pharmaceutical formulations by maintaining proper levels of ambient oxygen and temperature and by avoiding exposure to light. Antioxidant excipients can also be used to prevent oxidative degradation of proteins. It is envisaged that antioxidants for use in therapeutic protein formulations in accordance with the present invention can be water-soluble and maintain their activity throughout the shelf life of the product (the composition comprising the construct). Antioxidants can also damage proteins and should hence—among other things—be selected in a way to eliminate or sufficiently reduce the possibility of antioxidants damaging the construct or other proteins in the formulation.

Certain embodiments of the formulation or composition comprising the construct of the invention can comprise one or more preservatives. Preservatives are necessary for example when developing multi-dose parenteral formulations that involve more than one extraction from the same container. Their primary function is to inhibit microbial growth and ensure product sterility throughout the shelf-life or term of use of the drug product. Although preservatives have a long history of use with small-molecule parenterals, the development of protein formulations that include preservatives can be challenging. Preservatives very often have a destabilizing effect (aggregation) on proteins, and this has become a major factor in limiting their use in multi-dose protein formulations. To date, most protein drugs have been formulated for single-use only. However, when multi-dose formulations are possible, they have the added advantage of enabling patient convenience, and increased marketability. A good example is that of human growth hormone (hGH) where the development of preserved formulations has led to commercialization of more convenient, multi-use injection pen presentations. Several aspects need to be considered during the formulation and development of preserved dosage forms. The effective preservative concentration in the drug product must be optimized. This requires testing a given preservative in the dosage form with concentration ranges that confer anti-microbial effectiveness without compromising protein stability.

As might be expected, development of liquid formulations containing preservatives are more challenging than lyophilized formulations. Freeze-dried products can be lyophilized without the preservative and reconstituted with a preservative containing diluent at the time of use. This shortens the time during which a preservative is in contact with the construct, significantly minimizing the associated stability risks. With liquid formulations, preservative effectiveness and stability should be maintained over the entire product shelf-life. An important point to note is that preservative effectiveness should be demonstrated in the final formulation containing the active drug and all excipient components. Once the pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution, suspension, gel, emulsion, solid, crystal, or as a dehydrated or lyophilized powder. Such formulations may be stored either in a ready-to-use form or in a form (e.g., lyophilized) that is reconstituted prior to administration.

The biological activity of the pharmaceutical composition defined herein can be determined for instance by in vitro cytotoxicity assays, as described in the following examples, in WO 99/54440 or by Schlereth et al. (Cancer Immunol. Immunother. 20 (2005), 1-12). “Efficacy” or “in vivo efficacy” as used herein refers to the response to therapy by the pharmaceutical composition of formulation of the invention, using e.g. standardized NCI response criteria. The success or in vivo efficacy of the therapy using a pharmaceutical composition of the invention refers to the effectiveness of the composition for its intended purpose, i.e. the ability of the composition to cause its desired effect, i.e. depletion of pathologic cells, e.g. tumor cells. The in vivo efficacy may be monitored by established standard methods for the respective disease entities including, but not limited to, white blood cell counts, differentials, fluorescence activated cell sorting, bone marrow aspiration. In addition, various disease specific clinical chemistry parameters and other established standard methods may be used. Furthermore, computer-aided tomography, X-ray, nuclear magnetic resonance tomography, positron-emission tomography scanning, lymph node biopsies/histologies and other established standard methods may be used.

Another major challenge in the development of drugs such as the pharmaceutical composition of the invention is the predictable modulation of pharmacokinetic properties. To this end, a pharmacokinetic profile of the drug candidate, i.e. a profile of the pharmacokinetic parameters that affect the ability of a specific drug to treat a given condition, can be established. Pharmacokinetic parameters of the drug influencing the ability of a drug for treating a certain disease entity include, but are not limited to: half-life, volume of distribution, hepatic first-pass metabolism and the degree of blood serum binding. The efficacy of a given drug agent can be influenced by each of the parameters mentioned above.

“Half-life” is the time required for a quantity to reduce to half its initial value. The medical sciences refer to the half-life of substances or drugs in the human body. In a medical context, half-life may refer to the time it takes for a substance/drug to lose one-half of its activity, e.g. pharmacologic, physiologic, or radiological activity. The half-life may also describe the time that it takes for the concentration of a drug or substance (e.g., a construct of the invention) in blood plasma/serum to reach one-half of its steady-state value (“serum half-life”). Typically, the elimination or removal of an administered substance/drug refers to the body's cleansing through biological processes such as metabolism, excretion, also involving the function of kidneys and liver. The “first-pass metabolism” is a phenomenon of drug metabolism whereby the concentration of a drug is reduced before it reaches the circulation. It is the fraction of drug lost during the process of absorption. Accordingly, by “hepatic first-pass metabolism” is meant the propensity of a drug to be metabolized upon first contact with the liver, i.e. during its first pass through the liver. “Volume of distribution” (VD) means the degree to which a drug is distributed in body tissue rather than the blood plasma, a higher VD indicating a greater amount of tissue distribution. The retention of a drug can occur throughout the various compartments of the body, such as intracellular and extracellular spaces, tissues and organs, etc. “Degree of blood serum binding” means the propensity of a drug to interact with and bind to blood serum proteins, such as albumin, leading to a reduction or loss of biological activity of the drug.

Pharmacokinetic parameters also include bioavailability, lag time (T lag), Tmax, absorption rates, and/or Cmax for a given amount of drug administered. “Bioavailability” refers to the fraction of an administered dose of a drug/substance that reaches the systemic circulation (the blood compartment). When a medication is administered intravenously, its bioavailability is considered to be 100%. However, when a medication is administered via other routes (such as orally), its bioavailability generally decreases. “Lag time” means the time delay between the administration of the drug and its detection and measurability in blood or plasma. Cmax is the maximum plasma concentration that a drug achieves after its administration (and before the administration of a second dose). Tmax is the time at which Cmax is reached. The time to reach a blood or tissue concentration of the drug which is required for its biological effect is influenced by all parameters. Pharmacokinetic parameters of constructs exhibiting cross-species specificity may be determined in preclinical animal testing in non-chimpanzee primates as outlined above and set forth e.g. in Schlereth et al. (supra).

One embodiment provides the construct of the invention (or the construct produced according to the process of the invention), for the use as a medicament, particularly for the use in the prevention, treatment or amelioration (preferably treatment) of a disease, preferably a tumorous disease, more preferred a neoplasm, cancer or tumor. Another embodiment provides the use of the construct of the invention (or of the construct produced according to the process of the invention) in the manufacture of a medicament for the prevention, treatment or amelioration of a disease, preferably a tumorous disease, more preferred a neoplasm, cancer or tumor. It is also envisaged to provide a method for the prevention, treatment or amelioration of a disease, preferably a tumorous disease, more preferred a neoplasm, cancer or tumor, comprising the step of administering to a subject in need thereof the construct of the present invention (or the construct produced according to the process of the present invention). The terms “subject in need”, “patient” or those “in need of treatment” include those already with the disease, as well as those in which the disease is to be prevented. The terms also include human and other mammalian subjects that receive either prophylactic or therapeutic treatment.

The polypeptides/polypeptide constructs of the invention and the formulations/pharmaceutical compositions described herein are useful in the treatment, amelioration and/or prevention of the medical condition as described herein in a patient in need thereof. The term “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Treatment includes the application or administration of the polypeptides/polypeptide constructs/pharmaceutical composition to the body, to an isolated tissue, or to a cell from a patient or a subject in need who has a disease/disorder as described herein, a symptom of such disease/disorder, or a predisposition toward such disease/disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disease, the symptom of the disease, or the predisposition toward the disease. The term “amelioration” as used herein refers to any improvement of the disease state of a patient, by the administration of a polypeptide construct according to the invention to such patient or subject in need thereof. Such an improvement may be a slowing down or stopping of the progression of the disease of the patient, and/or as a decrease in severity of disease symptoms, an increase in frequency or duration of disease symptom-free periods or a prevention of impairment or disability due to the disease. The term “prevention” as used herein means the avoidance of the occurrence or of the re-occurrence of a disease as specified herein, by the administration of a construct according to the invention to a subject in need thereof.

The term “disease” refers to any condition that would benefit from treatment with the construct or the pharmaceutical composition described herein. This includes chronic and acute disorders or diseases including those pathological conditions that predispose the mammal to the disease in question. The disease is preferably a tumorous disease, more preferred a neoplasm, cancer or tumor. The disease, neoplasm, cancer or tumor is preferably positive for a tumor antigen, preferably such as those defined herein above, i.e. it is characterized by expression or overexpression of a tumor antigen, preferably such as those defined herein above. An overexpression of a tumor antigen means that there is an increase by at least 10%, in particular at least 25%, at least 50%, at least 100%, at least 250%, at least 500%, at least 750%, at least 1000% or even more. Expression is, preferably, only found in a diseased tissue, while expression in a corresponding healthy tissue is not or significantly not detectable. According to the invention, diseases associated with cells expressing a tumor antigen, preferably such as those defined herein above, include cancer diseases. Furthermore, according to the invention, cancer diseases preferably are those wherein the cancer cells express a tumor antigen. In accordance with the invention, the disease, preferably tumorous disease, more preferred neoplasm, tumor or cancer is preferably characterized by the presence of BCMA-positive, CD123-positive, CD19-positive, CD20-positive, CD22-positive, CD33-positive, CD70-positive, CDH19-positive, CDH3-positive, CLL1-positive, CS1-positive, CLDN6-positive, CLDN18.2-positive, DLL3-positive, EGFRvIII-positive, FLT3-positive, MAGEB2-positive, MART1-positive, MSLN-positive, MUC17-positive, PSMA-positive, or STEAP1-positive cells. In other words, the tumorous disease, more preferred neoplasm, tumor or cancer is preferably associated with the presence of BCMA-positive, CD123-positive, CD19-positive, CD20-positive, CD22-positive, CD33-positive, CD70-positive, CDH19-positive, CDH3-positive, CLL1-positive, CS1-positive, CLDN6-positive, CLDN18.2-positive, DLL3-positive, EGFRvIII-positive, FLT3-positive, MAGEB2-positive, MART1-positive, MSLN-positive, MUC17-positive, PSMA-positive, or STEAP1-positive cells; the tumorous disease, more preferred neoplasm, tumor or cancer can therefore be termed a BCMA-positive, CD123-positive, CD19-positive, CD20-positive, CD22-positive, CD33-positive, CD70-positive, CDH19-positive, CDH3-positive, CLL1-positive, CS1-positive, CLDN6-positive, CLDN18.2-positive, DLL3-positive, EGFRvIII-positive, FLT3-positive, MAGEB2-positive, MART1-positive, MSLN-positive, MUC17-positive, PSMA-positive, or STEAP1-positive neoplasm, tumor or cancer. It is understood herein, that each of said tumor antigen-positive neoplasms, tumors or cancers can be prevented, treated or ameliorated using a polypeptide or polypeptide construct according to the invention that comprises a binding domain against the tumor antigen expressed by the cells with which said neoplasm, tumor or cancer is associated with. A BCMA-positive, CD123-positive, CD19-positive, CD20-positive, CD22-positive, CD33-positive, CD70-positive, CDH19-positive, CDH3-positive, CLL1-positive, CS1-positive, CLDN6-positive, CLDN18.2-positive, DLL3-positive, EGFRvII-positive, FLT3-positive, MAGEB2-positive, MART1-positive, MSLN-positive, MUC17-positive, PSMA-positive, or STEAP1-positive neoplasm, tumor or cancer can be prevented, treated or ameliorated using a polypeptide or polypeptide construct according to the invention that comprises a binding domain against BCMA (for a BCMA-positive neoplasm, tumor or cancer), CD123 (for a CD123-positive neoplasm, tumor or cancer), CD19 (for a CD19-positive neoplasm, tumor or cancer), CD20 (for a CD20-positive neoplasm, tumor or cancer), CD22 (for a CD22-positive neoplasm, tumor or cancer), CD33 (for a CD33-positive neoplasm, tumor or cancer), CD70 (for a CD70-positive neoplasm, tumor or cancer), CDH19 (for a CDH19-positive neoplasm, tumor or cancer), CDH3 (for a CDH3-positive neoplasm, tumor or cancer), CLL1 (for a CLL1-positive neoplasm, tumor or cancer), CS1 (for a CS1-positive neoplasm, tumor or cancer), CLDN6 (for a CLDN6-positive neoplasm, tumor or cancer), CLDN18.2 (for a CLDN18.2-positive neoplasm, tumor or cancer), DLL3 (for a DLL3-positive neoplasm, tumor or cancer), EGFRvIII (for a EGFRvIII-positive neoplasm, tumor or cancer), FLT3 (for a FLT3-positive neoplasm, tumor or cancer), MAGEB2 (for a MAGEB2-positive neoplasm, tumor or cancer), MART1 (for a MART1-positive neoplasm, tumor or cancer), MSLN (for a MSLN-positive neoplasm, tumor or cancer), MUC17 (for a MUC17-positive neoplasm, tumor or cancer), PSMA (for a PSMA-positive neoplasm, tumor or cancer), and STEAP1 (for a STEAP1-positive neoplasm, tumor or cancer), respectively.

A “neoplasm” is an abnormal growth of tissue, usually but not always forming a mass. When also forming a mass, it is commonly referred to as a “tumor”. Neoplasms or tumors can be benign, potentially malignant (pre-cancerous), or malignant (cancerous). Malignant neoplasms/tumors are commonly called cancer. They usually invade and destroy the surrounding tissue and may form metastases, i.e., they spread to other parts, tissues or organs of the body. A “primary tumor” is a tumor growing at the anatomical site where tumor progression began and proceeded to yield a cancerous mass. Most cancers develop at their primary site but then go on to metastasize or spread to other parts (e.g. tissues and organs) of the body. These further tumors are “secondary tumors”. Most cancers continue to be called after their primary site, even after they have spread to other parts of the body.

Lymphomas and leukemias are lymphoid neoplasms. For the purposes of the present invention, they are also encompassed by the terms “tumor” and “cancer”. For the purposes of the present invention, the terms “neoplasm”, “tumor” and “cancer” may be used interchangeably, and they comprise both primary tumors/cancers and secondary tumors/cancers (or “metastases”) as well as mass-forming neoplasms (tumors) and lymphoid neoplasms (such as lymphomas and leukemias), and minimal residual disease (MRD).

The term “minimal residual disease” (MRD) refers to the evidence for the presence of small numbers of residual cancer cells that remain in the patient after cancer treatment, e.g. when the patient is in remission (no symptoms or signs of disease). A very small number of remaining cancer cells usually cannot be detected by routine means because the standard tests used to assess or detect cancer are not sensitive enough to detect MRD. Nowadays, very sensitive molecular biology tests for MRD are available, such as flow cytometry, PCR and next-generation sequencing. These tests can measure minimal levels of cancer cells in tissue samples, sometimes as low as one cancer cell in a million normal cells. In the context of the present invention, the terms “prevention”, “treatment” or “amelioration” of a cancer are envisaged to also encompass “prevention, treatment or amelioration of MRD”, whether the MRD was detected or not.

The construct of the invention will generally be designed for specific routes and methods of administration, for specific dosages and frequencies of administration, for specific treatments of specific diseases, with ranges of bio-availability and persistence, among other things. The materials of the composition are preferably formulated in concentrations that are acceptable for the site of administration. Formulations and compositions thus may be designed in accordance with the invention for delivery by any suitable route of administration. In the context of the present invention, the routes of administration include, but are not limited to topical routes, enteral routes and parenteral routes.

If the pharmaceutical composition has been lyophilized, the lyophilized material is first reconstituted in an appropriate liquid prior to administration. The lyophilized material may be reconstituted in, e.g., bacteriostatic water for injection (BWFI), physiological saline, phosphate buffered saline (PBS), or the same formulation the protein had been in prior to lyophilization. The pharmaceutical compositions and the construct of this invention are particularly useful for parenteral administration, e.g., intravenous delivery, for example by injection or infusion. Pharmaceutical compositions may be administered using a medical device. Examples of medical devices for administering pharmaceutical compositions are described in U.S. Pat. Nos. 4,475,196; 4,439,196; 4,447,224; 4,447,233; 4,486,194; 4,487,603; 4,596,556; 4,790,824; 4,941,880; 5,064,413; 5,312,335; 5,312,335; 5,383,851; and 5,399,163.

The compositions of the present invention can be administered to the subject at a suitable dose which can be determined e.g. in dose escalating studies. As set forth above, the construct of the invention exhibiting cross-species specificity as described herein can also be advantageously used in in preclinical testing in non-chimpanzee primates. The dosage regimen will be determined by the attending physician and clinical factors. As is well known in the medical art, dosages for any one patient depend upon many factors, including the patient's size, body surface area, age, the specific compound to be administered, sex, time and route of administration, general health, and other drugs being administered concurrently.

An “effective dose” is an amount of a therapeutic agent that is sufficient to achieve or at least partially achieve a desired effect. A “therapeutically effective dose” is an amount that is sufficient to cure or at least partially arrest the disease and its complications, signs and symptoms in a patient suffering from the disease. Amounts or doses effective for this use will depend on the disease to be treated (the indication), the delivered construct, the therapeutic context and objectives, the severity of the disease, prior therapy, the patient's clinical history and response to the therapeutic agent, the route of administration, the size (body weight, body surface) and/or condition (the age and general health) of the patient, and the general state of the patient's own immune system. The proper dose can be adjusted according to the judgment of the attending physician, to obtain the optimal therapeutic effect.

A therapeutically effective amount of a construct of the invention preferably results in a decrease in severity of disease symptoms, an increase in frequency or duration of disease symptom-free periods or a prevention of impairment or disability due to the disease. In the treatment of tumor antigen-expressing tumors, a therapeutically effective amount of the construct of the invention comprising a binding domain against said tumor antigen preferably inhibits tumor cell growth by at least about 20%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, or at least about 90% relative to untreated patients. The ability of a compound to inhibit tumor growth may also be evaluated in an animal model predictive of efficacy in human tumors.

In a further embodiment, the invention provides a kit comprising a construct of the invention, a construct produced according to the process of the invention, a polynucleotide of the invention, a vector of the invention, and/or a host cell of the invention. In the context of the present invention, the term “kit” means two or more components—one of which corresponding to the construct, the pharmaceutical composition, the polynucleotide, the vector or the host cell of the invention—packaged together in a container, recipient or otherwise. A kit can hence be described as a set of products and/or utensils that are sufficient to achieve a certain goal, which can be marketed as a single unit.

It is envisaged that a further component of the kit of the invention is an agent, preferably an antibody or construct, which binds to a protein of the immune checkpoint pathway (such as PD-1 or CTLA-4) or to a co-stimulatory immune checkpoint receptor (such as 4-1BB). These agents are described in more detail herein above. According to one embodiment, the kit comprises a construct of the invention and an antibody or construct which binds to PD-1. Anti-PD-1 binding proteins useful for this purpose are e.g. described in detail in PCT/US2019/013205. In certain embodiment, the kit allows for the simultaneous and/or sequential administration of the components.

The kit may comprise one or more recipients (such as vials, ampoules, containers, syringes, bottles, bags) of any appropriate shape, size and material (preferably waterproof, e.g. plastic or glass) containing the construct or the pharmaceutical composition of the present invention in an appropriate dosage for administration (see above). The kit may additionally contain directions for use (e.g. in the form of a leaflet or instruction manual), means for administering the construct or the pharmaceutical composition of the present invention such as a syringe, pump, infuser or the like, means for reconstituting the construct of the invention and/or means for diluting the construct of the invention.

The invention also provides kits for a single-dose administration unit. The kit of the invention may also contain a first recipient comprising a dried/lyophilized construct or pharmaceutical composition and a second recipient comprising an aqueous formulation. In certain embodiments of this invention, kits containing single-chambered and multi-chambered pre-filled syringes are provided.

Whenever the term “construct” is used herein, said term refers to the used polypeptide/polypeptide constructs of the invention or controls thereof as indicated.

As used herein, the singular forms “a”, “an”, and “the” include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “a reagent” includes one or more of such different reagents and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein.

Unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.

The term “and/or” wherever used herein includes the meaning of “and”, “or” and “all or any other combination of the elements connected by said term”.

The term “about” or “approximately” as used herein means within ±20%, preferably within +15%, more preferably within +10%, and most preferably within ±5% of a given value or range. It also includes the concrete value, e.g., “about 50” includes the value “50”.

Throughout this specification and the claims, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. When used herein the term “comprising” can be substituted with the term “containing” or “including” or sometimes when used herein with the term “having”.

When used herein “consisting of” excludes any element, step, or ingredient not specified in the claim element. When used herein, “consisting essentially of” does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.

In each instance herein, any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms.

The above description and the below examples provide exemplary arrangements, but the present invention is not limited to the specific methodologies, techniques, protocols, material, reagents, substances, etc., described herein and as such can vary. The terminology used herein serves to describe specific embodiments only. The terminology used herein does not intend to limit the scope of the present invention, which is defined solely by the claims. Aspects of the invention are provided in the independent claims. Some optional features of the invention are provided in the dependent claims.

All publications and patents cited throughout the text of this specification (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. To the extent the material incorporated by reference contradicts or is inconsistent with this specification, the specification will supersede any such material.

A better understanding of the present invention and of its advantages will be obtained from the following examples, offered for illustrative purposes only. The examples are not intended and should not be construed as to limit the scope of the present invention in any way.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 A): Effector cells: human unstimulated T cells; Target cells: CHO hu CD70 pEFDHR

Legend:

I2C: CD70 1-A9D CC×I2C×scFc

I2CA: CD70 1-A9D CC×I2C H109A×scFc

8A8.04: CD70 1-A9D CC×8A8.04×scFc

5C3.04: CD70 1-A9D CC×5C3.04×scFc

I2E: CD70 1-A9D CC×5C3.01×scFc

I2K: CD70 1-A9D CC×5G6.05×scFc

5G6.04: CD70 1-A9D CC×5G6.04×scFc

5G6.03: CD70 1-A9D CC×5G6.03×scFc

1D5.04: CD70 1-A9D CC×1D5.04×scFc

8A8.02: CD70 1-A9D CC×8A8.02×scFc

1D5.03: CD70 1-A9D CC×1D5.03×scFc

FIG. 1 B): Effector cells: human unstimulated T cells; Target cells: hu orl FLT3 v1 co CHO #12

Legend:

I2C: FL 7-H3 CC×I2C×scFc

5G6.04: FL 7-H3 CC×5G6.04×scFc

8A8.04: FL 7-H3 CC×8A8.04×scFc

5C3.04: FL 7-H3 CC×5C3.04×scFc

I2E: FL 7-H3 CC×5C3.01×scFc

I2K: FL 7-H3 CC×5G6.05×scFc

I2C CC 44/100: FL 7-H3 CC×I2C CC 44/100×scFc

EXAMPLES
Example 1: Thermal Stability

Purified monomeric BiTE® protein at 1 mg/ml formulated in screening buffer was analysed. Thermal stability was determined by Dynamic Light Scattering DLS and Differential Scanning Fluorometry DSF.

DLS

100 μl protein solution were transferred in doubles in a multi well plate, overlaid with paraffin oil and placed in a DLS plate reader (DynaPro Plate Reader II with temperature control, Wyatt Technology Europe GmbH, Dernbach—Germany). Thermal stability was determined in a linear increasing temperature scan from 40° C. to 70° C. while measuring the hydrodynamic radius at the different temperatures in this range. Aggregation temperature was defined at the temperature the radius begins to expand. The mean of both determined aggregation temperatures was calculated and used for candidate ranking.

DSF

Three glass capillaries were filled each with approx. 40 μl protein solution and placed simultaneously into a DSF reader with temperature control (Prometheus nanoDSF, NanoTemper Technologies GmbH, Munich—Germany). Protein internal fluorescence was measured at an excitation wavelength of 280 nm and emission wavelengths 330 and 350 nm in a linear increasing temperature scan from 20° C. to 95° C. Changes in the ratio of the two emission wavelength intensities indicate conformational changes in the protein therefore showing the melting temperature(s) of the analyzed BiTE proteins. The first maximum of the first derivate of the ratio 350/330 nm curve was defined as first melting temperature. The mean of all three determined first melting temperatures was calculated and used for candidate ranking.

The incorporation of specific amino acid mutations in the sequence of the anti-CD3 binder I2C (VH and VL defined in SEQ ID NO: 1854 and 1855, respectively, and linked with a peptide linker of SEQ ID NO: 2; CD70 target binder VH and VL defined in SEQ ID NOs: 2185 and 2186, respectively, and linked with a peptide linker of SEQ ID NO: 2; CD70 binding domain linked to CD3 binding domain with linker of SEQ ID NO: 6; HLE domain as specified in SEQ ID NO: 18 linked with a G4 linker to the C-terminus of the VL region of the CD3 binder; CD70 binding domain is at the N-terminus, followed by the CD3 binding domain with the HLE domain at the C-terminus of the BiTE® molecule) in the BiTE-HLE context resulted in aggregation temperature values of 57.5° C. to 62.0° C. determined by Dynamic Light Scattering (DLS) and melting temperature values of 62.9° C. to 70.3° C. determined by Differential scanning Fluorometry (DSF). The BiTE-HLE molecules harboring the I2C variants showed an aggregation temperature increase of 2.3° C. to 6.8° C. in comparison to the unmodified I2C. The same effect was observed in the melting temperature measurements of the I2C variants resulting in an increase of 2.1° C. to 9.5° C. as compared to the unmodified I2E.

Also the BiTE-HLE construct containing the anti-CD3 binder variant 12 CC44/100, in which an additional disulfide bond was engineered for stabilizing (Reiter, Y. et al., 1994) by replacing the amino acid residues with Cysteine residues at position 44 in the heavy chain variable region and at position 100 in the light chain variable region (numbering scheme according to Kabat et al., 1991), showed a thermostability increase of 3.2° C. for DLS and 5.3° C. for DSF as compared to the unmodified 120. However, said BiTE-HLE construct exhibited a significantly decreased cytotoxic activity (see further example) resulting in a construct which is therefore not suitable for further development and use as a part of T cell engagers.

TABLE 2

Aggregation and melting temperatures of BiTE-HLE molecules

harboring various CD3 binding domains determined

by Dynamic Light Scattering (DLS) or Differential

scanning Fluorometry (DSF), respectively.

Thermostability

CD3 binder
DLS
DSF
CD3 binding domain

in CD70 BITE-
aggregation
melting
SEQ ID NOs: VH, VL,

HLE
[° C.]
[° C.]
linker

I2E
59.4
68.7
2012, 2013, 2

I2K
58.8
64.6
2020, 2021, 2

I2L
60.4
69.3
2028, 2029, 2

I2M
60.3
67.3
2036, 2037, 2

I2M2
58.9
66.9
2044, 2045, 2

1D5.01
62.0
70.3
42, 43, 2

1D5.03
61.5
70.0
50, 51, 2

1D5.04
61.8
69.7
58, 59, 2

4G10.04
59.4
66.0
66, 67, 2

5B1.05
58.6
67.8
74, 75, 2

5B1.09
58.8
68.2
82, 83, 2

5C3.04
60.6
69.2
90, 91, 2

5C3.05
60.5
69.2
98, 99, 2

5G6.03
60.1
67.4
100, 101, 2

5G6.04
59.3
65.5
108, 109, 2

6H10.03
60.0
67.3
116, 117, 2

8A8.02
59.4
65.9
26, 27, 2

8A8.04
59.3
67.0
34, 35, 2

I2C CC44/100
58.4
66.1

I2C H109A
57.5
62.9
2560, 2561, 2

I2C
55.2
60.8
1854, 1855, 2

The mutation of single or more amino acids in the sequence of the anti-SD3 binder I2C in the BiTE-HLE context resulted in aggregation temperature values of 57.0° C. to 62.4C determined by Dynamic Light Scattering (DLS) and melting temperature values of 62.1° C. to 68.8° C. determined by Differential scanning Fluorometry (DSF). The BiTE-HLE molecules harboring the I2C mutants showed an aggregation temperature increase of 1.0° C. to 7.2° C. in comparison to the unmodified 120. The same effect was observed in the melting temperature measurements of the I2C mutants resulting in an increase of 1.0° C. to 7.7° C. as compared to the unmodified I2C. The CD3 binder as referenced in the below Table specifies the amino acid residue exchanges and their positions in the first column; for each entry it is shown in brackets the positions as used in reference to the base sequence of the VH region sequence as defined in SEQ ID NO: 1854 and the VL region sequence as defined in SEQ ID NO: 1855 which is the authoritative nomenclature in accordance with the invention.

TABLE 3

CD3

binding

Thermostability

domain

DLS
DSF
SEQ ID

CD3 binder
aggregation
melting
NOs: VH,

in CD70 BITE-HLE
[° C.]
[° C.]
VL, linker

I2C_HC_A89V_V107A_LC_L21I_Q46K_L83S_G141S
61.0
68.8

(I2C_HC_A81V_V99A_LC_L20I_Q40K_L69S_G102S)

I2C_HC_M41I_A89V_LC_L21I_Q46K_G141S
62.4
68.6
1898, 1899,

(I2C_HC_M34I_A81V_LC_L20I_Q40K_G102S)

2

I2C_HC_M41I_LC_L21I_Q46K_G141S
61.9
68.3
1904, 1905,

(I2C_HC_M34I_LC_L20I_Q40K_G102S)

2

I2C_HC_M41I_Q46E_A89V_LC_L21I_Q46K_G141S
61.4
68.2
1906, 1907,

(I2C_HC_M34I_Q39E_A81V_LC_L20I_Q40K_G102S)

2

I2C_HC_M41I_A89V_LC_Q46K
60.5
66.6
1900, 1901,

(I2C_HC_M34I_A81V_LC_Q40K)

2

I2C_HC_L52M_LC_L21I_Q46K_G141S
58.6
65.7
1866, 1867,

(I2C_HC_L45M_LC_L20I_Q40K_G102S)

2

I2C_HC_M41I_S73A_H109A_N114S
59.0
65.4

(I2C_HC_M34I_S65A_H101A_N106S)

I2C_LC_L21I_Q46K_L83S_G141S
59.0
65.3

(I2C_LC_L20I_Q40K_L69S_G102S)

I2C_HC_M41F_A89V (I2C_HC_M34F_A81V)
59.3
65.0
1884, 1885,

2

I2C_HC_L52M_LC_Q46K_G141S
59.5
65.0
1870, 1871,

(I2C_HC_L45M_LC_Q40K_G102S)

2

I2C_HC_Q46D_LC_L21I_Q46K_G141S
58.3
64.7
1918

(I2C_HC_Q39D_LC_L20I_Q40K_G102S)

1919, 2

I2C_HC_M41I_A89V (I2C_HC_M34I_A81V)
59.1
64.3
1896, 1897,

2

I2C_HC_Q46E_LC_L21I_Q46K_G141S
58.9
64.3
1932, 1933,

(I2C_HC_Q39E_LC_L20I_Q40K_G102S)

2

I2C_HC_L52M_LC_Q46K
58.9
64.3
1868, 1869.

(I2C_HC_L45M_LC_Q40K)

2

I2C_HC_M41I_S73A_A89V_V107A_H109A_N114S
58.1
64.2

(I2C_HC_M34I_S65A_A81V_V99A_H101A_N106S)

I2C_HC_Q46D_LC_L21I_Q46R_G141S
58.2
63.7
1928, 1929,

(I2C_HC_Q39D_LC_L20I_Q40R_G102S)

2

I2C_HC_M41I (I2C_HC_M34I)
58.2
63.6
1892, 1893,

2

I2C_LC_Q46K (I2C_LC_Q40K)
58.4
63.5
1974, 1975,

2

I2C_HC_Q46D_LC_Q46K_G141S
58.2
63.5
1922, 1923,

(I2C_HC_Q39D_LC_Q40K_G102S)

2

I2C_LC_L21I_G141S (I2C_LC_L20I_G102S)
57.4
63.2

I2C_HC_Q46K (I2C_HC_Q39K)
57.4
63.2
1944, 1945,

2

I2C_HC_Q46E_LC_Q46K_G141S
58.0
63.2
1938, 1939,

(I2C_HC_Q39E_LC_Q40K_G102S)

2

I2C_HC_Q46E_LC_L21I_Q46R_G141S
57.9
63.0
1934, 1935,

(I2C_HC_Q39E_LC_L20I_Q40R_G102S)

2

I2C_HC_Q46D_LC_Q46R_G141S
57.3
62.9
1926, 1927,

(I2C_HC_Q39D_LC_Q40R_G102S)

2

I2C_HC_A89V (I2C_HC_A81V)
58.2
62.9
1862, 1863,

2

I2C_HC_Q46D_LC_Q46K
57.1
62.8
1920, 1921,

(I2C_HC_Q39D_LC_Q40K)

2

I2C_HC_W136F (I2C_HC_W112F)
57.0
62.7
1958, 1959,

2

I2C_HC_W136F_LC_V44I
57.8
62.4
1960, 1961,

(I2C_HC_W112F_LC_V38I)

2

I2C_HC_Q46E_LC_Q46K
58.2
62.3
1936, 1937,

(I2C_HC_Q39E_LC_Q40K)

2

I2C_HC_M41V (I2C_HC_M34V)
57.6
62.1
1914, 1915,

2

I2C
55.2
60.8

Aggregation and melting temperatures of BiTE-HLE molecules harboring the CD3 binding domain “I2C” (SEQ ID NO: 1854 and 1855, respectively, linked by peptide linker (G₄S)3 (SEQ ID NO: 2)), respectively) with several amino acid mutations determined by Dynamic Light Scattering (DLS) or Differential scanning Fluorometry (DSF), respectively, as described herein above.

Example 2: Cytotoxic Activity

Cytotoxic Activity

Human peripheral blood mononuclear cells (PBMC) were prepared by Ficoll density gradient centrifugation from enriched lymphocyte preparations (buffy coats), a side product of blood banks collecting blood for transfusions. Buffy coats were supplied by a local blood bank and PBMC were prepared on the same day of blood collection. After Ficoll density centrifugation and extensive washes with Dulbecco's PBS (Gibco), remaining erythrocytes were removed from PBMC via incubation with erythrocyte lysis buffer (155 mM NH₄Cl, 10 mM KHCO₃, 100 μM EDTA). Platelets were removed via the supernatant upon centrifugation of PBMC at 100×g. Remaining lymphocytes mainly encompass B and T lymphocytes, NK cells and monocytes. PBMC were kept in culture at 37° C./5% CO₂in RPMI medium (Gibco) with 10% FCS (Gibco).

Depletion of CD14⁺ and CD56⁺ Cells

For depletion of CD14⁺ cells, human CD14 MicroBeads (Milteny Biotec, MACS, #130-050-201) were used, for depletion of NK cells human CD56 MicroBeads (MACS, #130-050-401). PBMC were counted and centrifuged for 10 min at room temperature with 300×g. The supernatant was discarded and the cell pellet resuspended in MACS isolation buffer [80 μL/10⁷cells; PBS (Invitrogen, #20012-043), 0.5% (v/v) FBS (Gibco, #10270-106), 2 mM EDTA (Sigma-Aldrich, #E-6511)]. CD14 MicroBeads and CD56 MicroBeads (20 μL/10⁷cells) were added and incubated for 15 min at 4-8° C. The cells were washed with MACS isolation buffer (1-2 mL/10⁷cells). After centrifugation (see above), supernatant was discarded and cells resuspended in MACS isolation buffer (500 μL/10⁸cells). CD14/CD56 negative cells were then isolated using LS Columns (Miltenyi Biotec, #130-042-401). PBMC w/o CD14+/CD56+ cells were cultured in RPMI complete medium i.e. RPMI1640 (Biochrom AG, #FG1215) supplemented with 10% FBS (Biochrom AG, #S0115), 1×non-essential amino acids (Biochrom AG, #K0293), 10 mM Hepes buffer (Biochrom AG, #L1613), 1 mM sodium pyruvate (Biochrom AG, #L0473) and 100 U/mL penicillin/streptomycin (Biochrom AG, #A2213) at 37° C. in an incubator until needed.

Target Cell Labeling

For the analysis of cell lysis in flow cytometry assays, the fluorescent membrane dye DiOC₁₈(DiO) (Molecular Probes, #V22886) was used to label human target-transfected CHO cells as target cells and distinguish them from effector cells. Briefly, cells were harvested, washed once with PBS and adjusted to 10⁶cell/mL in PBS containing 2% (v/v) FBS and the membrane dye DiO (5 μL/10⁶cells). After incubation for 3 min at 37° C., cells were washed twice in complete RPMI medium and the cell number adjusted to 1.25×10⁵cells/mL. The vitality of cells was determined using the NC-250 cell counter (Chemometec).

Flow Cytometry Based Analysis

This assay was designed to quantify the lysis of human target-transfected CHO cells in the presence of serial dilutions of anti-target multi-specific constructs. Equal volumes of DiO-labeled target cells and effector cells (i.e., PBMC w/o CD14⁺ and CD56⁺ cells) were mixed, resulting in an E:T cell ratio of 10:1. 80 μl of this suspension were transferred to each well of a 96-well plate. 20 μL of serial dilutions of the anti-target×anti-CD3 multi-specific constructs and a negative control (a CD3-based multi-specific construct recognizing an irrelevant target antigen) or RPMI complete medium as an additional negative control were added. The multi-specific construct-mediated cytotoxic reaction proceeded for 48 hours in a 7% CO₂humidified incubator. Then cells were transferred to a new 96-well plate and loss of target cell membrane integrity was monitored by adding propidium iodide (PI) at a final concentration of 1 pg/mL. PI is a membrane impermeable dye that normally is excluded from viable cells, whereas dead cells take it up and become identifiable by fluorescent emission.

Samples were measured by flow cytometry on an iQue Plus instrument and analyzed by Forecyt software (both from Intellicyt). Target cells were identified as DiO-positive cells. PI-negative target cells were classified as living target cells. Percentage of cytotoxicity was calculated according to the following formula:

$Cytotoxicity [%] = \frac{n_{dead target cells}}{n_{target cells}} \times 100$

$n = number of events$

Using GraphPad Prism 6 software (Graph Pad Software, San Diego), the percentage of cytotoxicity was plotted against the corresponding bispecific construct concentrations. Dose response curves were analyzed with the four parametric logistic regression models for evaluation of sigmoid dose response curves with fixed hill slope and EC50 values were calculated.

Results:

TABLE 4

EC50 values in pM of T-cell engager with different anti-CD3 scFvs

EC50 [pM]

I2C
0.2

I2CA
1.2

8A8.04
0.1

5C3.04
0.1

I2E
0.05

I2K
0.1

5G6.04
0.1

5G6.03
0.1

1D5.04
0.4

8A8.02
0.1

1D5.03
0.2

T-cell engager with anti-CD3 scFvs I2C, I2CA, 8A8.04, 5C3.04, 12E, I2K, 5G6.04, 5G6.03, 1D5.04, 8A8.02 and 1D5.03 show similar EC50 values in range from 0.05 pM to 0.4 pM (FIG. 1 A) and Table 4).

TABLE 5

EC50 values in pM of T-cell engager with different anti-CD3 scFvs

EC50 [pM]

I2C
5.3

5G6.04
5.1

8A8.04
7.0

I2E
4.5

I2K
4.5

I2C CC 44/100
1578

T-cell engager with anti-CD3 scFvs I2C, 5G6.04, 8A8.04, 12E and I2K show similar EC50 values in the range from 4.5 pM to 7.0 pM. T-cell engager with anti-CD3 scFv I2C CC 44/100 shows an EC50 value of 1578 pM and is 297-fold less active compared to T-cell engager with anti-CD3 scFv I2C (FIG. 1 B) and Table 5).

Sequences

The below sequence list is the authoritative list for SEQ ID NOs referred to in the specification text and claims and may contain (a) gap(s) as to consecutive numbering. Any further list, such as the list complying with WIPO Standard ST.25 that contains consecutive numberings has been generated of this list and the difference in Sequence numbers is to be reconciled with the below list. Sequence identity can be identified without further ado by reference to the unique entry in the second column identified as “designation” as well as a sequence alignment:

SEQ

ID

NO:
Designation
Organism
Sequence

1
(G4S)10-
artificial
GGGGGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

Linker

2
(G4S)3-
artificial
GGGGSGGGGSGGGGS

Linker

3
G(EAAAK)10-
artificial
GEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAK

Linker

4
G4-Linker
artificial
GGGG

5
G4Q-
artificial
GGGGQ

Linker

6
G4S-
artificial
GGGGS

Linker

7
S(G4S)10
artificial
SGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

Linker

8
S(G4S)3-
artificial
SGGGGSGGGGSGGGGS

Linker

9
SG(EAAAK)10-
artificial
SGEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAK

Linker

10
SG4Q-
artificial
SGGGGQ

Linker

11
SG4S-
artificial
SGGGGS

Linker

12
(EAAAK)10-
artificial
EAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAKEAAAK

Spacer

13
(G4S)10-
artificial
GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

Spacer

14
2x scFc-
artificial
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

Spacer

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS

GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQ

DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV

KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV

MHEALHNHYTQKSLSLSPGKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE

VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNG

KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP

SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL

HNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

15
G4S-
artificial
GGGGS

Spacer

16
Human Serum
artificial
DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADES

Albumin

AENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLV

(HSA)-

RPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADK

Spacer

AACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVS

KLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCI

AEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLR

LAKTYETTLEKCCAAADPHECYAKVEDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNA

LLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLH

EKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQ

IKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQ

AALGL

17
PD1 (ECM
artificial
LDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAF

25-167)

PEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRA

Spacer

ELRVTERRAEVPTAHPSPSPRPAGQFQ

18
ScFc-
artificial
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

Spacer

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGS

GGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMI

SRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQ

DWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLV

KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV

MHEALHNHYTQKSLSLSPGK

19
scFc_mod GQ-
artificial
CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEEPEVKENWYVDGVE

Spacer

VHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKG

QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD

SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGQGGGGQ

GGGGQGGGGQGGGGQGGGGQCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVV

VDVSHEEPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKC

KVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV

EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT

QKSLSLSPGK

20
16278-A8.2-
artificial
KYAIN

HCDR1

21
16278-A8.2-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

22
16278-A8.2-
artificial
AGNFGTSYISYWAY

HCDR3

23
16278-A8.2-
artificial
GSSTGAVTSGNYPN

LCDR1

24
16278-A8.2-
artificial
GTKFLAP

LCDR2

25
16278-A8.2-
artificial
ALWYSNRWV

LCDR3

26
16278-A8.2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARAGNFGTSYISYWAYWG

QGTLVTVSS

27
16278-A8.2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

L

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

28
16278-A8.4-
artificial
KYAIN

HCDR1

29
16278-A8.4-
artificial
RIRSKYNNYATYYAEAVKD

HCDR2

30
16278-A8.4-
artificial
AGNFGTSYISYWAY

HCDR3

31
16278-A8.4
artificial
GSSTGAVTSGNYPN

-LCDR1

32
16278-A8.4
artificial
GTKFLAP

-LCDR2

33
16278-A8.4
artificial
ALWYSNRWV

-LCDR3

34
16278-A8.4
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARAGNFGTSYISYWAYWG

QGTLVTVSS

35
16278-A8.4
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

36
16281-D5.1
artificial
KYAIN

-HCDR1

37
16281-D5.1
artificial
RIRSKYNNYATYYADAVKD

-HCDR2

38
16281-D5.1
artificial
AGNFGSSYISYFAY

-HCDR3

39
16281-D5.1
artificial
GSSTGAVTSGNYPN

-LCDR1

40
16281-D5.1
artificial
GTKFLAP

-LCDR2

41
16281-D5.1
artificial
ALWYSNRWV

-LCDR3

42
16281-D5.1
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWG

QGTLVTVSS

43
16281-D5.1
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

44
16281-D5.3
artificial
KYAIN

-HCDR1

45
16281-D5.3
artificial
RIRSKYNNYATYYAEAVKD

-HCDR2

46
16281-D5.3
artificial
AGNFGSSYISYFAY

-HCDR3

47
16281-D5.3
artificial
GSSTGAVTSGNYPN

-LCDR1

48
16281-D5.3
artificial
GTKFLAP

-LCDR2

49
16281-D5.3
artificial
ALWYSNRWV

-LCDR3

50
16281-D5.3
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWG

QGTLVTVSS

51
16281-D5.3
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

52
16281-D5.4
artificial
KYAIN

-HCDR1

53
16281-D5.4
artificial
RIRSKYNNYATYYAEAVKD

-HCDR2

54
16281-D5.4
artificial
AGNFGTSYISYFAY

-HCDR3

55
16281-D5.4
artificial
GSSTGAVTSGNYPN

-LCDR1

56
16281-D5.4
artificial
GTKFLAP

-LCDR2

57
16281-D5.4
artificial
ALWYSNRWV

-LCDR3

58
16281-D5.4
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRAGNFGTSYISYFAYWG

QGTLVTVSS

59
16281-D5.4
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

60
16334-G10.4
artificial
KYAMN

-HCDR1

61
16334-G10.4
artificial
RIRSKYNNYATYYAEAVKD

-HCDR2

62
16334-G10.4
artificial
AENIGTSYISYWAY

-HCDR3

63
16334-G10.4
artificial
GSSTGAVTSGNYPN

-LCDR1

64
16334-G10.4
artificial
GTKFLAP

-LCDR2

65
16334-G10.4
artificial
VLWYSNRWV

-LCDR3

66
16334-G10.4
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFSKYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRAENIGTSYISYWAYWG

QGTLVTVSS

67
16334-G10.4
artificial
QTVVTQEPSLTVSPGGTVTMTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

68
16335-B1.5
artificial
KYAMN

-HCDR1

69
16335-B1.5
artificial
RIRSKYNNYATYYAEAVKG

-HCDR2

70
16335-B1.5
artificial
AGNFGSSYISYWAY

-HCDR3

71
16335-B1.5
artificial
GSSTGAVTSGNYPN

-LCDR1

72
16335-B1.5
artificial
GTKFLAP

-LCDR2

73
16335-B1.5
artificial
VLWYSNRWV

-LCDR3

74
16335-B1.5
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFSKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRAGNFGSSYISYWAYWG

QGTLVTVSS

75
16335-B1.5
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

76
16335-B1.9
artificial
KYAMN

-HCDR1

77
16335-B1.9
artificial
RIRSKYNNYATYYADAVKG

-HCDR2

78
16335-B1.9
artificial
AGNFGTSYISYFAY

-HCDR3

79
16335-B1.9
artificial
GSSTGAVTSGNYPN

-LCDR1

80
16335-B1.9
artificial
GTKFLAP

-LCDR2

81
16335-B1.9
artificial
VLYYSNRWV

-LCDR3

82
16335-B1.9
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFSKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRAGNFGTSYISYFAYWG

QGTLVTVSS

83
16335-B1.9
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGGGTKLTVL

84
16335-C3.4
artificial
KYAIN

-HCDR1

85
16335-C3.4
artificial
RIRSKYNNYATYYADAVKD

-HCDR2

86
16335-C3.4
artificial
AENIGTSYISYWAY

-HCDR3

87
16335-C3.4
artificial
GSSTGAVTSGNYPN

-LCDR1

88
16335-C3.4
artificial
GTKFLAP

-LCDR2

89
16335-C3.4
artificial
VLWYSNRWV

-LCDR3

90
16335-C3.4
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAENIGTSYISYWAYWG

QGTLVTVSS

91
16335-C3.4
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

92
16335-C3.5
artificial
KYAIN

-HCDR1

93
16335-C3.5
artificial
RIRSKYNNYATYYAEAVKD

-HCDR2

94
16335-C3.5
artificial
AGNFGSSYISYWAY

-HCDR3

95
16335-C3.5
artificial
GSSTGAVTSGNYPN

-LCDR1

96
16335-C3.5
artificial
GTKFLAP

-LCDR2

97
16335-C3.5
artificial
VLYYSNRWV

-LCDR3

98
16335-C3.5
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWG

QGTLVTVSS

99
16335-C3.5
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

100
16335-G6.3
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRAGNFGSSYISYWAYWG

QGTLVTVSS

101
16335-G6.3
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

102
16335-G6.4
artificial
KYAMN

-HCDR1

103
16335-G6.4
artificial
RIRSKYNNYATYYADAVKG

-HCDR2

104
16335-G6.4
artificial
NENIGSSYISYWAY

-HCDR3

105
16335-G6.4
artificial
GSSTGAVTSGNYPN

-LCDR1

106
16335-G6.4
artificial
GTKFLAP

-LCDR2

107
16335-G6.4
artificial
VLWYSNRWV

-LCDR3

108
16335-G6.4
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGSSYISYWAYWG

QGTLVTVSS

109
16335-G6.4
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

110
16356-H10.3
artificial
KYAMN

-HCDR1

111
16356-H10.3
artificial
RIRSKYNNYATYYAEAVKD

-HCDR2

112
16356-H10.3
artificial
AGNFGTSYISYWAY

-HCDR3

113
16356-H10.3
artificial
GSSTGAVTSGNYPN

-LCDR1

114
16356-H10.3
artificial
GTKFLAP

-LCDR2

115
16356-H10.3
artificial
VLWYSNRWV

-LCDR3

116
16356-H10.3
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYAEAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWG

QGTLVTVSS

117
16356-H10.3
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

118
2B2_Comp1-
artificial
KYAIN

HCDR1

119
2B2_Comp1-
artificial
RIRSKYNNYATYYADQVKD

HCDR2

120
2B2_Comp1-
artificial
HANFGNSYISYWAY

HCDR3

121
2B2_Comp1-
artificial
ASSTGAVTSGNYPN

LCDR1

122
2B2_Comp1-
artificial
GTKFLVP

LCDR2

123
2B2_Comp1-
artificial
TLWYSNRWV

LCDR3

124
2B2_Comp1-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADQVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHANFGNSYISYWAYWG

QGTLVTVSS

125
2B2_Comp1-
artificial
QTVVTQEPSLTVSPGGTVTLTCASSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLVP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCTLWYSNRWVFGGGTKLTVL

126
2B2_Comp1_
artificial
KYAIN

I2E-HCDR1

127
2B2_Comp1_
artificial
RIRSKYNNYATYYADAVKD

I2E-HCDR2

128
2B2_Comp1_
artificial
AANFGSSYISYWAY

I2E-HCDR3

129
2B2_Comp1_
artificial
ASSTGAVTSGNYPN

I2E-LCDR1

130
2B2_Comp1_
artificial
GTKFLVP

I2E-LCDR2

131
2B2_Comp1_
artificial
TLWYSNRWV

I2E-LCDR3

132
2B2_Comp1_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

I2E-VH

ATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAANFGSSYISYWAYWG

QGTLVTVSS

133
2B2_Comp1_
artificial
QTVVTQEPSLTVSPGGTVTITCASSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLVP

I2E-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCTLWYSNRWVFGSGTKLTVL

134
2B2_Comp1_
artificial
KYAMN

I2K-HCDR1

135
2B2_Comp1_
artificial
RIRSKYNNYATYYAEAVKG

I2K-HCDR2

136
2B2_Comp1_
artificial
NENIGTSYISYWAY

I2K-HCDR3

137
2B2_Comp1_
artificial
ASSTGAVTSGNYPN

I2K-LCDR1

138
2B2_Comp1_
artificial
GTKFLVP

I2K-LCDR2

139
2B2_Comp1_
artificial
TLWYSNRWV

I2K-LCDR3

140
2B2_Comp1_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

2K-VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWG

QGTLVTVSS

141
2B2_Comp1_
artificial
QTVVTQEPSLTVSPGGTVTITCASSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLVP

I2K-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCTLWYSNRWVFGSGTKLTVL

142
2B2_Comp1_
artificial
KYAIN

I2L-HCDR1

143
2B2_Comp1_
artificial
RIRSKYNNYATYYADAVKD

I2L-HCDR2

144
2B2_Comp1_
artificial
AANFGSSYISYFAY

I2L-HCDR3

145
2B2_Comp1_
artificial
ASSTGAVTSGNYPN

I2L-LCDR1

146
2B2_Comp1_
artificial
GTKFLVP

I2L-LCDR2

147
2B2_Comp1_
artificial
TLYYSNRWV

I2L-LCDR3

148
2B2_Comp1_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGMEWVARIRSKYNNY

I2L-VH

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAANFGSSYISYFAYWG

QGTLVTVSS

149
2B2_Comp1_
artificial
QTVVTQEPSLTVSPGGTVTITCASSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLVP

I2L-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCTLYYSNRWVFGSGTKLTVL

150
2B2_Comp1_
artificial
KYAIN

I2M-HCDR1

151
2B2_Comp1_
artificial
RIRSKYNNYATYYADAVKD

I2M-HCDR2

152
2B2_Comp1_
artificial
AANFGTSYISYWAY

I2M-HCDR3

153
2B2_Comp1_
artificial
ASSTGAVTSGNYPN

I2M-LCDR1

154
2B2_Comp1_
artificial
GTKFLVP

I2M-LCDR2

155
2B2_Comp1_
artificial
TLWYSNRWV

I2M-LCDR3

156
2B2_Comp1_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGMEWVARIRSKYNNY

I2M-VH

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAANFGTSYISYWAYWG

QGTLVTVSS

157
2B2_Comp1_
artificial
QTVVTQEPSLTVSPGGTVTITCASSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLVP

I2M-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCTLWYSNRWVFGSGTKLTVL

158
2B2_Comp1_
artificial
KYAIN

I2M2-HCDR1

159
2B2_Comp1_
artificial
RIRSKYNNYATYYADAVKD

I2M2-HCDR2

160
2B2_Comp1_
artificial
NANFGTSYISYFAY

I2M2-HCDR3

161
2B2_Comp1_
artificial
ASSTGAVTSGNYPN

I2M2-LCDR1

162
2B2_Comp1_
artificial
GTKFLVP

I2M2-LCDR2

163
2B2_Comp1_
artificial
TLWYSNRWV

I2M2-LCDR3

164
2B2_Comp1_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

I2M2-VH

ATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWG

QGTLVTVSS

165
2B2_Comp1_
artificial
QTVVTQEPSLTVSPGGTVTLTCASSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLVP

I2M2-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCTLWYSNRWVFGSGTKLTVL

166
A2J-HCDR1
artificial
VYAMN

167
A2J-HCDR2
artificial
RIRSKYNNYATYYADSVKK

168
A2J-HCDR3
artificial
HGNFGNSYLSWWAY

169
A2J-LCDR1
artificial
RSSTGAVTSGYYPN

170
A2J-LCDR2
artificial
ATDMRPS

171
A2J-LCDR3
artificial
ALWYSNRWV

172
A2J-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

173
A2J-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

174
A2J_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

175
A2J_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

176
A2J_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

177
A2J_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

178
A2J_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

179
A2J_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

180
A2J_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

181
A2J_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

182
A2J_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

183
A2J_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

184
A2J_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-

QGTLVTVSS

VH

185
A2J_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-

VL

186
A2J_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

187
A2J_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

188
A2J_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-VH

QGTLVTVSS

189
A2J_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

190
A2J_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

191
A2J_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

192
A2J_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

193
A2J_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWFQQKPGQAPRGLIGATDMRPS

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

194
A2J_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

195
A2J_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWYQQKPGQAPRGLIGATDMRPS

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

196
A2J_HC_M41F_
artificial
VYAFN

A89V-

HCDR1

197
A2J_HC_M41F_
artificial
RIRSKYNNYATYYADSVKK

A89V-HCDR2

198
A2J_HC_M41F_
artificial
HGNFGNSYLSWWAY

A89V-HCDR3

199
A2J_HC_M41F_
artificial
RSSTGAVTSGYYPN

A89V-

LCDR1

200
A2J_HC_M41F
artificial
ATDMRPS

A89V-LCDR2

201
A2J_HC_M41F_
artificial
ALWYSNRWV

A89V-LCDR3

202
A2J_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

203
A2J_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

204
A2J_HC_M41I
artificial
VYAIN

-HCDR1

205
A2J_HC_M41I
artificial
RIRSKYNNYATYYADSVKK

-HCDR2

206
A2J_HC_M41I
artificial
HGNFGNSYLSWWAY

-HCDR3

207
A2J_HC_M41I
artificial
RSSTGAVTSGYYPN

-LCDR1

208
A2J_HC_M41I
artificial
ATDMRPS

-LCDR2

209
A2J_HC_M41I
artificial
ALWYSNRWV

-LCDR3

210
A2J_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

211
A2J_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

212
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

213
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

214
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

215
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

216
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_L21I_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46K_

QGTLVTVSS

G141S-VH

217
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

A89V_LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_

G141S-VL

218
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46K-VH

QGTLVTVSS

219
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

220
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

221
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWFQKKPGQAPRGLIGATDMRPS

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

V44F-VL

222
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

223
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

224
A2J_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

225
A2J_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

226
A2J_HC_M41V
artificial
VYAVN

-HCDR1

227
A2J_HC_M41V
artificial
RIRSKYNNYATYYADSVKK

-HCDR2

228
A2J_HC_M41V
artificial
HGNFGNSYLSWWAY

-HCDR3

229
A2J_HC_M41V
artificial
RSSTGAVTSGYYPN

-LCDR1

230
A2J_HC_M41V
artificial
ATDMRPS

-LCDR2

231
A2J_HC_M41V
artificial
ALWYSNRWV

-LCDR3

232
A2J_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

233
A2J_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

234
A2J_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

235
A2J_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

236
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

237
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

238
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

239
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

240
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

241
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

242
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-VH

QGTLVTVSS

243
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

244
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

245
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

246
A2J_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-VH

QGTLVTVSS

247
A2J_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

248
A2J_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

249
A2J_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

250
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

251
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S

VL

252
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

253
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

254
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

255
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

256
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-VH

QGTLVTVSS

257
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

258
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

VH

QGTLVTVSS

259
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

260
A2J_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

G141S-VH

QGTLVTVSS

261
A2J_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

262
A2J_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

263
A2J_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

264
A2J_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

265
A2J_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

266
A2J_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYLSWWAYWG

QGTLVTVSS

267
A2J_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

268
A2J_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYLSWWAYWG

QGTLVTVSS

269
A2J_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

270
A2J_HC_W136F-
artificial
VYAMN

HCDR1

271
A2J_HC_W136F-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

272
A2J_HC_W136F-
artificial
HGNFGNSYLSWFAY

HCDR3

273
A2J_HC_W136F-
artificial
RSSTGAVTSGYYPN

LCDR1

274
A2J_HC_W136F-
artificial
ATDMRPS

LCDR2

275
A2J_HC_W136F-
artificial
ALWYSNRWV

LCDR3

276
A2J_HC_W136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWFAYWG

QGTLVTVSS

277
A2J_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

278
A2J_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWFAYWG

VH

QGTLVTVSS

279
A2J_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWIQQKPGQAPRGLIGATDMRPS

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

280
A2J_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWFAYWG

VH

QGTLVTVSS

281
A2J_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWLQQKPGQAPRGLIGATDMRPS

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

282
A2J_I2E-
artificial
VYAIN

HCDR1

283
A2J_I2E-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

284
A2J_I2E-
artificial
AGNFGSSYLSWWAY

HCDR3

285
A2J_I2E-
artificial
RSSTGAVTSGYYPN

LCDR1

286
A2J_I2E-
artificial
ATDMRPS

LCDR2

287
A2J_I2E-
artificial
ALWYSNRWV

LCDR3

288
A2J_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYLSWWAYWG

QGTLVTVSS

289
A2J_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

290
A2J_I2K-
artificial
VYAMN

HCDR1

291
A2J_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

292
A2J_I2K-
artificial
NENIGTSYLSWWAY

HCDR3

293
A2J_I2K-
artificial
RSSTGAVTSGYYPN

LCDR1

294
A2J_I2K-
artificial
ATDMRPS

LCDR2

295
A2J_I2K-
artificial
ALWYSNRWV

LCDR3

296
A2J_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYLSWWAYWG

QGTLVTVSS

297
A2J_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

298
A2J_I2L-
artificial
VYAMN

HCDR1

299
A2J_I2L-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

300
A2J_I2L-
artificial
AGNFGSSYLSWFAY

HCDR3

301
A2J_I2L-
artificial
RSSTGAVTSGYYPN

LCDR1

302
A2J_I2L-
artificial
ATDMRPS

LCDR2

303
A2J_I2L-
artificial
ALYYSNRWV

LCDR3

304
A2J_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYLSWFAYWG

QGTLVTVSS

305
A2J_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWIQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

306
A2J_I2M-
artificial
VYAMN

HCDR1

307
A2J_I2M-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

308
A2J_I2M-
artificial
AGNFGTSYLSWWAY

HCDR3

309
A2J_I2M-
artificial
RSSTGAVTSGYYPN

LCDR1

310
A2J_I2M-
artificial
ATDMRPS

LCDR2

311
A2J_I2M-
artificial
ALWYSNRWV

LCDR3

312
A2J_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYLSWWAYWG

QGTLVTVSS

313
A2J_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

314
A2J_I2M2-
artificial
VYAIN

HCDR1

315
A2J_I2M2-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

316
A2J_I2M2-
artificial
NANFGTSYLSWFAY

HCDR3

317
A2J_I2M2-
artificial
RSSTGAVTSGYYPN

LCDR1

318
A2J_I2M2-
artificial
ATDMRPS

LCDR2

319
A2J_I2M2-
artificial
ALWYSNRWV

LCDR3

320
A2J_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYLSWFAYWG

QGTLVTVSS

321
A2J_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

322
A2J_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

323
A2J_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

324
A2J_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

325
A2J_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

326
A2J_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

327
A2J_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

328
A2J_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

329
A2J_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

330
A2J_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

331
A2J_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQEKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

332
A2J_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

333
A2J_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

334
A2J_LC_A107L-
artificial
VYAMN

HCDR1

335
A2J_LC_A107L-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

336
A2J_LC_A107L-
artificial
HGNFGNSYLSWWAY

HCDR3

337
A2J_LC_A107L-
artificial
RSSTGAVTSGYYPN

LCDR1

338
A2J_LC_A107L-
artificial
ATDMRPS

LCDR2

339
A2J_LC_A107L-
artificial
LLWYSNRWV

LCDR3

340
A2J_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

341
A2J_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

342
A2J_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

343
A2J_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWIQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

344
A2J_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

345
A2J_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWLQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

346
A2J_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

347
A2J_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWMQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

348
A2J_LC_W109Y-
artificial
VYAMN

HCDR1

349
A2J_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

350
A2J_LC_W109Y-
artificial
HGNFGNSYLSWWAY

HCDR3

351
A2J_LC_W109Y-
artificial
RSSTGAVTSGYYPN

LCDR1

352
A2J_LC_W109Y-
artificial
ATDMRPS

LCDR2

353
A2J_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

354
A2J_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSWWAYWG

QGTLVTVSS

355
A2J_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

356
E1L-HCDR1
artificial
KYAMN

357
E1L-HCDR2
artificial
RIRSKYNNYATYYADSVKS

358
E1L-HCDR3
artificial
HGNFGNSYTSYYAY

359
E1L-LCDR1
artificial
GSSTGAVTSGYYPN

360
E1L-LCDR2
artificial
GTKFLAP

361
E1L-LCDR3
artificial
ALWYSNRWV

362
E1L-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

363
E1L-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

364
E1L_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

365
E1L_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

366
E1L_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

367
E1L_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

368
E1L_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

369
E1L_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

370
E1L_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

371
E1L_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

372
E1L_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

373
E1L_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

374
E1L_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46K_G141S-

QGTLVTVSS

VH

375
E1L_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

376
E1L_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

377
E1L_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

378
E1L_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

4G11S-VH

QGTLVTVSS

379
E1L_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

380
E1L_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

381
E1L_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

382
E1L_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

383
E1L_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

384
E1L_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

385
E1L_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

386
E1L_HC_M41F_
artificial
KYAFN

A89V-

HCDR1

387
E1L_HC_M41F_
artificial
RIRSKYNNYATYYADSVKS

A89V-HCDR2

388
E1L_HC_M41F_
artificial
HGNFGNSYTSYYAY

A89V-

HCDR3

389
E1L_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-

LCDR1

390
E1L_HC_M41F_
artificial
GTKFLAP

A89V-

LCDR2

391
E1L_HC_M41F_
artificial
ALWYSNRWV

A89V-LCDR3

392
E1L_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

393
E1L_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

394
E1L_HC_M41I
artificial
KYAIN

-HCDR1

395
E1L_HC_M41I
artificial
RIRSKYNNYATYYADSVKS

-HCDR2

396
E1L_HC_M41I
artificial
HGNFGNSYTSYYAY

-HCDR3

397
E1L_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

398
E1L_HC_M41I
artificial
GTKFLAP

-LCDR2

399
E1L_HC_M41I
artificial
ALWYSNRWV

-LCDR3

400
E1L_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

401
E1L_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

402
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

403
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

404
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

405
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

406
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

407
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

408
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46K-VH

QGTLVTVSS

409
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

410
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

411
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

412
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46K_G141S-

QGTLVTVSS

VH

413
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

414
E1L_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

415
E1L_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

416
E1L_HC_M41V
artificial
KYAVN

-HCDR1

417
E1L_HC_M41V
artificial
RIRSKYNNYATYYADSVKS

-HCDR2

418
E1L_HC_M41V
artificial
HGNFGNSYTSYYAY

-HCDR3

419
E1L_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

420
E1L_HC_M41V
artificial
GTKFLAP

-LCDR2

421
E1L_HC_M41V
artificial
ALWYSNRWV

-LCDR3

422
E1L_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

423
E1L_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

424
E1L_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

425
E1L_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

426
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46K_G141S-

QGTLVTVSS

VH

427
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

428
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46R_G141S-

QGTLVTVSS

VH

429
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

430
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

431
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

432
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

G141S-VH

QGTLVTVSS

433
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

434
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

435
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

436
E1L_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

G141S-VH

QGTLVTVSS

437
E1L_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

438
E1L_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

439
E1L_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

440
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46K_G141S-

QGTLVTVSS

VH

441
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

442
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

Q46R_G141S-

QGTLVTVSS

VH

443
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

444
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

445
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

446
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

G141S-VH

QGTLVTVSS

447
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

448
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

VH

QGTLVTVSS

449
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

450
E1L_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

G141S-VH

QGTLVTVSS

451
E1L_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

452
E1L_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

453
E1L_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

454
E1L_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

455
E1L_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

456
E1L_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYTSYYAYWG

QGTLVTVSS

457
E1L_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

458
E1L_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYTSYYAYWG

QGTLVTVSS

459
E1L_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

460
E1L_HC_Y136F-
artificial
KYAMN

HCDR1

461
E1L_HC_Y136F-
artificial
RIRSKYNNYATYYADSVKS

HCDR2

462
E1L_HC_Y136F-
artificial
HGNFGNSYTSYFAY

HCDR3

463
E1L_HC_Y136F-
artificial
GSSTGAVTSGYYPN

LCDR1

464
E1L_HC_Y136F-
artificial
GTKFLAP

LCDR2

465
E1L_HC_Y136F-
artificial
ALWYSNRWV

LCDR3

466
E1L_HC_Y136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYFAYWG

QGTLVTVSS

467
E1L_HC_Y136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

468
E1L_HC_Y136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYFAYWG

VH

QGTLVTVSS

469
E1L_HC_Y136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

470
E1L_HC_Y136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYFAYWG

VH

QGTLVTVSS

471
E1L_HC_Y136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

472
E1L_I2E-
artificial
KYAIN

HCDR1

473
E1L_I2E-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

474
E1L_I2E-
artificial
AGNFGSSYTSYYAY

HCDR3

475
E1L_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

476
E1L_I2E-
artificial
GTKFLAP

LCDR2

477
E1L_I2E-
artificial
ALWYSNRWV

LCDR3

478
E1L_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYTSYYAYWG

QGTLVTVSS

479
E1L_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

480
E1L_I2K-
artificial
KYAMN

HCDR1

481
E1L_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

482
E1L_I2K-
artificial
NENIGTSYTSYYAY

HCDR3

483
E1L_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

484
E1L_I2K-
artificial
GTKFLAP

LCDR2

485
E1L_I2K-
artificial
ALWYSNRWV

LCDR3

486
E1L_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYTSYYAYWG

QGTLVTVSS

487
E1L_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

488
E1L_I2L-
artificial
KYAMN

HCDR1

489
E1L_I2L-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

490
E1L_I2L-
artificial
AGNFGSSYTSYFAY

HCDR3

491
E1L_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

492
E1L_I2L-
artificial
GTKFLAP

LCDR2

493
E1L_I2L-
artificial
ALYYSNRWV

LCDR3

494
E1L_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYTSYFAYWG

QGTLVTVSS

495
E1L_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

496
E1L_I2M-
artificial
KYAMN

HCDR1

497
E1L_I2M-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

498
E1L_I2M-
artificial
AGNFGTSYTSYYAY

HCDR3

499
E1L_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

500
E1L_I2M-
artificial
GTKFLAP

LCDR2

501
E1L_I2M-
artificial
ALWYSNRWV

LCDR3

502
E1L_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYTSYYAYWG

QGTLVTVSS

503
E1L_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

504
E1L_I2M2-
artificial
KYAIN

HCDR1

505
E1L_I2M2-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

506
E1L_I2M2-
artificial
NANFGTSYTSYFAY

HCDR3

507
E1L_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

508
E1L_I2M2-
artificial
GTKFLAP

LCDR2

509
E1L_I2M2-
artificial
ALWYSNRWV

LCDR3

510
E1L_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYTSYFAYWG

QGTLVTVSS

511
E1L_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

512
E1L_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

513
E1L_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

514
E1L_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

515
E1L_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

516
E1L_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

517
E1L_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

518
E1L_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

519
E1L_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

520
E1L_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

521
E1L_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

522
E1L_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

523
E1L_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

524
E1L_LC_A107L-
artificial
KYAMN

HCDR1

525
E1L_LC_A107L-
artificial
RIRSKYNNYATYYADSVKS

HCDR2

526
E1L_LC_A107L-
artificial
HGNFGNSYTSYYAY

HCDR3

527
E1L_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

528
E1L_LC_A107L-
artificial
GTKFLAP

LCDR2

529
E1L_LC_A107L-
artificial
LLWYSNRWV

LCDR3

530
E1L_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

531
E1L_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

532
E1L_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

533
E1L_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

534
E1L_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

535
E1L_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

536
E1L_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

537
E1L_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

538
E1L_LC_W109Y-
artificial
KYAMN

HCDR1

539
E1L_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKS

HCDR2

540
E1L_LC_W109Y-
artificial
HGNFGNSYTSYYAY

HCDR3

541
E1L_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

542
E1L_LC_W109Y-
artificial
GTKFLAP

LCDR2

543
E1L_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

544
E1L_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYTSYYAYWG

QGTLVTVSS

545
E1L_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

546
E2M-HCDR1
artificial
GYAMN

547
E2M-HCDR2
artificial
RIRSKYNNYATYYADSVKE

548
E2M-HCDR3
artificial
HRNFGNSYLSWFAY

549
E2M-LCDR1
artificial
RSSTGAVTSGYYPN

550
E2M-LCDR2
artificial
ATDMRPS

551
E2M-LCDR3
artificial
ALWYSNRWV

552
E2M-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

553
E2M-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

554
E2M_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

555
E2M_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

556
E2M_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

557
E2M_HC_A89L-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

558
E2M_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

559
E2M_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

560
E2M_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

561
E2M_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

562
E2M_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

563
E2M_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

564
E2M_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46K_G141S-

QGTLVTVSS

VH

565
E2M_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

6Q4K_G141S-

VL

566
E2M_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

567
E2M_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

568
E2M_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

G141S-VH

QGTLVTVSS

569
E2M_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

570
E2M_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

571
E2M_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

572
E2M_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

573
E2M_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWFQQKPGQAPRGLIGATDMRPS

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

574
E2M_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

575
E2M_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWYQQKPGQAPRGLIGATDMRPS

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

576
E2M_HC_M41F_
artificial
GYAFN

A89V-

HCDR1

577
E2M_HC_M41F_
artificial
RIRSKYNNYATYYADSVKE

A89V-

HCDR2

578
E2M_HC_M41F_
artificial
HRNFGNSYLSWFAY

A89V-HCDR3

579
E2M_HC_M41F_
artificial
RSSTGAVTSGYYPN

A89V-LCDR1

580
E2M_HC_M41F_
artificial
ATDMRPS

A89V-LCDR2

581
E2M_HC_M41F_
artificial
ALWYSNRWV

A89V-

LCDR3

582
E2M_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

583
E2M_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

584
E2M_HC_M41I
artificial
GYAIN

-HCDR1

585
E2M_HC_M41I
artificial
RIRSKYNNYATYYADSVKE

-HCDR2

586
E2M_HC_M41I
artificial
HRNFGNSYLSWFAY

-HCDR3

587
E2M_HC_M41I
artificial
RSSTGAVTSGYYPN

-LCDR1

588
E2M_HC_M41I
artificial
ATDMRPS

-LCDR2

589
E2M_HC_M41I
artificial
ALWYSNRWV

-LCDR3

590
E2M_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

591
E2M_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

592
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKERFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

593
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

594
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENGYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

595
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

596
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

L21I_Q46K_

QGTLVTVSS

1G14S-VH

597
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

598
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

6Q4K-VH

QGTLVTVSS

599
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

600
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

601
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWFQKKPGQAPRGLIGATDMRPS

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

FV44-VL

602
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46K_G141S-

QGTLVTVSS

VH

603
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

604
E2M_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

605
E2M_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

606
E2M_HC_M41V
artificial
GYAVN

-HCDR1

607
E2M_HC_M41V
artificial
RIRSKYNNYATYYADSVKE

-HCDR2

608
E2M_HC_M41V
artificial
HRNFGNSYLSWFAY

-HCDR3

609
E2M_HC_M41V
artificial
RSSTGAVTSGYYPN

-LCDR1

610
E2M_HC_M41V
artificial
ATDMRPS

-LCDR2

611
E2M_HC_M41V
artificial
ALWYSNRWV

-LCDR3

612
E2M_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

613
E2M_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

614
E2M_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

615
E2M_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

616
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46K_G141S-

QGTLVTVSS

VH

617
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

6Q4K_G141S-

VL

618
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46R_G141S-

QGTLVTVSS

VH

619
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

620
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

621
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

622
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

G141S-VH

QGTLVTVSS

623
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

624
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

625
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

626
E2M_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

4G11S-VH

QGTLVTVSS

627
E2M_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

628
E2M_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

629
E2M_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

630
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46K_G141S-

QGTLVTVSS

VH

631
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

632
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

Q46R_G141S-

QGTLVTVSS

VH

633
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

634
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

635
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

636
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

G141S-VH

QGTLVTVSS

637
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

638
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

VH

QGTLVTVSS

639
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

640
E2M_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

G141S-VH

QGTLVTVSS

641
E2M_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQRKPGQAPRGLIGATDMRPS

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

642
E2M_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

643
E2M_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

644
E2M_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

645
E2M_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

646
E2M_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHRNFGNSYLSWFAYWG

QGTLVTVSS

647
E2M_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

648
E2M_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHRNFGNSYLSWFAYWG

QGTLVTVSS

649
E2M_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

650
E2M_I2E-
artificial
GYAIN

HCDR1

651
E2M_I2E-
artificial
RIRSKYNNYATYYADAVKE

HCDR2

652
E2M_I2E-
artificial
ARNFGSSYLSWFAY

HCDR3

653
E2M_I2E-
artificial
RSSTGAVTSGYYPN

LCDR1

654
E2M_I2E-
artificial
ATDMRPS

LCDR2

655
E2M_I2E-
artificial
ALWYSNRWV

LCDR3

656
E2M_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKERFTISRDDSKNTVYLQMNNLKTEDTAVYYCARARNFGSSYLSWFAYWG

QGTLVTVSS

657
E2M_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

658
E2M_I2K-
artificial
GYAMN

HCDR1

659
E2M_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

660
E2M_I2K-
artificial
NENIGTSYLSWFAY

HCDR3

661
E2M_I2K-
artificial
RSSTGAVTSGYYPN

LCDR1

662
E2M_I2K-
artificial
ATDMRPS

LCDR2

663
E2M_I2K-
artificial
ALWYSNRWV

LCDR3

664
E2M_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYLSWFAYWG

QGTLVTVSS

665
E2M_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

666
E2M_I2L-
artificial
GYAMN

HCDR1

667
E2M_I2L-
artificial
RIRSKYNNYATYYAEAVKE

HCDR2

668
E2M_I2L-
artificial
ARNFGSSYLSWFAY

HCDR3

669
E2M_I2L-
artificial
RSSTGAVTSGYYPN

LCDR1

670
E2M_I2L-
artificial
ATDMRPS

LCDR2

671
E2M_I2L-
artificial
ALYYSNRWV

LCDR3

672
E2M_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKERFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRARNFGSSYLSWFAYWG

QGTLVTVSS

673
E2M_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWIQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

674
E2M_I2M-
artificial
GYAMN

HCDR1

675
E2M_I2M-
artificial
RIRSKYNNYATYYADAVKE

HCDR2

676
E2M_I2M-
artificial
ARNFGTSYLSWFAY

HCDR3

677
E2M_I2M-
artificial
RSSTGAVTSGYYPN

LCDR1

678
E2M_I2M-
artificial
ATDMRPS

LCDR2

679
E2M_I2M-
artificial
ALWYSNRWV

LCDR3

680
E2M_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKERFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRARNFGTSYLSWFAYWG

QGTLVTVSS

681
E2M_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

682
E2M_I2M2-
artificial
GYAIN

HCDR1

683
E2M_I2M2-
artificial
RIRSKYNNYATYYADAVKE

HCDR2

684
E2M_I2M2-
artificial
NANFGTSYLSFFAY

HCDR3

685
E2M_I2M2-
artificial
RSSTGAVTSGYYPN

LCDR1

686
E2M_I2M2-
artificial
ATDMRPS

LCDR2

687
E2M_I2M2-
artificial
ALWYSNRWV

LCDR3

688
E2M_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENGYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYLSYFAYWG

QGTLVTVSS

689
E2M_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

690
E2M_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

691
E2M_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

692
E2M_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

693
E2M_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

694
E2M_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

695
E2M_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

696
E2M_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

697
E2M_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

698
E2M_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

699
E2M_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQEKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

700
E2M_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

701
E2M_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQKKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

702
E2M_LC_A107L-
artificial
GYAMN

HCDR1

703
E2M_LC_A107L-
artificial
RIRSKYNNYATYYADSVKE

HCDR2

704
E2M_LC_A107L-
artificial
HRNFGNSYLSWFAY

HCDR3

705
E2M_LC_A107L-
artificial
RSSTGAVTSGYYPN

LCDR1

706
E2M_LC_A107L-
artificial
ATDMRPS

LCDR2

707
E2M_LC_A107L-
artificial
LLWYSNRWV

LCDR3

708
E2M_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

709
E2M_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

710
E2M_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

711
E2M_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWIQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

712
E2M_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

713
E2M_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWLQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

714
E2M_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNGYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

715
E2M_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWMQQKPGQAPRGLIGATDMRPS

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

716
E2M_LC_W109Y-
artificial
GYAMN

HCDR1

717
E2M_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKE

HCDR2

718
E2M_LC_W109Y-
artificial
HRNFGNSYLSWFAY

HCDR3

719
E2M_LC_W109Y-
artificial
RSSTGAVTSGYYPN

LCDR1

720
E2M_LC_W109Y-
artificial
ATDMRPS

LCDR2

721
E2M_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

722
E2M_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENGYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKERFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHRNFGNSYLSWFAYWG

QGTLVTVSS

723
E2M_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTSGYYPNWVQQKPGQAPRGLIGATDMRPS

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

724
F12Q-
artificial
SYAMN

HCDR1

725
F12Q-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

726
F12Q-
artificial
HGNFGNSYVSWWAY

HCDR3

727
F12Q-
artificial
GSSTGAVTSGNYPN

LCDR1

728
F12Q
artificial
GTKFLAP

LCDR2

729
F12Q
artificial
VLWYSNRWV

LCDR3

730
F12Q-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

731
F12Q-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

732
F12Q_HC_A89I-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

733
F12Q_HC_A89I-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

734
F12Q_HC_A89L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

735
F12Q_HC_A89L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

736
F12Q_HC_A89T-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

737
F12Q_HC_A89T-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

738
F12Q_HC_A89V-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

739
F12Q_HC_A89V-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

740
F12Q_HC_L52M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

741
F12Q_HC_L52M-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

742
F12Q_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

743
F12Q_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

744
F12Q_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

745
F12Q_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

746
F12Q_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

G141S-VH

QGTLVTVSS

747
F12Q_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

748
F12Q_HC_L52V-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGVEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

749
F12Q_HC_L52V-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

750
F12Q_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

751
F12Q_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

752
F12Q_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

753
F12Q_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

754
F12Q_HC_M41F_
artificial
SYAFN

A89V-

HCDR1

755
F12Q_HC_M41F_
artificial
RIRSKYNNYATYYADSVKG

A89V-HCDR2

756
F12Q_HC_M41F_
artificial
HGNFGNSYVSWWAY

A89V-HCDR3

757
F12Q_HC_M41F_
artificial
GSSTGAVTSGNYPN

A89V-

LCDR1

758
F12Q_HC_M41F_
artificial
GTKFLAP

A89V-

LCDR2

759
F12Q_HC_M41F_
artificial
VLWYSNRWV

A89V-

LCDR3

760
F12Q_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

761
F12Q_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

762
F12Q_HC_M41I-
artificial
SYAIN

HCDR1

763
F12Q_HC_M41I-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

764
F12Q_HC_M41I-
artificial
HGNFGNSYVSWWAY

HCDR3

765
F12Q_HC_M41I-
artificial
GSSTGAVTSGNYPN

LCDR1

766
F12Q_HC_M41I-
artificial
GTKFLAP

LCDR2

767
F12Q_HC_M41I-
artificial
VLWYSNRWV

LCDR3

768
F12Q_HC_M41I-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

769
F12Q_HC_M41I-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

770
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

771
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

772
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

773
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

774
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

L21I_Q46K_

QGTLVTVSS

4G11S-VH

775
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

776
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46K-VH

QGTLVTVSS

777
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

Q46K-VL

778
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

779
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

780
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

781
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

782
F12Q_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

783
F12Q_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

784
F12Q_HC_M41V-
artificial
SYAVN

HCDR1

785
F12Q_HC_M41V-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

786
F12Q_HC_M41V-
artificial
HGNFGNSYVSWWAY

HCDR3

787
F12Q_HC_M41V-
artificial
GSSTGAVTSGNYPN

LCDR1

788
F12Q_HC_M41V-
artificial
GTKFLAP

LCDR2

789
F12Q_HC_M41V-
artificial
VLWYSNRWV

LCDR3

790
F12Q_HC_M41V-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAVNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

791
F12Q_HC_M41V-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

792
F12Q_HC_Q46D-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

793
F12Q_HC_Q46D-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

794
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

795
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L211_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

796
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

797
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

798
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

799
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

800
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

G141S-VH

QGTLVTVSS

801
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

802
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

803
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

804
F12Q_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

G141S-VH

QGTLVTVSS

805
F12Q_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

806
F12Q_HC_Q46E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

807
F12Q_HC_Q46E-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

808
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

809
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

810
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

811
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

812
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

813
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

814
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

G141S-VH

QGTLVTVSS

815
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

816
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

817
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

818
F12Q_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

G141S-VH

QGTLVTVSS

819
F12Q_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

820
F12Q_HC_Q46K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRKAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

821
F12Q_HC_Q46K-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

822
F12Q_HC_Q46R-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRRAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

823
F12Q_HC_Q46R-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

824
F12Q_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYVSWWAYWG

QGTLVTVSS

825
F12Q_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

826
F12Q_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYVSWWAYWG

QGTLVTVSS

827
F12Q_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

828
F12Q_HC_W136F-
artificial
SYAMN

HCDR1

829
F12Q_HC_W136F-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

830
F12Q_HC_W136F-
artificial
HGNFGNSYVSWFAY

HCDR3

831
F12Q_HC_W136F-
artificial
GSSTGAVTSGNYPN

LCDR1

832
F12Q_HC_W136F-
artificial
GTKFLAP

LCDR2

833
F12Q_HC_W136F-
artificial
VLWYSNRWV

LCDR3

834
F12Q_HC_W136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWG

QGTLVTVSS

835
F12Q_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

836
F12Q_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWG

-VH

QGTLVTVSS

837
F12Q_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

-VL

838
F12Q_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWFAYWG

-VH

QGTLVTVSS

839
F12Q_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

-VL

840
F12Q_I2E-
artificial
SYAIN

HCDR1

841
F12Q_I2E-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

842
F12Q_I2E-
artificial
AGNFGSSYVSWWAY

HCDR3

843
F12Q_I2E-
artificial
GSSTGAVTSGNYPN

LCDR1

844
F12Q_I2E-
artificial
GTKFLAP

LCDR2

845
F12Q_I2E-
artificial
VLWYSNRWV

LCDR3

846
F12Q_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYVSWWAYWG

QGTLVTVSS

847
F12Q_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

848
F12Q_I2K-
artificial
SYAMN

HCDR1

849
F12Q_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

850
F12Q_I2K-
artificial
NENIGTSYVSWWAY

HCDR3

851
F12Q_I2K-
artificial
GSSTGAVTSGNYPN

LCDR1

852
F12Q_I2K-
artificial
GTKFLAP

LCDR2

853
F12Q_I2K-
artificial
VLWYSNRWV

LCDR3

854
F12Q_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYVSWWAYWG

QGTLVTVSS

855
F12Q_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

856
F12Q_I2L-
artificial
SYAMN

HCDR1

857
F12Q_I2L-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

858
F12Q_I2L-
artificial
AGNFGSSYVSWFAY

HCDR3

859
F12Q_I2L-
artificial
GSSTGAVTSGNYPN

LCDR1

860
F12Q_I2L-
artificial
GTKFLAP

LCDR2

861
F12Q_I2L-
artificial
VLYYSNRWV

LCDR3

862
F12Q_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYVSWFAYWG

QGTLVTVSS

863
F12Q_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

864
F12Q_I2M-
artificial
SYAMN

HCDR1

865
F12Q_I2M-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

866
F12Q_I2M-
artificial
AGNFGTSYVSWWAY

HCDR3

867
F12Q_I2M-
artificial
GSSTGAVTSGNYPN

LCDR1

868
F12Q_I2M-
artificial
GTKFLAP

LCDR2

869
F12Q_I2M-
artificial
VLWYSNRWV

LCDR3

870
F12Q_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYVSWWAYWG

QGTLVTVSS

871
F12Q_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

872
F12Q_I2M2-
artificial
SYAIN

HCDR1

873
F12Q_I2M2-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

874
F12Q_I2M2-
artificial
NANFGTSYVSWFAY

HCDR3

875
F12Q_I2M2-
artificial
GSSTGAVTSGNYPN

LCDR1

876
F12Q_I2M2-
artificial
GTKFLAP

LCDR2

877
F12Q_I2M2-
artificial
VLWYSNRWV

LCDR3

878
F12Q_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYVSWFAYWG

QGTLVTVSS

879
F12Q_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

880
F12Q_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

881
F12Q_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

882
F12Q_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

VH

QGTLVTVSS

883
F12Q_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

VL

884
F12Q_LC_L83E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

885
F12Q_LC_L83E-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

886
F12Q_LC_L83S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

887
F12Q_LC_L83S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

888
F12Q_LC_Q46E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

889
F12Q_LC_Q46E-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQEKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

890
F12Q_LC_Q46K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

891
F12Q_LC_Q46K-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

892
F12Q_LC_V107A-
artificial
SYAMN

HCDR1

893
F12Q_LC_V107A-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

894
F12Q_LC_V107A-
artificial
HGNFGNSYVSWWAY

HCDR3

895
F12Q_LC_V107A-
artificial
GSSTGAVTSGNYPN

LCDR1

896
F12Q_LC_V107A-
artificial
GTKFLAP

LCDR2

897
F12Q_LC_V107A-
artificial
ALWYSNRWV

LCDR3

898
F12Q_LC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

899
F12Q_LC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

900
F12Q_LC_V107L-
artificial
SYAMN

HCDR1

901
F12Q_LC_V107L-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

902
F12Q_LC_V107L-
artificial
HGNFGNSYVSWWAY

HCDR3

903
F12Q_LC_V107L-
artificial
GSSTGAVTSGNYPN

LCDR1

904
F12Q_LC_V107L-
artificial
GTKFLAP

LCDR2

905
F12Q_LC_V107L-
artificial
LLWYSNRWV

LCDR3

906
F12Q_LC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

907
F12Q_LC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

908
F12Q_LC_V44I-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

909
F12Q_LC_V44I-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWIQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

910
F12Q_LC_V44L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

911
F12Q_LC_V44L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWLQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

912
F12Q_LC_V44M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

913
F12Q_LC_V44M-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWMQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

914
F12Q_LC_W109Y-
artificial
SYAMN

HCDR1

915
F12Q_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

916
F12Q_LC_W109Y-
artificial
HGNFGNSYVSWWAY

HCDR3

917
F12Q_LC_W109Y-
artificial
GSSTGAVTSGNYPN

LCDR1

918
F12Q_LC_W109Y-
artificial
GTKFLAP

LCDR2

919
F12Q_LC_W109Y-
artificial
VLYYSNRWV

LCDR3

920
F12Q_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSWWAYWG

QGTLVTVSS

921
F12Q_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGGGTKLTVL

922
F6A-HCDR1
artificial
IYAMN

923
F6A-HCDR2
artificial
RIRSKYNNYATYYADSVKS

924
F6A-HCDR3
artificial
HGNFGNSYVSFFAY

925
F6A-LCDR1
artificial
GSSTGAVTSGYYPN

926
F6A-LCDR2
artificial
GTKFLAP

927
F6A-LCDR3
artificial
ALWYSNRWV

928
F6A-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

929
F6A-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

930
F6A_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

931
F6A_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

932
F6A_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

933
F6A_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

934
F6A_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

935
F6A_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

936
F6A_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

937
F6A_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

938
F6A_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

939
F6A_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

940
F6A_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46K_G141S-

QGTLVTVSS

VH

941
F6A_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

942
F6A_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

943
F6A_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

944
F6A_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

G141S-VH

QGTLVTVSS

945
F6A_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

946
F6A_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

947
F6A_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

948
F6A_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

949
F6A_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

950
F6A_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

951
F6A_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

952
F6A_HC_M41F_
artificial
IYAFN

A89V-

HCDR1

953
F6A_HC_M41F_
artificial
RIRSKYNNYATYYADSVKS

A89V-

HCDR2

954
F6A_HC_M41F_
artificial
HGNFGNSYVSFFAY

A89V-

HCDR3

955
F6A_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-

LCDR1

956
F6A_HC_M41F_
artificial
GTKFLAP

A89V-LCDR2

957
F6A_HC_M41F_
artificial
ALWYSNRWV

A89V-LCDR3

958
F6A_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

959
F6A_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

960
F6A_HC_M41I
artificial
IYAIN

-HCDR1

961
F6A_HC_M41I
artificial
RIRSKYNNYATYYADSVKS

-HCDR2

962
F6A_HC_M41I
artificial
HGNFGNSYVSFFAY

-HCDR3

963
F6A_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

964
F6A_HC_M41I
artificial
GTKFLAP

-LCDR2

965
F6A_HC_M41I
artificial
ALWYSNRWV

-LCDR3

966
F6A_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

967
F6A_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

968
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

969
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

970
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

971
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

972
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

973
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

974
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46K-VH

QGTLVTVSS

975
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

976
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

977
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

978
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46K_G141S-

QGTLVTVSS

VH

979
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

980
F6A_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

981
F6A_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

982
F6A_HC_M41V
artificial
IYAVN

-HCDR1

983
F6A_HC_M41V
artificial
RIRSKYNNYATYYADSVKS

-HCDR2

984
F6A_HC_M41V
artificial
HGNFGNSYVSFFAY

-HCDR3

985
F6A_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

986
F6A_HC_M41V
artificial
GTKFLAP

-LCDR2

987
F6A_HC_M41V
artificial
ALWYSNRWV

-LCDR3

988
F6A_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

989
F6A_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

990
F6A_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

991
F6A_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

992
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46K_G141S-

QGTLVTVSS

VH

993
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

994
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46R_G141S-

QGTLVTVSS

VH

995
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

996
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

997
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

998
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

G141S-VH

QGTLVTVSS

999
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1000
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

1001
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1002
F6A_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

G141S-VH

QGTLVTVSS

1003
F6A_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1004
F6A_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1005
F6A_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1006
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46K_G141S-

QGTLVTVSS

VH

1007
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1008
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

Q46R_G141S-

QGTLVTVSS

VH

1009
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1010
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

1011
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1012
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

G141S-VH

QGTLVTVSS

1013
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1014
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

VH

QGTLVTVSS

1015
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1016
F6A_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

G141S-VH

QGTLVTVSS

1017
F6A_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1018
F6A_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1019
F6A_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1020
F6A_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1021
F6A_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1022
F6A_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYVSFFAYWG

QGTLVTVSS

1023
F6A_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1024
F6A_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYVSFFAYWG

QGTLVTVSS

1025
F6A_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1026
F6A_I2E-
artificial
IYAIN

HCDR1

1027
F6A_I2E-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

1028
F6A_I2E-
artificial
AGNFGSSYVSFFAY

HCDR3

1029
F6A_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

1030
F6A_I2E-
artificial
GTKFLAP

LCDR2

1031
F6A_I2E-
artificial
ALWYSNRWV

LCDR3

1032
F6A_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYVSFFAYWG

QGTLVTVSS

1033
F6A_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1034
F6A_I2K-
artificial
IYAMN

HCDR1

1035
F6A_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

1036
F6A_I2K-
artificial
NENIGTSYVSFFAY

HCDR3

1037
F6A_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

1038
F6A_I2K-
artificial
GTKFLAP

LCDR2

1039
F6A_I2K-
artificial
ALWYSNRWV

LCDR3

1040
F6A_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYVSFFAYWG

QGTLVTVSS

1041
F6A_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1042
F6A_I2L-
artificial
IYAMN

HCDR1

1043
F6A_I2L-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

1044
F6A_I2L-
artificial
AGNFGSSYVSFFAY

HCDR3

1045
F6A_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

1046
F6A_I2L-
artificial
GTKFLAP

LCDR2

1047
F6A_I2L-
artificial
ALYYSNRWV

LCDR3

1048
F6A_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYVSFFAYWG

QGTLVTVSS

1049
F6A_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

1050
F6A_I2M-
artificial
IYAMN

HCDR1

1051
F6A_I2M-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

1052
F6A_I2M-
artificial
AGNFGTSYVSFFAY

HCDR3

1053
F6A_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

1054
F6A_I2M-
artificial
GTKFLAP

LCDR2

1055
F6A_I2M-
artificial
ALWYSNRWV

LCDR3

1056
F6A_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYVSFFAYWG

QGTLVTVSS

1057
F6A_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1058
F6A_I2M2-
artificial
IYAIN

HCDR1

1059
F6A_I2M2-
artificial
RIRSKYNNYATYYADAVKS

HCDR2

1060
F6A_I2M2-
artificial
NANFGTSYVSFFAY

HCDR3

1061
F6A_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

1062
F6A_I2M2-
artificial
GTKFLAP

LCDR2

1063
F6A_I2M2-
artificial
ALWYSNRWV

LCDR3

1064
F6A_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYVSFFAYWG

QGTLVTVSS

1065
F6A_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1066
F6A_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1067
F6A_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1068
F6A_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1069
F6A_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1070
F6A_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1071
F6A_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1072
F6A_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1073
F6A_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1074
F6A_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1075
F6A_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1076
F6A_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1077
F6A_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1078
F6A_LC_A107L-
artificial
IYAMN

HCDR1

1079
F6A_LC_A107L-
artificial
RIRSKYNNYATYYADSVKS

HCDR2

1080
F6A_LC_A107L-
artificial
HGNFGNSYVSFFAY

HCDR3

1081
F6A_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

1082
F6A_LC_A107L-
artificial
GTKFLAP

LCDR2

1083
F6A_LC_A107L-
artificial
LLWYSNRWV

LCDR3

1084
F6A_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1085
F6A_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1086
F6A_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1087
F6A_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1088
F6A_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1089
F6A_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1090
F6A_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1091
F6A_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1092
F6A_LC_W109Y-
artificial
IYAMN

HCDR1

1093
F6A_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKS

HCDR2

1094
F6A_LC_W109Y-
artificial
HGNFGNSYVSFFAY

HCDR3

1095
F6A_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

1096
F6A_LC_W109Y-
artificial
GTKFLAP

LCDR2

1097
F6A_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

1098
F6A_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNIYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKSRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYVSFFAYWG

QGTLVTVSS

1099
F6A_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

1100
F7O-HCDR1
artificial
VYAMN

1101
F7O-HCDR2
artificial
RIRSKYNNYATYYADSVKK

1102
F7O-HCDR3
artificial
HGNFGNSYISWWAY

1103
F7O-LCDR1
artificial
GSSTGAVTSGYYPN

1104
F7O-LCDR2
artificial
GTKFLAP

1105
F7O-LCDR3
artificial
ALWYSNRWV

1106
F7O-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1107
F7O-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1108
F7O_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1109
F7O_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1110
F7O_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1111
F7O_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1112
F7O_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1113
F7O_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1114
F7O_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1115
F7O_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1116
F7O_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1117
F7O_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1118
F7O_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1119
F7O_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1120
F7O_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1121
F7O_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1122
F7O_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

G141S-VH

QGTLVTVSS

1123
F7O_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1124
F7O_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1125
F7O_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1126
F7O_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1127
F7O_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1128
F7O_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1129
F7O_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1130
F7O_HC_M41F_
artificial
VYAFN

A89V-

HCDR1

1131
F7O_HC_M41F_
artificial
RIRSKYNNYATYYADSVKK

A89V-

HCDR2

1132
F7O_HC_M41F_
artificial
HGNFGNSYISWWAY

A89V-HCDR3

1133
F7O_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-LCDR1

1134
F7O_HC_M41F_
artificial
GTKFLAP

A89V-LCDR2

1135
F7O_HC_M41F_
artificial
ALWYSNRWV

A89V-LCDR3

1136
F7O_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1137
F7O_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1138
F7O_HC_M41I
artificial
VYAIN

-HCDR1

1139
F7O_HC_M41I-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

1140
F7O_HC_M41I
artificial
HGNFGNSYISWWAY

-HCDR3

1141
F7O_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

1142
F7O_HC_M41I
artificial
GTKFLAP

-LCDR2

1143
F7O_HC_M41I
artificial
ALWYSNRWV

-LCDR3

1144
F7O_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1145
F7O_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1146
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1147
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1148
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1149
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1150
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

1151
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

1152
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46K-VH

QGTLVTVSS

1153
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

1154
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

1155
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

1156
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1157
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1158
F7O_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

1159
F7O_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

1160
F7O_HC_M41V
artificial
VYAVN

-HCDR1

1161
F7O_HC_M41V
artificial
RIRSKYNNYATYYADSVKK

-HCDR2

1162
F7O_HC_M41V
artificial
HGNFGNSYISWWAY

-HCDR3

1163
F7O_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

1164
F7O_HC_M41V
artificial
GTKFLAP

-LCDR2

1165
F7O_HC_M41V
artificial
ALWYSNRWV

-LCDR3

1166
F7O_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1167
F7O_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1168
F7O_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1169
F7O_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1170
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1171
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1172
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1173
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1174
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1175
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1176
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_G1

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

41S-VH

QGTLVTVSS

1177
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1178
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1179
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1180
F7O_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

G141S-VH

QGTLVTVSS

1181
F7O_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1182
F7O_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1183
F7O_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1184
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1185
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1186
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1187
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1188
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1189
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1190
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

G141S-VH

QGTLVTVSS

1191
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1192
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

VH

QGTLVTVSS

1193
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1194
F7O_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

G141S-VH

QGTLVTVSS

1195
F7O_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1196
F7O_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1197
F7O_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1198
F7O_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1199
F7O_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1200
F7O_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYISWWAYWG

QGTLVTVSS

1201
F7O_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1202
F7O_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYISWWAYWG

QGTLVTVSS

1203
F7O_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1204
F7O_HC_W136F-
artificial
VYAMN

HCDR1

1205
F7O_HC_W136F-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

1206
F7O_HC_W136F-
artificial
HGNFGNSYISWFAY

HCDR3

1207
F7O_HC_W136F-
artificial
GSSTGAVTSGYYPN

LCDR1

1208
F7O_HC_W136F-
artificial
GTKFLAP

LCDR2

1209
F7O_HC_W136F-
artificial
ALWYSNRWV

LCDR3

1210
F7O_HC_W136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWFAYWG

QGTLVTVSS

1211
F7O_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1212
F7O_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWFAYWG

VH

QGTLVTVSS

1213
F7O_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1214
F7O_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWFAYWG

VH

QGTLVTVSS

1215
F7O_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1216
F7O_I2E-
artificial
VYAIN

HCDR1

1217
F7O_I2E-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

1218
F7O_I2E-
artificial
AGNFGSSYISWWAY

HCDR3

1219
F7O_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

1220
F7O_I2E-
artificial
GTKFLAP

LCDR2

1221
F7O_I2E-
artificial
ALWYSNRWV

LCDR3

1222
F7O_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISWWAYWG

QGTLVTVSS

1223
F7O_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1224
F7O_I2K-
artificial
VYAMN

HCDR1

1225
F7O_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

1226
F7O_I2K-
artificial
NENIGTSYISWWAY

HCDR3

1227
F7O_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

1228
F7O_I2K-
artificial
GTKFLAP

LCDR2

1229
F7O_I2K-
artificial
ALWYSNRWV

LCDR3

1230
F7O_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISWWAYWG

QGTLVTVSS

1231
F7O_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1232
F7O_I2L-
artificial
VYAMN

HCDR1

1233
F7O_I2L-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

1234
F7O_I2L-
artificial
AGNFGSSYISWFAY

HCDR3

1235
F7O_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

1236
F7O_I2L-
artificial
GTKFLAP

LCDR2

1237
F7O_I2L-
artificial
ALYYSNRWV

LCDR3

1238
F7O_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYISWFAYWG

QGTLVTVSS

1239
F7O_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

1240
F7O_I2M-
artificial
VYAMN

HCDR1

1241
F7O_I2M-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

1242
F7O_I2M-
artificial
AGNFGTSYISWWAY

HCDR3

1243
F7O_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

1244
F7O_I2M-
artificial
GTKFLAP

LCDR2

1245
F7O_I2M-
artificial
ALWYSNRWV

LCDR3

1246
F7O_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISWWAYWG

QGTLVTVSS

1247
F7O_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1248
F7O_I2M2-
artificial
VYAIN

HCDR1

1249
F7O_I2M2-
artificial
RIRSKYNNYATYYADAVKK

HCDR2

1250
F7O_I2M2-
artificial
NANFGTSYISWFAY

HCDR3

1251
F7O_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

1252
F7O_I2M2-
artificial
GTKFLAP

LCDR2

1253
F7O_I2M2-
artificial
ALWYSNRWV

LCDR3

1254
F7O_I2M2_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISWFAYWG

QGTLVTVSS

1255
F7O_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1256
F7O_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1257
F7O_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1258
F7O_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1259
F7O_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1260
F7O_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1261
F7O_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1262
F7O_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1263
F7O_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1264
F7O_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1265
F7O_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1266
F7O_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1267
F7O_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1268
F7O_LC_A107L-
artificial
VYAMN

HCDR1

1269
F7O_LC_A107L-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

1270
F7O_LC_A107L-
artificial
HGNFGNSYISWWAY

HCDR3

1271
F7O_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

1272
F7O_LC_A107L-
artificial
GTKFLAP

LCDR2

1273
F7O_LC_A107L-
artificial
LLWYSNRWV

LCDR3

1274
F7O_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1275
F7O_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1276
F7O_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1277
F7O_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1278
F7O_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1279
F7O_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1280
F7O_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1281
F7O_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1282
F7O_LC_W109Y-
artificial
VYAMN

HCDR1

1283
F7O_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKK

HCDR2

1284
F7O_LC_W109Y-
artificial
HGNFGNSYISWWAY

HCDR3

1285
F7O_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

1286
F7O_LC_W109Y-
artificial
GTKFLAP

LCDR2

1287
F7O_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

1288
F7O_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNVYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKKRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISWWAYWG

QGTLVTVSS

1289
F7O_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

1290
G4H-HCDR1
artificial
RYAMN

1291
G4H-HCDR2
artificial
RIRSKYNNYATYYADSVKG

1292
G4H-HCDR3
artificial
HGNFGNSYLSYFAY

1293
G4H-LCDR1
artificial
GSSTGAVTSGYYPN

1294
G4H-LCDR2
artificial
GTKFLAP

1295
G4H-LCDR3
artificial
ALWYSNRWV

1296
G4H-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1297
G4H-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1298
G4H_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1299
G4H_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1300
G4H_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1301
G4H_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1302
G4H_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1303
G4H_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1304
G4H_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1305
G4H_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1306
G4H_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1307
G4H_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1308
G4H_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46K_G141S-

QGTLVTVSS

VH

1309
G4H_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1310
G4H_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1311
G4H_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1312
G4H_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

G141S-VH

QGTLVTVSS

1313
G4H_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1314
G4H_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1315
G4H_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1316
G4H_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1317
G4H_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1318
G4H_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1319
G4H_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1320
G4H_HC_M41F_
artificial
RYAFN

A89V-

HCDR1

1321
G4H_HC_M41F_
artificial
RIRSKYNNYATYYADSVKG

A89V-

HCDR2

1322
G4H_HC_M41F_
artificial
HGNFGNSYLSYFAY

A89V-HCDR3

1323
G4H_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-LCDR1

1324
G4H_HC_M41F_
artificial
GTKFLAP

A89V-LCDR2

1325
G4H_HC_M41F_
artificial
ALWYSNRWV

A89V-LCDR3

1326
G4H_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1327
G4H_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1328
G4H_HC_M41I
artificial
RYAIN

-HCDR1

1329
G4H_HC_M41I
artificial
RIRSKYNNYATYYADSVKG

-HCDR2

1330
G4H_HC_M41I
artificial
HGNFGNSYLSYFAY

-HCDR3

1331
G4H_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

1332
G4H_HC_M41I
artificial
GTKFLAP

-LCDR2

1333
G4H_HC_M41I
artificial
ALWYSNRWV

-LCDR3

1334
G4H_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1335
G4H_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1336
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1337
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1338
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1339
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1340
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

1341
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

1G14S-VL

1342
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46K-VH

QGTLVTVSS

1343
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

1344
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

1345
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

1346
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46K_G141S-

QGTLVTVSS

VH

1347
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1348
G4H_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

1349
G4H_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

1350
G4H_HC_M41V
artificial
RYAVN

-HCDR1

1351
G4H_HC_M41V
artificial
RIRSKYNNYATYYADSVKG

-HCDR2

1352
G4H_HC_M41V
artificial
HGNFGNSYLSYFAY

-HCDR3

1353
G4H_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

1354
G4H_HC_M41V
artificial
GTKFLAP

-LCDR2

1355
G4H_HC_M41V
artificial
ALWYSNRWV

-LCDR3

1356
G4H_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1357
G4H_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1358
G4H_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1359
G4H_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1360
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46K_G141S-

QGTLVTVSS

VH

1361
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1362
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46R_G141S-

QGTLVTVSS

VH

1363
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1364
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1365
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1366
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

G141S-VH

QGTLVTVSS

1367
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1368
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1369
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1370
G4H_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

G141S-VH

QGTLVTVSS

1371
G4H_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1372
G4H_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1373
G4H_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1374
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

Q46K_G141S-

QGTLVTVSS

VH

1375
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1376
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

6Q4R_G141S-

QGTLVTVSS

VH

1377
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1378
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1379
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1380
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

4G11S-VH

QGTLVTVSS

1381
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1382
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

VH

QGTLVTVSS

1383
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1384
G4H_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

G141S-VH

QGTLVTVSS

1385
G4H_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1386
G4H_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1387
G4H_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1388
G4H_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1389
G4H_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1390
G4H_HC_V107
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

A-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYLSYFAYWG

QGTLVTVSS

1391
G4H_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1392
G4H_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYLSYFAYWG

QGTLVTVSS

1393
G4H_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1394
G4H_I2E-
artificial
RYAIN

HCDR1

1395
G4H_I2E-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1396
G4H_I2E-
artificial
AGNFGSSYLSYFAY

HCDR3

1397
G4H_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

1398
G4H_I2E-
artificial
GTKFLAP

LCDR2

1399
G4H_I2E-
artificial
ALWYSNRWV

LCDR3

1400
G4H_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYLSYFAYWG

QGTLVTVSS

1401
G4H_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1402
G4H_I2K-
artificial
RYAMN

HCDR1

1403
G4H_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

1404
G4H_I2K-
artificial
NENIGTSYLSYFAY

HCDR3

1405
G4H_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

1406
G4H_I2K-
artificial
GTKFLAP

LCDR2

1407
G4H_I2K-
artificial
ALWYSNRWV

LCDR3

1408
G4H_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYLSYFAYWG

QGTLVTVSS

1409
G4H_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1410
G4H_I2L-
artificial
RYAMN

HCDR1

1411
G4H_I2L-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1412
G4H_I2L-
artificial
AGNFGSSYLSYFAY

HCDR3

1413
G4H_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

1414
G4H_I2L-
artificial
GTKFLAP

LCDR2

1415
G4H_I2L-
artificial
ALYYSNRWV

LCDR3

1416
G4H_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYLSYFAYWG

QGTLVTVSS

1417
G4H_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

1418
G4H_I2M-
artificial
RYAMN

HCDR1

1419
G4H_I2M-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1420
G4H_I2M-
artificial
AGNFGTSYLSYFAY

HCDR3

1421
G4H_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

1422
G4H_I2M-
artificial
GTKFLAP

LCDR2

1423
G4H_I2M-
artificial
ALWYSNRWV

LCDR3

1424
G4H_I2M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYLSYFAYWG

QGTLVTVSS

1425
G4H_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1426
G4H_I2M2-
artificial
RYAIN

HCDR1

1427
G4H_I2M2-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1428
G4H_I2M2-
artificial
NANFGTSYLSYFAY

HCDR3

1429
G4H_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

1430
G4H_I2M2-
artificial
GTKFLAP

LCDR2

1431
G4H_I2M2-
artificial
ALWYSNRWV

LCDR3

1432
G4H_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYLSYFAYWG

QGTLVTVSS

1433
G4H_I2M2
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1434
G4H_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1435
G4H_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1436
G4H_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1437
G4H_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1438
G4H_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1439
G4H_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1440
G4H_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1441
G4H_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1442
G4H_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1443
G4H_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1444
G4H_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1445
G4H_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1446
G4H_LC_A107L-
artificial
RYAMN

HCDR1

1447
G4H_LC_A107L-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

1448
G4H_LC_A107L-
artificial
HGNFGNSYLSYFAY

HCDR3

1449
G4H_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

1450
G4H_LC_A107L-
artificial
GTKFLAP

LCDR2

1451
G4H_LC_A107L-
artificial
LLWYSNRWV

LCDR3

1452
G4H_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1453
G4H_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1454
G4H_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1455
G4H_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1456
G4H_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1457
G4H_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1458
G4H_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1459
G4H_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1460
G4H_LC_W109Y-
artificial
RYAMN

HCDR1

1461
G4H_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

1462
G4H_LC_W109Y-
artificial
HGNFGNSYLSYFAY

HCDR3

1463
G4H_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

1464
G4H_LC_W109Y-
artificial
GTKFLAP

LCDR2

1465
G4H_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

1466
G4H_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNRYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSYFAYWG

QGTLVTVSS

1467
G4H_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

1468
H1E-HCDR1
artificial
SYAMN

1469
H1E-HCDR2
artificial
RIRSKYNNYATYYADSVKG

1470
H1E-HCDR3
artificial
HGNFGNSYLSFWAY

1471
H1E-LCDR1
artificial
GSSTGAVTSGYYPN

1472
H1E-LCDR2
artificial
GTKFLAP

1473
H1E-LCDR3
artificial
ALWYSNRWV

1474
H1E-VH
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1475
H1E-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1476
H1E_HC_A89I
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1477
H1E_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1478
H1E_HC_A89L
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1479
H1E_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1480
H1E_HC_A89T
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1481
H1E_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1482
H1E_HC_A89V
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1483
H1E_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1484
H1E_HC_L52M
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1485
H1E_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1486
H1E_HC_L52M_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1487
H1E_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1488
H1E_HC_L52M_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1489
H1E_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1490
H1E_HC_L52M_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

G141S-VH

QGTLVTVSS

1491
H1E_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1492
H1E_HC_L52V
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1493
H1E_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1494
H1E_HC_L52V_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1495
H1E_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1496
H1E_HC_L52V_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1497
H1E_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1498
H1E_HC_M41F_
artificial
SYAFN

A89V-

HCDR1

1499
H1E_HC_M41F_
artificial
RIRSKYNNYATYYADSVKG

A89V-

HCDR2

1500
H1E_HC_M41F_
artificial
HGNFGNSYLSFWAY

A89V-

HCDR3

1501
H1E_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-

LCDR1

1502
H1E_HC_M41F_
artificial
GTKFLAP

A89V-LCDR2

1503
H1E_HC_M41F_
artificial
ALWYSNRWV

A89V-

LCDR3

1504
H1E_HC_M41F_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1505
H1E_HC_M41F
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1506
H1E_HC_M41I
artificial
SYAIN

-HCDR1

1507
H1E_HC_M41I
artificial
RIRSKYNNYATYYADSVKG

-HCDR2

1508
H1E_HC_M41I
artificial
HGNFGNSYLSFWAY

-HCDR3

1509
H1E_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

1510
H1E_HC_M41I
artificial
GTKFLAP

-LCDR2

1511
H1E_HC_M41I
artificial
ALWYSNRWV

-LCDR3

1512
H1E_HC_M41I
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1513
H1E_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1514
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1515
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1516
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1517
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1518
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

1519
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

1520
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46K-VH

QGTLVTVSS

1521
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

1522
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

FV44-VH

1523
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

1524
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1525
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1526
H1E_HC_M41I_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

1527
H1E_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

1528
H1E_HC_M41V
artificial
SYAVN

-HCDR1

1529
H1E_HC_M41V
artificial
RIRSKYNNYATYYADSVKG

-HCDR2

1530
H1E_HC_M41V
artificial
HGNFGNSYLSFWAY

-HCDR3

1531
H1E_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

1532
H1E_HC_M41V
artificial
GTKFLAP

-LCDR2

1533
H1E_HC_M41V
artificial
ALWYSNRWV

-LCDR3

1534
H1E_HC_M41V
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1535
H1E_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1536
H1E_HC_Q46D
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1537
H1E_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1538
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1539
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1540
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1541
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1542
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1543
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1544
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

G141S-VH

QGTLVTVSS

1545
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1546
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1547
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1548
H1E_HC_Q46D_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

G141S-VH

QGTLVTVSS

1549
H1E_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1550
H1E_HC_Q46E
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1551
H1E_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1552
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1553
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1554
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1555
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1556
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1557
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1558
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

G141S-VH

QGTLVTVSS

1559
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1560
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

VH

QGTLVTVSS

1561
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1562
H1E_HC_Q46E_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

G141S-VH

QGTLVTVSS

1563
H1E_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1564
H1E_HC_Q46K
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1565
H1E_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1566
H1E_HC_Q46R
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1567
H1E_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1568
H1E_HC_V107A-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYLSFWAYWG

QGTLVTVSS

1569
H1E_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1570
H1E_HC_V107L-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYLSFWAYWG

QGTLVTVSS

1571
H1E_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1572
H1E_HC_W136F-
artificial
SYAMN

HCDR1

1573
H1E_HC_W136F-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

1574
H1E_HC_W136F-
artificial
HGNFGNSYLSFFAY

HCDR3

1575
H1E_HC_W136F-
artificial
GSSTGAVTSGYYPN

LCDR1

1576
H1E_HC_W136F-
artificial
GTKFLAP

LCDR2

1577
H1E_HC_W136F-
artificial
ALWYSNRWV

LCDR3

1578
H1E_HC_W136F-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFFAYWG

QGTLVTVSS

1579
H1E_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1580
H1E_HC_W136F_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFFAYWG

VH

QGTLVTVSS

1581
H1E_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1582
H1E_HC_W136F_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFFAYWG

VH

QGTLVTVSS

1583
H1E_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1584
H1E_I2E-
artificial
SYAIN

HCDR1

1585
H1E_I2E-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1586
H1E_I2E-
artificial
AGNFGSSYLSFWAY

HCDR3

1587
H1E_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

1588
H1E_I2E-
artificial
GTKFLAP

LCDR2

1589
H1E_I2E-
artificial
ALWYSNRWV

LCDR3

1590
H1E_I2E-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYLSFWAYWG

QGTLVTVSS

1591
H1E_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1592
H1E_I2K-
artificial
SYAMN

HCDR1

1593
H1E_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

1594
H1E_I2K-
artificial
NENIGTSYLSFWAY

HCDR3

1595
H1E_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

1596
H1E_I2K-
artificial
GTKFLAP

LCDR2

1597
H1E_I2K-
artificial
ALWYSNRWV

LCDR3

1598
H1E_I2K-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYLSFWAYWG

QGTLVTVSS

1599
H1E_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1600
H1E_I2L-
artificial
SYAMN

HCDR1

1601
H1E_I2L-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1602
H1E_I2L-
artificial
AGNFGSSYLSFFAY

HCDR3

1603
H1E_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

1604
H1E_I2L-
artificial
GTKFLAP

LCDR2

1605
H1E_I2L-
artificial
ALYYSNRWV

LCDR3

1606
H1E_I2L-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYLSFFAYWG

QGTLVTVSS

1607
H1E_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

1608
H1E_I2M-
artificial
SYAMN

HCDR1

1609
H1E_I2M-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1610
H1E_I2M-
artificial
AGNFGTSYLSFWAY

HCDR3

1611
H1E_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

1612
H1E_I2M-
artificial
GTKFLAP

LCDR2

1613
H1E_I2M-
artificial
ALWYSNRWV

LCDR3

1614
H1E_I2M-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYLSFWAYWG

QGTLVTVSS

1615
H1E_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1616
H1E_I2M2-
artificial
SYAIN

HCDR1

1617
H1E_I2M2-
artificial
RIRSKYNNYATYYADAVKG

HCDR2

1618
H1E_I2M2-
artificial
NANFGTSYLSFFAY

HCDR3

1619
H1E_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

1620
H1E_I2M2-
artificial
GTKFLAP

LCDR2

1621
H1E_I2M2-
artificial
ALWYSNRWV

LCDR3

1622
H1E_I2M2-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYLSFFAYWG

QGTLVTVSS

1623
H1E_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1624
H1E_LC_G141S-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1625
H1E_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1626
H1E_LC_G141S_
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTENSYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1627
H1E_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1628
H1E_LC_L83E
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1629
H1E_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1630
H1E_LC_L83S
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1631
H1E_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1632
H1E_LC_Q46E
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1633
H1E_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1634
H1E_LC_Q46K
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1635
H1E_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1636
H1E_LC_A107L-
artificial
SYAMN

HCDR1

1637
H1E_LC_A107L-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

1638
H1E_LC_A107L-
artificial
HGNFGNSYLSFWAY

HCDR3

1639
H1E_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

1640
H1E_LC_A107L-
artificial
GTKFLAP

LCDR2

1641
H1E_LC_A107L-
artificial
LLWYSNRWV

LCDR3

1642
H1E_LC_A107L-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1643
H1E_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1644
H1E_LC_V44I
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1645
H1E_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1646
H1E_LC_V44L
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1647
H1E_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1648
H1E_LC_V44M
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1649
H1E_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1650
H1E_LC_W109Y-
artificial
SYAMN

HCDR1

1651
H1E_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKG

HCDR2

1652
H1E_LC_W109Y-
artificial
HGNFGNSYLSFWAY

HCDR3

1653
H1E_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

1654
H1E_LC_W109Y-
artificial
GTKFLAP

LCDR2

1655
H1E_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

1656
H1E_LC_W109Y-
artificial
EVQLVESGGGLEQPGGSLKLSCAASGFTFNSYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKGRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYLSFWAYWG

QGTLVTVSS

1657
H1E_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

1658
H2C-HCDR1
artificial
KYAMN

1659
H2C-HCDR2
artificial
RIRSKYNNYATYYADSVKD

1660
H2C-HCDR3
artificial
HGNFGNSYISYWAY

1661
H2C-LCDR1
artificial
GSSTGAVTSGYYPN

1662
H2C-LCDR2
artificial
GTKFLAP

1663
H2C-LCDR3
artificial
ALWYSNRWV

1664
H2C-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1665
H2C-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1666
H2C_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1667
H2C_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1668
H2C_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1669
H2C_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1670
H2C_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1671
H2C_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1672
H2C_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1673
H2C_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1674
H2C_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1675
H2C_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1676
H2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1677
H2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S

VL

1678
H2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1679
H2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1680
H2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1681
H2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1682
H2C_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1683
H2C_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1684
H2C_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1685
H2C_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1686
H2C_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1687
H2C_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1688
H2C_HC_M41F_
artificial
KYAFN

A89V-HCDR1

1689
H2C_HC_M41F_
artificial
RIRSKYNNYATYYADSVKD

A89V-HCDR2

1690
H2C_HC_M41F_
artificial
HGNFGNSYISYWAY

A89V-HCDR3

1691
H2C_HC_M41F_
artificial
GSSTGAVTSGYYPN

A89V-

LCDR1

1692
H2C_HC_M41F_
artificial
GTKFLAP

A89V-

LCDR2

1693
H2C_HC_M41F_
artificial
ALWYSNRWV

A89V-

LCDR3

1694
H2C_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1695
H2C_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1696
H2C_HC_M41I
artificial
KYAIN

-HCDR1

1697
H2C_HC_M41I
artificial
RIRSKYNNYATYYADSVKD

-HCDR2

1698
H2C_HC_M41I
artificial
HGNFGNSYISYWAY

-HCDR3

1699
H2C_HC_M41I
artificial
GSSTGAVTSGYYPN

-LCDR1

1700
H2C_HC_M41I
artificial
GTKFLAP

-LCDR2

1701
H2C_HC_M41I
artificial
ALWYSNRWV

-LCDR3

1702
H2C_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1703
H2C_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1704
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1705
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1706
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1707
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1708
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

1709
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

1710
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K-VH

QGTLVTVSS

1711
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

Q46K-VL

1712
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

1713
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

1714
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1715
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1716
H2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

LC_L21I_

QGTLVTVSS

KQ46_G141S-

VH

1717
H2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

1718
H2C_HC_M41V
artificial
KYAVN

-HCDR1

1719
H2C_HC_M41V
artificial
RIRSKYNNYATYYADSVKD

-HCDR2

1720
H2C_HC_M41V
artificial
HGNFGNSYISYWAY

-HCDR3

1721
H2C_HC_M41V
artificial
GSSTGAVTSGYYPN

-LCDR1

1722
H2C_HC_M41V
artificial
GTKFLAP

-LCDR2

1723
H2C_HC_M41V
artificial
ALWYSNRWV

-LCDR3

1724
H2C_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1725
H2C_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1726
H2C_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1727
H2C_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1728
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1729
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1730
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1731
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1732
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1733
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1734
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1735
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

4G11S-VL

1736
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1737
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1738
H2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1739
H2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1740
H2C_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1741
H2C_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1742
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1743
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1744
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

6Q4R_G141S-

QGTLVTVSS

VH

1745
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1746
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1747
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1748
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1749
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1750
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1751
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1752
H2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

4G11S-VH

QGTLVTVSS

1753
H2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

G141S-VL

1754
H2C_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1755
H2C_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1756
H2C_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1757
H2C_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1758
H2C_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYISYWAYWG

QGTLVTVSS

1759
H2C_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1760
H2C_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYISYWAYWG

QGTLVTVSS

1761
H2C_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1762
H2C_HC_W136F-
artificial
KYAMN

HCDR1

1763
H2C_HC_W136F-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1764
H2C_HC_W136F-
artificial
HGNFGNSYISYFAY

HCDR3

1765
H2C_HC_W136F-
artificial
GSSTGAVTSGYYPN

LCDR1

1766
H2C_HC_W136F-
artificial
GTKFLAP

LCDR2

1767
H2C_HC_W136F-
artificial
ALWYSNRWV

LCDR3

1768
H2C_HC_W136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

QGTLVTVSS

1769
H2C_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1770
H2C_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

VH

QGTLVTVSS

1771
H2C_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1772
H2C_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

VH

QGTLVTVSS

1773
H2C_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

1774
H2C_I2E-
artificial
KYAIN

HCDR1

1775
H2C_I2E-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

1776
H2C_I2E-
artificial
AGNFGSSYISYWAY

HCDR3

1777
H2C_I2E-
artificial
GSSTGAVTSGYYPN

LCDR1

1778
H2C_I2E-
artificial
GTKFLAP

LCDR2

1779
H2C_I2E-
artificial
ALWYSNRWV

LCDR3

1780
H2C_I2E-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWG

QGTLVTVSS

1781
H2C_I2E-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1782
H2C_I2K-
artificial
KYAMN

HCDR1

1783
H2C_I2K-
artificial
RIRSKYNNYATYYAEAVKG

HCDR2

1784
H2C_I2K-
artificial
NENIGTSYISYWAY

HCDR3

1785
H2C_I2K-
artificial
GSSTGAVTSGYYPN

LCDR1

1786
H2C_I2K-
artificial
GTKFLAP

LCDR2

1787
H2C_I2K-
artificial
ALWYSNRWV

LCDR3

1788
H2C_I2K-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWG

QGTLVTVSS

1789
H2C_I2K-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1790
H2C_I2L-
artificial
KYAMN

HCDR1

1791
H2C_I2L-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

1792
H2C_I2L-
artificial
AGNFGSSYISYFAY

HCDR3

1793
H2C_I2L-
artificial
GSSTGAVTSGYYPN

LCDR1

1794
H2C_I2L-
artificial
GTKFLAP

LCDR2

1795
H2C_I2L-
artificial
ALYYSNRWV

LCDR3

1796
H2C_I2L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWG

QGTLVTVSS

1797
H2C_I2L-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWIQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGSGTKLTVL

1798
H2C_I2M-
artificial
KYAMN

HCDR1

1799
H2C_I2M-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

1800
H2C_I2M-
artificial
AGNFGTSYISYWAY

HCDR3

1801
H2C_I2M-
artificial
GSSTGAVTSGYYPN

LCDR1

1802
H2C_I2M-
artificial
GTKFLAP

LCDR2

1803
H2C_I2M-
artificial
ALWYSNRWV

LCDR3

1804
H2C_I2M-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

VH

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWG

QGTLVTVSS

1805
H2C_I2M-
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1806
H2C_I2M2-
artificial
KYAIN

HCDR1

1807
H2C_I2M2-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

1808
H2C_I2M2-
artificial
NANFGTSYISYFAY

HCDR3

1809
H2C_I2M2-
artificial
GSSTGAVTSGYYPN

LCDR1

1810
H2C_I2M2-
artificial
GTKFLAP

LCDR2

1811
H2C_I2M2-
artificial
ALWYSNRWV

LCDR3

1812
H2C_I2M2-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

VH

ATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWG

QGTLVTVSS

1813
H2C_I2M2-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1814
H2C_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1815
H2C_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1816
H2C_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1817
H2C_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGSGTKLTVL

1818
H2C_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1819
H2C_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1820
H2C_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1821
H2C_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1822
H2C_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1823
H2C_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1824
H2C_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1825
H2C_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1826
H2C_LC_A107L-
artificial
KYAMN

HCDR1

1827
H2C_LC_A107L-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1828
H2C_LC_A107L-
artificial
HGNFGNSYISYWAY

HCDR3

1829
H2C_LC_A107L-
artificial
GSSTGAVTSGYYPN

LCDR1

1830
H2C_LC_A107L-
artificial
GTKFLAP

LCDR2

1831
H2C_LC_A107L-
artificial
LLWYSNRWV

LCDR3

1832
H2C_LC_A107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1833
H2C_LC_A107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1834
H2C_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1835
H2C_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1836
H2C_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1837
H2C_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1838
H2C_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1839
H2C_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1840
H2C_LC_W109Y-
artificial
KYAMN

HCDR1

1841
H2C_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1842
H2C_LC_W109Y-
artificial
HGNFGNSYISYWAY

HCDR3

1843
H2C_LC_W109Y-
artificial
GSSTGAVTSGYYPN

LCDR1

1844
H2C_LC_W109Y-
artificial
GTKFLAP

LCDR2

1845
H2C_LC_W109Y-
artificial
ALYYSNRWV

LCDR3

1846
H2C_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1847
H2C_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALYYSNRWVFGGGTKLTVL

1848
I2C-HCDR1
artificial
KYAMN

1849
I2C-HCDR2
artificial
RIRSKYNNYATYYADSVKD

1850
I2C-HCDR3
artificial
HGNFGNSYISYWAY

1851
I2C-LCDR1
artificial
GSSTGAVTSGNYPN

1852
I2C-LCDR2
artificial
GTKFLAP

1853
I2C-LCDR3
artificial
VLWYSNRWV

1854
I2C-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1855
I2C-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1856
I2C_HC_A89I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTIYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1857
I2C_HC_A89I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1858
I2C_HC_A89L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1859
I2C_HC_A89L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1860
I2C_HC_A89T
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTTYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1861
I2C_HC_A89T
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1862
I2C_HC_A89V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1863
I2C_HC_A89V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1864
I2C_HC_L52M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1865
I2C_HC_L52M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1866
I2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1867
I2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

6Q4K_G141S-

VL

1868
I2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1869
I2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1870
I2C_HC_L52M_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1871
I2C_HC_L52M_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

1872
I2C_HC_L52V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1873
I2C_HC_L52V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1874
I2C_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44F-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1875
I2C_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWFQQKPGQAPRGLIGGTKFLAP

LC_V44F-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1876
I2C_HC_L52V_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGVEWVARIRSKYNNY

LC_V44Y-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1877
I2C_HC_L52V_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWYQQKPGQAPRGLIGGTKFLAP

LC_V44Y-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1878
I2C_HC_M41F_
artificial
KYAFN

A89V-HCDR1

1879
I2C_HC_M41F_
artificial
RIRSKYNNYATYYADSVKD

A89V-

HCDR2

1880
I2C_HC_M41F_
artificial
HGNFGNSYISYWAY

A89V-

HCDR3

1881
I2C_HC_M41F_
artificial
GSSTGAVTSGNYPN

A89V-

LCDR1

1882
I2C_HC_M41F_
artificial
GTKFLAP

A89V-LCDR2

1883
I2C_HC_M41F_
artificial
VLWYSNRWV

A89V-LCDR3

1884
I2C_HC_M41F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAFNWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1885
I2C_HC_M41F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1886
I2C_HC_M41I
artificial
KYAIN

-HCDR1

1887
I2C_HC_M41I
artificial
RIRSKYNNYATYYADSVKD

-HCDR2

1888
I2C_HC_M41I
artificial
HGNFGNSYISYWAY

-HCDR3

1889
I2C_HC_M41I
artificial
GSSTGAVTSGNYPN

-LCDR1

1890
I2C_HC_M41I
artificial
GTKFLAP

-LCDR2

1891
I2C_HC_M41I
artificial
VLWYSNRWV

-LCDR3

1892
I2C_HC_M41I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1893
I2C_HC_M41I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1894
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89L-VH

ATYYADSVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1895
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89L-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1896
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V-VH

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1897
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

A89V-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1898
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

L21I_Q46K_

QGTLVTVSS

G141S-VH

1899
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

L21I_Q46K_

G141S-VL

1900
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

A89V_LC_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

6Q4K-VH

QGTLVTVSS

1901
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

A89V_LC_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

Q46K-VL

1902
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGKGVEWVARIRSKYNNY

L52V_A89V_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S_

V44F-VH

1903
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWFQKKPGQAPRGLIGGTKFLAP

L52V_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S_

V44F-VL

1904
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1905
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1906
I2C_HC_M41I_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

Q46E_A89V_

ATYYADSVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

LC_L21I_

QGTLVTVSS

Q46K_G141S-

VH

1907
I2C_HC_M41I_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

Q46E_A89V_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

LC_L21I_

Q46K_G141S-

VL

1908
I2C_HC_M41V
artificial
KYAVN

-HCDR1

1909
I2C_HC_M41V
artificial
RIRSKYNNYATYYADSVKD

-HCDR2

1910
I2C_HC_M41V
artificial
HGNFGNSYISYWAY

-HCDR3

1911
I2C_HC_M41V
artificial
GSSTGAVTSGNYPN

-LCDR1

1912
I2C_HC_M41V
artificial
GTKFLAP

-LCDR2

1913
I2C_HC_M41V
artificial
VLWYSNRWV

-LCDR3

1914
I2C_HC_M41V
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAVNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1915
I2C_HC_M41V
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1916
I2C_HC_Q46D
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1917
I2C_HC_Q46D
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1918
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1919
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1920
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1921
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1922
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

4G11S-VH

QGTLVTVSS

1923
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

1924
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1925
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1926
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1927
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

1928
I2C_HC_Q46D_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRDAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1929
I2C_HC_Q46D_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1930
I2C_HC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVREAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1931
I2C_HC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1932
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46K_G141S-

QGTLVTVSS

VH

1933
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46K_G141S-

VL

1934
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_L21I_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

Q46R_G141S-

QGTLVTVSS

VH

1935
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_L21I_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

Q46R_G141S-

VL

1936
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1937
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1938
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46K_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1939
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

LC_Q46K_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

1940
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

1941
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1942
I2C_HC_Q46E_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVREAPGKGLEWVARIRSKYNNY

LC_Q46R_

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

G141S-VH

QGTLVTVSS

1943
I2C_HC_Q46E_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQRKPGQAPRGLIGGTKFLAP

LC_Q46R_

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

G141S-VL

1944
I2C_HC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRKAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1945
I2C_HC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1946
I2C_HC_Q46R
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRRAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1947
I2C_HC_Q46R
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1948
I2C_HC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCARHGNFGNSYISYWAYWG

QGTLVTVSS

1949
I2C_HC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1950
I2C_HC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCLRHGNFGNSYISYWAYWG

QGTLVTVSS

1951
I2C_HC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1952
I2C_HC_W136F-
artificial
KYAMN

HCDR1

1953
I2C_HC_W136F-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1954
I2C_HC_W136F-
artificial
HGNFGNSYISYFAY

HCDR3

1955
I2C_HC_W136F-
artificial
GSSTGAVTSGNYPN

LCDR1

1956
I2C_HC_W136F-
artificial
GTKFLAP

LCDR2

1957
I2C_HC_W136F-
artificial
VLWYSNRWV

LCDR3

1958
I2C_HC_W136F-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

QGTLVTVSS

1959
I2C_HC_W136F-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1960
I2C_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44I-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

VH

QGTLVTVSS

1961
I2C_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWIQQKPGQAPRGLIGGTKFLAP

LC_V44I-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1962
I2C_HC_W136F_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

LC_V44L-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYFAYWG

VH

QGTLVTVSS

1963
I2C_HC_W136F_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWLQQKPGQAPRGLIGGTKFLAP

LC_V44L-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

1964
I2C_LC_G141S-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1965
I2C_LC_G141S-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

1966
I2C_LC_G141S_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

L21I-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1967
I2C_LC_G141S_
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

L21I-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

1968
I2C_LC_L83E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1969
I2C_LC_L83E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1970
I2C_LC_L83S
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1971
I2C_LC_L83S
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1972
I2C_LC_Q46E
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1973
I2C_LC_Q46E
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQEKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1974
I2C_LC_Q46K
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1975
I2C_LC_Q46K
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1976
I2C_LC_V107A-
artificial
KYAMN

HCDR1

1977
I2C_LC_V107A-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1978
I2C_LC_V107A-
artificial
HGNFGNSYISYWAY

HCDR3

1979
I2C_LC_V107A-
artificial
GSSTGAVTSGNYPN

LCDR1

1980
I2C_LC_V107A-
artificial
GTKFLAP

LCDR2

1981
I2C_LC_V107A-
artificial
ALWYSNRWV

LCDR3

1982
I2C_LC_V107A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1983
I2C_LC_V107A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

1984
I2C_LC_V107L-
artificial
KYAMN

HCDR1

1985
I2C_LC_V107L-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

1986
I2C_LC_V107L-
artificial
HGNFGNSYISYWAY

HCDR3

1987
I2C_LC_V107L-
artificial
GSSTGAVTSGNYPN

LCDR1

1988
I2C_LC_V107L-
artificial
GTKFLAP

LCDR2

1989
I2C_LC_V107L-
artificial
LLWYSNRWV

LCDR3

1990
I2C_LC_V107L-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1991
I2C_LC_V107L-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCLLWYSNRWVFGGGTKLTVL

1992
I2C_LC_V44I
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1993
I2C_LC_V44I
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWIQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1994
I2C_LC_V44L
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1995
I2C_LC_V44L
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWLQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1996
I2C_LC_V44M
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

-VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

1997
I2C_LC_V44M
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWMQQKPGQAPRGLIGGTKFLAP

-VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

1998
I2C_LC_W109Y-
artificial
KYAMN

HCDR1

1999
I2C_LC_W109Y-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

2000
I2C_LC_W109Y-
artificial
HGNFGNSYISYWAY

HCDR3

2001
I2C_LC_W109Y-
artificial
GSSTGAVTSGNYPN

LCDR1

2002
I2C_LC_W109Y-
artificial
GTKFLAP

LCDR2

2003
I2C_LC_W109Y-
artificial
VLYYSNRWV

LCDR3

2004
I2C_LC_W109Y-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

QGTLVTVSS

2005
I2C_LC_W109Y-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGGGTKLTVL

2006
I2E-HCDR1
artificial
KYAIN

2007
I2E-HCDR2
artificial
RIRSKYNNYATYYADAVKD

2008
I2E-HCDR3
artificial
AGNFGSSYISYWAY

2009
I2E-LCDR1
artificial
GSSTGAVTSGNYPN

2010
I2E-LCDR2
artificial
GTKFLAP

2011
I2E-LCDR3
artificial
VLWYSNRWV

2012
I2E-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNY

ATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWG

QGTLVTVSS

2013
I2E-VL
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2014
I2K-HCDR1
artificial
KYAMN

2015
I2K-HCDR2
artificial
RIRSKYNNYATYYAEAVKG

2016
I2K-HCDR3
artificial
NENIGTSYISYWAY

2017
I2K-LCDR1
artificial
GSSTGAVTSGNYPN

2018
I2K-LCDR2
artificial
GTKFLAP

2019
I2K-LCDR3
artificial
VLWYSNRWV

2020
I2K-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

ATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWG

QGTLVTVSS

2021
I2K-VL
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2022
I2L-HCDR1
artificial
KYAMN

2023
I2L-HCDR2
artificial
RIRSKYNNYATYYADAVKD

2024
I2L-HCDR3
artificial
AGNFGSSYISYFAY

2025
I2L-LCDR1
artificial
GSSTGAVTSGNYPN

2026
I2L-LCDR2
artificial
GTKFLAP

2027
I2L-LCDR3
artificial
VLYYSNRWV

2028
I2L-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWG

QGTLVTVSS

2029
I2L-VL
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

2030
I2M-HCDR1
artificial
KYAMN

2031
I2M-HCDR2
artificial
RIRSKYNNYATYYADAVKD

2032
I2M-HCDR3
artificial
AGNFGTSYISYWAY

2033
I2M-LCDR1
artificial
GSSTGAVTSGNYPN

2034
I2M-LCDR2
artificial
GTKFLAP

2035
I2M-LCDR3
artificial
VLWYSNRWV

2036
I2M-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNY

ATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWG

QGTLVTVSS

2037
I2M-VL
artificial
QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2038
I2M2-
artificial
KYAIN

HCDR1

2039
I2M2-
artificial
RIRSKYNNYATYYADAVKD

HCDR2

2040
I2M2-
artificial
NANFGTSYISYFAY

HCDR3

2041
I2M2-
artificial
GSSTGAVTSGNYPN

LCDR1

2042
I2M2-
artificial
GTKFLAP

LCDR2

2043
I2M2-
artificial
VLWYSNRWV

LCDR3

2044
I2M2-VH
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNY

ATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWG

QGTLVTVSS

2045
I2M2-VL
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2046
consensus_
artificial
KYAMN

sequence_1-

HCDR1

2047
consensus_
artificial
RIRSKYNNYATYYADSVKD

sequence_1-

HCDR2

2048
consensus_
artificial
HGNFGNSYJSXWAY

sequence_1-

HCDR3

2049
consensus_
artificial
GSSTGAVTSGYYPN

sequence_1-

LCDR1

2050
consensus_
artificial
GTKFLAP

sequence_1-

LCDR2

2051
consensus_
artificial
ALWYSNRWV

sequence_1-

LCDR3

2052
consensus_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

sequence_1-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYJSXWAYWG

VH

QGTLVTVSS

2053
consensus_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

sequence_1-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

2054
consensus_
artificial
KYAMN

sequence_2

HCDR1

2055
consensus_
artificial
RIRSKYNNYATYYADSVKX

sequence_2

HCDR2

2056
consensus_
artificial
HGNFGNSYJSYWAY

sequence_2

HCDR3

2057
consensus_
artificial
GSSTGAVTSGYYPN

sequence_2

LCDR1

2058
consensus_
artificial
GTKFLAP

sequence_2

LCDR2

2059
consensus_
artificial
ALWYSNRWV

sequence_2

LCDR3

2060
consensus_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

sequence_2

ATYYADSVKXRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYJSYWAYWG

VH

QGTLVTVSS

2061
consensus_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

sequence_2

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

2062
consensus_
artificial
KYAMN

sequence_3-

HCDR1

2063
consensus_
artificial
RIRSKYNNYATYYADSVKX

sequence_3-

HCDR2

2064
consensus_
artificial
HGNFGNSYISYWAY

sequence_3-

HCDR3

2065
consensus_
artificial
GSSTGAVTSGYYPN

sequence_3-

LCDR1

2066
consensus_
artificial
GTKFLAP

sequence_3-

LCDR2

2067
consensus_
artificial
ALWYSNRWV

sequence_3-

LCDR3

2068
consensus_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

sequence_3-

ATYYADSVKXRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

2069
consensus_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGYYPNWVQQKPGQAPRGLIGGTKFLAP

sequence_3-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNRWVFGGGTKLTVL

VL

2070
consensus_
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

sequence_4-

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWG

VH

QGTLVTVSS

2071
consensus_
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

sequence_4-

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

VL

2072
BC A7 27-
artificial
NHIIH

C4-G7-

HCDR1

2073
BC A7 27-
artificial
YINPYPGYHAYNEKFQG

C4-G7-

HCDR2

2074
BC A7 27-
artificial
DGYYRDTDVLDY

C4-G7-

HCDR3

2075
BC A7 27-
artificial
QASQDISNYLN

C4-G7-

LCDR1

2076
BC A7 27-
artificial
YTSRLHT

C4-G7-

LCDR2

2077
BC A7 27-
artificial
QQGNTLPWT

C4-G7-

LCDR3

2078
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7-VH

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

VTVSS

2079
BC A7 27-
artificial
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGV

C4-G7-VL

PSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK

2080
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC-

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

VH

VTVSS

2081
BC A7 27-
artificial
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGV

C4-G7 CC-

PSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGCGTKVEIK

VL

2082
BC A7 27-
artificial
EIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGV

C4-G7 CC EI

PSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGCGTKVEIK

GQ-VL

2083
BC A7 27-
artificial
EIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGV

C4-G7 EI GQ

PSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPWTFGQGTKVEIK

-VL

2084
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2C

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

2085
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2E

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2086
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2K

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2087
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2L

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

2088
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2M

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2089
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQGLEWMGYINPYPGYH

C4-G7X I2M2

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

-Full

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Sequence

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

TFGQGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2090
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2C x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

-Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2091
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2E x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

-Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2092
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2K x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2093
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2L x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

-Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2094
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2M x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

-Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2095
BC A7 27-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQAPGQCLEWMGYINPYPGYH

C4-G7 CC X

AYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCARDGYYRDTDVLDYWGQGTL

I2M2 x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQ

-Full

KPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSLEPEDIATYYCQQGNTLPW

Sequence

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2096
CD123 24-
artificial
HYAMS

B4-f NK CC

-HCDR1

2097
CD123 24-
artificial
AVSGGGDKTLYADAVKG

B4-f NK CC

-HCDR2

2098
CD123 24-
artificial
LRGFYYGMDV

B4-f NK CC

-HCDR3

2099
CD123 24-
artificial
RSSQSLLHSNKYNYLD

B4-f NK CC

-LCDR1

2100
CD123 24-
artificial
LGSNRAS

B4-f NK CC

-LCDR2

2101
CD123 24-
artificial
MQALQTPPIT

B4-f NK CC

-LCDR3

2102
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

-VH

VSS

2103
CD123 24-
artificial
DIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSN

B4-f NK CC

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIK

-VL

2104
CD123 24-
artificial
EIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSN

B4-f NK CC

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIK

EI GQ-VL

2105
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2C x

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

ScFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2106
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2E x

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

scFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWV

RQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2107
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2K x

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

scFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2108
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2L x

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

scFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGG

KAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2109
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2M X

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

scFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2110
CD123 24-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVRQAPGKCLEWVSAVSGGGDKT

B4-f NK CC

LYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYCARLRGFYYGMDVWGQGTTVT

x I2M2 X

VSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNKYNYLDW

ScFc-Full

YLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQ

Sequence

TPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWV

REAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2111
CD19 97-
artificial
SYGMH

G1RE-C2 LH

CC-HCDR1

2112
CD19 97-
artificial
VISYEGSNKYYAESVKG

G1RE-C2 LH

CC-HCDR2

2113
CD19 97-
artificial
DRGTIFGNYGLEV

G1RE-C2 LH

CC-HCDR3

2114
CD19 97-
artificial
RSSQSLLHKNAFNYLD

G1RE-C2 LH

CC-LCDR1

2115
CD19 97-
artificial
LGSNRAS

G1RE-C2 LH

CC-LCDR2

2116
CD19 97-
artificial
MQALQTPFT

G1RE-C2 LH

CC-LCDR3

2117
CD19 97-
artificial
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAVISYEGSNK

G1RE-C2 LH

YYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFGNYGLEVWGQGT

CC-VH

TVTVSS

2118
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIK

CC-VL

2119
CD19 97-
artificial
EIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIK

CC EI GQ-

VL

2120
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2C x

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT

AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLL

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2121
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2E X

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAIN

WVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDT

AVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2122
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2K X

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDT

AVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2123
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2L x

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDT

AVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLE

GGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2124
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2M X

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDT

AVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2125
CD19 97-
artificial
DIVMTQSPLSLPVISGEPASISCRSSQSLLHKNAFNYLDWYLQKPGQSPQLLIYLGSN

G1RE-C2 LH

RASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPFTFGCGTKVDIKGGGG

CC x I2M2 x

SGGGGSGGGGSQVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKCLEW

scFc-Full

VAVISYEGSNKYYAESVKGRFTISRDNSKNTLYLQMNSLRDEDTAVYYCARDRGTIFG

Sequence

NYGLEVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAIN

WVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDT

AVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLL

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2126
CD20 99-E5
artificial
SYWMH

CC-HCDR1

2127
CD20 99-E5
artificial
YITPSTGYTEYNQKFKG

CC-HCDR2

2128
CD20 99-E5
artificial
VHDYDRAMEY

CC-HCDR3

2129
CD20 99-E5
artificial
KASQDINKYIA

CC-LCDR1

2130
CD20 99-E5
artificial
YTSTLQP

CC-LCDR2

2131
CD20 99-E5
artificial
LQYASYPFT

CC-LCDR3

2132
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC-VH

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

VSS

2133
CD20 99-E5
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGV

CC-VL

PSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIK

2134
CD20 99-E5
artificial
EIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGV

CC EI GQ-

PSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIK

VL

2135
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x I2C x

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

scFc-Full

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

Sequence

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRH

GNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2136
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x I2E X

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

scFc-Full

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

Sequence

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARA

GNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2137
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x I2K x

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

scFc-Full

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

Sequence

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRN

ENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2138
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x I2L x

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

scFc-Full

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

Sequence

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTL

SGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

2139
CD20 99-E5
artificial
EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

CC x I2M X

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

scFc-Full

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

Sequence

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVEL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2140
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x I2M2 x

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

scFc-Full

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

Sequence

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

GCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRN

ANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKE

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2141
CD22 28-
artificial
SYGIS

B7N65S CC-

HCDR1

2142
CD22 28-
artificial
WISAYSGNAIYAQKLQG

B7N65S CC-

HCDR2

2143
CD22 28-
artificial
DPDYYGSGSYSDY

B7N65S CC-

HCDR3

2144
CD22 28-
artificial
RASQSVSSNLA

B7N65S CC-

LCDR1

2145
CD22 28-
artificial
GASSRAT

B7N65S CC-

LCDR2

2146
CD22 28-
artificial
QQYHSWPLLT

B7N65S CC-

LCDR3

2147
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC-

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

VH

LVTVSS

2148
CD22 28-
artificial
EIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGI

B7N65S CC-

PARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWPLLTFGCGTKVEIK

VL

2149
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2C x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ

APGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY

CVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKA

ALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2150
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2E x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQ

APGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYY

CARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2151
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2K x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ

APGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYY

CVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2152
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2L x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQ

APGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYY

CVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKA

ALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2153
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2M x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ

APGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYY

CVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2154
CD22 28-B7
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

N65S CC X

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2M2 x scFc

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

-Full

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

Sequence

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRE

APGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY

CVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

GTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKA

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQY

GSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS

REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV

DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGG

GSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP

EVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALP

APIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQP

ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP

GK

2155
CD33 E11-
artificial
NYGMN

HCDR1

2156
CD33 E11-
artificial
WINTYTGEPTYADKFQG

HCDR2

2157
CD33 E11-
artificial
WSWSDGYYVYFDY

HCDR3

2158
CD33 E11-
artificial
KSSQSVLDSSTNKNSLA

LCDR1

2159
CD33 E11-
artificial
WASTRES

LCDR2

2160
CD33 E11-
artificial
QQSAHFPIT

LCDR3

2161
CD33 E11-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

VH

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

SVTVSS

2162
CD33 E11-
artificial
DIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKNSLAWYQQKPGQPPKLLLSWAS

VL

TRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQQSAHFPITFGQGTRLEIK

2163
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

-VH

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

SVTVSS

2164
CD33 E11 CC
artificial
DIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKNSLAWYQQKPGQPPKLLLSWAS

-VL

TRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQQSAHFPITFGCGTRLEIK

2165
CD33 E11 CC
artificial
EIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKNSLAWYQQKPGQPPKLLLSWAS

EI GQ-VL

TRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQQSAHFPITFGCGTRLEIK

2166
CD33 E11 EI
artificial
EIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKNSLAWYQQKPGQPPKLLLSWAS

GQ-VL

TRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQQSAHFPITFGQGTRLEIK

2167
E11 x I2C-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED

TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL

LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

2168
E11 x I2E-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAI

NWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTED

TAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2169
E11 x I2K-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTED

TAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2170
E11 x I2L-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTED

TAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

EGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

2171
E11 x I2M-
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAM

NWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTED

TAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2172
E11 x I2M2
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQGLEWMGWINTYTGEP

-Full

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

Sequence

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGQGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAI

NWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTED

TAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2173
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

x I2C x

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

scFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTED

TAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL

LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2174
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

x I2E X

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

ScFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAI

NWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTED

TAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2175
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

x I2K x

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

scFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAM

NWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTED

TAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2176
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

x I2L x

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

scFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTED

TAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

EGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2177
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

x I2M X

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

scFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAM

NWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTED

TAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

SGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2178
CD33 E11 CC
artificial
QVQLVQSGAEVKKPGESVKVSCKASGYTFTNYGMNWVKQAPGQCLEWMGWINTYTGEP

X I2M2 X

TYADKFQGRVTMTTDTSTSTAYMEIRNLGGDDTAVYYCARWSWSDGYYVYFDYWGQGT

scFc-Full

SVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLTVSLGERTTINCKSSQSVLDSSTNKN

Sequence

SLAWYQQKPGQPPKLLLSWASTRESGIPDRFSGSGSGTDFTLTIDSPQPEDSATYYCQ

QSAHFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAI

NWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTED

TAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSL

TVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSL

LGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPE

LLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKP

CEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVY

TLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLY

SKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGG

GSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDV

SHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVS

NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE

SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK

2179
CD70 1 C7D
artificial
TYAMS

CC-HCDR1

2180
CD70 1 C7D
artificial
AISGSGGRTFYAESVEG

CC-HCDR2

2181
CD70 1 C7D
artificial
HDYSNYPYFDY

CC-HCDR3

2182
CD70 1 C7D
artificial
RASQSVRSTYLA

CC-LCDR1

2183
CD70 1 C7D
artificial
GASSRAT

CC-LCDR2

2184
CD70 1 C7D
artificial
QQYGDLPFT

CC-LCDR3

2185
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC-VH

FYAESVEGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

TVSS

2186
CD70 1 C7D
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQKPGQAPRLLIYGASSRATG

CC-VL

IPDRESGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPFTFGCGTKLEIK

2187
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2C x

FYAESVEGRETISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

ScFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2188
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2E X

FYAESVEGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2189
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2K X

FYAESVEGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRESGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2190
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2L x

FYAESVEGRETISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2191
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2M x

FYAESVEGRETISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2192
CD70 1 C7D
artificial
EVQLLESGGGMVQPGGSLRLSCAASGFTFSTYAMSWVRQAPGKCLEWVSAISGSGGRT

CC x I2M2 X

FYAESVEGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKHDYSNYPYFDYWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERATLSCRASQSVRSTYLAWYQQ

Sequence

KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYSCQQYGDLPF

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2193
CH19
artificial
SYGMH

2G6.007 CC

-HCDR1

2194
CH19
artificial
FIWYEGSNKYYAESVKD

2G6.007 CC

-HCDR2

2195
CH19
artificial
RAGIIGTIGYYYGMDV

2G6.007 CC

-HCDR3

2196
CH19
artificial
SGDRLGEKYTS

2G6.007 CC

-LCDR1

2197
CH19
artificial
QDTKRPS

2G6.007 CC

-LCDR2

2198
CH19
artificial
QAWESSTVV

2G6.007 CC

-LCDR3

2199
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CC

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

-VH

QGTTVTVSS

2200
CH19
artificial
SYELTQPPSVSVSPGQTASITCSGDRLGEKYTSWYQQRPGQSPLLVIYQDTKRPSGIP

2G6.007 CC

ERFSGSNSGNTATLTISGTQAMDEADYYCQAWESSTVVFGCGTKLTVL

-VL

2201
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2C x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVR

QAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2202
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2C x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVR

Sequence

QAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2203
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2E x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVR

QAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2204
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2E x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVR

Sequence

QAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2205
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2K x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2206
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2K x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

Sequence

QAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2207
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2L x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVR

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGK

AALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2208
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2L x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

Sequence

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGK

AALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2209
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2M x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2210
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2M x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVR

Sequence

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2211
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2M2 x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

-Full

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Sequence

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVR

EAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2212
CH19
artificial
QVQLVESGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKCLEWVAFIWYEGSNK

2G6.007 CCx

YYAESVKDRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRAGIIGTIGYYYGMDVWG

I2M2 x scFc

QGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGDRLGEKYTSW

delGK-

YQQRPGQSPLLVIYQDTKRPSGIPERFSGSNSGNTATLTISGTQAMDEADYYCQAWES

Full

STVVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVR

Sequence

EAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2213
CH3 15-E11
artificial
NYWMN

CC-HCDR1

2214
CH3 15-E11
artificial
NIAYGVKGTNYNQKFQG

CC-HCDR2

2215
CH3 15-E11
artificial
RYFYVMDY

CC-HCDR3

2216
CH3 15-E11
artificial
RASQDISNYLN

CC-LCDR1

2217
CH3 15-E11
artificial
YTSRLHS

CC-LCDR2

2218
CH3 15-E11
artificial
VQYAQFPLT

CC-LCDR3

2219
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC-VH

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

S

2220
CH3 15-E11
artificial
DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKVPKLLIYYTSRLHSGV

CC-VL

PSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGCGTKVEIK

2221
CH3 15-E11
artificial
EIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKVPKLLIYYTSRLHSGV

CC EI GQ-

PSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGCGTKVEIK

VL

2222
CH3 G8A 6-
artificial
SYPIN

B12-HCDR1

2223
CH3 G8A 6-
artificial
VIWTGGGTNYASSVKG

B12-HCDR2

2224
CH3 G8A 6-
artificial
SRGVYDFDGRGAMDY

B12-HCDR3

2225
CH3 G8A 6-
artificial
KSSQSLLYSSNQKNYFA

B12-LCDR1

2226
CH3 G8A 6-
artificial
WASTRES

B12-LCDR2

2227
CH3 G8A 6-
artificial
QQYYSYPYT

B12-LCDR3

2228
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12-VH

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

TLVTVSS

2229
CH3 G8A 6-
artificial
DIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWAS

B12-VL

TRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK

2230
CH3 G8A 6-
artificial
EIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQKNYFAWYQQKPGQPPKLLIYWAS

B12 EI GQ-

TRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSYPYTFGQGTKLEIK

VL

2231
CH3 R170R
artificial
SYWMH

CC-HCDR1

2232
CH3 R170R
artificial
KIDPSDDYTNYNQKVKG

CC-HCDR2

2233
CH3 R170R
artificial
WDYSHFDV

CC-HCDR3

2234
CH3 R170R
artificial
RASSSVSYMH

CC-LCDR1

2235
CH3 R170R
artificial
GTSNLVS

CC-LCDR2

2236
CH3 R170R
artificial
QQWSSYPLT

CC-LCDR3

2237
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC-VH

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

S

2238
CH3 R170R
artificial
EIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVP

CC-VL

ARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCGTKVEIK

2239
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2C x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

scFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGL

EWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLT

CGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2240
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2E x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

scFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGL

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGN

FGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2241
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2K x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

scFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGL

EWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNEN

IGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2242
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2L x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

ScFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGM

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGN

FGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTLSG

VQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2243
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2M x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

scFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGM

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGN

FGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2244
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2M2 x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

scFc-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

Sequence

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGL

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNAN

FGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2245
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2C x

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

scFc-Full

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Sequence

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTE

DTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS

LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2246
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2E x

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

scFc-Full

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Sequence

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

INWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTE

DTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2247
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2K x

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

scFc-Full

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Sequence

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTE

DTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2248
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2L x

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

scFc-Full

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Sequence

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTE

DTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2249
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2M x

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

scFc-Full

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Sequence

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTE

DTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2250
CH3 G8A 6-
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFSFSSYPINWVRQAPGKGLEWVGVIWTGGGTN

B12 x I2M2

YASSVKGRFTISRDNSKNTVYLQMNSLRAEDTAVYYCAKSRGVYDFDGRGAMDYWGQG

x scFc-

TLVTVSSGGGGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLLYSSNQK

Full

NYFAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC

Sequence

QQYYSYPYTFGQGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

INWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTE

DTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAP

ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTK

PCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL

YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGG

GGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD

VSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKV

SNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW

ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQK

SLSLSPGK

2251
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2C x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLE

WVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNF

GNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTC

GSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV

QPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2252
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2E x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGLE

WVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGNF

GSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITC

GSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGV

QPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2253
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2K x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLE

WVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNENI

GTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITC

GSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGV

QPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2254
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2L x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGME

WVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNF

GSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITC

GSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTLSGV

QPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2255
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2M x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHEDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGKGME

WVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNE

GTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTITC

GSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSGV

QPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2256
CH3 R170R
artificial
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWVRQTPGKCLEWVSKIDPSDDYT

CC x I2M2 x

NYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYYCARWDYSHFDVWGQGTTVTVS

scFc-Full

SGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATLTCRASSSVSYMHWYQQKPGQA

Sequence

PRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQWSSYPLTFGCG

TKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLE

WVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANF

GTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTC

GSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGV

QPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCV

SVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKN

QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWY

VDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI

SKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT

PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2257
CL1 7-D7 CC
artificial
NYYMH

-HCDR1

2258
CL1 7-D7 CC
artificial
WINPTSGGANYAQKFQG

-HCDR2

2259
CL1 7-D7 CC
artificial
ESHAIQEGIWFDY

-HCDR3

2260
CL1 7-D7 CC
artificial
RASQSISNYLN

-LCDR1

2261
CL1 7-D7 CC
artificial
DASSLQS

-LCDR2

2262
CL1 7-D7 CC
artificial
QQSYSFPLT

-LCDR3

2263
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

-VH

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

LVTVSS

2264
CL1 7-D7 CC
artificial
DIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQQKPGKAPKLLIYDASSLQSGV

-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPLTFGCGTKVEIK

2265
CL1 7-D7 CC
artificial
EIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQQKPGKAPKLLIYDASSLQSGV

EI GQ-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPLTFGCGTKVEIK

2266
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x I2Cx scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQA

PGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2267
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x I2Ex scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQA

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

ARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2268
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x 12Kx scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

VRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2269
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x I2Lx scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

VRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAA

LTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2270
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x I2M2x

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

ScFc-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREA

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2271
CL1 7-D7 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQCLEWMGWINPTSGGA

x I2Mx scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYFCARESHAIQEGIWFDYWGQGT

-Full

LVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTISCRASQSISNYLNWYQ

Sequence

QKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFP

LTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

VRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VELFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2272
CS
artificial
SSWMN

PDL241.12.LH

CC-

HCDR1

2273
CS
artificial
RIYPGDADAKYNAKFKG

PDL241.12.LH

CC-

HCDR2

2274
CS
artificial
STMIATGAMDY

PDL241.12.LH

CC-

HCDR3

2275
CS
artificial
KASQDVSTAVA

PDL241.12.LH

CC-

LCDR1

2276
CS
artificial
SASYRYT

PDL241.12.LH

CC-

LCDR2

2277
CS
artificial
QQHYSTPPYT

PDL241.12.LH

CC-

LCDR3

2278
CS
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGRIYPGDADA

PDL241.12.LH

KYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMDYWGQGTLV

CC-VH

TVSS

2279
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKR

CC-VL

2280
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12_LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CC x I2C

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

x scFc-

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

Full

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQA

Sequence

PGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2281
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12 LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CC x I2E

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

x scFc-

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

Full

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQA

Sequence

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

ARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2282
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12 LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CC x I2K

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

x scFc-

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

Full

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQA

Sequence

PGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

VRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

2283
CS
artificial
PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

PDL241.12 LH

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

CC x I2L

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x scFc-

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

Full

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

Sequence

VRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAA

LTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2284
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12 LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CC x I2M

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

x scFc-

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

Full

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

Sequence

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

VRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2285
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12 LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CC x I2M2

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

x scFc-

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

Full

YWGQGTLVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREA

Sequence

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2286
CL6 3D4-
artificial
GYYMH

01.G2 LH-

HCDR1

2287
CL6 3D4-
artificial
WINPNSGETNYAQKFQG

01.G2 LH-

HCDR2

2288
CL6 3D4-
artificial
DALIVVAPVTRDYYYYGMDV

01.G2 LH-

HCDR3

2289
CL6 3D4-
artificial
RASQSVSSSYLA

01.G2 LH-

LCDR1

2290
CL6 3D4-
artificial
GASSRAT

01.G2 LH-

LCDR2

2291
CL6 3D4-
artificial
QQYGSSPLT

01.G2 LH-

LCDR3

2292
CL6 3D4-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGET

01.G2 LH-

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTRDYYYYGM

VH

DVWGQGTTVTVSS

2293
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH-

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIK

VL

2294
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

I2Cx scFc-

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKT

EDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSG

SLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2295
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

12Ex SCFc-

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKT

EDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSG

SLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2296
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

I2Kx scFc-

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKT

EDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSG

SLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2297
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRESGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

I2Lx scFc-

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKT

EDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSG

SLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2298
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

I2M2x scFc

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

-Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKT

EDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSG

SLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2299
CL6 3D4-
artificial
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATG

01.G2 LH x

IPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGCGTKLEIKGGGGSGGG

I2Mx scFc-

GSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWI

Full

NPNSGETNYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDALIVVAPVTR

Sequence

DYYYYGMDVWGQGTTVTVSSSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKY

AMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKT

EDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEP

SLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSG

SLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKT

KPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ

VYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSG

GGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVV

DVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCK

VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE

WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

2300
CL 10D8 CC
artificial
GYYMH

-HCDR1

2301
CL 10D8 CC
artificial
WINPNSGGTKYAQKFQG

-HCDR2

2302
CL 10D8 CC
artificial
DRITVAGTYYYYGMDV

-HCDR3

2303
CL 10D8 CC
artificial
RASQGVNNWLA

-LCDR1

2304
CL 10D8 CC
artificial
TASSLQS

-LCDR2

2305
CL 10D8 CC
artificial
QQANSFPIT

-LCDR3

2306
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

-VH

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

QGTTVTVSS

2307
CL 10D8 CC
artificial
DIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGV

-VL

PSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIK

2308
CL 10D8 CC
artificial
EIQMTQSPSSVSASVGDRVTITCRASQGVNNWLAWYQQKPGKAPKLLIYTASSLQSGV

EI GQ-VL

PSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQANSFPITFGCGTRLEIK

2309
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2C x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2310
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2E x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWV

RQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2311
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2K x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2312
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2L x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGG

KAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2313
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2M x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2314
CL 10D8 CC
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQCLEWMGWINPNSGGT

x I2M2 x

KYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARDRITVAGTYYYYGMDVWG

scFc-Full

QGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGVNNWLA

Sequence

WYQQKPGKAPKLLIYTASSLQSGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQAN

SFPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWV

REAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2315
DL 8-A7 CC
artificial
SYYWS

-HCDR1

2316
DL 8-A7 CC
artificial
YVYYSGTTNYNPSLKS

-HCDR2

2317
DL 8-A7 CC
artificial
IAVTGFYFDY

-HCDR3

2318
DL 8-A7 CC
artificial
RASQRVNNNYLA

-LCDR1

2319
DL 8-A7 CC
artificial
GASSRAT

-LCDR2

2320
DL 8-A7 CC
artificial
QQYDRSPLT

-LCDR3

2321
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

-VH

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

SS

2322
DL 8-A7 CC
artificial
EIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRPGQAPRLLIYGASSRATG

-VL

IPDRESGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTFGCGTKLEIK

2323
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2C x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

SCFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRESGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRH

GNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2324
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2E x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

scFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARA

GNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2325
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2K x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

ScFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRN

ENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVEL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2326
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2L x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

scFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRESGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTL

SGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2327
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2M x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

scFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2328
DL 8-A7 CC
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKCLEWIGYVYYSGTTN

x I2M2 x

YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCASIAVTGFYFDYWGQGTLVTV

scFc-Full

SSGGGGSGGGGSGGGGSEIVLTQSPGTLSLSPGERVTLSCRASQRVNNNYLAWYQQRP

Sequence

GQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYDRSPLTF

GCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRN

ANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2329
EGFRvIII CC
artificial
NYGMH

-HCDR1

2330
EGFRvIII CC
artificial
VIWYDGSDKYYADSVRG

-HCDR2

2331
EGFRvIII CC
artificial
DGYDILTGNPRDEDY

-HCDR3

2332
EGFRvIII CC
artificial
RSSQSLVHSDGNTYLS

-LCDR1

2333
EGFRvIII CC
artificial
RISRRFS

-LCDR2

2334
EGFRvIII CC
artificial
MQSTHVPRT

-LCDR3

2335
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

-VH

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQ

GTLVTVSS

2336
EGFRvIII CC
artificial
DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIYRISR

-VL

RFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTFGCGTKVEIK

2337
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2C-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTE

DTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS

LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

2338
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2E-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYA

INWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTE

DTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2339
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2K-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDEDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTE

DTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2340
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2L-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRESGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTE

DTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

2341
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2M-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDEDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

MNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTE

DTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2342
EGFRvIII CC
artificial
QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDK

x I2M2-

YYADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDEDYWGQ

Full

GTLVTVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGN

Sequence

TYLSWLQQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYC

MQSTHVPRTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYA

INWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTE

DTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPS

LTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGS

LLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2343
FL 7-A8 CC
artificial
NARMGVS

-HCDR1

2344
FL 7-A8 CC
artificial
HIFSNDEKSYSTSLKN

-HCDR2

2345
FL 7-A8 CC
artificial
IVGYGSGWYGFFDY

-HCDR3

2346
FL 7-A8 CC
artificial
RASQGIRNDLG

-LCDR1

2347
FL 7-A8 CC
artificial
AASTLQS

-LCDR2

2348
FL 7-A8 CC
artificial
LQHNSYPLT

-LCDR3

2349
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

-VH

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

GTLVTVSS

2350
FL 7-A8 CC
artificial
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASTLQSGV

-VL

PSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPLTFGCGTKVEIK

2351
FL 7-A8 CC
artificial
EIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKRLIYAASTLQSGV

EI GQ-VL

PSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNSYPLTFGCGTKVEIK

2352
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2Cx scFc

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2353
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2Ex scFc

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVR

QAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2354
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2Kx scFc

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVY

YCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2355
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2Lx scFc

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGK

AALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2356
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2M2x

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

ScFc-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVR

EAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVY

YCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSSGGGGGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2357
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

x I2Mx scFc

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

-Full

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

Sequence

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

YPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVR

QAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVY

YCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSP

GGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGK

AALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGG

PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQ

YGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGG

GGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED

PEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKAL

PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS

PGK

2358
MA 10-B5 CC
artificial
NAWMS

-HCDR1

2359
MA 10-B5 CC
artificial
RIRSRSYGGTTDYAAPVKG

-HCDR2

2360
MA 10-B5 CC
artificial
PSYSGSYYNYFSVMDV

HCDR3

2361
MA 10-B5 CC
artificial
RTSQSISSYLN

LCDR1

2362
MA 10-B5 CC
artificial
AASSLQG

-LCDR2

2363
MA 10-B5 CC
artificial
QQTYSMPFT

-LCDR3

2364
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

-VH

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

WGQGTTVTVSS

2365
MA 10-B5 CC
artificial
DIQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGRAPKLLIFAASSLQGGV

-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSMPFTFGCGTKVEIK

2366
MA 10-B5 CC
artificial
EIQMTQSPSSLSASVGDRVTITCRTSQSISSYLNWYQQKPGRAPKLLIFAASSLQGGV

EI GQ-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSMPFTFGCGTKVEIK

2367
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2C x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

scFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMN

WVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDT

AVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLL

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2368
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2E x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

scFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAIN

WVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDT

AVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2369
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2K x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

scFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDT

AVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2370
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2L x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

scFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDT

AVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLE

GGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2371
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2M x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

scFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMN

WVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDT

AVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLS

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2372
MA 10-B5 CC
artificial
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNAWMSWVRQAPGKCLEWVGRIRSRSYGG

x I2M2 x

TTDYAAPVKGRFTISRDDSKNTLFLQMNSLKTEDTAVYYCTTPSYSGSYYNYFSVMDV

ScFc-Full

WGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRTSQSISSY

Sequence

LNWYQQKPGRAPKLLIFAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

TYSMPFTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAIN

WVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDT

AVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLT

VSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLL

GGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPEL

LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPC

EEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGG

SGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVS

HEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSN

KALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWES

NGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL

SLSPGK

2373
MA A103 CC
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

x I2C x

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

scFc-Full

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

Sequence

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2374
MA A103 CC
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

x I2E x

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

scFc-Full

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

Sequence

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQA

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

ARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2375
MA A103 CC
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

x I2K x

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

scFc-Full

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

Sequence

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYC

VRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2376
MA A103 CC
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

x I2L x

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

scFc-Full

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

Sequence

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

VRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAA

LTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2377
MA A103 CC
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

x I2M x

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

scFc-Full

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

Sequence

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQA

PGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYC

VRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

2378
MA A103 CC
artificial
KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

x I2M2 x

TVTVSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQ

scFc-Full

QKPDGTVKLLIYYTSSLHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLP

Sequence

RTFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREA

PGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYC

VRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGG

TVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAA

LTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPS

VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYG

STYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR

EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVD

KSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGG

SGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPE

VKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPA

PIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

K

2379
MART A103
artificial
TSGMNVG

CC-HCDR1

2380
MART A103
artificial
HIWWNDDKYYNPALKS

CC-HCDR2

2381
MART A103
artificial
SYFGDYVWYFDV

CC-HCDR3

2382
MART A103
artificial
SASQGIHNYLN

CC-LCDR1

2383
MART A103
artificial
YTSSLHS

CC-LCDR2

2384
MART A103
artificial
QQYSKLPRT

CC-LCDR3

2385
MART A103
artificial
QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMNVGWIRQPSGKCLDWLAHIWWNDD

CC-VH

KYYNPALKSRLTISKDTSNNQVFLKIASVVTADTATYYCVRSYFGDYVWYFDVWGAGT

TVTVSS

2386
MART A103
artificial
DIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQQKPDGTVKLLIYYTSSLHSGV

CC-VL

PSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLPRTFGCGTKLEIK

2387
MART A103
artificial
EIQMTQTTSSLSASLGDRVTISCSASQGIHNYLNWYQQKPDGTVKLLIYYTSSLHSGV

CC EI GQ-

PSRFSGSGSGTDYSLTISNLEPEDIATYFCQQYSKLPRTFGCGTKLEIK

VL

2388
MS 15-B12
artificial
SSSYFWG

CC-HCDR1

2389
MS 15-B12
artificial
NIYYSGSSNYNPSLKS

CC-HCDR2

2390
MS 15-B12
artificial
LPRGDRDAFDI

CC-HCDR3

2391
MS 15-B12
artificial
RASQGISNYLA

CC-LCDR1

2392
MS 15-B12
artificial
AASTLQS

CC-LCDR2

2393
MS 15-B12
artificial
QQSYSTPFT

CC-LCDR3

2394
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC-VH

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

VTVSS

2395
MS 15-B12
artificial
DIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLIYAASTLQSGV

CC-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGCGTKVEIK

2396
MS 15-B12
artificial
EIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLIYAASTLQSGV

CC EI GQ-

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGCGTKVEIK

VL

2397
MS 5-F11
artificial
DYYMT

HCDR1

2398
MS 5-F11
artificial
YISSSGSTIYYADSVKG

HCDR2

2399
MS 5-F11
artificial
DRNSHFDY

HCDR3

2400
MS 5-F11
artificial
RASQGINTWLA

LCDR1

2401
MS 5-F11
artificial
GASGLQS

LCDR2

2402
MS 5-F11-
artificial
QQAKSFPRT

LCDR3

2403
MS 5-F11
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

VH

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

S

2404
MS 5-F11
artificial
DIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGKAPKLLIYGASGLQSGV

VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQGTKVEIK

2405
MS 5-F11 EI
artificial
EIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGKAPKLLIYGASGLQSGV

GQ-VL

PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQGTKVEIK

2406
MS R4L CC-
artificial
GYYIH

HCDR1

2407
MS R4L CC-
artificial
WINPNSGGTNYAQKFQG

HCDR2

2408
MS R4L CC-
artificial
VEAVAGREYYYFSGMDV

HCDR3

2409
MS R4L CC-
artificial
SGEKLGDKYVY

LCDR1

2410
MS R4L CC-
artificial
QSTKRPS

LCDR2

2411
MS R4L CC-
artificial
QAYHASTAV

LCDR3

2412
MS R4L CC-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

VH

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

GQGTTVTVSS

2413
MS R4L CC-
artificial
SYELTQPPSVSVSPGQTASITCSGEKLGDKYVYWYQQKPGQSPVLVIYQSTKRPSGVP

VL

ERFSGSNSGNTATLTISGTQAMDEADYYCQAYHASTAVFGCGTKLTVL

2414
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2C x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

scFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2415
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2E x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

ScFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2416
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2K x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

scFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2417
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2L x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

scFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2418
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2M x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

ScFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2419
MS 15-B12
artificial
QVQLQESGPGLVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGS

CC x I2M2 x

SNYNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTM

scFc-Full

VTVSSGGGGSGGGGSGGGGSDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQ

Sequence

KPGKVPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPF

TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2420
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2Cx scFc-

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGL

EWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN

FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLT

CGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2421
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2Ex scFc-

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGKGL

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARAGN

FGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2422
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2Kx scFc-

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGL

EWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRNEN

IGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2423
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2Lx scFc-

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGM

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGN

FGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTLSG

VQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2424
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2M2x scFc

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

-Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGL

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNAN

FGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2425
MS 5-F11 x
artificial
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMTWIRQAPGKGLEWLSYISSSGSTI

I2Mx scFc-

YYADSVKGRFTISRDNAKNSLFLQMNSLRAEDTAVYYCARDRNSHFDYWGQGTLVTVS

Full

SGGGGSGGGGSGGGGSDIQMTQSPSSVSASVGDRVTITCRASQGINTWLAWYQQKPGK

Sequence

APKLLIYGASGLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAKSFPRTFGQ

GTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGM

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGN

FGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTIT

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTLSG

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRC

VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK

NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ

QGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGGGG

SDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENW

YVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT

ISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT

TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2426
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2C x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

-Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2427
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2E x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

-Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWV

RQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2428
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2K x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

-Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAV

YYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2429
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2L x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGG

KAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2430
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2M x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

-Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWV

RQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAV

YYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSL

SPGK

2431
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

I2M2 x scFc

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

-Full

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

Sequence

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

ASTAVFGCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWV

REAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAV

YYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVS

PGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGG

KAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLG

GPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEE

QYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSG

GGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHE

DPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKA

LPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG

QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSI

SPGK

2432
MU 8-B7 CC
artificial
GYYWS

-HCDR1

2433
MU 8-B7 CC
artificial
DIDASGSTKYNPSLKS

-HCDR2

2434
MU 8-B7 CC
artificial
KKYSTVWSYFDN

-HCDR3

2435
MU 8-B7 CC
artificial
SGDKLGDKYAS

-LCDR1

2436
MU 8-B7 CC
artificial
QDRKRPS

LCDR2

2437
MU 8-B7 CC
artificial
QAWGSSTAV

-LCDR3

2438
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

-VH

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

TVSS

2439
MU 8-B7 CC
artificial
SYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKPGQSPVLVIYQDRKRPSGVP

-VL

ERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVFGCGTKLTVL

2440
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2Cx scFc

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVF

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRH

GNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVEL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2441
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2Ex scFc

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVF

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCARA

GNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2442
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2Kx scFc

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVF

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCVRN

ENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2443
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2Lx scFc

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVF

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTL

SGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2444
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2M2x

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

scFc-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVE

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAPGK

GLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRN

ANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

LTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2445
MU 8-B7 CC
artificial
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKCLEWIGDIDASGSTK

x I2Mx scFc

YNPSLKSRVTISLDTSKNQFSLKLNSVTAADTAVYFCARKKYSTVWSYFDNWGQGTLV

-Full

TVSSGGGGSGGGGSGGGGSSYELTQPSSVSVPPGQTASITCSGDKLGDKYASWYQQKP

Sequence

GQSPVLVIYQDRKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAWGSSTAVF

GCGTKLTVLSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAPGK

GMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRA

GNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVT

ITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAALTL

SGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTY

RCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM

TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR

WQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGSGG

GGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKE

NWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY

KTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2446
PM 76-B10-
artificial
DYYMY

HCDR1

2447
PM 76-B10-
artificial
IISDGGYYTYYSDIIKG

HCDR2

2448
PM 76-B10-
artificial
GFPLLRHGAMDY

HCDR3

2449
PM 76-B10-
artificial
KASQNVDTNVA

LCDR1

2450
PM 76-B10-
artificial
SASYRYS

LCDR2

2451
PM 76-B10-
artificial
QQYDSYPYT

LCDR3

2452
PM 76-B10-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

VH

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

VTVSS

2453
PM 76-B10-
artificial
DIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDV

VL

PSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIK

2454
PM 76-B10
artificial
EIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYRYSDV

EI GQ-VL

PSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPYTFGGGTKLEIK

2455
PM 76-
artificial
DYYMY

B10.11 CC-

HCDR1

2456
PM 76-
artificial
IISDGGYYTYYSDIIKG

B10.11 CC-

HCDR2

2457
PM 76-
artificial
GFPLLRHGAMDY

B10.11 CC-

HCDR3

2458
PM 76-
artificial
KASQNVDTNVA

B10.11 CC-

LCDR1

2459
PM 76-
artificial
SASYVYW

B10.11 CC-

LCDR2

2460
PM 76-
artificial
QQYDQQLIT

B10.11 CC-

LCDR3

2461
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC-

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

VH

VTVSS

2462
PM 76-
artificial
DIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYVYWDV

B10.11 CC-

PSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLITFGCGTKLEIK

VL

2463
PM 76-
artificial
EIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQKPGQAPKSLIYSASYVYWDV

B10.11 CC

PSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLITFGCGTKLEIK

EI GQ-VL

2464
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2C-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

2465
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2E-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2466
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2K-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2467
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2L-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

2468
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2M-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2469
PM 76-B10x
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKGLEWVAIISDGGYYT

I2M2-Full

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

Sequence

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

KPGQAPKSLIYSASYRYSDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDSYPY

TFGGGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

2470
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2C x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2471
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2E x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRQAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYYCA

RAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2472
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2K x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYYCV

RNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2473
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2L x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAAL

TLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2474
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2M x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQAP

GKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCV

RAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2475
PM 76-
artificial
QVQLVESGGGLVKPGESLRLSCAASGFTFSDYYMYWVRQAPGKCLEWVAIISDGGYYT

B10.11 CC x

YYSDIIKGRFTISRDNAKNSLYLQMNSLKAEDTAVYYCARGFPLLRHGAMDYWGQGTL

I2M2 x scFc

VTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQNVDTNVAWYQQ

-Full

KPGQAPKSLIYSASYVYWDVPSRFSGSASGTDFTLTISSVQSEDFATYYCQQYDQQLI

Sequence

TFGCGTKLEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAP

GKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCV

RNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGT

VTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAAL

TLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTHTCPPCPAPELLGGPSV

FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGS

TYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRE

EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK

SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSGGGGS

GGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV

KFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAP

IEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

2505
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x CD22

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

28-B7 N65S

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

CC x I2C x

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

scFc-Full

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

Sequence

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAY

LQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

2506
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x CD22

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

28-B7 N65S

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

CC x I2E x

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

scFc-Full

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

Sequence

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVY

LQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

2507
CD20 99-E5
artificial
EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

CC x CD22

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

28-B7 N65S

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

CC x I2K x

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

scFc-Full

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

Sequence

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVY

LQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

2508
CD20 99-E5
artificial
EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

CC x CD22

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

28-B7 N65S

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

CC x I2L x

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

scFc-Full

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

Sequence

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLY

LQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

2509
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x CD22

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

28-B7 N65S

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

CC x I2M x

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

scFc-Full

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

Sequence

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLY

LQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

2510
CD20 99-E5
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQCLEWIGYITPSTGYT

CC x CD22

EYNQKFKGRVTMTRDKSTSTVYMELSSLTSEDTAVYYCARVHDYDRAMEYWGQGTTVT

28-B7 N65S

VSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCKASQDINKYIAWYQQKP

CC x I2M2 x

GKGPKLLIYYTSTLQPGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQYASYPFTF

scFc-Full

GCGTRLEIKSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQ

Sequence

CLEWMGWISAYSGNAIYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPD

YYGSGSYSDYWGQGTLVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLS

CRASQSVSSNLAWYQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQYHSWPLLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAA

SGFTFNKYAINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAY

LQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGS

QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAP

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKT

HTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDG

VEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA

KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV

LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGG

GSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRT

PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWL

NGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGF

YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE

ALHNHYTQKSLSLSPGK

2511
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2C x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

scFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQ

(G4S) 3 x

APGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY

CD20 99E5

CVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2C-

GTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKA

Full

ALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTIS

RDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGL

IGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLT

VL

2512
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2E x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S ) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

ScFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVRQ

(G4S) 3 x

APGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYLQMNNLKTEDTAVYY

CD20 99E5

CARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2E-

GTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

Full

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTIS

RDDSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGL

IGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLT

VL

2513
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2K x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

ScFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ

(G4S) 3 x

APGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYLQMNNLKTEDTAVYY

CD20 99E5

CVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2K-

GTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

Full

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTIS

RDDSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGL

IGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLT

VL

2514
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2L x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

ScFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQ

(G4S) 3 x

APGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYY

CD20 99E5

CVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2L-

GTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKA

Full

ALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTIS

RDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGL

IGGTKFLAPGTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLT

VL

2515
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2M x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

ScFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAMNWVRQ

(G4S) 3 x

APGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYY

CD20 99E5

CVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2M-

GTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLSGGKA

Full

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTIS

RDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGL

IGGTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLT

VL

2516
CD22 28-
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQCLEWMGWISAYSGNA

B7N65S CC x

IYAQKLQGRVTMTRDTSTSTAYMELRSLRSDDTAVYYCARDPDYYGSGSYSDYWGQGT

I2M2 x

LVTVSSGGGGSGGGGSGGGGSEIVLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQ

(G4S) 3 x

QKPGQAPRLLIYGASSRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYHSWP

ScFc x

LLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVRE

(G4S) 3 x

APGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYY

CD20 99E5

CVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPG

CC x I2M2-

GTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKA

Full

ALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGSGGGGSGGGGSDKTHTCP

Sequence

PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVH

NAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

REPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD

GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGG

GGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVT

CVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKE

YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD

IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHN

HYTQKSLSLSPGKGGGGSGGGGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFT

SYWMHWVRQAPGQCLEWIGYITPSTGYTEYNQKFKGRVTMTRDKSTSTVYMELSSLTS

EDTAVYYCARVHDYDRAMEYWGQGTTVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLS

ASVGDRVTITCKASQDINKYIAWYQQKPGKGPKLLIYYTSTLQPGVPSRFSGSGSGTD

FTFTISSLQPEDIATYYCLQYASYPFTFGCGTRLEIKSGGGGSEVQLVESGGGLVQPG

GSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTIS

RDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSG

GGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGL

IGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLT

VL

2517
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2Cx scFc

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTA

YLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA

PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2518
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2Ex scFc

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTV

YLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLA

PGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2519
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2Kx scFc

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTV

YLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLA

PGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2520
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2Lx scFc

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTL

YLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLA

PGTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2521
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2M2x

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

scFc-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTA

YLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLA

PGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2522
CS
artificial
DIQMTQSPSSLSASVGDRVTITCKASQDVSTAVAWYQQKPGKAPKLLIYSASYRYTGV

PDL241.12.LH

PDRFTGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPPYTFGCGTKVEIKRGGGGSGG

CCx BC A7

GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYAFSSSWMNWVRQAPGQCLEWIGR

27-C4-G7 CC

IYPGDADAKYNAKFKGKATLTADKSTSTAYMELSSLRSEDTAVYYCARSTMIATGAMD

x I2Mx scFc

YWGQGTLVTVSSSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGYTFTNHIIHWVRQA

-Full

PGQCLEWMGYINPYPGYHAYNEKFQGRATMTSDTSTSTVYMELSSLRSEDTAVYYCAR

Sequence

DGYYRDTDVLDYWGQGTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVT

ITCQASQDISNYLNWYQQKPGKAPKLLIYYTSRLHTGVPSRFSGSGSGTDFTFTISSL

EPEDIATYYCQQGNTLPWTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCA

ASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTL

YLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGG

SQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLA

PGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDK

THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVD

GVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISK

AKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP

VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGG

GGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR

TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKG

FYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMH

EALHNHYTQKSLSLSPGK

2523
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2C x

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRD

DSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIG

GTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

2524
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2E X

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRD

DSKNTVYLQMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIG

GTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

2525
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2K X

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRD

DSKNTVYLQMNNLKTEDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIG

GTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

2526
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2L x

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRD

DSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIG

GTKFLAPGTPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVE

SCSVMHEALHNHYTQKSLSLSPGK

2527
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2M x

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRD

DSKNTLYLQMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIG

GTKFLAPGTPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

2528
FL 7-A8 CC
artificial
QVTLKESGPTLVKPTETLTLTCTLSGFSLNNARMGVSWIRQPPGKCLEWLAHIFSNDE

xCD123 24-

KSYSTSLKNRLTISKDSSKTQVVLTMTNVDPVDTATYYCARIVGYGSGWYGFFDYWGQ

B4-f NK CC

GTLVTVSSGGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW

x I2M2 X

YQQKPGKAPKRLIYAASTLQSGVPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQHNS

scFc-Full

YPLTFGCGTKVEIKSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSHYAMSWVR

Sequence

QAPGKCLEWVSAVSGGGDKTLYADAVKGRFTISRDNSKNTLFLQMNSLRAEDTAIYYC

ARLRGFYYGMDVWGQGTTVTVSSGGGGSGGGGSGGGGSDIVLTQSPLSLPVTPGEPAS

ISCRSSQSLLHSNKYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTL

KISRVEAEDVGVYYCMQALQTPPITFGCGTRLEIKSGGGGSEVQLVESGGGLVQPGGS

LKLSCAASGFTFNKYAINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRD

DSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGG

GSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIG

GTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVL

GGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVK

FNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN

YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKG

GGGSGGGGSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

2529
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x I2Lopt

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

x G4 x scFc

SGGGGQGGGGQGGGGQDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

x G4 x MS

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

15-B12 CC x

GTKVEIKSGGGGQEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGM

I2L GQ

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGN

27109-1-

FGSSYISYFAYWGQGTLVTVSSGGGGQGGGGQGGGGQQTVVTQEPSLTVSPGGTVTIT

Full

CGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTLSG

Sequence

VQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGCPPCPAPELLGGPSVFLFPPKPKD

TLMISRTPEVTCVVVDVSHEEPEVKENWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGKGGGGQGGGGQGGGGQGGGGQGGGGQGGGGQCPPC

PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEEPEVKENWYVDGVEVHNA

KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGQVQLQESGPG

LVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGSSNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTMVTVSSGGGGQ

GGGGQGGGGQDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLI

YAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGCGTKVEI

KSGGGGQEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGMEWVARI

RSKYNNYATYYADAVKDRFTISRDDSKNTLYLQMNNLKTEDTAVYYCVRAGNFGSSYI

SYFAYWGQGTLVTVSSGGGGQGGGGQGGGGQQTVVTQEPSLTVSPGGTVTITCGSSTG

AVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPGTPARFSGSLEGGKAALTLSGVQPEDE

AEYYCVLYYSNRWVFGSGTKLTVL

2530
CH3 15-E11
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMNWVRQAPGQCLEWMGNIAYGVKGT

CC x

NYNQKFQGRVTMTVDTSSSTAYMELSRLRSDDTAVYYCATRYFYVMDYWGQGTLVTVS

I2M2opt x

SGGGGQGGGGQGGGGQDIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGK

G4 x scFc x

VPKLLIYYTSRLHSGVPSRFSGSGSGTDFTLTISSLQPEDVATYYCVQYAQFPLTFGC

G4 x MS 15-

GTKVEIKSGGGGQEVQLVESGGGLVQPGGSLKLSCAASGFTENKYAINWVREAPGKGL

B12 CC x

EWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNAN

I2M2_GQ

FGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLT

27109-1-

CGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSG

Full

VQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGCPPCPAPELLGGPSVFLFPPKPKD

Sequence

TLMISRTPEVTCVVVDVSHEEPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLT

VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSL

TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGKGGGGQGGGGQGGGGQGGGGQGGGGQGGGGQCPPC

PAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEEPEVKENWYVDGVEVHNA

KTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

PQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGQVQLQESGPG

LVKPSETLSLTCTVSGGSISSSSYFWGWIRQPPGKCLEWIGNIYYSGSSNYNPSLKSR

VTISVDTSKNQFSLKLSSVTAADTAVYYCARLPRGDRDAFDIWGQGTMVTVSSGGGGQ

GGGGQGGGGQDIVMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKVPKLLI

YAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGCGTKVEI

KSGGGGQEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAINWVREAPGKGLEWVARI

RSKYNNYATYYADAVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRNANFGTSYI

SYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTG

AVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDE

AEYYCVLWYSNRWVFGSGTKLTVL

2531
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2C x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYL

QMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPG

TPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2532
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2E x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAINWVRQAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTVYL

QMNNLKTEDTAVYYCARAGNFGSSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPG

TPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2533
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2K x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYATYYAEAVKGRFTISRDDSKNTVYL

QMNNLKTEDTAVYYCVRNENIGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPG

TPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2534
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2L x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYL

QMNNLKTEDTAVYYCVRAGNFGSSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWIQKKPGQAPRGLIGGTKFLAPG

TPARFSGSLEGGKAALTLSGVQPEDEAEYYCVLYYSNRWVFGSGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2535
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2M x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAMNWVRQAPGKGMEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTLYL

QMNNLKTEDTAVYYCVRAGNFGTSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTITCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPG

TPARFSGSLSGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2536
MS R4L CC x
artificial
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQCLEWMGWINPNSGGT

CH3 R170R

NYAQKFQGRVTMTRDTSISTAYMELSRLRSDDTAVYYCARVEAVAGREYYYFSGMDVW

CC x I2M2 x

GQGTTVTVSSGGGGSGGGGSGGGGSSYELTQPPSVSVSPGQTASITCSGEKLGDKYVY

scFc-Full

WYQQKPGQSPVLVIYQSTKRPSGVPERFSGSNSGNTATLTISGTQAMDEADYYCQAYH

Sequence

ASTAVFGCGTKLTVLSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMHWV

RQTPGKCLEWVSKIDPSDDYTNYNQKVKGRFTISIDKSKNTLYLQMNSLRAEDTAVYY

CARWDYSHFDVWGQGTTVTVSSGGGGSGGGGSGGGGSEIVMTQSPATLSVSPGERATL

TCRASSSVSYMHWYQQKPGQAPRLLIYGTSNLVSGVPARFSGSGSGTEFTLTISSLQS

EDFAVYYCQQWSSYPLTFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAAS

GFTFNKYAINWVREAPGKGLEWVARIRSKYNNYATYYADAVKDRFTISRDDSKNTAYL

QMNNLKTEDTAVYYCVRNANFGTSYISYFAYWGQGTLVTVSSGGGGSGGGGSGGGGSQ

TVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQKKPGQAPRGLIGGTKFLAPG

TPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGSGTKLTVLGGGGDKTH

TCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGV

EVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK

GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL

DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGG

SGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP

EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFY

PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA

LHNHYTQKSLSLSPGK

2551
(G4Q)3-
artificial
GGGGQGGGGQGGGGQ

Linker

2552
Human
artificial
QDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDE

CD3epsilon

DHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMD

ECD

2553
Human
artificial
QDGNEEMGGITQTPYKVSISGTTVILT

CD3epsilon

ECD/pos.

1-27

2554
I2C_HC_H109A-
artificial
KYAMN

HCDR1

2555
I2C_HC_H109A-
artificial
RIRSKYNNYATYYADSVKD

HCDR2

2556
I2C_HC_H109A-
artificial
AGNFGNSYISYWAY

HCDR3

2557
I2C_HC_H109A-
artificial
GSSTGAVTSGNYPN

LCDR1

2558
I2C_HC_H109A-
artificial
GTKFLAP

LCDR2

2559
I2C_HC_H109A-
artificial
VLWYSNRWV

LCDR3

2560
I2C_HC_H109A-
artificial
EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNY

VH

ATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRAGNFGNSYISYWAYWG

QGTLVTVSS

2561
I2C_HC_H109A-
artificial
QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAP

VL

GTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL

POLYPEPTIDE CONSTRUCTS BINDING TO CD3

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

PCT Information

Provisional Applications (1)