ANTI-NOVEL CORONAVIRUS MONOCLONAL ANTIBODY AND APPLICATION THEREOF

Information

  • Patent Application
  • 20230174628
  • Publication Number
    20230174628
  • Date Filed
    April 27, 2021
    3 years ago
  • Date Published
    June 08, 2023
    a year ago
Abstract
The present invention relates to the fields of immunology and molecular virology, and in particular, to the field of diagnosis, prevention and treatment of a novel coronavirus. Specifically, the present invention relates to an anti-novel coronavirus monoclonal antibody and a composition (for example, a diagnostic agent and a therapeutic agent) containing same. In addition, the present invention also relates to use of the antibody. The antibody of the present invention can be used for diagnosing, preventing and/or treating novel coronavirus infections and/or diseases (for example, novel coronavirus pneumonia) caused by the infections.
Description
TECHNICAL FIELD

The present invention relates to the fields of immunology and molecular virology, and in particular, to the field of diagnosis, prevention and treatment of a novel coronavirus. Specifically, the present invention relates to an anti-novel coronavirus antibody and a composition (for example, a diagnostic agent and a therapeutic agent) containing same. In addition, the present invention also relates to use of the antibody. The antibody of the present invention can be used for diagnosing, preventing and/or treating novel coronavirus infections and/or diseases (for example, novel coronavirus pneumonia) caused by the infections.


BACKGROUND ART

As a single-stranded RNA virus, the novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is the pathogen of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19), and is a member of the Coronaviridae family, alongside the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic in 2002-2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in 2012. Coronavirus is a relatively large virus with round, oval or pleomorphic particles having a diameter of 50-200 nm. Coronavirus is an enveloped virus. The capsid of the virus is enveloped with a lipid envelope, on which a wide spike protein (Spike, S protein, SEQ ID No: 1460) is arranged forming a sun halo shape. Studies have confirmed that the S protein is located on the surface of the novel coronavirus SARS-CoV-2, and can bind to a receptor, angiotensin converting enzyme 2 (ACE2) molecule of a host cell via a receptor binding domain (RBD) contained therein during the virus infection of the host, thereby initiating the fusion of the viral membrane with the host cell membrane and causing the virus to infect the host cell.


So far, a neutralizing antibody has been proved to be an effective method for treating viral diseases. In general, upon stimulated by an antigen, a B lymphocyte in a patient is activated and then transformed and differentiated into a variety of different cells, and antibodies are produced. According to existing researches and reports, there is an anti-novel coronavirus antibody in the peripheral blood of patients recovered from novel coronavirus pneumonia, which is produced and secreted by activated B cells. However, there are a variety of B cells in the plasma of the recovered patients, and the binding activities and neutralizing titers of antibodies produced by different B cells are also different. So far, there is no study reporting an anti-novel coronavirus antibody with a high binding activity and/or a high neutralizing activity.


Therefore, there is a need to develop an antibody with a high binding activity and/or a high neutralizing activity against novel coronavirus SARS-CoV-2, thereby providing effective means for diagnosing, preventing and/or treating novel coronavirus infections.


SUMMARY OF THE INVENTION

The following technical solutions provided herein meet the above-mentioned needs and provide relevant advantages.


In one aspect, provided herein is an antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, and/or wherein the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110.


In some embodiments, the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.


In some embodiments, the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.


In some embodiments, the VH CDR1 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935. In some embodiments, the VH CDR1 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935. In some embodiments, the VH CDR1 of the antigen-binding unit comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935. In some embodiments, the VH CDR1 of the antigen-binding unit comprises the same sequence as CDR1 contained in SEQ ID NOs: 721-1080 and 3111-3145.


In some embodiments, the VH CDR2 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970. In some embodiments, the VH CDR2 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970. In some embodiments, the VH CDR2 of the antigen-binding unit comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970. In some embodiments, the VH CDR2 of the antigen-binding unit comprises the same sequence as CDR2 contained in SEQ ID NOs: 721-1080 and 3111-3145.


In some embodiments, the VL CDR1 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040. In some embodiments, the VL CDR1 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040. In some embodiments, the VL CDR1 of the antigen-binding unit comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040. In some embodiments, the VL CDR1 of the antigen-binding unit comprises the same sequence as CDR1 contained in SEQ ID NOs: 1081-1440 and 3146-3180.


In some embodiments, the VL CDR2 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075. In some embodiments, the VL CDR2 of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075. In some embodiments, the VL CDR2 of the antigen-binding unit comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075. In some embodiments, the VL CDR2 of the antigen-binding unit comprises the same sequence as CDR2 contained in SEQ ID NOs: 1081-1440 and 3146-3180.


In some embodiments, the VH of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.


In some embodiments, the VL of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.


In another aspect, provided herein is an antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935, or the same sequence as CDR1 contained in SEQ ID NOs: 721-1080 and 3111-3145, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970, or the same sequence as CDR2 contained in SEQ ID NOs: 721-1080 and 3111-3145, and wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, or the same sequence as CDR3 contained in SEQ ID NOs: 721-1080 and 3111-3145, and/or wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040, or the same sequence as CDR1 contained in SEQ ID NOs: 1081-1440 and 3146-3180, the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075, or the same sequence as CDR2 contained in SEQ ID NOs: 1081-1440 and 3146-3180, and the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110, or the same sequence as CDR3 contained in SEQ ID NOs: 1081-1440 and 3146-3180.


In another aspect, provided herein is an antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970, and wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, and/or wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040, the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075, and the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110.


In some embodiments, the VH of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145. In some embodiments, the VH of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.


In some embodiments, the VL of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180. In some embodiments, the VL of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.


In some embodiments, the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.


In some embodiments, the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.


In another aspect, provided herein is an antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145, and/or wherein the VL comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.


In some embodiments, the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.


In some embodiments, the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.


In some embodiments, the antigen-binding unit further comprises a heavy chain constant region (CH). In some embodiments, the CH of the antigen-binding unit comprises a sequence of SEQ ID NO: 1457 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NO: 1457. In some embodiments, the CH of the antigen-binding unit comprises a sequence selected from SEQ ID NO: 1457. In some embodiments, the CH of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NO: 1457. In some embodiments, the CH of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NO: 1457.


In some embodiments, the antigen-binding unit further comprises a light chain constant region (CL). In some embodiments, the CL of the antigen-binding unit comprises a sequence of SEQ ID NO: 1458 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NO: 1458. In some embodiments, the CL of the antigen-binding unit comprises a sequence selected from SEQ ID NO: 1458. In some embodiments, the CL of the antigen-binding unit comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NO: 1458. In some embodiments, the CL of the antigen-binding unit comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NO: 1458.


In another aspect, provided herein is an isolated nucleic acid molecule encoding the antigen-binding unit of the present invention as defined above.


In another aspect, provided herein is a vector, comprising the isolated nucleic acid molecule as defined above. The vector of the present invention can be a cloning vector and can also be an expression vector. In some embodiments, the vector of the present invention is for example, a plasmid, a cosmid, a phage or the like.


In another aspect, further provided is a host cell comprising the isolated nucleic acid molecule or the vector of the present invention. Such host cells include, but are not limited to, a prokaryotic cell, for example an Escherichia coli cell, and a eukaryotic cell such as a yeast cell, an insect cell, a plant cell, and an animal cell (such as, a mammal cell, e.g., a mouse cell, a human cell, etc.). The cell of the present invention can also be a cell line, for example, an HEK293 cell.


In another aspect, further provided is a method for preparing the antigen-binding unit of the present invention, comprising culturing the host cell of the present invention under suitable conditions, and recovering the antigen-binding unit of the present invention from a cell culture.


In another aspect, provided herein is a composition, comprising the antigen-binding unit, the isolated nucleic acid molecule, the vector or the host cell as described above.


In another aspect, provided herein is a kit comprising the antigen-binding unit of the present invention. In some embodiments, the antigen-binding unit of the present invention further comprises a detectable label. In some embodiments, the kit further comprises a second antibody, which specifically recognizes the antigen-binding unit of the present invention. Preferably, the second antibody further comprises a detectable label. Such detectable labels are well known to a person skilled in the art and include, but are not limited to, a radioisotope, a fluorescent material, a luminescent material, a colored material, an enzyme (e.g., horseradish peroxidase), etc.


In another aspect, provided herein is a method for detecting presence of a novel coronavirus, an S protein thereof or a RBD of the S protein, or a level thereof in a sample, comprising using the antigen-binding unit of the present invention. In some embodiments, the antigen-binding unit of the present invention further comprises a detectable label. In another preferred embodiment, the method further comprises detecting the antigen-binding unit of the present invention by using a second antibody carrying a detectable label. The method can be used for a diagnostic purpose (for example, the sample is a sample from a patient), or for a non-diagnostic purpose (for example, the sample is a cell sample rather than a sample from a patient).


In another aspect, provided herein is a method for diagnosing whether a subject is infected with a novel coronavirus, comprising: using the antigen-binding unit of the present invention to detect presence of a novel coronavirus, or an S protein thereof or a RBD of the S protein in a sample from the subject. In some embodiments, the antigen-binding unit of the present invention further comprises a detectable label. In another preferred embodiment, the method further comprises detecting the antigen-binding unit of the present invention by using a second antibody carrying a detectable label.


In another aspect, provided is the use of the antigen-binding unit of the present invention in the preparation of a kit, wherein the kit is used for detecting presence of a novel coronavirus, an S protein thereof or a RBD of the S protein, or a level thereof in a sample, or for diagnosing whether a subject is infected with the novel coronavirus.


In another aspect, provided herein is a pharmaceutical composition, comprising the antigen-binding unit of the present invention, and a pharmaceutically acceptable carrier and/or excipient.


In another aspect, provided herein is a method for neutralizing virulence of a novel coronavirus in a sample, comprising contacting the sample comprising the novel coronavirus with the antigen-binding unit of the present invention. Such methods can be used for therapeutic purposes, or for non-therapeutic purposes (for example, the sample is a cell sample, rather than a sample of or from a patient).


In another aspect, provided is the use of the antigen-binding unit of the present invention for preparing a drug, wherein the drug is used for neutralizing virulence of a novel coronavirus in a sample. In another aspect, provided herein is the antigen-binding unit as described above for neutralizing virulence of a novel coronavirus in a sample.


In another aspect, provided is the use of the antigen-binding unit of the present invention in the preparation of a pharmaceutical composition, wherein the pharmaceutical composition is used for preventing or treating novel coronavirus infections or diseases related to the novel coronavirus infections (e.g., novel coronavirus pneumonia) of a subject. In another aspect, provided herein is the antigen-binding unit as described above, for preventing and treating novel coronavirus infections or diseases related to the novel coronavirus infections (e.g., novel coronavirus pneumonia) of a subject.


In another aspect, provided herein is a method for preventing and treating novel coronavirus infections or diseases related to the novel coronavirus infections (e.g., novel coronavirus pneumonia) of a subject, comprising administering to a subject in need thereof a prophylactically or therapeutically effective amount of the antigen-binding unit of the present invention, or the pharmaceutical composition of the present invention.


In some embodiments, the subject is a mammal, for example human.


The antigen-binding unit of the present invention, or the pharmaceutical composition of the present invention can be administered to a subject by any suitable route of administration. Such routes of administration include, but are not limited to, oral, buccal, sublingual, topical, parenteral, rectal, intravaginal, or nasal routes.


The drug and pharmaceutical composition provided in the present invention can be used alone or in combination, or can be used in combination with other pharmacologically active agents (e.g., an antiviral drug, such as favipiravir, remdesivir and interferon). In some embodiments, the pharmaceutical composition also contains a pharmaceutically acceptable carrier and/or excipient.


In another aspect, provided herein is a conjugate comprising the antigen-binding unit as described above, wherein the antigen-binding unit is conjugated to a chemically functional moiety. In some embodiments, the chemically functional moiety is selected from a radioisotope, an enzyme, a fluorescent compound, a chemiluminescent compound, a bioluminescent compound, a substrate, a cofactor and an inhibitor.





BRIEF DESCRIPTION OF THE DRAWINGS


FIGS. 1A-1C exemplarily show SDS-PAGE detection results of antigen-binding units ABU-174, ABU-175 and ABU190.



FIGS. 2A-2E exemplarily show measurement results regarding the affinity of antigen-binding units ABU-174 (A), ABU-175 (B), ABU190 (C), ABU297 (D) and ABU367 (E) for the S protein by using SPR technology.



FIGS. 3A-3C exemplarily show measurement results regarding the neutralizing inhibitory activity of antigen-binding units ABU-174 (A), ABU-175 (B) and ABU190 (C) against SARS-CoV-2 pseudovirus.



FIG. 4 exemplarily shows CPE measurement results regarding the neutralizing inhibitory activity of ABU-175 antibody against SARS-CoV-2 euvirus.



FIG. 5 exemplarily shows PRNT measurement results of the neutralizing inhibitory activity of antigen-binding units ABU-174, ABU-175 and ABU190 against SARS-CoV-2 euvirus.





DETAILED DESCRIPTION OF EMBODIMENTS

While preferred embodiments of the present invention have been shown and described herein, it would have been obvious to a person skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to a person skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be employed during practicing the processes described herein. It is intended that the following claims define the scope of the present invention so as to encompass methods and structures within the scope of these claims, and equivalents thereof.


When a numerical range is provided, it should be understood that each intervening value between the upper and lower limits of that range (accurate to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise) and any other stated or intervening values within the stated range are encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included in the smaller ranges, and are also encompassed within the present invention, except for any specifically excluded limit within the stated range. Where the stated range encompasses one or both limits, ranges excluding either or both of those limits included therein are also encompassed within the present invention.


As used herein, the terms “polypeptide”, “peptide” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymers can be linear, cyclic or branched, can comprise modified amino acids, and can be interrupted by non-amino acids. The terms also include an amino acid polymer that has been modified; for example, by sulfation, glycosylation, lipidation, acetylation, phosphorylation, iodination, methylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenylation, transfer RNA-mediated addition of an amino acid to a protein (e.g., arginylation), ubiquitination, or any other manipulation, such as conjugation to a labeled component. As used herein, the term “amino acid” refers to natural and/or non-natural or synthetic amino acids, including glycine and a D or L optical isomer, as well as an amino acid analog and a peptidomimetic. A polypeptide or amino acid sequence “derived from” an specified protein refers to the origin of the polypeptide. Preferably, the polypeptide has an amino acid sequence that is substantially identical to the amino acid sequence of the polypeptide encoded in a sequence, or a portion thereof, wherein the portion consists of at least 10-20 amino acids or at least 20-30 amino acids or at least 30-50 amino acids, or can be identified immunologically with the polypeptide encoded in the sequence. The term also includes a polypeptide expressed by a specified nucleic acid sequence. As used herein, the term “domain” refers to a portion of a protein that is physically or functionally distinct from other portions of the protein or peptide. A physically defined domain includes an amino acid sequence which is extremely hydrophobic or hydrophilic, such as those membrane or cytoplasm-bound sequences. A domain can also be defined by internal homology that results, for example, from gene duplication. Functionally defined domains have distinct biological functions. For example, an antigen-binding domain refers to the portion of an antigen-binding unit or antibody that binds to an antigen. A functionally defined domain does not need to be encoded by a contiguous amino acid sequence, and a functionally defined domain can contain one or more physically defined domains.


As used herein, the term “amino acid” refers to natural and/or non-natural or synthetic amino acids, including but not limited to a D or L optical isomer, as well as an amino acid analog and a peptidomimetic. Standard one-letter or three-letter code is used to designate an amino acid. In the present invention, an amino acid is generally represented by one-letter and three-letter abbreviations well known in the art. For example, alanine can be represented by A or Ala.


As used herein, the term “antibody” refers to an immunoglobulin molecule generally consisting of two pairs of polypeptide chains, wherein each pair has one “light” (L) chain and one “heavy” (H) chain. Light chains of an antibody can be classified as a κ light chain and a λ light chain. Heavy chains can be classified as μ, δ, γ, α, and ε, and the isotypes of an antibody are defined as IgM, IgD, IgG, IgA, and IgE, respectively. In light and heavy chains, variable regions and constant regions are connected by a “J” region having about 12 or more amino acids, and a heavy chain also contains a “D” region having about 3 or more amino acids. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region consists of 3 domains (CH1, CH2 and CH3). Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region consists of one domain CL. The constant region of the antibody can mediate the binding of the immunoglobulin to a host tissue or factor, comprising various cells (e.g., effector cells) of the immune system and the first component of the classical complement system (C1q). VH and VL regions can also be subdivided into regions with high variability (called complementarity determining regions (CDRs)), which are interspersed with more conserved regions called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4 from amino terminus to carboxy terminus. The variable regions of each heavy/light chain pair (VH and VL) form an antibody binding site, respectively. Distribution of amino acids in various regions or domains follows the definitions in: Kabat Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), or Chothia & Lesk (1987) J. Mol. Biol. 196:901-917; Chothia et al. (1989) Nature 342:878-883, or IMGT (ImMunoGenTics) (Lefranc, M.-P., The Immunologist, 7, 132-136 (1999); Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003)). Unless indicated otherwise, the CDRs in the VH and VL of the antibody in the present application are defined on the basis of the IMGT numbering system. According to the Kabat numbering system, the CDR amino acid residues in VH are numbered 31-35 (CDR1), 50-65 (CDR2) and 95-102 (CDR3); and the CDR amino acid residues in VL are numbered 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3). According to Chothia, the CDR amino acids in VH are numbered 26-32 (CDR1), 52-56 (CDR2) and 95-102 (CDR3); and the amino acid residues in VL are numbered 24-34 (CDR1), 50-56 (CDR2) and 89-97 (CDR3). According to the IMGT numbering system, the CDR amino acid residues in VH are numbered approximately 26-33 (CDR1), 51-56 (CDR2) and 93-102 (CDR3); and the CDR amino acid residues in VL are numbered approximately 27-32 (CDR1), 50-51 (CDR2) and 89-97 (CDR3) (as disclosed in https://www.novoprolabs.com/tools/cdr).


The term “antibody” is not limited by any particular method for producing an antibody. For example, the antibody comprises a recombinant antibody, a monoclonal antibody and a polyclonal antibody. The antibody can be antibodies of different isotypes, for example, an IgG (e.g., an IgG1, IgG2, IgG3 or IgG4 subtype), IgA1, IgA2, IgD, IgE or IgM antibody.


As used herein, the term “antigen-binding fragment” of an antibody refers to a polypeptide comprising a fragment of a full-length antibody that retains the ability to specifically bind to the same antigen to which the full-length antibody binds and/or competes with the full-length antibody for specific binding to the antigen, which is also referred to as an “antigen-binding moiety”. See generally, Fundamental Immunology, Ch. 7 Paul, W., ed., 2nd Edition, Raven Press, N.Y. (1989), which is incorporated herein by reference in its entirety for all purposes. An antigen-binding fragment of an antibody can be generated by recombinant DNA techniques or by enzymatic or chemical cleavage of an intact antibody. In some cases, an antigen-binding fragment comprises Fab, Fab′, F(ab′)2, Fd, Fv, dAb and a complementarity determining region (CDR) fragment, a single chain antibody (e.g., scFv), a chimeric antibody, a diabody and a polypeptide comprising at least a portion of an antibody sufficient to confer a specific antigen-binding ability to the polypeptide. In some cases, an antigen-binding fragment of an antibody is a single chain antibody (e.g., scFv), wherein VL and VH domains are paired by a linker which enables them to be produced as a single polypeptide chain, thereby forming a monovalent molecule (see, e.g., Bird et al., Science 242:423 426 (1988) and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879 5883 (1988)). Such scFv molecules can have a general structure of NH2-VL-linker-VH—COOH or NH2-VH-linker-VL-COOH. Suitable linkers in the prior art consist of a repeated GGGGS amino acid sequence or a variant thereof. For example, a linker having an amino acid sequence (GGGGS)4 can be used, and a variant thereof can also be used (Holliger et al. (1993), Proc. Natl. Acad. Sci. USA 90: 6444-6448). Other linkers which can be used in the present invention are described in Alfthan et al. (1995), Protein Eng. 8:725-731, Choi et al. (2001), Eur. J. Immunol. 31: 94-106, Hu et al. (1996), Cancer Res. 56:3055-3061, Kipriyanov et al. (1999), J. Mol. Biol. 293:41-56 and Roovers et al. (2001), Cancer Immunol.


In some cases, an antigen-binding fragment of an antibody is a diabody, i.e., a bivalent antibody, wherein VH and VL domains are expressed on a single polypeptide chain; however, the linker used is too short to allow pairing between the two domains of the same chain, thereby forcing the domain to pair with the complementary domains of another chain and producing two antigen-binding sites (see, e.g., Holliger P. et al., Proc. Natl. Acad. Sci. USA 90:6444 6448 (1993), and Poljak R. J. et al., Structure 2:1121 1123 (1994)).


An antigen-binding fragment of an antibody (e.g., the above-mentioned antibody fragment) can be obtained from a given antibody (e.g., the antibody provided in the present invention) by using conventional techniques known to a person skilled in the art (e.g., recombinant DNA techniques or enzymatic or chemical cleavage) and the antigen-binding fragment of the antibody can be screened for specificity in the same manner as for an intact antibody.


Unless the context clearly dictates, the term “antibody” when referred to herein comprises not only an intact antibody but also an antigen-binding fragment of an antibody.


Unless the context clearly dictates, the term “antigen-binding unit” herein includes the antibody and the antigen-binding fragment thereof as defined above.


As used herein, the term “monoclonal antibody” refers to an antibody or a fragment of an antibody from a population of highly homologous antibody molecules, i.e., a population of identical antibody molecules, except for possible naturally occurring mutations. The monoclonal antibody is highly specific for a single epitope on an antigen. Relative to a monoclonal antibody, a polyclonal antibody generally comprises at least 2 or more different antibodies, and these different antibodies generally recognize different epitopes on an antigen. A monoclonal antibody can usually be obtained by using the hybridoma technique first reported by Kohler et al. (Nature, 256:495, 1975), and can also be obtained by using recombinant DNA techniques (for example, see Journal of virological methods, 2009, 158(1-2): 171-179).


As used herein, a “neutralizing antibody” refers to an antibody or antibody fragment that can clear or significantly reduce virulence (e.g., ability to infect cells) of a target virus.


As used herein, in the case of a polypeptide, a “sequence” is the order of amino acids in the polypeptide that are arranged in the direction from the amino terminus to the carboxy terminus, wherein residues adjacent to each other in the sequence are contiguous in the primary structure of the polypeptide. The sequence can also be a linear sequence of a portion of a polypeptide known to contain additional residues in one or both directions.


As used herein, “identity”, “homology” or “sequence identity” refers to the sequence similarity or interchangeability between two or more polynucleotide sequences or between two or more polypeptide sequences. When a program, such as Emboss Needle or BestFit is used to determine sequence identity, similarity or homology between two different amino acid sequences, a default setting can be used, or an appropriate scoring matrix, such as blosum45 or blosum80, can be selected to optimize the score of identity, similarity or homology. Preferably, homologous polynucleotides are those polynucleotides that hybridize under stringent conditions as defined herein and have at least 70%, preferably at least 80%, more preferably at least 90%, more preferably 95%, more preferably 97%, more preferably 98% and even more preferably 99% sequence identity to these sequences. When sequences of comparable lengths are optimally aligned, the homologous polypeptide preferably has at least 80%, or at least 90%, or at least 95%, or at least 97%, or at least 98% sequence identity, or at least 99% sequence identity.


With respect to the antigen-binding units determined herein, “percent sequence identity (%)” is defined as the percentage of amino acid residues in the query sequence that are identical to amino acid residues of the second, reference polypeptide sequence or a portion thereof, after aligning the sequences and introducing gaps, if necessary, to achieve maximum percentage of sequence identity, and not considering any conservative replacements as a part of sequence identity. The alignment aimed at determining the percent amino acid sequence identity can be achieved in various ways within the skill in the art, for example, by using a publicly available computer software, such as BLAST, BLAST-2, ALIGN, NEEDLE or Megalign (DNASTAR) software. A person skilled in the art can determine appropriate parameters for measuring the alignment, including any algorithm needed to achieve the maximal alignment over the full length of the sequences being compared. The percent identity may be measured over the length of the entire defined polypeptide sequence, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, such as a fragment of at least 5, at least 10, at least 15, at least 20, at least 50, at least 100 or at least 200 contiguous residues. These lengths are exemplary only, and it should be understood that any fragment length supported by the sequences shown in the Tables, Figures or Sequence Listing of the present invention can be used to describe the length over which percent identity can be measured.


The antigen-binding unit described herein may have one or more modifications relative to a reference sequence. The modifications may be deletions, insertions or additions, or substitutions or replacements of amino acid residues. “Deletion” refers to a change in an amino acid sequence due to the lack of one or more amino acid residues. “Insertion” or “addition” refers to a change in an amino acid sequence due to the addition of one or more amino acid residues compared with a reference sequence. “Substitution” or “replacement” refers to that one or more amino acids are substituted with different amino acids. In the present invention, mutations of the antigen-binding unit relative to the reference sequence can be determined by comparing the antigen-binding unit with the reference sequence. Optimal alignment of sequences for comparison can be performed according to any method known in the art.


As used herein, the term “antigen” refers to a substance that is recognized and specifically bound by an antigen-binding unit. An antigen can include a peptide, a protein, a glycoprotein, a polysaccharide, and a lipid; a portion thereof, and a combination thereof. Non-limiting exemplary antigens include a protein from a coronavirus such as SARS-CoV-2, and other homologs thereof.


As used herein, the term “isolated” refers to being isolated from cellular and other ingredients with which polynucleotides, peptides, polypeptides, proteins, antibodies or fragments thereof are associated under normal circumstances in nature. It is known to a person skilled in the art that a non-naturally occurring polynucleotide, peptide, polypeptide, protein, antibody or a fragment thereof does not need to be “isolated” to distinguish same from a naturally occurring counterpart thereof. In addition, the “concentrated”, “isolated” or “diluted” polynucleotide, peptide, polypeptide, protein, antibody, or the fragment thereof is distinguishable from the naturally occurring counterpart thereof, because the concentration or number of molecules per unit volume is greater than (“concentrated”) or less than the naturally occurring counterpart thereof (“isolated”). Enrichment may be measured on the basis of an absolute amount, such as the weight of a solution per unit volume, or same can be measured relative to a second, potentially interfering substance present in the source mixture.


The terms “polynucleotides”, “nucleic acids”, “nucleotides” and “oligonucleotides” are used interchangeably. They refer to polymerized nucleotides (deoxyribonucleotides or ribonucleotides) or analogs thereof of any length. A polynucleotide can have any three-dimensional structure and can perform any known or unknown function. The following are non-limiting examples of a polynucleotide: a coding region or a non-coding region of a gene or a gene fragment, a locus determined by linkage analysis, an exon, an intron, messenger RNA (mRNA), transfer RNA, ribosomal RNA, a ribozyme, cDNA, a recombinant polynucleotide, a branched polynucleotide, a plasmid, a vector, an isolated DNA of any sequence, an isolated RNA of any sequence, a nucleic acid probe, a primer, an oligonucleotide, or a synthetic DNA. A polynucleotide may contain a modified nucleotide, such as a methylated nucleotide, and a nucleotide analog. If present, a modification to a nucleotide structure can be implemented before or after the assembly of a polymer. The sequence of a nucleotide can be interrupted by non-nucleotide components. A polynucleotide can be further modified after polymerization, for example, by conjugation with a labeled component.


When used for a polynucleotide, “recombinant” means that the polynucleotide is a product of various combinations of cloning, restriction digestion and/or ligation steps, and other procedures that produce a construct different from the polynucleotide found in nature.


The term “gene” or “gene fragment” can be used interchangeably herein. They refer to polynucleotides containing at least one open reading frame capable of encoding a specific protein following transcription and translation. The gene or gene fragment may be genomic, cDNA, or synthetic, as long as the polynucleotide contains at least one open reading frame, which may cover the entire coding region or a segment thereof.


The term “operably linked” or “effectively linked” refers to the state of being juxtaposed in which the components so described are allowed to function in a intended manner. For example, if a promoter sequence promotes the transcription of a coding sequence, the promoter sequence is operably linked to the coding sequence.


As used herein, “expression” refers to the process by which polynucleotides are transcribed into mRNA, and/or the process by which the transcribed mRNA (also called “transcript”) is subsequently translated into peptides, polypeptides or proteins. The transcript and the encoded polypeptide are collectively referred to as the gene product. If the polynucleotide is derived from genomic DNA, the expression can include splicing of mRNA in an eukaryotic cell.


As used herein, the term “vector” refers to a nucleic acid delivery vehicle into which a polynucleotide can be inserted. When the vector allows for the expression of the protein encoded by the inserted polynucleotide, the vector is called an expression vector. A vector can be introduced into a host cell by transformation, transduction or transfection, and the genetic substance elements carried thereby can be expressed in the host cell. The vector is well known to a person skilled in the art, and includes but is not limited to: a plasmid; a phagemid; an artificial chromosome such as a yeast artificial chromosome (YAC), a bacterial artificial chromosome (BAC) or a P1-derived artificial chromosome (PAC); a phage such as a λ phage or an M13 phage, and an animal virus. The animal virus that can be used as a vector includes but is not limited to a retrovirus (comprising a lentivirus), an adenovirus, an adeno-associated virus, a herpes virus (e.g., a herpes simplex virus), a poxvirus, a baculovirus, a papilloma virus and a papovavirus (such as SV40). A vector can contain a variety of elements that control expression, including, but not limited to: a promoter sequence, a transcription initiation sequence, an enhancer sequence, a selection element, and a reporter gene. In addition, the vector also can contain a replication initiation site.


As used herein, the term “host cell” refers to a cell that can be used to introduce a vector, including but not limited to a prokaryotic cell such as Escherichia coli or Bacillus subtilis, a fungal cell such as a yeast cell or Aspergillus, an insect cell such as Drosophila S2 cell or Sf9, and an animal cell such as a fibroblast, a CHO cell, a COS cell, a NSO cell, an HeLa cell, a BHK cell, an HEK293 cell or a human cell.


As used herein, the term “biological sample” includes various types of samples obtained from an organism and can be used in a diagnostic or monitoring experiment. The term includes blood and other liquid samples derived from an organism, a solid tissue sample such as a biopsy specimen or tissue culture, or a cell derived therefrom and a progeny thereof. The term includes a sample that has been treated in any way following acquisition, such as by treatment with a reagent, dissolution, or enrichment of certain components. The term includes a clinical sample, and further includes cells in a cell culture, a cell supernatant, a cell lysate, serum, plasma, a biological fluid, and a tissue sample.


As used herein, the terms “recipient”, “individual”, “subject”, “host” and “patient” are used interchangeably herein and refer to any mammalian subject, particularly human, for whom diagnosis, treatment or treating is desired.


As used herein, the terms “treating”, “treatment”, etc. are used herein to generally refer to a process of obtaining a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of completely or partially preventing a disease or a symptom thereof, and/or may be therapeutic in terms of partially or completely stabilizing or curing a disease and/or adverse effects attributable to the disease. “Treating” as used herein encompasses any treatment of a disease in a mammal, such as a mouse, a rat, a rabbit, a pig, and a primate including human and other apes, particularly human, and the term includes: (a) preventing the occurrence of a disease or symptom in a subject who may be susceptible to the disease or symptom but has not yet been diagnosed; (b) inhibiting the symptom of the disease; (c) preventing the progression of the disease; (d) alleviating the symptom of the disease; (e) causing regression of the diseases or symptom; or any combination thereof. As used herein, the term “specifically binding” refers to a non-random binding reaction between two molecules, such as a reaction between an antibody and its corresponding antigen. In certain embodiments, an antibody specifically binding to an antigen (or an antibody specific for an antigen) refers to an antibody that binds to the antigen with an affinity (KD) less than about 10−5 M, for example less than about 10−6 M, 10−7 M, 10−8 M, 10−9 M or 10−10 M or less.


As used herein, the term “KD” refers to the dissociation equilibrium constant of a particular antibody-antigen interaction, which is used to describe the binding affinity between an antibody and an antigen. In the present invention, KD is defined as the ratio of two kinetic rate constants Ka/Kd, wherein “Ka” refers to the rate constant for the binding of an antibody to an antigen and “Kd” refers to the rate constant for the dissociation of the antibody from the antibody/antigen complex. The smaller the equilibrium dissociation constant KD, the tighter the antibody-antigen-binding and the higher the affinity between the antibody and the antigen. Generally, an antibody binds to an antigen with a dissociation equilibrium constant (KD) less than about 10−5 M. The property of the specific binding between two molecules can be determined using a method well known in the art, e.g. determined by surface plasmon resonance (SPR) in a BIACORE instrument.


As used herein, the term “neutralizing activity” refers to the functional activity of an antibody or antibody fragment binding to an antigen protein on a virus, thereby preventing viral infection of cells and/or maturation of viral progeny and/or release of viral progeny. The antibody or antibody fragment with a neutralizing activity can prevent the amplification of the virus, thereby inhibiting or eliminating virus infection. In some embodiments, the neutralizing activity is represented by the IC50 of an antibody or an antibody fragment in term of viral inhibition. The “half-maximal inhibitory concentration” (IC50) is a measure of a drug, such as an antibody, in terms of inhibiting biological or biochemical functions, etc., such as viral potency. The IC50 herein is calculated by a Reed-Muench method according to the neutralization inhibition rate of the antigen-binding fragment against viral (e.g., pseudoviral or euviral) infection in a cell. Provided herein is an antigen-binding unit which can specifically recognize and target an S protein of a novel coronavirus, particularly a receptor binding domain (RBD) of the S protein, and shows an efficient ability to neutralize the virus. Therefore, the antigen-binding unit of the present invention is particularly suitable for diagnosing, preventing and treating novel coronavirus infections or diseases related to the novel coronavirus infections (e.g., novel coronavirus pneumonia).


Antigen-Binding Unit

In one aspect, the antigen-binding unit of the present invention comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3.


The VH of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145. When the VH of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH of the antigen-binding unit of the present invention can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 additions, deletions, or substitutions compared with the reference polypeptide. When the VH of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 additions, deletions, or substitutions compared with the reference polypeptide. When the VH of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH of the antigen-binding unit of the present invention can have less than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 additions, deletions, or substitutions compared with the reference polypeptide.


The VH CDR1 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935. When the VH CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR1 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR1 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR1 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VH CDR2 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970. When the VH CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR2 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR2 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR2 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VH CDR3 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1-360 and 2971-3005. When the VH CDR3 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR3 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR3 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR3 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VH CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VH CDR3 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VL of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180. When the VL of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL of the antigen-binding unit of the present invention can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 additions, deletions, or substitutions compared with the reference polypeptide. When the VL of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid additions, deletions, or substitutions compared with the reference polypeptide. When the VL of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL of the antigen-binding unit of the present invention can have less than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 additions, deletions, or substitutions compared with the reference polypeptide.


The VL CDR1 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040. When the VL CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR1 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR1 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR1 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR1 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VL CDR2 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075. When the VL CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR2 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR2 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR2 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR2 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VL CDR3 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 361-720 and 3076-3110. When the VL CDR3 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR3 of the antigen-binding unit of the present invention can have 1, 2, 3, 4 or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR3 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR3 of the antigen-binding unit of the present invention can have more than 1, 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide. When the VL CDR3 of the antigen-binding unit of the present invention has amino acid additions, deletions, or substitutions compared with the reference polypeptide sequence, the VL CDR3 of the antigen-binding unit of the present invention can have less than 2, 3, 4, or 5 additions, deletions, or substitutions compared with the reference polypeptide.


The VH CDR1 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935; and the VL CDR1 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040.


The VH CDR2 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970; and the VL CDR2 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075.


The VH CDR3 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1-360 and 2971-3005; and the VL CDR3 of the antigen-binding unit of the present invention can comprise a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 361-720 and 3076-3110.


The VH of the antigen-binding unit of the present invention can comprise VH CDR1, VH CDR2 and VH CDR3, wherein the VH CDR1 is a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935; wherein the VH CDR2 is a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970; and wherein the VH CDR3 is a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1-360 and 2971-3005.


The VL of the antigen-binding unit of the present invention can comprise VL CDR1, VL CDR2 and VL CDR3, wherein the VL CDR1 is a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040; wherein the VL CDR2 is a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075; and wherein the VL CDR3 is a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, or a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 361-720 and 3076-3110.


The VH of the antigen-binding unit described herein can comprise a sequence selected from combinations of CDR1, CDR2, and CDR3 as following:























HCDR1
HCDR2
HCDR3
ABU No.
HCDR1
HCDR2
HCDR3
ABU No.
HCDR1
HCDR2
HCDR3
ABU No.


























1461
1821
1
ABU-1
1581
1941
121
ABU-121
1701
2061
241
ABU-241


1462
1822
2
ABU-2
1582
1942
122
ABU-122
1702
2062
242
ABU-242


1463
1823
3
ABU-3
1583
1943
123
ABU-123
1703
2063
243
ABU-243


1464
1824
4
ABU-4
1584
1944
124
ABU-124
1704
2064
244
ABU-244


1465
1825
5
ABU-5
1585
1945
125
ABU-125
1705
2065
245
ABU-245


1466
1826
6
ABU-6
1586
1946
126
ABU-126
1706
2066
246
ABU-246


1467
1827
7
ABU-7
1587
1947
127
ABU-127
1707
2067
247
ABU-247


1468
1828
8
ABU-8
1588
1948
128
ABU-128
1708
2068
248
ABU-248


1469
1829
9
ABU-9
1589
1949
129
ABU-129
1709
2069
249
ABU-249


1470
1830
10
ABU-10
1590
1950
130
ABU-130
1710
2070
250
ABU-250


1471
1831
11
ABU-11
1591
1951
131
ABU-131
1711
2071
251
ABU-251


1472
1832
12
ABU-12
1592
1952
132
ABU-132
1712
2072
252
ABU-252


1473
1833
13
ABU-13
1593
1953
133
ABU-133
1713
2073
253
ABU-253


1474
1834
14
ABU-14
1594
1954
134
ABU-134
1714
2074
254
ABU-254


1475
1835
15
ABU-15
1595
1955
135
ABU-135
1715
2075
255
ABU-255


1476
1836
16
ABU-16
1596
1956
136
ABU-136
1716
2076
256
ABU-256


1477
1837
17
ABU-17
1597
1957
137
ABU-137
1717
2077
257
ABU-257


1478
1838
18
ABU-18
1598
1958
138
ABU-138
1718
2078
258
ABU-258


1479
1839
19
ABU-19
1599
1959
139
ABU-139
1719
2079
259
ABU-259


1480
1840
20
ABU-20
1600
1960
140
ABU-140
1720
2080
260
ABU-260


1481
1841
21
ABU-21
1601
1961
141
ABU-141
1721
2081
261
ABU-261


1482
1842
22
ABU-22
1602
1962
142
ABU-142
1722
2082
262
ABU-262


1483
1843
23
ABU-23
1603
1963
143
ABU-143
1723
2083
263
ABU-263


1484
1844
24
ABU-24
1604
1964
144
ABU-144
1724
2084
264
ABU-264


1485
1845
25
ABU-25
1605
1965
145
ABU-145
1725
2085
265
ABU-265


1486
1846
26
ABU-26
1606
1966
146
ABU-146
1726
2086
266
ABU-266


1487
1847
27
ABU-27
1607
1967
147
ABU-147
1727
2087
267
ABU-267


1488
1848
28
ABU-28
1608
1968
148
ABU-148
1728
2088
268
ABU-268


1489
1849
29
ABU-29
1609
1969
149
ABU-149
1729
2089
269
ABU-269


1490
1850
30
ABU-30
1610
1970
150
ABU-150
1730
2090
270
ABU-270


1491
1851
31
ABU-31
1611
1971
151
ABU-151
1731
2091
271
ABU-271


1492
1852
32
ABU-32
1612
1972
152
ABU-152
1732
2092
272
ABU-272


1493
1853
33
ABU-33
1613
1973
153
ABU-153
1733
2093
273
ABU-273


1494
1854
34
ABU-34
1614
1974
154
ABU-154
1734
2094
274
ABU-274


1495
1855
35
ABU-35
1615
1975
155
ABU-155
1735
2095
275
ABU-275


1496
1856
36
ABU-36
1616
1976
156
ABU-156
1736
2096
276
ABU-276


1497
1857
37
ABU-37
1617
1977
157
ABU-157
1737
2097
277
ABU-277


1498
1858
38
ABU-38
1618
1978
158
ABU-158
1738
2098
278
ABU-278


1499
1859
39
ABU-39
1619
1979
159
ABU-159
1739
2099
279
ABU-279


1500
1860
40
ABU-40
1620
1980
160
ABU-160
1740
2100
280
ABU-280


1501
1861
41
ABU-41
1621
1981
161
ABU-161
1741
2101
281
ABU-281


1502
1862
42
ABU-42
1622
1982
162
ABU-162
1742
2102
282
ABU-282


1503
1863
43
ABU-43
1623
1983
163
ABU-163
1743
2103
283
ABU-283


1504
1864
44
ABU-44
1624
1984
164
ABU-164
1744
2104
284
ABU-284


1505
1865
45
ABU-45
1625
1985
165
ABU-165
1745
2105
285
ABU-285


1506
1866
46
ABU-46
1626
1986
166
ABU-166
1746
2106
286
ABU-286


1507
1867
47
ABU-47
1627
1987
167
ABU-167
1747
2107
287
ABU-287


1508
1868
48
ABU-48
1628
1988
168
ABU-168
1748
2108
288
ABU-288


1509
1869
49
ABU-49
1629
1989
169
ABU-169
1749
2109
289
ABU-289


1510
1870
50
ABU-50
1630
1990
170
ABU-170
1750
2110
290
ABU-290


1511
1871
51
ABU-51
1631
1991
171
ABU-171
1751
2111
291
ABU-291


1512
1872
52
ABU-52
1632
1992
172
ABU-172
1752
2112
292
ABU-292


1513
1873
53
ABU-53
1633
1993
173
ABU-173
1753
2113
293
ABU-293


1514
1874
54
ABU-54
1634
1994
174
ABU-174
1754
2114
294
ABU-294


1515
1875
55
ABU-55
1635
1995
175
ABU-175
1755
2115
295
ABU-295


1516
1876
56
ABU-56
1636
1996
176
ABU-176
1756
2116
296
ABU-296


1517
1877
57
ABU-57
1637
1997
177
ABU-177
1757
2117
297
ABU-297


1518
1878
58
ABU-58
1638
1998
178
ABU-178
1758
2118
298
ABU-298


1519
1879
59
ABU-59
1639
1999
179
ABU-179
1759
2119
299
ABU-299


1520
1880
60
ABU-60
1640
2000
180
ABU-180
1760
2120
300
ABU-300


1521
1881
61
ABU-61
1641
2001
181
ABU-181
1761
2121
301
ABU-301


1522
1882
62
ABU-62
1642
2002
182
ABU-182
1762
2122
302
ABU-302


1523
1883
63
ABU-63
1643
2003
183
ABU-183
1763
2123
303
ABU-303


1524
1884
64
ABU-64
1644
2004
184
ABU-184
1764
2124
304
ABU-304


1525
1885
65
ABU-65
1645
2005
185
ABU-185
1765
2125
305
ABU-305


1526
1886
66
ABU-66
1646
2006
186
ABU-186
1766
2126
306
ABU-306


1527
1887
67
ABU-67
1647
2007
187
ABU-187
1767
2127
307
ABU-307


1528
1888
68
ABU-68
1648
2008
188
ABU-188
1768
2128
308
ABU-308


1529
1889
69
ABU-69
1649
2009
189
ABU-189
1769
2129
309
ABU-309


1530
1890
70
ABU-70
1650
2010
190
ABU-190
1770
2130
310
ABU-310


1531
1891
71
ABU-71
1651
2011
191
ABU-191
1771
2131
311
ABU-311


1532
1892
72
ABU-72
1652
2012
192
ABU-192
1772
2132
312
ABU-312


1533
1893
73
ABU-73
1653
2013
193
ABU-193
1773
2133
313
ABU-313


1534
1894
74
ABU-74
1654
2014
194
ABU-194
1774
2134
314
ABU-314


1535
1895
75
ABU-75
1655
2015
195
ABU-195
1775
2135
315
ABU-315


1536
1896
76
ABU-76
1656
2016
196
ABU-196
1776
2136
316
ABU-316


1537
1897
77
ABU-77
1657
2017
197
ABU-197
1777
2137
317
ABU-317


1538
1898
78
ABU-78
1658
2018
198
ABU-198
1778
2138
318
ABU-318


1539
1899
79
ABU-79
1659
2019
199
ABU-199
1779
2139
319
ABU-319


1540
1900
80
ABU-80
1660
2020
200
ABU-200
1780
2140
320
ABU-320


1541
1901
81
ABU-81
1661
2021
201
ABU-201
1781
2141
321
ABU-321


1542
1902
82
ABU-82
1662
2022
202
ABU-202
1782
2142
322
ABU-322


1543
1903
83
ABU-83
1663
2023
203
ABU-203
1783
2143
323
ABU-323


1544
1904
84
ABU-84
1664
2024
204
ABU-204
1784
2144
324
ABU-324


1545
1905
85
ABU-85
1665
2025
205
ABU-205
1785
2145
325
ABU-325


1546
1906
86
ABU-86
1666
2026
206
ABU-206
1786
2146
326
ABU-326


1547
1907
87
ABU-87
1667
2027
207
ABU-207
1787
2147
327
ABU-327


1548
1908
88
ABU-88
1668
2028
208
ABU-208
1788
2148
328
ABU-328


1549
1909
89
ABU-89
1669
2029
209
ABU-209
1789
2149
329
ABU-329


1550
1910
90
ABU-90
1670
2030
210
ABU-210
1790
2150
330
ABU-330


1551
1911
91
ABU-91
1671
2031
211
ABU-211
1791
2151
331
ABU-331


1552
1912
92
ABU-92
1672
2032
212
ABU-212
1792
2152
332
ABU-332


1553
1913
93
ABU-93
1673
2033
213
ABU-213
1793
2153
333
ABU-333


1554
1914
94
ABU-94
1674
2034
214
ABU-214
1794
2154
334
ABU-334


1555
1915
95
ABU-95
1675
2035
215
ABU-215
1795
2155
335
ABU-335


1556
1916
96
ABU-96
1676
2036
216
ABU-216
1796
2156
336
ABU-336


1557
1917
97
ABU-97
1677
2037
217
ABU-217
1797
2157
337
ABU-337


1558
1918
98
ABU-98
1678
2038
218
ABU-218
1798
2158
338
ABU-338


1559
1919
99
ABU-99
1679
2039
219
ABU-219
1799
2159
339
ABU-339


1560
1920
100
ABU-100
1680
2040
220
ABU-220
1800
2160
340
ABU-340


1561
1921
101
ABU-101
1681
2041
221
ABU-221
1801
2161
341
ABU-341


1562
1922
102
ABU-102
1682
2042
222
ABU-222
1802
2162
342
ABU-342


1563
1923
103
ABU-103
1683
2043
223
ABU-223
1803
2163
343
ABU-343


1564
1924
104
ABU-104
1684
2044
224
ABU-224
1804
2164
344
ABU-344


1565
1925
105
ABU-105
1685
2045
225
ABU-225
1805
2165
345
ABU-345


1566
1926
106
ABU-106
1686
2046
226
ABU-226
1806
2166
346
ABU-346


1567
1927
107
ABU-107
1687
2047
227
ABU-227
1807
2167
347
ABU-347


1568
1928
108
ABU-108
1688
2048
228
ABU-228
1808
2168
348
ABU-348


1569
1929
109
ABU-109
1689
2049
229
ABU-229
1809
2169
349
ABU-349


1570
1930
110
ABU-110
1690
2050
230
ABU-230
1810
2170
350
ABU-350


1571
1931
111
ABU-111
1691
2051
231
ABU-231
1811
2171
351
ABU-351


1572
1932
112
ABU-112
1692
2052
232
ABU-232
1812
2172
352
ABU-352


1573
1933
113
ABU-113
1693
2053
233
ABU-233
1813
2173
353
ABU-353


1574
1934
114
ABU-114
1694
2054
234
ABU-234
1814
2174
354
ABU-354


1575
1935
115
ABU-115
1695
2055
235
ABU-235
1815
2175
355
ABU-355


1576
1936
116
ABU-116
1696
2056
236
ABU-236
1816
2176
356
ABU-356


1577
1937
117
ABU-117
1697
2057
237
ABU-237
1817
2177
357
ABU-357


1578
1938
118
ABU-118
1698
2058
238
ABU-238
1818
2178
358
ABU-358


1579
1939
119
ABU-119
1699
2059
239
ABU-239
1819
2179
359
ABU-359


1580
1940
120
ABU-120
1700
2060
240
ABU-240
1820
2180
360
ABU-360


2901
2936
2971
ABU-361
2913
2948
2983
ABU-373
2925
2960
2995
ABU-385


2902
2937
2972
ABU-362
2914
2949
2984
ABU-374
2926
2961
2996
ABU-386


2903
2938
2973
ABU-363
2915
2950
2985
ABU-375
2927
2962
2997
ABU-387


2904
2939
2974
ABU-364
2916
2951
2986
ABU-376
2928
2963
2998
ABU-388


2905
2940
2975
ABU-365
2917
2952
2987
ABU-377
2929
2964
2999
ABU-389


2906
2941
2976
ABU-366
2918
2953
2988
ABU-378
2930
2965
3000
ABU-390


2907
2942
2977
ABU-367
2919
2954
2989
ABU-379
2931
2966
3001
ABU-391


2908
2943
2978
ABU-368
2920
2955
2990
ABU-380
2932
2967
3002
ABU-392


2909
2944
2979
ABU-369
2921
2956
2991
ABU-381
2933
2968
3003
ABU-393


2910
2945
2980
ABU-370
2922
2957
2992
ABU-382
2934
2969
3004
ABU-394


2911
2946
2981
ABU-371
2923
2958
2993
ABU-383
2935
2970
3005
ABU-395


2912
2947
2982
ABU-372
2924
2959
2994
ABU-384










The VL of the antigen binding unit of the present invention can comprise a sequence selected from combinations of CDR1, CDR2, and CDR3 as following:























LCDR1
LCDR2
LCDR3
ABU No.
LCDR1
LCDR2
LCDR3
ABU No.
LCDR1
LCDR2
LCUR3
ABU No.


























2181
2541
361
ABU-1
2301
2661
481
ABU-121
2421
2781
601
ABU-241


2182
2542
362
ABU-2
2302
2662
482
ABU-122
2422
2782
602
ABU-242


2183
2543
363
ABU-3
2303
2663
483
ABU-123
2423
2783
603
ABU-243


2184
2544
364
ABU-4
2304
2664
484
ABU-124
2424
2784
604
ABU-244


2185
2545
365
ABU-5
2305
2665
485
ABU-125
2425
2785
605
ABU-245


2186
2546
366
ABU-6
2306
2666
486
ABU-126
2426
2786
606
ABU-246


2187
2547
367
ABU-7
2307
2667
487
ABU-127
2427
2787
607
ABU-247


2188
2548
368
ABU-8
2308
2668
488
ABU-128
2428
2788
608
ABU-248


2189
2549
369
ABU-9
2309
2669
489
ABU-129
2429
2789
609
ABU-249


2190
2550
370
ABU-10
2310
2670
490
ABU-130
2430
2790
610
ABU-250


2191
2551
371
ABU-11
2311
2671
491
ABU-131
2431
2791
611
ABU-251


2192
2552
372
ABU-12
2312
2672
492
ABU-132
2432
2792
612
ABU-252


2193
2553
373
ABU-13
2313
2673
493
ABU-133
2433
2793
613
ABU-253


2194
2554
374
ABU-14
2314
2674
494
ABU-134
2434
2794
614
ABU-254


2195
2555
375
ABU-15
2315
2675
495
ABU-135
2435
2795
615
ABU-255


2196
2556
376
ABU-16
2316
2676
496
ABU-136
2436
2796
616
ABU-256


2197
2557
377
ABU-17
2317
2677
497
ABU-137
2437
2797
617
ABU-257


2198
2558
378
ABU-18
2318
2678
498
ABU-138
2438
2798
618
ABU-258


2199
2559
379
ABU-19
2319
2679
499
ABU-139
2439
2799
619
ABU-259


2200
2560
380
ABU-20
2320
2680
500
ABU-140
2440
2800
620
ABU-260


2201
2561
381
ABU-21
2321
2681
501
ABU-141
2441
2801
621
ABU-261


2202
2562
382
ABU-22
2322
2682
502
ABU-142
2442
2802
622
ABU-262


2203
2563
383
ABU-23
2323
2683
503
ABU-143
2443
2803
623
ABU-263


2204
2564
384
ABU-24
2324
2684
504
ABU-144
2444
2804
624
ABU-264


2205
2565
385
ABU-25
2325
2685
505
ABU-145
2445
2805
625
ABU-265


2206
2566
386
ABU-26
2326
2686
506
ABU-146
2446
2806
626
ABU-266


2207
2567
387
ABU-27
2327
2687
507
ABU-147
2447
2807
627
ABU-267


2208
2568
388
ABU-28
2328
2688
508
ABU-148
2448
2808
628
ABU-268


2209
2569
389
ABU-29
2329
2689
509
ABU-149
2449
2809
629
ABU-269


2210
2570
390
ABU-30
2330
2690
510
ABU-150
2450
2810
630
ABU-270


2211
2571
391
ABU-31
2331
2691
511
ABU-151
2451
2811
631
ABU-271


2212
2572
392
ABU-32
2332
2692
512
ABU-152
2452
2812
632
ABU-272


2213
2573
393
ABU-33
2333
2693
513
ABU-153
2453
2813
633
ABU-273


2214
2574
394
ABU-34
2334
2694
514
ABU-154
2454
2814
634
ABU-274


2215
2575
395
ABU-35
2335
2695
515
ABU-155
2455
2815
635
ABU-275


2216
2576
396
ABU-36
2336
2696
516
ABU-156
2456
2816
636
ABU-276


2217
2577
397
ABU-37
2337
2697
517
ABU-157
2457
2817
637
ABU-277


2218
2578
398
ABU-38
2338
2698
518
ABU-158
2458
2818
638
ABU-278


2219
2579
399
ABU-39
2339
2699
519
ABU-159
2459
2819
639
ABU-279


2220
2580
400
ABU-40
2340
2700
520
ABU-160
2460
2820
640
ABU-280


2221
2581
401
ABU-41
2341
2701
521
ABU-161
2461
2821
641
ABU-281


2222
2582
402
ABU-42
2342
2702
522
ABU-162
2462
2822
642
ABU-282


2223
2583
403
ABU-43
2343
2703
523
ABU-163
2463
2823
643
ABU-283


2224
2584
404
ABU-44
2344
2704
524
ABU-164
2464
2824
644
ABU-284


2225
2585
405
ABU-45
2345
2705
525
ABU-165
2465
2825
645
ABU-285


2226
2586
406
ABU-46
2346
2706
526
ABU-166
2466
2826
646
ABU-286


2227
2587
407
ABU-47
2347
2707
527
ABU-167
2467
2827
647
ABU-287


2228
2588
408
ABU-48
2348
2708
528
ABU-168
2468
2828
648
ABU-288


2229
2589
409
ABU-49
2349
2709
529
ABU-169
2469
2829
649
ABU-289


2230
2590
410
ABU-50
2350
2710
530
ABU-170
2470
2830
650
ABU-290


2231
2591
411
ABU-51
2351
2711
531
ABU-171
2471
2831
651
ABU-291


2232
2592
412
ABU-52
2352
2712
532
ABU-172
2472
2832
652
ABU-292


2233
2593
413
ABU-53
2353
2713
533
ABU-173
2473
2833
653
ABU-293


2234
2594
414
ABU-54
2354
2714
534
ABU-174
2474
2834
654
ABU-294


2235
2595
415
ABU-55
2355
2715
535
ABU-175
2475
2835
655
ABU-295


2236
2596
416
ABU-56
2356
2716
536
ABU-176
2476
2836
656
ABU-296


2237
2597
417
ABU-57
2357
2717
537
ABU-177
2477
2837
657
ABU-297


2238
2598
418
ABU-58
2358
2718
538
ABU-178
2478
2838
658
ABU-298


2239
2599
419
ABU-59
2359
2719
539
ABU-179
2479
2839
659
ABU-299


2240
2600
420
ABU-60
2360
2720
540
ABU-180
2480
2840
660
ABU-300


2241
2601
421
ABU-61
2361
2721
541
ABU-181
2481
2841
661
ABU-301


2242
2602
422
ABU-62
2362
2722
542
ABU-182
2482
2842
662
ABU-302


2243
2603
423
ABU-63
2363
2723
543
ABU-183
2483
2843
663
ABU-303


2244
2604
424
ABU-64
2364
2724
544
ABU-184
2484
2844
664
ABU-304


2245
2605
425
ABU-65
2365
2725
545
ABU-185
2485
2845
665
ABU-305


2246
2606
426
ABU-66
2366
2726
546
ABU-186
2486
2846
666
ABU-306


2247
2607
427
ABU-67
2367
2727
547
ABU-187
2487
2847
667
ABU-307


2248
2608
428
ABU-68
2368
2728
548
ABU-188
2488
2848
668
ABU-308


2249
2609
429
ABU-69
2369
2729
549
ABU-189
2489
2849
669
ABU-309


2250
2610
430
ABU-70
2370
2730
550
ABU-190
2490
2850
670
ABU-310


2251
2611
431
ABU-71
2371
2731
551
ABU-191
2491
2851
671
ABU-311


2252
2612
432
ABU-72
2372
2732
552
ABU-192
2492
2852
672
ABU-312


2253
2613
433
ABU-73
2373
2733
553
ABU-193
2493
2853
673
ABU-313


2254
2614
434
ABU-74
2374
2734
554
ABU-194
2494
2854
674
ABU-314


2255
2615
435
ABU-75
2375
2735
555
ABU-195
2495
2855
675
ABU-315


2256
2616
436
ABU-76
2376
2736
556
ABU-196
2496
2856
676
ABU-316


2257
2617
437
ABU-77
2377
2737
557
ABU-197
2497
2857
677
ABU-317


2258
2618
438
ABU-78
2378
2738
558
ABU-198
2498
2858
678
ABU-318


2259
2619
439
ABU-79
2379
2739
559
ABU-199
2499
2859
679
ABU-319


2260
2620
440
ABU-80
2380
2740
560
ABU-200
2500
2860
680
ABU-320


2261
2621
441
ABU-81
2381
2741
561
ABU-201
2501
2861
681
ABU-321


2262
2622
442
ABU-82
2382
2742
562
ABU-202
2502
2862
682
ABU-322


2263
2623
443
ABU-83
2383
2743
563
ABU-203
2503
2863
683
ABU-323


2264
2624
444
ABU-84
2384
2744
564
ABU-204
2504
2864
684
ABU-324


2265
2625
445
ABU-85
2385
2745
565
ABU-205
2505
2865
685
ABU-325


2266
2626
446
ABU-86
2386
2746
566
ABU-206
2506
2866
686
ABU-326


2267
2627
447
ABU-87
2387
2747
567
ABU-207
2507
2867
687
ABU-327


2268
2628
448
ABU-88
2388
2748
568
ABU-208
2508
2868
688
ABU-328


2269
2629
449
ABU-89
2389
2749
569
ABU-209
2509
2869
689
ABU-329


2270
2630
450
ABU-90
2390
2750
570
ABU-210
2510
2870
690
ABU-330


2271
2631
451
ABU-91
2391
2751
571
ABU-211
2511
2871
691
ABU-331


2272
2632
452
ABU-92
2392
2752
572
ABU-212
2512
2872
692
ABU-332


2273
2633
453
ABU-93
2393
2753
573
ABU-213
2513
2873
693
ABU-333


2274
2634
454
ABU-94
2394
2754
574
ABU-214
2514
2874
694
ABU-334


2275
2635
455
ABU-95
2395
2755
575
ABU-215
2515
2875
695
ABU-335


2276
2636
456
ABU-96
2396
2756
576
ABU-216
2516
2876
696
ABU-336


2277
2637
457
ABU-97
2397
2757
577
ABU-217
2517
2877
697
ABU-337


2278
2638
458
ABU-98
2398
2758
578
ABU-218
2518
2878
698
ABU-338


2279
2639
459
ABU-99
2399
2759
579
ABU-219
2519
2879
699
ABU-339


2280
2640
460
ABU-100
2400
2760
580
ABU-220
2520
2880
700
ABU-340


2281
2641
461
ABU-101
2401
2761
581
ABU-221
2521
2881
701
ABU-341


2282
2642
462
ABU-102
2402
2762
582
ABU-222
2522
2882
702
ABU-342


2283
2643
463
ABU-103
2403
2763
583
ABU-223
2523
2883
703
ABU-343


2284
2644
464
ABU-104
2404
2764
584
ABU-224
2524
2884
704
ABU-344


2285
2645
465
ABU-105
2405
2765
585
ABU-225
2525
2885
705
ABU-345


2286
2646
466
ABU-106
2406
2766
586
ABU-226
2526
2886
706
ABU-346


2287
2647
467
ABU-107
2407
2767
587
ABU-227
2527
2887
707
ABU-347


2288
2648
468
ABU-108
2408
2768
588
ABU-228
2528
2888
708
ABU-348


2289
2649
469
ABU-109
2409
2769
589
ABU-229
2529
2889
709
ABU-349


2290
2650
470
ABU-110
2410
2770
590
ABU-230
2530
2890
710
ABU-350


2291
2651
471
ABU-111
2411
2771
591
ABU-231
2531
2891
711
ABU-351


2292
2652
472
ABU-112
2412
2772
592
ABU-232
2532
2892
712
ABU-352


2293
2653
473
ABU-113
2413
2773
593
ABU-233
2533
2893
713
ABU-353


2294
2654
474
ABU-114
2414
2774
594
ABU-234
2534
2894
714
ABU-354


2295
2655
475
ABU-115
2415
2775
595
ABU-235
2535
2895
715
ABU-355


2296
2656
476
ABU-116
2416
2776
596
ABU-236
2536
2896
716
ABU-356


2297
2657
477
ABU-117
2417
2777
597
ABU-237
2537
2897
717
ABU-357


2298
2658
478
ABU-118
2418
2778
598
ABU-238
2538
2898
718
ABU-358


2299
2659
479
ABU-119
2419
2779
599
ABU-239
2539
2899
719
ABU-359


2300
2660
480
ABU-120
2420
2780
600
ABU-240
2540
2900
720
ABU-360


3006
3041
3076
ABU-361
3018
3053
3088
ABU-373
3030
3065
3100
ABU-385


3007
3042
3077
ABU-362
3019
3054
3089
ABU-374
3031
3066
3101
ABU-386


3008
3043
3078
ABU-363
3020
3055
3090
ABU-375
3032
3067
3102
ABU-387


3009
3044
3079
ABU-364
3021
3056
3091
ABU-376
3033
3068
3103
ABU-388


3010
3045
3080
ABU-365
3022
3057
3092
ABU-377
3034
3069
3104
ABU-389


3011
3046
3081
ABU-366
3023
3058
3093
ABU-378
3035
3070
3105
ABU-390


3012
3047
3082
ABU-367
3024
3059
3094
ABU-379
3036
3071
3106
ABU-391


3013
3048
3083
ABU-368
3025
3060
3095
ABU-380
3037
3072
3107
ABU-392


3014
3049
3084
ABU-369
3026
3061
3096
ABU-381
3038
3073
3108
ABU-393


3015
3050
3085
ABU-370
3027
3062
3097
ABU-382
3039
3074
3109
ABU-394


3016
3051
3086
ABU-371
3028
3063
3098
ABU-383
3040
3075
3110
ABU-395


3017
3052
3087
ABU-372
3029
3064
3099
ABU-384










In the antigen binding unit of the present invention, the VH can comprise a sequence selected from combinations of CDR1, CDR2, and CDR3 as following:























HCDR1
HCDR2
HCDR3
ABU No.
HCDR1
HCDR2
HCDR3
ABU No.
HCDR1
HCDR2
HCDR3
ABU No.


























1461
1821
1
ABU-1
1581
1941
121
ABU-121
1701
2061
241
ABU-241


1462
1822
2
ABU-2
1582
1942
122
ABU-122
1702
2062
242
ABU-242


1463
1823
3
ABU-3
1583
1943
123
ABU-123
1703
2063
243
ABU-243


1464
1824
4
ABU-4
1584
1944
124
ABU-124
1704
2064
244
ABU-244


1465
1825
5
ABU-5
1585
1945
125
ABU-125
1705
2065
245
ABU-245


1466
1826
6
ABU-6
1586
1946
126
ABU-126
1706
2066
246
ABU-246


1467
1827
7
ABU-7
1587
1947
127
ABU-127
1707
2067
247
ABU-247


1468
1828
8
ABU-8
1588
1948
128
ABU-128
1708
2068
248
ABU-248


1469
1829
9
ABU-9
1589
1949
129
ABU-129
1709
2069
249
ABU-249


1470
1830
10
ABU-10
1590
1950
130
ABU-130
1710
2070
250
ABU-250


1471
1831
11
ABU-11
1591
1951
131
ABU-131
1711
2071
251
ABU-251


1472
1832
12
ABU-12
1592
1952
132
ABU-132
1712
2072
252
ABU-252


1473
1833
13
ABU-13
1593
1953
133
ABU-133
1713
2073
253
ABU-253


1474
1834
14
ABU-14
1594
1954
134
ABU-134
1714
2074
254
ABU-254


1475
1835
15
ABU-15
1595
1955
135
ABU-135
1715
2075
255
ABU-255


1476
1836
16
ABU-16
1596
1956
136
ABU-136
1716
2076
256
ABU-256


1477
1837
17
ABU-17
1597
1957
137
ABU-137
1717
2077
257
ABU-257


1478
1838
18
ABU-18
1598
1958
138
ABU-138
1718
2078
258
ABU-258


1479
1839
19
ABU-19
1599
1959
139
ABU-139
1719
2079
259
ABU-259


1480
1840
20
ABU-20
1600
1960
140
ABU-140
1720
2080
260
ABU-260


1481
1841
21
ABU-21
1601
1961
141
ABU-141
1721
2081
261
ABU-261


1482
1842
22
ABU-22
1602
1962
142
ABU-142
1722
2082
262
ABU-262


1483
1843
23
ABU-23
1603
1963
143
ABU-143
1723
2083
263
ABU-263


1484
1844
24
ABU-24
1604
1964
144
ABU-144
1724
2084
264
ABU-264


1485
1845
25
ABU-25
1605
1965
145
ABU-145
1725
2085
265
ABU-265


1486
1846
26
ABU-26
1606
1966
146
ABU-146
1726
2086
266
ABU-266


1487
1847
27
ABU-27
1607
1967
147
ABU-147
1727
2087
267
ABU-267


1488
1848
28
ABU-28
1608
1968
148
ABU-148
1728
2088
268
ABU-268


1489
1849
29
ABU-29
1609
1969
149
ABU-149
1729
2089
269
ABU-269


1490
1850
30
ABU-30
1610
1970
150
ABU-150
1730
2090
270
ABU-270


1491
1851
31
ABU-31
1611
1971
151
ABU-151
1731
2091
271
ABU-271


1492
1852
32
ABU-32
1612
1972
152
ABU-152
1732
2092
272
ABU-272


1493
1853
33
ABU-33
1613
1973
153
ABU-153
1733
2093
273
ABU-273


1494
1854
34
ABU-34
1614
1974
154
ABU-154
1734
2094
274
ABU-274


1495
1855
35
ABU-35
1615
1975
155
ABU-155
1735
2095
275
ABU-275


1496
1856
36
ABU-36
1616
1976
156
ABU-156
1736
2096
276
ABU-276


1497
1857
37
ABU-37
1617
1977
157
ABU-157
1737
2097
277
ABU-277


1498
1858
38
ABU-38
1618
1978
158
ABU-158
1738
2098
278
ABU-278


1499
1859
39
ABU-39
1619
1979
159
ABU-159
1739
2099
279
ABU-279


1500
1860
40
ABU-40
1620
1980
160
ABU-160
1740
2100
280
ABU-280


1501
1861
41
ABU-41
1621
1981
161
ABU-161
1741
2101
281
ABU-281


1502
1862
42
ABU-42
1622
1982
162
ABU-162
1742
2102
282
ABU-282


1503
1863
43
ABU-43
1623
1983
163
ABU-163
1743
2103
283
ABU-283


1504
1864
44
ABU-44
1624
1984
164
ABU-164
1744
2104
284
ABU-284


1505
1865
45
ABU-45
1625
1985
165
ABU-165
1745
2105
285
ABU-285


1506
1866
46
ABU-46
1626
1986
166
ABU-166
1746
2106
286
ABU-286


1507
1867
47
ABU-47
1627
1987
167
ABU-167
1747
2107
287
ABU-287


1508
1868
48
ABU-48
1628
1988
168
ABU-168
1748
2108
288
ABU-288


1509
1869
49
ABU-49
1629
1989
169
ABU-169
1749
2109
289
ABU-289


1510
1870
50
ABU-50
1630
1990
170
ABU-170
1750
2110
290
ABU-290


1511
1871
51
ABU-51
1631
1991
171
ABU-171
1751
2111
291
ABU-291


1512
1872
52
ABU-52
1632
1992
172
ABU-172
1752
2112
292
ABU-292


1513
1873
53
ABU-53
1633
1993
173
ABU-173
1753
2113
293
ABU-293


1514
1874
54
ABU-54
1634
1994
174
ABU-174
1754
2114
294
ABU-294


1515
1875
55
ABU-55
1635
1995
175
ABU-175
1755
2115
295
ABU-295


1516
1876
56
ABU-56
1636
1996
176
ABU-176
1756
2116
296
ABU-296


1517
1877
57
ABU-57
1637
1997
177
ABU-177
1757
2117
297
ABU-297


1518
1878
58
ABU-58
1638
1998
178
ABU-178
1758
2118
298
ABU-298


1519
1879
59
ABU-59
1639
1999
179
ABU-179
1759
2119
299
ABU-299


1520
1880
60
ABU-60
1640
2000
180
ABU-180
1760
2120
300
ABU-300


1521
1881
61
ABU-61
1641
2001
181
ABU-181
1761
2121
301
ABU-301


1522
1882
62
ABU-62
1642
2002
182
ABU-182
1762
2122
302
ABU-302


1523
1883
63
ABU-63
1643
2003
183
ABU-183
1763
2123
303
ABU-303


1524
1884
64
ABU-64
1644
2004
184
ABU-184
1764
2124
304
ABU-304


1525
1885
65
ABU-65
1645
2005
185
ABU-185
1765
2125
305
ABU-305


1526
1886
66
ABU-66
1646
2006
186
ABU-186
1766
2126
306
ABU-306


1527
1887
67
ABU-67
1647
2007
187
ABU-187
1767
2127
307
ABU-307


1528
1888
68
ABU-68
1648
2008
188
ABU-188
1768
2128
308
ABU-308


1529
1889
69
ABU-69
1649
2009
189
ABU-189
1769
2129
309
ABU-309


1530
1890
70
ABU-70
1650
2010
190
ABU-190
1770
2130
310
ABU-310


1531
1891
71
ABU-71
1651
2011
191
ABU-191
1771
2131
311
ABU-311


1532
1892
72
ABU-72
1652
2012
192
ABU-192
1772
2132
312
ABU-312


1533
1893
73
ABU-73
1653
2013
193
ABU-193
1773
2133
313
ABU-313


1534
1894
74
ABU-74
1654
2014
194
ABU-194
1774
2134
314
ABU-314


1535
1895
75
ABU-75
1655
2015
195
ABU-195
1775
2135
315
ABU-315


1536
1896
76
ABU-76
1656
2016
196
ABU-196
1776
2136
316
ABU-316


1537
1897
77
ABU-77
1657
2017
197
ABU-197
1777
2137
317
ABU-317


1538
1898
78
ABU-78
1658
2018
198
ABU-198
1778
2138
318
ABU-318


1539
1899
79
ABU-79
1659
2019
199
ABU-199
1779
2139
319
ABU-319


1540
1900
80
ABU-80
1660
2020
200
ABU-200
1780
2140
320
ABU-320


1541
1901
81
ABU-81
1661
2021
201
ABU-201
1781
2141
321
ABU-321


1542
1902
82
ABU-82
1662
2022
202
ABU-202
1782
2142
322
ABU-322


1543
1903
83
ABU-83
1663
2023
203
ABU-203
1783
2143
323
ABU-323


1544
1904
84
ABU-84
1664
2024
204
ABU-204
1784
2144
324
ABU-324


1545
1905
85
ABU-85
1665
2025
205
ABU-205
1785
2145
325
ABU-325


1546
1906
86
ABU-86
1666
2026
206
ABU-206
1786
2146
326
ABU-326


1547
1907
87
ABU-87
1667
2027
207
ABU-207
1787
2147
327
ABU-327


1548
1908
88
ABU-88
1668
2028
208
ABU-208
1788
2148
328
ABU-328


1549
1909
89
ABU-89
1669
2029
209
ABU-209
1789
2149
329
ABU-329


1550
1910
90
ABU-90
1670
2030
210
ABU-210
1790
2150
330
ABU-330


1551
1911
91
ABU-91
1671
2031
211
ABU-211
1791
2151
331
ABU-331


1552
1912
92
ABU-92
1672
2032
212
ABU-212
1792
2152
332
ABU-332


1553
1913
93
ABU-93
1673
2033
213
ABU-213
1793
2153
333
ABU-333


1554
1914
94
ABU-94
1674
2034
214
ABU-214
1794
2154
334
ABU-334


1555
1915
95
ABU-95
1675
2035
215
ABU-215
1795
2155
335
ABU-335


1556
1916
96
ABU-96
1676
2036
216
ABU-216
1796
2156
336
ABU-336


1557
1917
97
ABU-97
1677
2037
217
ABU-217
1797
2157
337
ABU-337


1558
1918
98
ABU-98
1678
2038
218
ABU-218
1798
2158
338
ABU-338


1559
1919
99
ABU-99
1679
2039
219
ABU-219
1799
2159
339
ABU-339


1560
1920
100
ABU-100
1680
2040
220
ABU-220
1800
2160
340
ABU-340


1561
1921
101
ABU-101
1681
2041
221
ABU-221
1801
2161
341
ABU-341


1562
1922
102
ABU-102
1682
2042
222
ABU-222
1802
2162
342
ABU-342


1563
1923
103
ABU-103
1683
2043
223
ABU-223
1803
2163
343
ABU-343


1564
1924
104
ABU-104
1684
2044
224
ABU-224
1804
2164
344
ABU-344


1565
1925
105
ABU-105
1685
2045
225
ABU-225
1805
2165
345
ABU-345


1566
1926
106
ABU-106
1686
2046
226
ABU-226
1806
2166
346
ABU-346


1567
1927
107
ABU-107
1687
2047
227
ABU-227
1807
2167
347
ABU-347


1568
1928
108
ABU-108
1688
2048
228
ABU-228
1808
2168
348
ABU-348


1569
1929
109
ABU-109
1689
2049
229
ABU-229
1809
2169
349
ABU-349


1570
1930
110
ABU-110
1690
2050
230
ABU-230
1810
2170
350
ABU-350


1571
1931
111
ABU-111
1691
2051
231
ABU-231
1811
2171
351
ABU-351


1572
1932
112
ABU-112
1692
2052
232
ABU-232
1812
2172
352
ABU-352


1573
1933
113
ABU-113
1693
2053
233
ABU-233
1813
2173
353
ABU-353


1574
1934
114
ABU-114
1694
2054
234
ABU-234
1814
2174
354
ABU-354


1575
1935
115
ABU-115
1695
2055
235
ABU-235
1815
2175
355
ABU-355


1576
1936
116
ABU-116
1696
2056
236
ABU-236
1816
2176
356
ABU-356


1577
1937
117
ABU-117
1697
2057
237
ABU-237
1817
2177
357
ABU-357


1578
1938
118
ABU-118
1698
2058
238
ABU-238
1818
2178
358
ABU-358


1579
1939
119
ABU-119
1699
2059
239
ABU-239
1819
2179
359
ABU-359


1580
1940
120
ABU-120
1700
2060
240
ABU-240
1820
2180
360
ABU-360


2901
2936
2971
ABU-361
2913
2948
2983
ABU-373
2925
2960
2995
ABU-385


2902
2937
2972
ABU-362
2914
2949
2984
ABU-374
2926
2961
2996
ABU-386


2903
2938
2973
ABU-363
2915
2950
2985
ABU-375
2927
2962
2997
ABU-387


2904
2939
2974
ABU-364
2916
2951
2986
ABU-376
2928
2963
2998
ABU-388


2905
2940
2975
ABU-365
2917
2952
2987
ABU-377
2929
2964
2999
ABU-389


2906
2941
2976
ABU-366
2918
2953
2988
ABU-378
2930
2965
3000
ABU-390


2907
2942
2977
ABU-367
2919
2954
2989
ABU-379
2931
2966
3001
ABU-391


2908
2943
2978
ABU-368
2920
2955
2990
ABU-380
2932
2967
3002
ABU-392


2909
2944
2979
ABU-369
2921
2956
2991
ABU-381
2933
2968
3003
ABU-393


2910
2945
2980
ABU-370
2922
2957
2992
ABU-382
2934
2969
3004
ABU-394


2911
2946
2981
ABU-371
2923
2958
2993
ABU-383
2935
2970
3005
ABU-395


2912
2947
2982
ABU-372
2924
2959
2994
ABU-384










and the VL can comprise a sequence selected from combinations of CDR1, CDR2, and CDR3 as following:























LCDR1
LCDR2
LCDR3
ABU No.
LCDR1
LCDR2
LCDR3
ABU No.
LCDR1
LCDR2
LCDR3
ABU No.


























2181
2541
361
ABU-1
2301
2661
481
ABU-121
2421
2781
601
ABU-241


2182
2542
362
ABU-2
2302
2662
482
ABU-122
2422
2782
602
ABU-242


2183
2543
363
ABU-3
2303
2663
483
ABU-123
2423
2783
603
ABU-243


2184
2544
364
ABU-4
2304
2664
484
ABU-124
2424
2784
604
ABU-244


2185
2545
365
ABU-5
2305
2665
485
ABU-125
2425
2785
605
ABU-245


2186
2546
366
ABU-6
2306
2666
486
ABU-126
2426
2786
606
ABU-246


2187
2547
367
ABU-7
2307
2667
487
ABU-127
2427
2787
607
ABU-247


2188
2548
368
ABU-8
2308
2668
488
ABU-128
2428
2788
608
ABU-248


2189
2549
369
ABU-9
2309
2669
489
ABU-129
2429
2789
609
ABU-249


2190
2550
370
ABU-10
2310
2670
490
ABU-130
2430
2790
610
ABU-250


2191
2551
371
ABU-11
2311
2671
491
ABU-131
2431
2791
611
ABU-251


2192
2552
372
ABU-12
2312
2672
492
ABU-132
2432
2792
612
ABU-252


2193
2553
373
ABU-13
2313
2673
493
ABU-133
2433
2793
613
ABU-253


2194
2554
374
ABU-14
2314
2674
494
ABU-134
2434
2794
614
ABU-254


2195
2555
375
ABU-15
2315
2675
495
ABU-135
2435
2795
615
ABU-255


2196
2556
376
ABU-16
2316
2676
496
ABU-136
2436
2796
616
ABU-256


2197
2557
377
ABU-17
2317
2677
497
ABU-137
2437
2797
617
ABU-257


2198
2558
378
ABU-18
2318
2678
498
ABU-138
2438
2798
618
ABU-258


2199
2559
379
ABU-19
2319
2679
499
ABU-139
2439
2799
619
ABU-259


2200
2560
380
ABU-20
2320
2680
500
ABU-140
2440
2800
620
ABU-260


2201
2561
381
ABU-21
2321
2681
501
ABU-141
2441
2801
621
ABU-261


2202
2562
382
ABU-22
2322
2682
502
ABU-142
2442
2802
622
ABU-262


2203
2563
383
ABU-23
2323
2683
503
ABU-143
2443
2803
623
ABU-263


2204
2564
384
ABU-24
2324
2684
504
ABU-144
2444
2804
624
ABU-264


2205
2565
385
ABU-25
2325
2685
505
ABU-145
2445
2805
625
ABU-265


2206
2566
386
ABU-26
2326
2686
506
ABU-146
2446
2806
626
ABU-266


2207
2567
387
ABU-27
2327
2687
507
ABU-147
2447
2807
627
ABU-267


2208
2568
388
ABU-28
2328
2688
508
ABU-148
2448
2808
628
ABU-268


2209
2569
389
ABU-29
2329
2689
509
ABU-149
2449
2809
629
ABU-269


2210
2570
390
ABU-30
2330
2690
510
ABU-150
2450
2810
630
ABU-270


2211
2571
391
ABU-31
2331
2691
511
ABU-151
2451
2811
631
ABU-271


2212
2572
392
ABU-32
2332
2692
512
ABU-152
2452
2812
632
ABU-272


2213
2573
393
ABU-33
2333
2693
513
ABU-153
2453
2813
633
ABU-273


2214
2574
394
ABU-34
2334
2694
514
ABU-154
2454
2814
634
ABU-274


2215
2575
395
ABU-35
2335
2695
515
ABU-155
2455
2815
635
ABU-275


2216
2576
396
ABU-36
2336
2696
516
ABU-156
2456
2816
636
ABU-276


2217
2577
397
ABU-37
2337
2697
517
ABU-157
2457
2817
637
ABU-277


2218
2578
398
ABU-38
2338
2698
518
ABU-158
2458
2818
638
ABU-278


2219
2579
399
ABU-39
2339
2699
519
ABU-159
2459
2819
639
ABU-279


2220
2580
400
ABU-40
2340
2700
520
ABU-160
2460
2820
640
ABU-280


2221
2581
401
ABU-41
2341
2701
521
ABU-161
2461
2821
641
ABU-281


2222
2582
402
ABU-42
2342
2702
522
ABU-162
2462
2822
642
ABU-282


2223
2583
403
ABU-43
2343
2703
523
ABU-163
2463
2823
643
ABU-283


2224
2584
404
ABU-44
2344
2704
524
ABU-164
2464
2824
644
ABU-284


2225
2585
405
ABU-45
2345
2705
525
ABU-165
2465
2825
645
ABU-285


2226
2586
406
ABU-46
2346
2706
526
ABU-166
2466
2826
646
ABU-286


2227
2587
407
ABU-47
2347
2707
527
ABU-167
2467
2827
647
ABU-287


2228
2588
408
ABU-48
2348
2708
528
ABU-168
2468
2828
648
ABU-288


2229
2589
409
ABU-49
2349
2709
529
ABU-169
2469
2829
649
ABU-289


2230
2590
410
ABU-50
2350
2710
530
ABU-170
2470
2830
650
ABU-290


2231
2591
411
ABU-51
2351
2711
531
ABU-171
2471
2831
651
ABU-291


2232
2592
412
ABU-52
2352
2712
532
ABU-172
2472
2832
652
ABU-292


2233
2593
413
ABU-53
2353
2713
533
ABU-173
2473
2833
653
ABU-293


2234
2594
414
ABU-54
2354
2714
534
ABU-174
2474
2834
654
ABU-294


2235
2595
415
ABU-55
2355
2715
535
ABU-175
2475
2835
655
ABU-295


2236
2596
416
ABU-56
2356
2716
536
ABU-176
2476
2836
656
ABU-296


2237
2597
417
ABU-57
2357
2717
537
ABU-177
2477
2837
657
ABU-297


2238
2598
418
ABU-58
2358
2718
538
ABU-178
2478
2838
658
ABU-298


2239
2599
419
ABU-59
2359
2719
539
ABU-179
2479
2839
659
ABU-299


2240
2600
420
ABU-60
2360
2720
540
ABU-180
2480
2840
660
ABU-300


2241
2601
421
ABU-61
2361
2721
541
ABU-181
2481
2841
661
ABU-301


2242
2602
422
ABU-62
2362
2722
542
ABU-182
2482
2842
662
ABU-302


2243
2603
423
ABU-63
2363
2723
543
ABU-183
2483
2843
663
ABU-303


2244
2604
424
ABU-64
2364
2724
544
ABU-184
2484
2844
664
ABU-304


2245
2605
425
ABU-65
2365
2725
545
ABU-185
2485
2845
665
ABU-305


2246
2606
426
ABU-66
2366
2726
546
ABU-186
2486
2846
666
ABU-306


2247
2607
427
ABU-67
2367
2727
547
ABU-187
2487
2847
667
ABU-307


2248
2608
428
ABU-68
2368
2728
548
ABU-188
2488
2848
668
ABU-308


2249
2609
429
ABU-69
2369
2729
549
ABU-189
2489
2849
669
ABU-309


2250
2610
430
ABU-70
2370
2730
550
ABU-190
2490
2850
670
ABU-310


2251
2611
431
ABU-71
2371
2731
551
ABU-191
2491
2851
671
ABU-311


2252
2612
432
ABU-72
2372
2732
552
ABU-192
2492
2852
672
ABU-312


2253
2613
433
ABU-73
2373
2733
553
ABU-193
2493
2853
673
ABU-313


2254
2614
434
ABU-74
2374
2734
554
ABU-194
2494
2854
674
ABU-314


2255
2615
435
ABU-75
2375
2735
555
ABU-195
2495
2855
675
ABU-315


2256
2616
436
ABU-76
2376
2736
556
ABU-196
2496
2856
676
ABU-316


2257
2617
437
ABU-77
2377
2737
557
ABU-197
2497
2857
677
ABU-317


2258
2618
438
ABU-78
2378
2738
558
ABU-198
2498
2858
678
ABU-318


2259
2619
439
ABU-79
2379
2739
559
ABU-199
2499
2859
679
ABU-319


2260
2620
440
ABU-80
2380
2740
560
ABU-200
2500
2860
680
ABU-320


2261
2621
441
ABU-81
2381
2741
561
ABU-201
2501
2861
681
ABU-321


2262
2622
442
ABU-82
2382
2742
562
ABU-202
2502
2862
682
ABU-322


2263
2623
443
ABU-83
2383
2743
563
ABU-203
2503
2863
683
ABU-323


2264
2624
444
ABU-84
2384
2744
564
ABU-204
2504
2864
684
ABU-324


2265
2625
445
ABU-85
2385
2745
565
ABU-205
2505
2865
685
ABU-325


2266
2626
446
ABU-86
2386
2746
566
ABU-206
2506
2866
686
ABU-326


2267
2627
447
ABU-87
2387
2747
567
ABU-207
2507
2867
687
ABU-327


2268
2628
448
ABU-88
2388
2748
568
ABU-208
2508
2868
688
ABU-328


2269
2629
449
ABU-89
2389
2749
569
ABU-209
2509
2869
689
ABU-329


2270
2630
450
ABU-90
2390
2750
570
ABU-210
2510
2870
690
ABU-330


2271
2631
451
ABU-91
2391
2751
571
ABU-211
2511
2871
691
ABU-331


2272
2632
452
ABU-92
2392
2752
572
ABU-212
2512
2872
692
ABU-332


2273
2633
453
ABU-93
2393
2753
573
ABU-213
2513
2873
693
ABU-333


2274
2634
454
ABU-94
2394
2754
574
ABU-214
2514
2874
694
ABU-334


2275
2635
455
ABU-95
2395
2755
575
ABU-215
2515
2875
695
ABU-335


2276
2636
456
ABU-96
2396
2756
576
ABU-216
2516
2876
696
ABU-336


2277
2637
457
ABU-97
2397
2757
577
ABU-217
2517
2877
697
ABU-337


2278
2638
458
ABU-98
2398
2758
578
ABU-218
2518
2878
698
ABU-338


2279
2639
459
ABU-99
2399
2759
579
ABU-219
2519
2879
699
ABU-339


2280
2640
460
ABU-100
2400
2760
580
ABU-220
2520
2880
700
ABU-340


2281
2641
461
ABU-101
2401
2761
581
ABU-221
2521
2881
701
ABU-341


2282
2642
462
ABU-102
2402
2762
582
ABU-222
2522
2882
702
ABU-342


2283
2643
463
ABU-103
2403
2763
583
ABU-223
2523
2883
703
ABU-343


2284
2644
464
ABU-104
2404
2764
584
ABU-224
2524
2884
704
ABU-344


2285
2645
465
ABU-105
2405
2765
585
ABU-225
2525
2885
705
ABU-345


2286
2646
466
ABU-106
2406
2766
586
ABU-226
2526
2886
706
ABU-346


2287
2647
467
ABU-107
2407
2767
587
ABU-227
2527
2887
707
ABU-347


2288
2648
468
ABU-108
2408
2768
588
ABU-228
2528
2888
708
ABU-348


2289
2649
469
ABU-109
2409
2769
589
ABU-229
2529
2889
709
ABU-349


2290
2650
470
ABU-110
2410
2770
590
ABU-230
2530
2890
710
ABU-350


2291
2651
471
ABU-111
2411
2771
591
ABU-231
2531
2891
711
ABU-351


2292
2652
472
ABU-112
2412
2772
592
ABU-232
2532
2892
712
ABU-352


2293
2653
473
ABU-113
2413
2773
593
ABU-233
2533
2893
713
ABU-353


2294
2654
474
ABU-114
2414
2774
594
ABU-234
2534
2894
714
ABU-354


2295
2655
475
ABU-115
2415
2775
595
ABU-235
2535
2895
715
ABU-355


2296
2656
476
ABU-116
2416
2776
596
ABU-236
2536
2896
716
ABU-356


2297
2657
477
ABU-117
2417
2777
597
ABU-237
2537
2897
717
ABU-357


2298
2658
478
ABU-118
2418
2778
598
ABU-238
2538
2898
718
ABU-358


2299
2659
479
ABU-119
2419
2779
599
ABU-239
2539
2899
719
ABU-359


2300
2660
480
ABU-120
2420
2780
600
ABU-240
2540
2900
720
ABU-360


3006
3041
3076
ABU-361
3018
3053
3088
ABU-373
3030
3065
3100
ABU-385


3007
3042
3077
ABU-362
3019
3054
3089
ABU-374
3031
3066
3101
ABU-386


3008
3043
3078
ABU-363
3020
3055
3090
ABU-375
3032
3067
3102
ABU-387


3009
3044
3079
ABU-364
3021
3056
3091
ABU-376
3033
3068
3103
ABU-388


3010
3045
3080
ABU-365
3022
3057
3092
ABU-377
3034
3069
3104
ABU-389


3011
3046
3081
ABU-366
3023
3058
3093
ABU-378
3035
3070
3105
ABU-390


3012
3047
3082
ABU-367
3024
3059
3094
ABU-379
3036
3071
3106
ABU-391


3013
3048
3083
ABU-368
3025
3060
3095
ABU-380
3037
3072
3107
ABU-392


3014
3049
3084
ABU-369
3026
3061
3096
ABU-381
3038
3073
3108
ABU-393


3015
3050
3085
ABU-370
3027
3062
3097
ABU-382
3039
3074
3109
ABU-394


3016
3051
3086
ABU-371
3028
3063
3098
ABU-383
3040
3075
3110
ABU-395


3017
3052
3087
ABU-372
3029
3064
3099
ABU-384









The VH CDR1 of the antigen-binding unit of the present invention can comprise the same sequence as CDR1 contained in SEQ ID NOs: 721-1080 and 3111-3145; the VH CDR2 of the antigen-binding unit of the present invention can comprise the same sequence as CDR2 contained in SEQ ID NOs: 721-1080 and 3111-3145; the VH CDR3 of the antigen-binding unit of the present invention can comprise the same sequence as CDR3 contained in SEQ ID NOs: 721-1080 and 3111-3145; the VL CDR1 of the antigen-binding unit can comprise the same sequence as CDR1 contained in SEQ ID NOs: 1081-1440 and 3146-3180; the VL CDR2 of the antigen-binding unit can comprise the same sequence as CDR2 contained in SEQ ID NOs: 1081-1440 and 3146-3180; and/or the VL CDR3 of the antigen-binding unit can comprise the same sequence as CDR3 contained in SEQ ID NOs: 1081-1440 and 3146-3180.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 2354, SEQ ID NO: 2355, SEQ ID NO: 2370, SEQ ID NO: 2477, and SEQ ID NO: 3012;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 2714, SEQ ID NO: 2715, SEQ ID NO: 2730, SEQ ID NO: 2837, and SEQ ID NO: 3047;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 534, SEQ ID NO: 535, SEQ ID NO: 550, SEQ ID NO: 657, and SEQ ID NO: 3082;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 1634, SEQ ID NO: 1635, SEQ ID NO: 1650, SEQ ID NO: 1757, and SEQ ID NO: 2907;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 1994, SEQ ID NO: 1995, SEQ ID NO: 2010, SEQ ID NO: 2117, and SEQ ID NO: 2942; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 190, SEQ ID NO: 297, and SEQ ID NO: 2977.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 2354;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 2714;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 534;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 1634;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 1994; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 174.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 2355;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 2715;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 535;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 1635;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 1995; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 175.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 2370;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 2730;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 550;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 1650;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 2010; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 190.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 2477;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 2837;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 657;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 1757;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 2117; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 297.


In one embodiment, the antibody provided in the present invention comprises one, two, three, four, five or six amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of light chain variable region CDR1: SEQ ID NO: 3012;


b. amino acid sequences of light chain variable region CDR2: SEQ ID NO: 3047;


c. amino acid sequences of light chain variable region CDR3: SEQ ID NO: 3082;


d. amino acid sequences of heavy chain variable region CDR1: SEQ ID NO: 2907;


e. amino acid sequences of heavy chain variable region CDR2: SEQ ID NO: 2942; and


f. amino acid sequences of heavy chain variable region CDR3: SEQ ID NO: 2977.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 1377 and SEQ ID NO: 3152; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 1017 and SEQ ID NO: 3117.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 1254; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 894.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 1255; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 895.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 1270; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 910.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 1377; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 1017.


In one embodiment, the antibody provided in the present invention comprises one or two amino acid sequences, wherein each amino acid sequence is independently selected from the amino acid sequences listed below:


a. amino acid sequences of a light chain variable region: SEQ ID NO: 3152; and


b. amino acid sequences of a heavy chain variable region: SEQ ID NO: 3117.


The antigen-binding unit of the present invention can bind to the S protein of a novel coronavirus (SARS-CoV-2). The antigen-binding unit of the present invention can bind to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2). Binding of the antigen-binding unit to the RBD can be characterized or represented by any method known in the art. For example, binding can be characterized by binding affinity, which can be the strength of the interaction between the antigen-binding unit and the antigen. Binding affinity can be determined by any method known in the art, such as in vitro binding experiment. The binding affinity of the antigen-binding unit of the present invention can be represented by KD, which is defined as the ratio of two kinetic rate constants Ka/Kd, wherein “Ka” refers to the rate constant for the binding of an antibody to an antigen and “Kd” refers to the rate constant for the dissociation of the antibody from the antibody/antigen complex. The antigen-binding unit as disclosed herein specifically binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with a KD in the range of about 10 μM to about 1 fM. For example, the antigen-binding unit can specifically bind to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with a KD of less than about 10 μM, 1 μM, 0.1 μM, 50 nM, 20 nM, 15 nM, 10 nM, 5 nM, 4 nM, 3 nM, 2 nM, 1 nM, 0.5 nM, 0.1 nM, 50 pM, 10 pM, 1 pM, 0.1 pM, 10 fM, 1 fM, 0.1 fM or less than 0.1 fM. The antigen-binding unit disclosed herein can bind to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.


The antigen-binding unit of the present invention has a neutralizing activity against a novel coronavirus (SARS-CoV-2). The neutralizing activity of the antigen-binding unit of the present invention against the novel coronavirus (SARS-CoV-2) can be analyzed using pseudovirus. The pseudovirus has similar cell infection characteristics to the euvirus, can be used to simulate the early process of euvirus infection in a cell, and can be safely and quickly detected and analyzed. The neutralizing activity of the antigen-binding unit of the present invention against the novel coronavirus (SARS-CoV-2) can be detected by a method known in the art, such as using cell microneutralization assay, which is performed with reference to the description of Temperton N J et al., Emerg Infect Dis, 2005, 11(3), 411-416.


The neutralizing activity of the antigen-binding unit of the present invention against the novel coronavirus (SARS-CoV-2) can be detected by using an experimental cell, such as Huh-7 cell and pseudovirus SARS-CoV-2. The antigen-binding unit of the present invention can neutralize the novel coronavirus (SARS-CoV-2) pseudovirus with an IC50 of less than 100 μg/ml, less than 50 μg/ml, less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, less than 1 ng/ml, less than 0.5 ng/ml, less than 0.25 ng/ml, less than 0.2 ng/ml, less than 0.1 ng/ml, less than 50 pg/ml, less than 25 pg/ml, less than 20 pg/ml, less than 10 pg/ml, less than 5 pg/ml, less than 2.5 pg/ml, less than 2 pg/ml, or less than 1 pg/ml.


The neutralizing activity of the antigen-binding unit of the present invention against the novel coronavirus (SARS-CoV-2) can be detected by Plaque Reduction Neutralization Test (PRNT) using a SARS-CoV-2 euvirus, wherein the IC50 of the antigen-binding unit of the present invention for neutralization of the SARS-CoV-2 euvirus is calculated according to the reduction of plaques after incubation. The antigen-binding unit of the present invention can neutralize the novel coronavirus (SARS-CoV-2) euvirus with an IC50 of less than 100 μg/ml, less than 50 μg/ml, less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, less than 1 ng/ml, less than 0.5 ng/ml, less than 0.25 ng/ml, less than 0.2 ng/ml, less than 0.1 ng/ml, less than 50 pg/ml, less than 25 pg/ml, less than 20 pg/ml, less than 10 pg/ml, less than 5 pg/ml, less than 2.5 pg/ml, less than 2 pg/ml, or less than 1 pg/ml.


Preparation of Antigen-Binding Unit

Provided herein is a method for producing any of the antigen-binding units disclosed herein, wherein the method comprises culturing a host cell expressing the antigen-binding unit under conditions suitable for the expression of the antigen-binding unit and isolating the antigen-binding unit expressed by the host cell.


The expressed antigen-binding unit can be isolated using various protein purification techniques known in the art. Generally, the antigen-binding units are isolated from media as secreted polypeptides, although they can also be recovered from a host cell lysate or bacterial periplasm when produced directly in the absence of a signal peptide. If the antigen-binding units are membrane-bound, they can be dissolved in a suitable detergent solution commonly used by a person skilled in the art. The recovered antigen-binding units can be further purified by salt precipitation (e.g., with ammonium sulfate), ion exchange chromatography (e.g., running on a cation or anion exchange column at neutral pH and eluting with a step gradient of increasing ionic strength), gel filtration chromatography (including gel filtration HPLC) and tag affinity column chromatography, or affinity resin, such as protein A, protein G, hydroxyapatite and anti-immunoglobulins.


The derived immunoglobulins to which the following moieties are added can be used in the methods and compositions of the present invention: a chemical linker, a detectable moiety such as a fluorescent dye, an enzyme, a substrate, a chemiluminescent moiety, a specific binding moiety such as streptavidin, avidin or biotin, or a drug conjugate.


The present invention further provides an antigen-binding unit conjugated to a chemically functional moiety. Generally, the moiety is a label capable of producing a detectable signal. These conjugated antigen-binding units can be used, for example, in a detection system, such as for detecting the severity of viral infection, imaging of infection focus, etc. Such labels are known in the art and include but are not limited to a radioisotope, an enzyme, a fluorescent compound, a chemiluminescent compound, a bioluminescent compound, a substrate, a cofactor and an inhibitor. See U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241 for examples of patents teaching the use of such labels. The moiety can be covalently linked or recombinantly linked to the antigen-binding unit, or conjugated to the antigen-binding unit via a second reagent such as a second antibody, protein A or a biotin-avidin complex.


Other functional moieties include a signal peptide, a reagent enhancing immunoreactivity, a reagent facilitating coupling to a solid support, a vaccine carrier, a biological response modifier, a paramagnetic label, and a drug. The signal peptide is a short amino acid sequence that guides a newly synthesized protein through the cell membrane (usually the endoplasmic reticulum in an eukaryotic cell) and the inner membrane or both inner and outer membranes of a bacterium. The signal peptide can be located at the N-terminal portion of a polypeptide or the C-terminal portion of a polypeptide, and can be enzymatically removed from the cell between the biosynthesis and secretion of the polypeptide. Such peptides can be introduced into the antigen-binding unit to allow secretion of a synthetic molecule.


The reagent enhancing immunoreactivity includes but is not limited to a bacterial superantigen. The reagent facilitating coupling to a solid support includes but is not limited to biotin or avidin. The immunogen carrier includes but is not limited to, any physiologically acceptable buffers. The biological response modifier includes a cytokine, particularly tumor necrosis factor (TNF), interleukin-2, interleukin-4, granulocyte macrophage colony stimulating factor and y-interferon.


The chemically functional moiety can be prepared recombinantly, for example by generating a fusion gene encoding the antigen-binding unit and the functional moiety. Alternatively, the antigen-binding unit can be chemically bonded to the moiety by any of various well-known chemical procedures. For example, when the moiety is a protein, the linkage can be achieved by a heterobifunctional crosslinking agent, e.g., SPDP, carbodiimide glutaraldehyde, etc. The moiety can be covalently linked or conjugated via a second reagent, such as a second antibody, protein A or a biotin-avidin complex. The paramagnetic moiety and the conjugation thereof to an antibody are well known in the art. See, for example, Miltenyi et al. (1990) Cytometry 11:231-238.


Nucleic Acids

In one aspect, provided herein is an isolated polynucleotide encoding the antigen-binding unit of the present invention. Nucleotide sequences corresponding to various regions of the L or H chain of an existing antibody can be readily obtained and sequenced using conventional techniques including, but not limited to, hybridization, PCR, and DNA sequencing. The hybridoma cell producing a monoclonal antibody is used as a preferred source of an antibody nucleotide sequence. Large numbers of hybridoma cells producing a series of monoclonal antibodies may be obtained from a public or private repositories. The largest storage institution is the American Type Culture Collection, which provides a variety of well-characterized hybridoma cell lines. Alternatively, the antibody nucleotide can be obtained from an immunized or non-immunized rodent or human, and from an organ such as spleen and peripheral blood lymphocyte. Specific techniques suitable for extraction and synthesis of antibody nucleotides are described in Orlandi et al. (1989) Proc. Natl. Acad. Sci. U.S.A 86: 3833-3837; Larrick et al. (1989) biochem. Biophys. Res. Commun. 160: 1250-1255; Sastry et al. (1989) Proc. Natl. Acad. Sci., U.S.A. 86: 5728-5732; and U.S. Pat. No. 5,969,108.


The antibody nucleotide sequence can also be modified, for example, by substituting human heavy and light chain constant regions with coding sequences, to replace homologous non-human sequences. The chimeric antibody prepared in this manner retains the binding specificity of the original antibody.


In addition, the polynucleotide encoding the heavy chain and/or light chain of the antigen-binding unit can be subjected to codon optimization to achieve optimized expression of the antigen-binding unit of the subject in a desired host cell. For example, in one codon optimization method, a natural codon is substituted by the most common codon from the reference genome, wherein the translation rate of the codon for each amino acid is designed to be relatively high. Additional exemplary methods for generating a codon-optimized polynucleotide for expressing the desired protein are described in Kanaya et al., Gene, 238:143-155 (1999), Wang et al., Mol. Biol. Evol., 18(5):792-800 (2001), U.S. Pat. No. 5,795,737, US Publication No. 2008/0076161 and WO 2008/000632, and the methods can be applied to the heavy chain and/or light chain of the antigen-binding unit.


The polynucleotides of the present invention includes polynucleotides encoding a functional equivalent of the exemplary polypeptide and a fragment thereof.


Due to the degeneracy of the genetic code, there can be considerable variation in the nucleotides of the L and H sequences and a heterodimerization sequence suitable for construction of the polynucleotide and vector of the present invention. These variations are included in the present invention.


Method of Treatment

Provided herein is a method for preventing or treating a novel coronavirus (SARS-CoV-2) infection in a subject by using the antigen-binding unit of the present invention, comprising administering to the subject the antigen-binding unit of the present invention.


Provided herein is a method for treating a disease, condition or disorder in a mammal using the antigen-binding unit of the present invention in combination with a second agent. The second agent can be administered with, before or after an antibody. The second agent may be an antiviral agent. The antiviral agent includes but is not limited to telaprevir, boceprevir, semiprevir, sofosbuvir, daclastavir, asunaprevir, lamivudine, adefovir, entecavir, tenofovir, telbivudine, interferon α and PEGylated interferon α. The second agent can be selected from hydroxychloroquine, chloroquine, favipiravir, Gimsilumab, AdCOVID (University of Alabama at Birmingham), AT-100 (Airway Therapeutics), TZLS-501 (Tiziana Life Sciences), OYA1 (OyaGen), BPI-002 (BeyondSpring), INO-4800 (Inovio Pharmaceutical), NP-120 (ifenprodil), remdesivir (GS-5734), Actemra (Roche), Galidesivir (BCX4430), SNG001 (Synairgen Research), or a combination thereof.


The second agent may be an agent for alleviating symptoms of a concurrent inflammatory condition in a subject. The anti-inflammatory agent includes non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. NSAID includes but is not limited to salicylate, such as acetylsalicylic acid; diflunisal, salicylic acid and salsalate; propionic acid derivative, such as ibuprofen; naproxen; dexibuprofen, dexketoprofen, flurbiprofen, oxaprozin, fenoprofen, loxoprofen, and ketoprofen; acetic acid derivative such as indomethacin, diclofenac, tolmetin, aceclofenac, sulindac, nabumetone, etodolac and ketorolac; enolic acid derivative such as piroxicam, lornoxicam, meloxicam, isoxicam, tenoxicam, phenylbutazone and droxicam; anthranilic acid derivative such as mefenamic acid, flufenamic acid, meclofenamic acid and tolfenamic acid; selective COX-2 inhibitor, such as celecoxib, lumiracoxib, rofecoxib, etoricoxib, valdecoxib, firocoxib, and parecoxib; sulfonanilide, such as nimesulide; and other non-steroidal anti-inflammatory drugs such as clonixin and licofelone. The corticosteroids include but are not limited to cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisone, and prednisolone.


The second agent may be an immunosuppressive agent. The immunosuppressive agent that can be used in combination with the antigen-binding unit includes but is not limited to hydroxychloroquine, sulfasalazine, leflunomide, etanercept, infliximab, adalimumab, D-penicillamine, oral gold compound, injectable gold compound (by intramuscular injection), minocycline, gold sodium thiomalate, auranofin, D-penicillamine, lobenzarit, bucillamine, actarit, cyclophosphamide, azathioprine, methotrexate, mizoribine, cyclosporin and tacrolimus.


The specific dose will vary depending on the specific antigen-binding unit selected, the dosing regimen to be followed, whether it is administered in combination with other agents, the time of administration, the tissue to which it is administered, and the physical delivery system carrying the specific antigen-binding unit. In some embodiments, during the treatment cycle, the antigen-binding unit is administered to the subject at a dose of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 or 70 mg per week on average. For example, the antigen-binding unit is administered to the subject at a dose of about 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 or 55 mg per week. In some embodiments, the antigen-binding unit is administered to the subject at a dose of about 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 or 55 mg per week.


During the treatment cycle, the antigen-binding unit can be administered to the subject at a dose of greater than 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 mg per day on average. For example, during the treatment cycle, the antigen-binding unit is administered to the subject at a dose of about 6 to 10 mg, about 6.5 to 9.5 mg, about 6.5 to 8.5 mg, about 6.5 to 8 mg, or about 7 to 9 mg per day on average.


The dose of the antigen-binding unit can be about, at least about, or at most about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975, 1000 mg or mg/kg, or any range derived therefrom. It is contemplated that the dose in mg/kg refers to the amount of the antigen-binding unit in mg per kilogram of the total body weight of the subject. It is contemplated that when multiple doses are administered to a patient, the doses can vary in amount or can be the same.


Pharmaceutical Composition

Provided herein is a pharmaceutical composition comprising a subject antibody or a functional fragment thereof and a pharmaceutically acceptable carrier, excipient or stabilizer, including, but not limited to, an inert solid diluent and a filler, a diluent, a sterile aqueous solution and various organic solvents, a penetration enhancer, a solubilizer and an adjuvant. (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)).


The pharmaceutical composition can be in a unit dosage form suitable for single administration at a precise dose. The pharmaceutical composition can further comprise an antigen-binding unit as an active ingredient, and may include a conventional pharmaceutical carrier or excipient. In addition, it may include other drugs or agents, carriers, adjuvants, etc. An exemplary parenteral administration form includes a solution or suspension of an active polypeptide and/or PEG-modified polypeptide in a sterile aqueous solution, such as aqueous propylene glycol or dextrose solution. If desired, such dosage forms can be suitably buffered with a salt such as histidine and/or phosphate.


The composition can further include one or more pharmaceutically acceptable additives and excipients. These additives and excipients include but are not limited to an anti-adhesive agent, an anti-foaming agent, a buffer, a polymer, an antioxidant, a preservative, a chelating agent, a viscomodulator, a tension regulator, a flavoring agent, a colorant, a flavor enhancer, an opacifier, a suspending agent, a binder, a filler, a plasticizer, a lubricant and a mixture thereof.


Kit

The kit of the present invention comprises the antigen-binding unit of the present invention or a conjugate thereof of the present invention. Further provided is the use of the antigen-binding unit of the present invention in the preparation of a kit, wherein the kit is used for detecting presence of a novel coronavirus, an S protein thereof or a RBD of the S protein, or a level thereof in a sample, or for diagnosing whether a subject is infected with the novel coronavirus.


In some embodiments, the sample includes, but is not limited to, an excrement, an oral or nasal secretion, an alveolar lavage fluid, etc. from a subject (e.g., mammal, preferably human).


General methods for detecting presence of a target virus or antigen (e.g., a novel coronavirus, or an S protein thereof or a RBD of the S protein) or a level thereof in a sample by using an antibody or an antigen-binding fragment thereof is well known to a person skilled in the art. In some embodiments, the detection method may involve enzyme linked immunosorbent assay (ELISA), enzyme immunodetection, chemiluminescence immunodetection, radioimmunodetection, fluorescence immunodetection, immunochromatography, a competition method, and a similar detection method.


EXAMPLES

The present invention is described with reference to the following examples, which are meant to illustrate the present invention (but not limit the present invention).


Unless specifically stated, the molecular biology experimental methods and immunodetection methods used in the present invention were basically carried out with reference to J. Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press, 1989 and F. M. Ausubel et al., Short Protocols in Molecular Biology, 3rd Edition, John Wiley & Sons, Inc., 1995; and restriction enzymes were used under the conditions as recommended by the product manufacturer. If no specific conditions are indicated in the examples, conventional conditions or the conditions suggested by the manufacturer shall be followed. The reagents or instruments used without indicating the manufacturers are commercially available conventional products. It is known to a person skilled in the art that the examples illustrate the present invention by way of example and are not intended to limit the claimed scope of the present invention.


Example 1: Isolation of Memory B Cell

Blood was collected from people once infected with SARS-CoV-2 virus but recovered and discharged (provided by Beijing Youan Hospital), and PBMCs were extracted using STEMCELL SepMate™-15 (Stemcell Technologies, Cat #86415) in a Biosafety Physical Containment Level-2+ Laboratory. Then, memory B cells were enriched from the extracted PBMCs using STEMCELL EasySep Human Memory B Cell Isolation Kit (Stemcell Technologies, Cat #17864) according to the manufacturer's instructions.


Example 2: Acquisition and Identification of Sequence of Antigen-Binding Unit

Single-cell transcriptome VDJ sequencing of the above-mentioned enriched memory B cells was performed using Chromium Single Cell V(D)J Reagent Kits (purchased from 10× genomics, Cat #100006) according to the manufacturer's instructions. The sequencing results were analyzed, and 360 antigen-binding units were obtained and named as ABU 1-395. The sequence information of the obtained antigen-binding units is as shown in Table 1 below.









TABLE 1







Exemplary antigen-binding units obtained herein











ABU No.
VH SEQ ID No.
VL SEQ ID NO.















ABU-1
721
1081



ABU-2
722
1082



ABU-3
723
1083



ABU-4
724
1084



ABU-5
725
1085



ABU-6
726
1086



ABU-7
727
1087



ABU-8
728
1088



ABU-9
729
1089



ABU-10
730
1090



ABU-11
731
1091



ABU-12
732
1092



ABU-13
733
1093



ABU-14
734
1094



ABU-15
735
1095



ABU-16
736
1096



ABU-17
737
1097



ABU-18
738
1098



ABU-19
739
1099



ABU-20
740
1100



ABU-21
741
1101



ABU-22
742
1102



ABU-23
743
1103



ABU-24
744
1104



ABU-25
745
1105



ABU-26
746
1106



ABU-27
747
1107



ABU-28
748
1108



ABU-29
749
1109



ABU-30
750
1110



ABU-31
751
1111



ABU-32
752
1112



ABU-33
753
1113



ABU-34
754
1114



ABU-35
755
1115



ABU-36
756
1116



ABU-37
757
1117



ABU-38
758
1118



ABU-39
759
1119



ABU-40
760
1120



ABU-41
761
1121



ABU-42
762
1122



ABU-43
763
1123



ABU-44
764
1124



ABU-45
765
1125



ABU-46
766
1126



ABU-47
767
1127



ABU-48
768
1128



ABU-49
769
1129



ABU-50
770
1130



ABU-51
771
1131



ABU-52
772
1132



ABU-53
773
1133



ABU-54
774
1134



ABU-55
775
1135



ABU-56
776
1136



ABU-57
777
1137



ABU-58
778
1138



ABU-59
779
1139



ABU-60
780
1140



ABU-61
781
1141



ABU-62
782
1142



ABU-63
783
1143



ABU-64
784
1144



ABU-65
785
1145



ABU-66
786
1146



ABU-67
787
1147



ABU-68
788
1148



ABU-69
789
1149



ABU-70
790
1150



ABU-71
791
1151



ABU-72
792
1152



ABU-73
793
1153



ABU-74
794
1154



ABU-75
795
1155



ABU-76
796
1156



ABU-77
797
1157



ABU-78
798
1158



ABU-79
799
1159



ABU-80
800
1160



ABU-81
801
1161



ABU-82
802
1162



ABU-83
803
1163



ABU-84
804
1164



ABU-85
805
1165



ABU-86
806
1166



ABU-87
807
1167



ABU-88
808
1168



ABU-89
809
1169



ABU-90
810
1170



ABU-91
811
1171



ABU-92
812
1172



ABU-93
813
1173



ABU-94
814
1174



ABU-95
815
1175



ABU-96
816
1176



ABU-97
817
1177



ABU-98
818
1178



ABU-99
819
1179



ABU-100
820
1180



ABU-101
821
1181



ABU-102
822
1182



ABU-103
823
1183



ABU-104
824
1184



ABU-105
825
1185



ABU-106
826
1186



ABU-107
827
1187



ABU-108
828
1188



ABU-109
829
1189



ABU-110
830
1190



ABU-111
831
1191



ABU-112
832
1192



ABU-113
833
1193



ABU-114
834
1194



ABU-115
835
1195



ABU-116
836
1196



ABU-117
837
1197



ABU-118
838
1198



ABU-119
839
1199



ABU-120
840
1200



ABU-121
841
1201



ABU-122
842
1202



ABU-123
843
1203



ABU-124
844
1204



ABU-125
845
1205



ABU-126
846
1206



ABU-127
847
1207



ABU-128
848
1208



ABU-129
849
1209



ABU-130
850
1210



ABU-131
851
1211



ABU-132
852
1212



ABU-133
853
1213



ABU-134
854
1214



ABU-135
855
1215



ABU-136
856
1216



ABU-137
857
1217



ABU-138
858
1218



ABU-139
859
1219



ABU-140
860
1220



ABU-141
861
1221



ABU-142
862
1222



ABU-143
863
1223



ABU-144
864
1224



ABU-145
865
1225



ABU-146
866
1226



ABU-147
867
1227



ABU-148
868
1228



ABU-149
869
1229



ABU-150
870
1230



ABU-151
871
1231



ABU-152
872
1232



ABU-153
873
1233



ABU-154
874
1234



ABU-155
875
1235



ABU-156
876
1236



ABU-157
877
1237



ABU-158
878
1238



ABU-159
879
1239



ABU-160
880
1240



ABU-161
881
1241



ABU-162
882
1242



ABU-163
883
1243



ABU-164
884
1244



ABU-165
885
1245



ABU-166
886
1246



ABU-167
887
1247



ABU-168
888
1248



ABU-169
889
1249



ABU-170
890
1250



ABU-171
891
1251



ABU-172
892
1252



ABU-173
893
1253



ABU-174
894
1254



ABU-175
895
1255



ABU-176
896
1256



ABU-177
897
1257



ABU-178
898
1258



ABU-179
899
1259



ABU-180
900
1260



ABU-181
901
1261



ABU-182
902
1262



ABU-183
903
1263



ABU-184
904
1264



ABU-185
905
1265



ABU-186
906
1266



ABU-187
907
1267



ABU-188
908
1268



ABU-189
909
1269



ABU-190
910
1270



ABU-191
911
1271



ABU-192
912
1272



ABU-193
913
1273



ABU-194
914
1274



ABU-195
915
1275



ABU-196
916
1276



ABU-197
917
1277



ABU-198
918
1278



ABU-199
919
1279



ABU-200
920
1280



ABU-201
921
1281



ABU-202
922
1282



ABU-203
923
1283



ABU-204
924
1284



ABU-205
925
1285



ABU-206
926
1286



ABU-207
927
1287



ABU-208
928
1288



ABU-209
929
1289



ABU-210
930
1290



ABU-211
931
1291



ABU-212
932
1292



ABU-213
933
1293



ABU-214
934
1294



ABU-215
935
1295



ABU-216
936
1296



ABU-217
937
1297



ABU-218
938
1298



ABU-219
939
1299



ABU-220
940
1300



ABU-221
941
1301



ABU-222
942
1302



ABU-223
943
1303



ABU-224
944
1304



ABU-225
945
1305



ABU-226
946
1306



ABU-227
947
1307



ABU-228
948
1308



ABU-229
949
1309



ABU-230
950
1310



ABU-231
951
1311



ABU-232
952
1312



ABU-233
953
1313



ABU-234
954
1314



ABU-235
955
1315



ABU-236
956
1316



ABU-237
957
1317



ABU-238
958
1318



ABU-239
959
1319



ABU-240
960
1320



ABU-241
961
1321



ABU-242
962
1322



ABU-243
963
1323



ABU-244
964
1324



ABU-245
965
1325



ABU-246
966
1326



ABU-247
967
1327



ABU-248
968
1328



ABU-249
969
1329



ABU-250
970
1330



ABU-251
971
1331



ABU-252
972
1332



ABU-253
973
1333



ABU-254
974
1334



ABU-255
975
1335



ABU-256
976
1336



ABU-257
977
1337



ABU-258
978
1338



ABU-259
979
1339



ABU-260
980
1340



ABU-261
981
1341



ABU-262
982
1342



ABU-263
983
1343



ABU-264
984
1344



ABU-265
985
1345



ABU-266
986
1346



ABU-267
987
1347



ABU-268
988
1348



ABU-269
989
1349



ABU-270
990
1350



ABU-271
991
1351



ABU-272
992
1352



ABU-273
993
1353



ABU-274
994
1354



ABU-275
995
1355



ABU-276
996
1356



ABU-277
997
1357



ABU-278
998
1358



ABU-279
999
1359



ABU-280
1000
1360



ABU-281
1001
1361



ABU-282
1002
1362



ABU-283
1003
1363



ABU-284
1004
1364



ABU-285
1005
1365



ABU-286
1006
1366



ABU-287
1007
1367



ABU-288
1008
1368



ABU-289
1009
1369



ABU-290
1010
1370



ABU-291
1011
1371



ABU-292
1012
1372



ABU-293
1013
1373



ABU-294
1014
1374



ABU-295
1015
1375



ABU-296
1016
1376



ABU-297
1017
1377



ABU-298
1018
1378



ABU-299
1019
1379



ABU-300
1020
1380



ABU-301
1021
1381



ABU-302
1022
1382



ABU-303
1023
1383



ABU-304
1024
1384



ABU-305
1025
1385



ABU-306
1026
1386



ABU-307
1027
1387



ABU-308
1028
1388



ABU-309
1029
1389



ABU-310
1030
1390



ABU-311
1031
1391



ABU-312
1032
1392



ABU-313
1033
1393



ABU-314
1034
1394



ABU-315
1035
1395



ABU-316
1036
1396



ABU-317
1037
1397



ABU-318
1038
1398



ABU-319
1039
1399



ABU-320
1040
1400



ABU-321
1041
1401



ABU-322
1042
1402



ABU-323
1043
1403



ABU-324
1044
1404



ABU-325
1045
1405



ABU-326
1046
1406



ABU-327
1047
1407



ABU-328
1048
1408



ABU-329
1049
1409



ABU-330
1050
1410



ABU-331
1051
1411



ABU-332
1052
1412



ABU-333
1053
1413



ABU-334
1054
1414



ABU-335
1055
1415



ABU-336
1056
1416



ABU-337
1057
1417



ABU-338
1058
1418



ABU-339
1059
1419



ABU-340
1060
1420



ABU-341
1061
1421



ABU-342
1062
1422



ABU-343
1063
1423



ABU-344
1064
1424



ABU-345
1065
1425



ABU-346
1066
1426



ABU-347
1067
1427



ABU-348
1068
1428



ABU-349
1069
1429



ABU-350
1070
1430



ABU-351
1071
1431



ABU-352
1072
1432



ABU-353
1073
1433



ABU-354
1074
1434



ABU-355
1075
1435



ABU-356
1076
1436



ABU-357
1077
1437



ABU-358
1078
1438



ABU-359
1079
1439



ABU-360
1080
1440



ABU-361
3111
3146



ABU-362
3112
3147



ABU-363
3113
3148



ABU-364
3114
3149



ABU-365
3115
3150



ABU-366
3116
3151



ABU-367
3117
3152



ABU-368
3118
3153



ABU-369
3119
3154



ABU-370
3120
3155



ABU-371
3121
3156



ABU-372
3122
3157



ABU-373
3123
3158



ABU-374
3124
3159



ABU-375
3125
3160



ABU-376
3126
3161



ABU-377
3127
3162



ABU-378
3128
3163



ABU-379
3129
3164



ABU-380
3130
3165



ABU-381
3131
3166



ABU-382
3132
3167



ABU-383
3133
3168



ABU-384
3134
3169



ABU-385
3135
3170



ABU-386
3136
3171



ABU-387
3137
3172



ABU-388
3138
3173



ABU-389
3139
3174



ABU-390
3140
3175



ABU-391
3141
3176



ABU-392
3142
3177



ABU-393
3143
3178



ABU-394
3144
3179



ABU-395
3145
3180










Example 3: Preparation and Purification of Antigen-Binding Unit of the Present Invention

According to the sequence information of the antigen-binding units obtained in example 2, Sino Biological Inc. was entrusted to express and purify the obtained antigen-binding units, and the antigenic reactivity thereof was detected.


In short, nucleic acid molecules encoding the heavy and light chains of the antibody were synthesized in vitro and then cloned into expression vectors, respectively, thereby obtaining recombinant expression vectors encoding the heavy and light chains of the antibody, respectively. HEK293 cells were co-transfected with the above-mentioned recombinant expression vectors encoding the heavy and light chains of the antibody, respectively. 4-6 hours after the transfection, the cell culture solution was changed to a serum-free medium, which was cultured at 37° C. for another 6 days. After cultivation, the antibody protein expressed by the cells was purified from the culture by an affinity purification column. Then, the purified protein of interest was detected by reducing and non-reducing SDS-PAGE. By taking ABU-174, ABU-175 and ABU190 as examples, the electrophoresis results thereof after preparation are shown in FIGS. 1A-1C, respectively. The results show that the purities of purified ABU-174, ABU-175 and ABU190 are 95.9%, 96.4% and 98.2%, respectively.


Then, the antigenic reactivity of the purified antibody to be detected was detected by ELISA experiments using the RBD of the recombinantly expressed S protein as a coating antigen and using Goat anti-human IgG Fc labeled with horseradish peroxidase (HRP) as a secondary antibody. In short, a 96-well plate was coated with the RBD of the recombinantly expressed S protein (with an amino acid sequence as shown in SEQ ID NO: 1459 and at a concentration of 0.01 μg/ml or 1 μg/ml), and then the 96-well plate was blocked with a blocking solution. Then, the monoclonal antibodies to be detected (a control antibody, ABU-174, ABU-175 and ABU190; each at a concentration of 0.1 μg/ml) were added and incubated, respectively. After the plate was washed with an ELISA washing liquid, Goat anti-human IgG Fc labeled with horseradish peroxidase (HRP) was added as a secondary antibody (diluted at 1:500); and the plate was again incubated. Then, the ELISA plate was washed with PBST, and a color developing agent was added to develop the color. Then, the absorbance at OD450 nm was read on a microplate reader. The results are as shown in Table 2. It can be seen from Table 2 that ABU-174, ABU-175 and ABU190 can specifically recognize and bind to RBD of S protein.









TABLE 2







Reactivity of antigen-binding units of ABU-174, ABU-175 and ABU190


with RBD of S protein detected by ELISA (OD450 reading)










Concentration of RBD protein












Sample to be detected
0.01 μg/ml
1 μg/ml















Irrelevant antibody (1 ug/ml)
0.006
0.025



ABU-174 (1 ug/ml)
1.261
2.909



ABU-175 (1 ug/ml)
2.274
2.963



ABU190 (1 ug/ml)
0.288
3.057










Example 4: Evaluation of Binding Ability of Antigen-Binding Unit of the Present Invention to S Protein

In the example, surface plasmon resonance (SPR) was used to detect the affinity of the antibody to the RBD region of the Spike protein. Biacore T200 was used for measurement. The biotin-labeled SARS-COV-2 RBD domain was first coupled to the SA chip (GE), and the RU value of the signal resonance unit was increased by 100 units. The running buffer was PBS at PH 7.4 plus 0.005% P20, ensuring that the buffer in the analyte (such as antibody) was the same as the running buffer. The purified antibody was subjected to 3-fold gradient dilution to a concentration between 50-0.78125 nM. The measurement results were analyzed using Biacore Evaluation software, all the curves were fitted to a 1:1 model to obtain the rate constant Ka for the binding of the antibody to the antigen and the rate constant Kd for the dissociation of the antibody from the antibody/antigen complex, and the dissociation equilibrium constant KD was calculated, wherein KD=Kd/Ka. The results are shown in Table 3 below.


The binding affinity of the exemplary antigen-binding unit of the present invention for the RBD region of the Spike protein is listed in Table 3, wherein the KD value of each antigen-binding unit is less than 20 nM.









TABLE 3







KD value of the binding affinity of the exemplary antigen-binding


unit of the present invention for the RBD region of Spike protein










AUB No.
KD (Kd/Ka, nM)














ABU-145
<10



ABU-149
<10



ABU-174
<1



ABU-175
<1



ABU-181
<10



ABU-190
<10



ABU-205
<10



ABU-207
<10



ABU-208
<1



ABU-210
<10



ABU-211
<20



ABU-254
<10



ABU-257
<10



ABU-258
<1



ABU-288
<1



ABU-289
<10



ABU-290
<1



ABU-291
<1



ABU-296
<1



ABU-297
<1



ABU-298
<20



ABU-305
<20



ABU-308
<10



ABU-312
<20



ABU-316
<10



ABU-317
<20



ABU-319
<10



ABU-320
<10



ABU-322
<1



ABU-323
<20



ABU-325
<10



ABU-327
<20



ABU-328
<10



ABU-329
<10



ABU-330
<10



ABU-337
<20



ABU-339
<20



ABU-340
<10



ABU-341
<10



ABU-343
<20



ABU-344
<1



ABU-346
<10



ABU-348
<10



ABU-349
<1



ABU-351
<10



ABU-352
<10



ABU-354
<1



ABU-355
<1



ABU-356
<10



ABU-357
<10



ABU-358
<10



ABU-359
<10



ABU-360
<1



ABU-361
<20



ABU-362
<20



ABU-365
<10



ABU-367
<1



ABU-368
<20



ABU-369
<10



ABU-371
<20



ABU-372
<20



ABU-373
<10



ABU-375
<10



ABU-376
<10



ABU-377
<10



ABU-379
<10



ABU-380
<1



ABU-381
<1



ABU-382
<10



ABU-383
<20



ABU-384
<20



ABU-385
<20



ABU-386
<10



ABU-390
<10



ABU-391
<20



ABU-392
<10



ABU-393
<20



ABU-394
<20



ABU-395
<10











FIGS. 2A-2E further exemplarily show the binding affinity of ABU-174, ABU-175, ABU190, ABU297 and ABU367 for the RBD region of the Spike protein. It can be seen from FIGS. 2A-2E that ABU-174 has a KD value of 0.29 nM, ABU-175 has a KD value of 0.039 nM, ABU190 has a KD value of 2.8 nM, ABU297 has a KD value of 0.824 nM, and ABU has a KD value of 0.18 nM. FIGS. 2A-2E show that ABU-174, ABU-175, ABU190, ABU297 and ABU367 all have good affinity for the S protein of the novel coronavirus.


Example 5: Evaluation of Ability of Antigen-Binding Unit of the Present Invention to Neutralize SARS-CoV-2 Pseudovirus

In this example, the cell microneutralization assay was used to detect the neutralizing activity of the antigen-binding unit of the present invention against SARS-CoV-2 pseudovirus with reference to the description of Temperton N J et al., Emerg Infect Dis, 2005, 11(3), 411-416. The SARS-CoV-2 pseudovirus used in this example was provided by China National Institutes for Food and Drug Control, has similar cell infection characteristics to the euvirus, can be used to simulate the early process of euvirus infection of a cell, and carries reporter gene luciferase, which can be quickly and easily detected and analyzed. The safety for operating the pseudovirus is high, and the neutralization experiment can be completed in Biosafety Physical Containment Level-2 Laboratory to detect the neutralization activity (Neutralization titer) of the antibody. The specific steps of the experiment method are as follows:


1. Reagent for Equilibration

The reagent (0.25% trypsin-EDTA, DMEM complete medium) stored at 2° C.-8° C. was taken out and equilibrated at room temperature for more than 30 minutes.


2. Experimental Operation

(1) A 96-well plate was taken, and the arrangement of the samples was set up as shown in Table 4; A2-H2 wells were set as cell control wells (CC), which only contain experimental cells; A3-H3 wells were set as virus control wells (VV), which contain experimental cells and pseudovirus; A4-A11, B4-B11, C4-C11, D4-D11, E4-E11, F4-F11, G4-G11 and H4-H11 wells were set as experimental wells, which contain experimental cells, pseudovirus and different concentrations of antibody to be detected; and other wells were set as blank. The experimental cells and pseudovirus used in this example were Huh-7 cells and SARS-CoV-2 virus (both provided by China National Institutes for Food and Drug Control), respectively.









TABLE 4







Arrangement of samples in 96-well plate















1
2
3
4
5-10
11
12


















A

CC
VV
Dilution 1
Dilution 1
Dilution 1



B

CC
VV
Dilution 2
Dilution 2
Dilution 2



C

CC
VV
Dilution 3
Dilution 3
Dilution 3



D

CC
VV
Dilution 4
Dilution 4
Dilution 4



E

CC
VV
Dilution 5
Dilution 5
Dilution 5



F

CC
VV
Dilution 6
Dilution 6
Dilution 6



G

CC
VV
Dilution 7
Dilution 7
Dilution 7



H

CC
VV
Dilution 8
Dilution 8
Dilution 8










(2) DMEM complete mediums (containing 1% antibiotic, 25 mM HEPES, 10% FBS) were added at 100 μl/well to the cell control wells; DMEM complete mediums were added at 100 μl/well to the virus control wells; and the indicated concentration of the antibody to be detected diluted in DMEM complete mediums was added to the experimental wells at 50 μl/well. The antibody concentrations of dilutions 1-8 used in Table 4 were 1/30 μg/μl, 1/90 μg/μl, 1/270 μg/μl, 1/810 μg/μl, 1/2430 μg/μl, 1/7290 μg/μl, 1/21870 μg/μl, and 1/65610 μg/μl, respectively.


(3) The SARS-CoV-2 pseudovirus was diluted to about 1.3×104/ml (TCID50) with DMEM complete mediums; and then, the SARS-CoV-2 pseudovirus was added at 50 μl/well to the virus control wells and the experimental wells.


(4) The 96-well plate was placed in a cell incubator (37° C., 5% CO2) and incubated for 1 hour.


(5) The pre-cultured Huh-7 cells were diluted to 2×105 cells/ml with DMEM complete mediums. After the incubation in the previous step, cells were added at 100 μl/well to the cell control wells, virus control wells and experimental wells.


(6) The 96-well plate was placed in a cell incubator (37° C., 5% CO2) and cultured for 20-28 hours.


(7) The 96-well plate was taken out from the cell incubator; 150 μl of the supernatant was aspirated from each well and discarded; and then 100 μl of luciferase detection reagents were added, and reacted at room temperature for 2 minutes in the dark.


(8) After the reaction was completed, the liquid in each well was pipetted 6 to 8 times repeatedly using a pipette until the cells were fully lysed. Then, 150 μl of liquid was aspirated from each well and transferred to the corresponding 96-well chemiluminescence detection plate, and the luminescence value was read with a chemiluminescence detector (Perkinelmer EnSight multimode microplate reader).


(9) Calculation of neutralization inhibition rate:





Inhibition rate=[1−(mean luminescence intensity of experimental wells−mean luminescence intensity of CC wells)/(mean luminescence intensity of VV wells−mean luminescence intensity of CC wells)]×100%.


(10) IC50 of the antibody to be detected was calculated by Reed-Muench method according to the result of the neutralization inhibition rate.


Table 5 lists IC50 of the exemplary antigen-binding unit of the present invention for neutralizing SARS-CoV-2 pseudovirus, wherein the IC50 value of each antigen-binding unit is less than 1 μg/ml.









TABLE 5







IC50 of exemplary antigen-binding unit of the present


invention for neutralizing SARS-CoV-2 pseudovirus










ABU No.
IC50 (μg/ml)














ABU-174
<0.1



ABU-175
<0.1



ABU-190
<0.1



ABU-207
<0.5



ABU-208
<0.5



ABU-257
<0.5



ABU-290
<0.1



ABU-291
<0.5



ABU-296
<0.1



ABU-297
<0.1



ABU-308
<0.5



ABU-322
<0.1



ABU-340
<0.5



ABU-341
<0.1



ABU-344
<1



ABU-349
<0.1



ABU-351
<0.1



ABU-352
<0.1



ABU-354
<0.1



ABU-355
<0.1



ABU-356
<0.1



ABU-357
<1



ABU-358
<0.1



ABU-359
<0.1



ABU-360
<0.1



ABU-361
<0.5



ABU-362
<0.5



ABU-365
<0.1



ABU-367
<0.1



ABU-368
<0.5



ABU-369
<0.1



ABU-371
<1



ABU-372
<0.5



ABU-373
<0.5



ABU-375
<0.1



ABU-376
<0.1



ABU-377
<0.5



ABU-379
<0.5



ABU-380
<0.1



ABU-381
<0.1



ABU-382
<0.1



ABU-386
<0.1



ABU-391
<1



ABU-392
<0.1



ABU-395
<0.1











FIGS. 3A-3C further exemplarily show the neutralizing activity of ABU-174, ABU-175 and ABU190 against the SARS-CoV-2 pseudovirus. It can be seen from FIGS. 3A-3C that ABU-174, ABU-175 and ABU190 all have a good neutralizing activity, and the IC50 thereof are 0.026 μg/ml (ABU-174), 0.0086 μg/ml (ABU-175), and 0.039 μg/ml (ABU190), respectively.


Example 6: Evaluation of Ability of Antigen-Binding Unit of the Present Invention to Neutralize SARS-CoV-2 Euvirus

In this example, neutralizing activities of the antibodies to be detected were evaluated by cytopathic effect (CPE) assay and Plaque Reduction Neutralization Test (PRNT), respectively. The SARS-CoV-2 virus used was provided by Academy of Military Medical Sciences, the titer thereof (TCID50) was 105/ml, and all experimental operations were completed in a BSL-3 laboratory.


6.1 Cytopathic Effect (CPE) Assay

(1) 100 μl of Vero E6 cells were added to each well of a 96-well culture plate at a concentration of 5×104/ml, and cultured at 37° C., 5% CO2 for 24 hours.


(2) The antibody to be detected was diluted to 10 concentrations: 1/10 μg/μl, 1/30 μg/μl, 1/90 μg/μl, 1/270 μg/μl, 1/810 μg/μl, 1/2430 μg/μl, 1/7290 μg/μl, 1/21870 μg/μl 1/65610 μg/μl, and 1/196830 μg/μl. 100 μl of the antibody to be detected at a specified concentration was taken out; an equal volume of SARS-CoV-2 euvirus (100 TCID50) was added; and the mixture was incubated at 37° C., 5% CO2 for 1 h.


(3) After cultivation in step (1), the cell culture solution in the 96-well culture plate was discarded, and the mixture solution (200 μl) containing the antibody to be detected and the euvirus prepared in step (2) was added as an experimental group. After the mixture was incubated for 1 h, the supernatant was aspirated from the wells, and 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well.


During the experiment, the cell control group and the virus control group were set in parallel. In the cell control group (4 replicate wells), after the cell culture solution in the wells was discarded; 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well. In the virus control group (3 replicate wells), after the cell culture solution in the wells was discarded; 100 TCID50 of euvirus (100 μl) was added to each well, and the mixture was incubated at 37° C. for 1 h; after the incubation, the supernatant was aspirated from the wells, and 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well.


(4) The cells were cultured for 4-5 days at 37° C., 5% CO2.


(5) The cytopathic effect (CPE) was observed under the optical microscope, and the inhibitory activities of different concentrations of a monoclonal antibody against CPE were evaluated according to conditions of the cytopathic effect.


The detection results of the antigen-binding unit ABU-174 are shown in Table 6 below. The results show that the antigen-binding unit ABU-174 has an inhibitory effect on the virus at a cellular level, and the neutralizing antibody titer is 1.6 ng/μl.









TABLE 6







Neutralizing activity effect of antigen-


binding unit ABU-174 on SARS-CoV-2









Antibody to be




detected
Dilution
Results (3 replicate wells)














Antigen-binding
1:10





unit ABU-174
1:30






1:90






1:270






1:810

+
+



1:2430
+
+
+



1:7290
+
+
+



1:21870
+
+
+



1:65610
+
+
+



1:196830
+
+
+


Cell control
200 μl DMEM





Negative control
100TCID50
+
+
+





“+” means that the cell has CPE change, and means “−” that the cell does not have CPE change or has a normal cell morphology






The detection results of the antigen-binding unit ABU-175 are shown in Table 7 and FIG. 4 below. The results show that the antigen-binding unit ABU-175 has an inhibitory effect on the virus at a cellular level, and the neutralizing antibody titer is 0.7 ng/μl.









TABLE 7







Neutralizing activity effect of antigen-


binding unit ABU-175 on SARS-CoV-2









Antibody to be




detected
Dilution
Results (3 replicate wells)














Antigen-binding
1:10





unit ABU-175
1:30






1:90






1:270






1:810






1:2430
+
+
+



1:7290
+
+
+



1:21870
+
+
+



1:65610
+
+
+



1:196830
+
+
+


Cell control
200 μl DMEM





Negative control
100TCID50
+
+
+





“+” means that the cell has CPE change, and “−” means that the cell does not have CPE change or has a normal cell morphology






6.2 Plaque Reduction Neutralization Test (PRNT):

(1) 100 μl of Vero E6 cells were added to each well of a 96-well culture plate at a concentration of 5×104/ml, and cultured at 37° C., 5% CO2 for 24 hours.


(2) The antibody to be detected was diluted to 5 concentrations: 50 μg/ml, 10 μg/ml, 2 μg/ml, 0.4 μg/ml, and 0.08 μg/ml.


(3) After cultivation in step (1), the cell culture solution in the 96-well culture plate was discarded, and the mixture solution (200 μl) containing the antibody to be detected and the euvirus prepared in step (2) was added as an experimental group. After the mixture was incubated for 1 h, the supernatant was aspirated from the wells, and 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well.


During the experiment, the cell control group and the virus control group were set in parallel. In the cell control group, after the cell culture solution in the wells was discarded; 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well. In the virus control group (4 replicate wells), after the cell culture solution in the wells was discarded; 100 TCID50 of euvirus (100 μl) was added to each well, and the mixture was incubated at 37° C. for 1 h; after the incubation, the supernatant was aspirated from the wells, and 200 μl of DMEM mediums (containing 2% antibiotic and 16 μg/ml of trypsin) were added to each well.


(4) The cells were cultured for 4 days at 37° C., 5% CO2.


(5) After fixed with formaldehyde, the cells were labeled with rabbit anti-SARS-COV serum (Sino Biological) and peroxidase-labeled goat anti-rabbit IgG (Dako). The plaques were observed after the cells were developed with TMB (True Blue, KPL), the inhibition rate was calculated and the dose-response curve was drawn.



FIG. 5 shows dose-response curves for the exemplary antigen-binding units ABU-174, ABU-175 and ABU190 of the present invention. It can be seen from FIG. 5 that the antigen-binding units ABU-174, ABU-175 and ABU190 all have good neutralizing activities against SARS-CoV-2 euvirus, and can effectively inhibit virus infection and cell invasion, and the IC50 are 0.5 μg/ml (ABU-174), 0.3 μg/ml (ABU-175) and 0.8 μg/ml (ABU-190), respectively.


Example 7. In Vivo Potency of the Antigen-Binding Unit of the Present Invention

SARS-CoV-2 infects a cell by interaction with the hACE2 receptor. The neutralizing potency of the antigen-binding unit of the present invention against SARS-CoV-2 in vivo was evaluated in two different animal models.


7.1 Potency of the Antigen-Binding Unit in hACE2 Transgenic Mice


In the first model, hACE2 transgenic mice were used as a animal model and treated with 2 different modes, i.e., pre-exposure prophylaxis and post-exposure prophylaxis. Specifically, hACE2 transgenic mice were intranasally infected with SARS-CoV-2 viruses (2019-nCoV Beta CoV/Wuhan/AMMS01/2020) at a dose of 105 TCID50.


In the pre-exposure prophylaxis treatment mode, the antigen-binding unit of the present invention was injected intraperitoneally at a dose of 20 mg/kg into hACE2 transgenic mice 24 hours prior to viral infection and the potency of the antigen-binding unit as a pre-exposure prophylactic intervention was detected.


In the post-exposure prophylaxis mode, 2 hours after viral infection, mice were injected with the antigen-binding unit at a dose of 20 mg/kg. HG1K (IgG1 antibody against H7N9 virus) was used as a negative control, and 2 hours after virus infection, same was injected at 20 mg/kg. Body weights that reflect the health condition of the infected mice were recorded daily for 5 consecutive days.


7.2 In Vivo Potency of Antigen-Binding Unit in Hamster

In the second model, hamsters (Mesocricetus auratus) were used as a animal model and treated with 2 different modes, i.e., pre-exposure prophylaxis and post-exposure prophylaxis. Specifically, hamsters were intranasally infected with SARS-CoV-2 proviruses (SARS-COV-2/WH-09/human/020/CHN) at a dose of 105 TCID50, which is similar to hACE2 transgenic mice.


In the pre-exposure prophylaxis treatment mode of hamsters, the antigen-binding units of the present invention were injected at a dose of 20 mg/kg into hamsters 1 day prior to viral infection. In the control group, 2 hours after infection, animals were injected with PBS.


In the post-exposure prophylaxis treatment mode of hamsters, 2 hours after infection, the antigen-binding units of the present invention were injected intraperitoneally into hamsters at different doses (including 20, 10, 5 and 2 mg/kg) according to body weights. In addition, the hamster injected with phosphate buffered saline (PBS) was used as a control. Body weights of the infected hamsters were recorded daily for 7 consecutive days. Hamsters were sacrificed 7 days after infection and lungs were collected for viral load analysis.


Sequence Information

The information of partial sequences involved herein is as shown in Table 8 below.









TABLE 8







Sequence Listing








SEQ ID
Sequence











1
ARDVTLVRGTASPRFDY





2
ARDVTLVRGTASPRFDY





3
ARSTRRWLQFVFPFDY





4
ARSTRRWLQFVFPFDY





5
ARSTRRWLQFVFPFDY





6
ARSTRRWLQFVFPFDY





7
ARSTRRWLQFVFPFDY





8
ARQAPGGGLLGYYHGLDV





9
ARQAPGGGLLGYYHGLDV





10
ARDRYCGGDCSGPHYYYYGMDV





11
ARWDCSGGSCNYYYYYNMDV





12
ARWDCSGGSCNYYYYYNMDV





13
AREDILLVPAASNFYYFGMDV





14
ARGDYYDPDDRYNAYYSLGA





15
TKGSMLLEVY





16
ARAPSDSSGINGAFDI





17
ARPKAPGYSYLSLDY





18
CGFGVVTTDAYGMDV





19
VKDKACTTTSCYEGTFFDY





20
VRGDDSILTPTFDH





21
ARAGKGFMVITHFDY





22
ARPHTNSWDQFDY





23
ARPQGGSSWYRDYYYGMDV





24
ATSTAVLRYFAPTGGWFDP





25
AKDNGHSYGYSWFDP





26
ATDGATIPINYYGMDV





27
ARSPITMIVVVNAFDI





28
ARARITMIVVVNHFDY





29
ARVQSTGYKYWYFDI





30
ARGFDY





31
ARARDYGSGSPMDV





32
ARDGVYYGSVIYHHYDLHV





33
ARGGGELLRYPFDY





34
AKAGLGLETSGGNYFES





35
AKDRVTMNYFDY





36
ARVREGYTSGWYADY





37
ARDRSYYHSSGYHYYFDY





38
VRDRIVGGYSYGGDY





39
AKGRLSPRL





40
ARVKVDNVVFDL





41
ARDRGLAARPAGWVDL





42
ARENFHFSGTPPLY





43
ARKYTYDTSGFFLSSSRNAFDV





44
ARLGSNGYGL





45
ARTYSYDSSGFFLTSSREAFDI





46
VRKYSFDVSGFFLSSSRHAFDV





47
ARKYSYDTSGFFLTSSRDAFDV





48
VRKFSYDISGFFLTSSRDAFDV





49
ATEGV





50
LLIEGMGATSGD





51
ATTNDGYYYGMDV





52
ATNPHNTAMVLDYYGMDV





53
AGAYIAAAGWGWELFQYYFDY





54
AHQAPFEWFGVDY





55
TTDGLYCSGGSCYYHSYYYYYGMDV





56
ARDGLGNYDILTGYTERAFDI





57
ARVKPILRVVVVAATPCDY





58
ARHARGYQLLSPRLGELSLYRSFDY





59
ARATTTKMIVVVINAFDI





60
ARHWITMIVVVIKGGWFDP





61
ARIRGQWLVGKYYYGMDV





62
AHRGWGFSSSFFDY





63
ARMSSSLQHYYGMDV





64
ARMSSSLQHYYGMDV





65
ARDVTLVRGTASPRFDY





66
ARDVTLVRGTASPRFDY





67
AQEGRNYDRNWFDP





68
ARLIPIDGRDV





69
TTYWDQYTSTWT





70
ASIVKYDSSGYNFDY





71
TRDPWHESEHRFDP





72
AKDNKVSSWYSFDI





73
ARGLGYYVAL





74
VRGGQEVSLRRLDWFVGY





75
AKERGGSGKMYDY





76
ARRGAAVAGTTGGSAFDI





77
TKTSDLLYYGSGSYLPY





78
TRDGGAWD





79
ARGIPREYTTRWENAFDI





80
ARDRGADKDSNSGDVFDI





81
VGPQGAY





82
ARDPRGSSTSCSYDY





83
TGQERITIFGVVIISSDY





84
ARRLNDGANHS





85
SWDATVYYDMAV





86
ARPSSGSYADPFDI





87
VASRSSSLDY





88
ARSRGYGGLAGVDY





89
ARAYFDDSSGGFDY





90
AGSTYGDYVPHFYF





91
ARGLSSFTTIVVVFVGASFYFDS





92
ARGTTSTTMIVIVITAVSTWFDP





93
ARHPLKVDTIFGVVIIDPAPFDY





94
ARIASYYYDSSGYYQTRPIGHAFDI





95
AKDRAQLLWFGQSRGMDV





96
TSTSDW





97
TRLRSGLVGFDWLPLYGMDV





98
ARRGVGILKDLPVYAMDV





99
AREARQIFITMMTTKTSWFDP





100
ARVSSTAVVTGLDYYYGMDV





101
TTISVGLLWFGLAVRDHYYFDY





102
ARSYYDSSTGYYPDALDL





103
AKSGSVWGSYHKTYYFDY





104
AKEILKGYSSGWKYYYYGMDV





105
ARATTTMVRGVIYHYYYYGMDV





106
ARERLGRMVRGVNWFDP





107
ASWTMVRGVIRWFDP





108
ARQFHYVGIVVVVAPHYYYGMDV





109
ASPRGYSYGPFDY





110
ARVLYYDILTGYWWYYYGMDV





11
ARGAPITIFGVVISTWFDP





112
ARAHTDSLELGI





113
VRKYTYDTSGFFLTSTRSAFDV





114
ARKHVYDTSGFFLSSSRNAFDV





115
ARKYSFDISGFFLSSSRYALDV





116
ARDEGVTFHDHWANEIRYGMDV





117
ARARTTMIVVVSQFDY





118
ARDRGGWLLGSYYYYGMDV





119
ARGQISHYGFGESH





120
AHSGIAVVGNQLFHYYAMDV





121
AKERSSGSQWGWTYYYYGMDV





122
ARDPYGGNRRFHGWVYYYYGMDV





123
ARESTPDVRGVMNY





124
AKDAVASAGSPDY





125
ARDKLLWFGEPVVGYYYYYYMDV





126
ARDGGGDYAQIYFDY





127
ARDRLMTTYNYYSSMDV





128
AREPGDCSGGSCYYYGMDV





129
ARATRGYSYDDAFDI





130
ASPSYTDLLTGYYVPVDY





131
AKDPRVNELLWFGSLTQFYFDD





132
AKSGGPFHLSLYYYMDV





133
ARAFYGHAFDF





134
AKGLTIPFDK





135
AKGLTIPFDK





136
ARRGKYCSGGRCYSWWFDP





137
ARVASLIGDDY





138
ARVASLIGDDY





139
AHKPSGWSLRFDS





140
ARESLFNWFDS





141
AKGLTIPFDN





142
ARVDYDSSRNY





143
ARVERWLVLGYYYYGMDV





144
GSIDY





145
AKMYSDYDDNYYGLDV





146
ARDRYCSSTSCGGYYYYMDV





147
ARAPNDFWSGYPYYFDY





148
TRDGSTAAIFGNIDY





149
ARGVVRNDYGDPGFDY





150
ATAPAYCSGGSCPENNWFDP





151
AILWFGEFYFYDLFYNAVDV





152
AILWFGEFYFYDLFYNAVDV





153
ASRREQWLGDLGYYYYGMDV





154
ARGGAHSEDY





155
ARHQDPLDIVATVDWGGLDY





156
ARVASLIGDDY





157
ATTGTDNYYYYMDV





158
ARKNCSGGICYFHDY





159
AHKPSGWSLRFDS





160
AKGQTIQLWLFGAL





161
ALTVSSWYPGIFEN





162
AKAFSGSYWDAFDI





163
AKAASGARGYYGMDV





164
ARSSSGHYVSDLGY





165
ARALNGYRYNDY





166
AREEGGGSSTHFDC





167
ARTREGSYYYGMDV





168
VRGGLQFVVAVGPYGVDV





169
VRGGLQFVVAVGPYGVDV





170
ARDIGGGAPDY





171
AIKPSIPGYFDP





172
ARVGGWQRSPRPN





173
ARVGGWQRSPRPN





174
ARGQGYGRVLLWFGE





175
ARGQGYGRVLLWFGE





176
ARPSSGSRFDY





177
ARGFDY





178
AKARGVVLFDY





179
ARHSYGSGTYLDPFDY





180
ARQPHLAYYYDSSGYNDAFDI





181
ARGAVVTPFGLDS





182
ASEDYYDSSGYYWY





183
ARLSAIAVVGYYYYAMDV





184
ARDFIAASPFYYYYYMDV





185
ATSPGGYGVRRTVLEDFRH





186
WTMEYDDYSFVYDY





187
ARGGKQQLVRNYYLDS





188
ATGFGGVIVRGFDY





189
ARVYGDYSYYMDV





190
ARDLGEAGGMDV





191
VREIESGVDFWSGHYY





192
ARDSAYYDTIGYYSGDY





193
GRSFRGSCFDYL





194
ALGTGSYYGVNY





195
AKDMGGRYSSGLYYYYYGMDV





196
ARELRGYFDY





197
ARDPNDFWSGFPRGAFDI





198
ASHARYEEETFDY





199
VRDSYTSAWTPAGYFDL





200
AKDHYGSIDY





201
ARPYTSRWFWSN





202
ALLPPNAYDYGDGLLDH





203
ARHRAAGGNYYYGMDV





204
ARERVGPAAGYMDV





205
ARAAYYYDSSGYGWFDP





206
ARGDYTEYSYYYMDV





207
ALPTGASSSYSGPNY





208
ARDEVIAVATGEGMDV





209
AKDMGYDILTGSGLGDY





210
AKEPLFGETYGMDV





211
ARDKGSGSYYSGAYYYYMDV





212
ATFNSGNDNAYEY





213
AREYPDFWSGHYYYYMDV





214
ARLPYGMDV





215
ARGLYDKSGYRSDGFDS





216
ARGFEGYCSGGRCYSYFDY





217
ARVKNWDYGLY





218
ARDGQSDWHFDL





219
ARVYGDYLDH





220
AHRSFLYNIFNGYSYAPFDY





221
AKDLFSGDRDF





222
AKDSGAVLLWFGADF





223
AREGAYDIWRGSYMRAYDH





224
ARYIEMFDP





225
ARQAYGDYGWDYYYGMDV





226
LKDWDWEYEDSRPTLRGSVY





227
ARGSVFWFGEGKNWFDP





228
ARGSVFWFGEGKNWFDP





229
AREDSSGWSRGDY





230
ARRFVVREVEYNWFDP





231
ARDGYCNSMRCYRYYHGMDV





232
ATGPTAKPNKQWGYWFDP





233
ASPVSVEQDFDI





234
TTPVGDF





235
STSHPPFFDY





236
ARGLWQLVSPVFDY





237
AKVTNRGVRGLYFDY





238
ASPVSVEQDFDI





239
AINTLLVTA





240
VHRSFLYDIFSGYSYAPFDY





241
AHRSFLYNIFDGYSYAPFDY





242
AGGADCRRTSCHYLVSNREEYMGV





243
ARGLVLSGTRYSYFYGMDV





244
VKDWDWEYEDNRPTLRGSVY





245
VKDWDWEYEESRPTLRGSVY





246
AKGGPIFWLGEGKNWFDA





247
ARDKGGILMLRGADF





248
ARTLIAAAGSAFDI





249
ARGPTSITMIVVVDDAFDI





250
ARVMNSSWYTRYYYNYMDV





251
ARRGGGCSEGVCYNFDR





252
ARGDPRDY





253
ARGSYYYDSSGYYLDY





254
ARAAYYYDSSGYGWFDP





255
TTDLGATGIYYYYYMDV





256
ARFPRDYYDSSGYLIQEGNFDY





257
ARVTRAGAAGDGGAFDI





258
ARSVVPVAGTDY





259
ARDQHPGYPALVYYYYYMDV





260
ARDNIQTFDY





261
ATSSPVAGYNSWFDP





262
ATGPAVIPLRWFDP





263
ATAPAAAGPTDWFDP





264
AISPSVHSLWWFDP





265
ARDEIHYDILTGYYNRFWFHP





266
ARDAETGYYDSSGYPINWFDP





267
ARHYYDTGAYYVPFDH





268
AHFQGFGESEYFQH





269
AHRHPLTGFDS





270
ATPRGYSYGPLDY





271
ASPRGYSYGPFDY





272
ARDRVDKGYDFWSSWYFDL





273
ASGGGSYFDAFDI





274
ARDRSGSYYGGFDY





275
AKAVYGGNSVYFDY





276
ARIYGGNYENYFDY





277
ARESEAGTTPSFDY





278
ARSLVRGVITYFDY





279
ARGLSMEV





280
ARGGYSSSWYGTKYYFDY





281
ARGPTVTTFFRRNAWFDP





282
ARGRYSSGWYGSRNWFDP





283
ARLSMGAARQSGFDP





284
ARDGGRDGYNELGARVYYYYGMDV





285
ARIGSYGI





286
AKLGCSGGSCYYYYGMDV





287
ARGDHYYDRSGPHKFDY





288
ARDSPLKFDSFGYPLYGMDV





289
ARGIVGATPGYFDY





290
AKAVSGWPIYFDA





291
AKAVSGWPIYFDA





292
AHTIHSGYDRTFDS





293
AREESYSSSSPLDY





294
AAGSDFWSGYYVNYYMDV





295
ARLTAAGVYFDY





296
AKTRGRGLYDYVWGSKDY





297
AKTRGRGLYDYVWGSKDY





298
ARDESGSYYGDQAFDI





299
ARDRRARAYEIPFGSDHYYFGMDV





300
ARDYYGSGSYPIGYMDV





301
TTSYCSTKVCFDYWFDP





302
ASNLYATSPYGGVKN





303
AKDIGSGSPDAFDI





304
VKDLEFRGGTGGFDL





305
ARDGHSAWGAFDI





306
ARDHPTLRRAFDY





307
ARDRGSSSWWGWLDP





308
ATRRGYSGYGAAYYFDY





309
AREVYVGGEDDYSYYYGLDV





310
TTDLGEAGPTEWLRSSLFDY





311
TTSYCNPKVCFDYWFDP





312
AKEYYYDSSGYYYREDAFDI





313
AKDGGLTAYLEY





314
ATEKWEVVDVCFDY





315
AKDIGWDVVVVAATHGVFDY





316
AKDPYYYGSGSSNFFDY





317
ARGPDYYDTGGYFDL





318
ARDGYKQIYWYLDL





319
AKGEGVYGSGSRYFLDY





320
AREWSRGAVAGTGYFDY





321
AKVAKLPGDYYGMDV





322
ARELRGAFDI





323
ARDWGEYYFDY





324
ARDYGDLYFDY





325
ARDRRVGSPYYYYYMDV





326
ARDLGDNAFDI





327
ARDRYSGYDF





328
ARLSGTGYGGDGGWFDP





329
AGKKIYYGSSFDP





330
ARGGSGSGWYGGRFDY





331
ARVWRETYYYDSSGDSFDY





332
ARGRSITGIRDVDF





333
ARGRGNYMFRWFDP





334
ARGGLWYDSINYYGMDV





335
ARLILRWPTTWDYFDY





336
ARVDGPFDY





337
ARCPFWNYGHCYLDN





338
ARPSVRWYYHAMDV





339
AKERRPVLRYFDWLPIEAPDY





340
ARGQYDILTGYQYGAFDI





341
AAHYYSRTDAFHI





342
ARDSVSGSGSYYKGLWFDP





343
VVGIGYCSSPSCPPLRWFDY





344
ARERGYSGSGSLYYFDY





345
AHYSSSRPPLFDY





346
AKGHWST





347
ANGAYYYGSGSYYNGAAY





348
AKGGYYDILTGYFPFDY





349
ARDLVVYGMDV





350
ARDPIRNGMDV





351
ARDLVVYGMDV





352
ARDAMSYGMDV





353
ARDRVVYGMDV





354
ARDAAVYGIDV





355
ARDLISRGMDV





356
ARDRVVYGMDV





357
ARDLVSYGMDV





358
ARDLVVYGMDV





359
ARDAQNYGMDV





360
ARDRGLVSDY





361
QQTYIIPYS





362
QQYYSYPYT





363
SSYAGSNNLV





364
QRYDSYRT





365
QQSYSTPYT





366
QQYDNLPLT





367
QQYATSPWT





368
AAWDDSLSSWG





369
QTWGTGTVV





370
QSADSSGTWV





371
QQRSDWTPT





372
QQFNSYPRT





373
CSYAGNTTF





374
STWDASLKEVL





375
MQGTHWPLT





376
QQYDSYPWT





377
QQLTTYPRT





378
QSADSSGTWV





379
QQFYSTPVT





380
QSYDGSNVV





381
QQYYSTPLT





382
QQYYDTPMYT





383
QQYNSYPYT





384
SSYTSSSTFV





385
QSADSSGTYSNWV





386
SSYTSSSTW





387
QQYGSSPLT





388
QQYGSSPLT





389
QQYGA





390
QQYGSSPWT





391
AVWDDSLNGVV





392
SSFAGSNNPYV





393
QQYYSTPYT





394
HQYDSWPPT





395
QNRDDWPPLFT





396
QQYYSTPRT





397
QQAHSFLSLT





398
QSADTSGTYLWV





399
QQYDSLPIT





400
QQYYGIPT





401
QKCDNFPWT





402
AAWDDSLSVVV





403
QQSYSSPPT





404
QSYDDTLTI





405
QQSYGAPPT





406
QQSYSTPPT





407
QQSFSTPPT





408
QQSYSSPPT





409
YSTDSSGNHWV





410
LLSYSGVRI





411
QSYDSSLSKV





412
QAWDSSTFYV





413
GTWDSSLSAVV





414
QQYNNWPWT





415
LLSYSGARPV





416
QQSYSTPPYT





417
SSYTSSSTRVV





418
QQYYSTPIT





419
QQYGSSPLT





420
GTWDSSLSVVV





421
SSYTSSSTFAV





422
MQALQTPLT





423
MQALQTVFT





424
MQALQTVFT





425
QQTYIIPYS





426
QQYYSYPYT





427
QVWDSSSDHVV





428
QAWDSSTSYW





429
GTWDSSLSVGV





430
NSYTSNSTAV





431
QQSYNWPRT





432
LQHNSYPYT





433
QQYNGYPHT





434
QQYSYYSA





435
QQYGT





436
SAWDSSLSAWV





437
QQYYSTPIT





438
QSFDDNDQV





439
LLYVGGGIWV





440
QQYNIWLT





441
MQGTLLLT





442
ETWDSSLDAVI





443
AAWDDSLSGRV





444
MQGTHWPHPT





445
MQGTPWPT





446
QQSGSSYT





447
MQSLPSGFT





448
MQSLDLPPT





449
QQGSSFPLT





450
QQYDSSPIT





451
NSRDSSGQLHVVV





452
NSRDNNDDLPL





453
SSYAGSNNLGV





454
QSYDSSLSGVV





455
QQYYSTPFT





456
MQGTHWPIT





457
SSYTSSSTLVV





458
QQSYSTPYT





459
CSYAGSYVV





460
QQSYSTLHT





461
NSRDSSGNHLV





462
QAWDTITHEEV





463
QQYNYYPVA





464
TQATQFPLT





465
QQSYSTPPYT





466
QSYDSSLSSPVV





467
AAWDDSLSGPV





468
NSRDSSGNHLV





469
QQYDNLPYT





470
GTWDSSLSAGV





471
QQYNNWPPWT





472
QAWDSSTYW





473
QQSYSSPPT





474
QQSYSSPPT





475
QQSYSSPPT





476
HHYGTSPPFT





477
QQYGSSPLT





478
QSADSSGTYYV





479
QQSYSTPRT





480
QAWDSSTVV





481
MQSIQLPLT





482
MQSIQLPFT





483
MQALQTYT





484
YSTDSSGNHRRV





485
SSYTSSSTLV





486
YSTDSSGNHRGV





487
QQYNSFPYT





488
QQRSNWPVT





489
LQHNSYPLT





490
LQHNSYPFT





491
QQYGTSAGT





492
QQYGNLPPFT





493
QQYYSTPLT





494
MQNRHLYT





495
MQNRHLYT





496
MQTLQTSIT





497
QQYGSSQYS





498
QQYGSSQYT





499
QHYDTLLT





500
QQYFDTPWT





501
MQNRQLYT





502
QQFDNLPPFT





503
QQSYSARMST





504
MQGTQWPWT





505
QQFDNSPPWT





506
QSADSSGTYVV





507
CSYAGSYTLV





508
QQSYSTPFT





509
MQGTHSYT





510
QAWDSSTASYV





511
SSYTSASTW





512
SSYTSASTW





513
MQGTHSPWT





514
GTWDSSLSAWV





515
QSADGRGDWV





516
QQYGSSQYS





517
QQYDSYSGT





518
ETWDSPYW





519
QHYDSLLT





520
SSYTSSSTW





521
MQALQTLT





522
QQYNSYPLFT





523
MQGTHWPMT





524
QQYGSSPMYT





525
QQANSFPA





526
QAWDSHTVV





527
QQYNSYSWT





528
QQYTSWPLT





529
QQYTSWPLT





530
YSPKV





531
QQYNILPHT





532
QQYYNAPLS





533
QQYYNAPLS





534
QQRSNWIT





535
QQRSNWIT





536
AAWDDSLNGPV





537
QQYGSSPQT





538
QQYNNWPPLT





539
QQYYSYSLT





540
CSYAGSSTFYV





541
QSADSSGTWV





542
QQYGSSPEMYT





543
HQYGSGLGT





544
MQSIQLRT





545
QQCSSWPLSLT





546
QQYNNWPPIT





547
QQSNSFPPT





548
QSYDISLSAYV





549
QQYNTYSLT





550
QQLNSYPPA





551
QQYYRTPLT





552
LQHHTYPLT





553
MQSIQLWS





554
LLSYSGPWV





555
SSYAGSNNYV





556
QQYDNLPSFT





557
CSYAGSYTLV





558
CSYAGSSTVV





559
QQSYNVPPWT





560
MQGTHWPWT





561
QSYDINLSAV





562
HQYHNSPWT





563
MQALQTPYT





564
QVWDSSSDHYV





565
QQYGSSPRT





566
QQYDNWLPYT





567
LLSYSGAYVL





568
QQYSNWPLYT





569
AAWDDSLNGPYV





570
SSYTSISTVL





571
QVWDGGSDDRGYV





572
SSFTSNGAWV





573
QQNYIRPYT





574
QQYDNLPIT





575
ATWDDSLNGV





576
QQYNNWPYT





577
GADHGSGSNFVYV





578
CSYAGSSTLV





579
QQHDSAPYT





580
QQYNSYVT





581
MQGKHLRWT





582
YSTDYSGNHGV





583
QQCSNWPNT





584
QSADSNDSWV





585
GTWDSSLSAGV





586
QQGHNFPWT





587
QQYGSLPLT





588
QQYGSLPLT





589
QSYDSSLSGWV





590
QQRRNWPLT





591
QHRSNWPYT





592
AAWDDSLNGW





593
MQTTQFPRT





594
QSQDSSATYVV





595
QAWDSSIEV





596
QQYGSSPPWT





597
QSGDSSGTYVV





598
MQTTQFPRT





599
LQYNTYSYS





600
QQYNSYIT





601
QQYNSYVT





602
YSTDSSDNQRV





603
QHLKSYPLT





604
QQGHNFPWT





605
QQGHNFPWT





606
QQYHNFP





607
QSYDSSLSVV





608
QAWDSNTGV





609
QSYDSSLSGSV





610
QSVDNTGASPHVV





611
QQYHTYWT





612
QAWDSGT





613
QQYGSSPRT





614
QQYGSSPRT





615
QHYGTSPYT





616
QQYGSSTLVT





617
CSYAGSSLWV





618
QSYDSSFWV





619
GTWDSSLSAVV





620
YSTDRSGNHRGV





621
NSRDSSGNHLYWV





622
QSYDSSLSGHVV





623
GTWDSSLSAGGV





624
CSYAGSSTFVV





625
GTWDSSLSAVV





626
QQLNSYPPT





627
QQSYSTLWT





628
QQYGDSPET





629
QAWDSSTVV





630
QQYDNLPYT





631
QQYDNLPYT





632
QQRSNWPSIT





633
QQANSFPLA





634
QQSYSTPFG





635
LSYDSSLSGSV





636
QQFNNYPLT





637
QQYDNLPFT





638
SSYTSSSAYV





639
NSRDSSGNHW





640
CSYAGSYPVV





641
SSYAGSNKV





642
QQYGSSGGYT





643
QQSYSTPYT





644
QQYGSSSWT





645
QQSYSTPYT





646
QAWDSSTANWV





647
SSFTDSSTLVV





648
QQSYSVPHT





649
QQYNNWLT





650
QQYNNWPPIT





651
QQYNNWPPIT





652
SSYAGTNKIL





653
QQSYSTPLT





654
SSYTSSSTWV





655
QQSYSTPYT





656
MQALQTPGT





657
MQALQTPGT





658
QQYNSYSA





659
QAWDRTTAT





660
QSYDSSLSGWV





661
SSYTSLNTLEVV





662
MQALQTPYS





663
QVWDSSSDRTVV





664
ASWDDKVRGWV





665
QQYGSSPWT





666
QQYNSYSRT





667
QQYNTSPLT





668
QSYDSSLSGSL





669
QSADSSGTYRV





670
QQYGRT





671
SSYTNIDTLEIV





672
LQHNSYPRT





673
QVWHSSFDPWV





674
QQSYSTPPTT





675
QQYNSYFPT





676
QVWDSSSDHYWV





677
GTWDSSLSAGV





678
QTWGTGPQVL





679
QQYDNLLT





680
QVWDSSGDHWV





681
QQRSNWLT





682
QQHDNLPSFT





683
QQYGSSPRT





684
QQYGSSPRT





685
LLYYGGAPV





686
QQLNSYPPA





687
QQYDNLPQT





688
CSYAGSSLWV





689
QSYDSSNQV





690
QQRSNWLFT





691
GTWDSSLSAGV





692
MQASQFPLT





693
CSFAGSNRE





694
QQYGSSPWT





695
GTWDSSLSAWV





696
QHYSSSAPIT





697
QQRNKWPGT





698
QQYGDSPYT





699
QQLNSYPLT





700
CTYAGSSTWV





701
QQSYSSPYT





702
QQANSFPRT





703
QQFNDYPLT





704
QSYDSSLSGSV





705
QQYSTYYT





706
MQGSHWPWT





707
AAWDDSLNGPWV





708
CSYAGSYTWV





709
QQLNSYPFT





710
QQYDNLPRT





711
QQLNSYPLT





712
QQSYSTPPDT





713
QQYDNLPPT





714
QQSYTTPLFT





715
QQLNGYPHSA





716
HQYDNLPPT





717
QQLNSYPLT





718
QQLNSNPPIT





719
QQSYSTPPYT





720
HQYDNLPRT





721
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRA



EDTAVYYCAREGVDTAMVGFDYWGQGTLVTVSS





722
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAREGVDTAM



VGFDYWGQGTLVTVSS





723
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQ



FVFPFDYWGQGTLVTVSS





724
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQ



FVFPFDYWGQGTLVTVSS





725
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQ



FVFPFDYWGQGTLVTVSS





726
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQ



FVFPFDYWGQGTLVTVSS





727
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCARSTRRWLQ



FVFPFDYWGQGTLVTVSS





728
QMQLQESGPGLVEPSETLALTCTVSGGSINRNHFW



AWLRRPPGKGLEWIGSASYTGTTHDNPSLRSRLTI



SVDTSKNQFSLKMTSVTVADTAVYFCARQAPGGGL



LGYYHGLDVWGQGTTVTVSP





729
QMQLQESGPGLVEPSETLALTCTVSGGSINRNHFW



AWLRRPPGKGLEWIGSASYTGTTHDNPSLRSRLTI



SVDTSKNQFSLKMTSVTVADTAVYFCARQAPGGGL



LGYYHGLDVWGQGTTVTVSP





730
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDRYCGGD



CSGPHYYYYGMDVWGQGTTVTVSS





731
EVQLVESGGGLVQPGGSLRLSCAASGFTFSYFEMN



WVRQAPGKGLEWISYISSSGTNIYYADSVKGRFTI



SRDNAENSLYLQMNSLRVEDTAVYYCARWDCSGGS



CNYYYYYNMDVWGQGTRVTVSS





732
EVQLVESGGGLVQPGGSLRLSCAASGFTFSYFEMN



WVRQAPGKGLEWISYISSSGTNIYYADSVKGRFTI



SRDNAENSLYLQMNSLRVEDTAVYYCARWDCSGGS



CNYYYYYNMDVWGQGTRVTVSS





733
QVQLVQSGAEVKKPGASVKVSCKASGYKFSNYYIH



WVRQAPGQGLEWMGWINPYSGETNYAQKFQGRVTM



TRDTSTSTAYMELSRLRADDTAVFFCAREDILLVP



AASNFYYFGMDVWGQGTTVAVSS





734
QVQLVQSGAEVRKPGASVKISCKSSGYIFTNFYVD



WVRQAPGRGLEWMGRVNPNDGSSIYAQKFRDRFSL



TSDTSTSTVFLNLRGLTSEDTALYFCARGDYYDPD



DRYNAYYSLGAWGQGTTVIVSS





735
EVQLLESGGGLQQRGGSLRLSCAASGFNFSSYAMS



WVRQAPGKGLEWVSSISATGGTTFYADSEKGRFTI



SRDNSKNILYLQMNSLRAEDTAVYYCTKGSMLLEV



YWGQGTLVTVSS





736
EVQLVESGGGLVQPGGSLRLSCGVSGIIVSRNEMS



WVRQAPGKGLEWVSYISSSGTGVHYADSVKGRFTS



SRDSAKNSVYLQMHSLRAEDTAVYYCARAPSDSSG



INGAFDIWGQGTMVTVSS





737
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSTYAIS



WVRQAPGQGLEWMGGIIPIFGTPTYAQRFQGRVTI



TADESTSTAYMELTSLRSDDTAVFYCARPKAPGYS



YLSLDYWGQGTLVTVSS





738
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCCGFGVVTTD



AYGMDVWGQGTTVTVSS





739
EVQLVESGGGLVQPGGSLRLSCSASGFTFNNYAMH



WVRQAPGKGLEHVSVISSYGDNTFYADSVKGRFTI



SRDNSKNTLYLQMSSLRAEDTAVYYCVKDKACTTT



SCYEGTFFDYWGQGTLVTVSS





740
EVQLVESGGGLVQPGGSLRLSCAASGFVFSNYWMT



WVRQAPGKGLEWVANIKQDESEEYYRDSLKGRFTI



SRDNAKNSVFLQMDSLRVEDSAVYYCVRGDDSILT



PTFDHWGQGTLVTVSS





741
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARAGKGFM



VITHFDYWGQGTLVTVSS





742
EVELVQSGAEMKEPGESLKISCKGFGYNFNNYWVA



WVRQTPGKGLEWMGIIYGGDSDTRYNPSMQGQVTI



SADKSINTIYLEWDVLRASDSGIYYCARPHTNSWD



QFDYWGQGTLVTVSS





743
QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMN



WVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAVYYCARPQGGSSW



YRDYYYGMDVWGQGTTVTVSS





744
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATSTAVLRY



FAPTGGWFDPWGQGTLVTVSS





745
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKDNGHSYG



YSWFDPWGQGTLVTVSS





746
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYPMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCATDGATIPI



NYYGMDVWGQGTTVTVSS





747
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARSPITMI



VVVNAFDIWGQGTMVTVSS





748
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARARITMI



VVVNHFDYWGQGTLVTVSS





749
EVQLVESGGRSVQPGGSLRLSCEASGFTVSSNYMN



WVRQAPGKGLEWLSVLYSGGNEYYADSVRGRFTIS



RHSSKNTLFLQMNRLRPEDTAVYYCARVQSTGYKY



WYFDIWGRGTLVIVSS





750
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARGFDYWGQG



TLVTVSS





751
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYFIY



WVRQAPGQGLEWMGRINPSSGVANYAQKFQGRVTM



TRDTSITTAYMELSRLTSDDTVVYYCARARDYGSG



SPMDVWGQGTTVTVSS





752
EVQLVESGGGLVQPGGSLRLSCVASGFTASSNYMN



WVRQAPGKGLEWVSVIYAGGGTHYADSVKGRFTIS



RDNFKNTVYLQMNSLRSEDTAVYYCARDGVYYGSV



IYHHYDLHVWGQGTTVTVSS





753
QVQLVQSGPEVKKPGSSVKVSCKVSGGTFSSYGIS



WVRLAPGRGLEWMGRILPVLDTTTYAPKFEGRVTI



TADESTTTAYMELTSLKSDDTAVYYCARGGGELLR



YPFDYWGQGTPVTVSS





754
QVHLVQSGPEVKKPGSSVKVSCKASGGRFGSFAFS



WLRQAPGQGLEWMGKVTPIVGVPVYAEKFQGTVTI



SADESTNTAYMEVSSLRSEDTALYYCAKAGLGLET



SGGNYFESWGQGTLVTVSS





755
QVRLVESGGGLVQPGRSLRLSCAASGFTFTDYAIH



WVRQAPGKGLEWMATISYDGNDKYFAASVRGRFSI



SRDNSNNTLFLQMNNLRAEDTAVYYCAKDRVTMNY



FDYWGQGTLVSVSS





756
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARVREGYTSG



WYADYWGQGTLVTVSS





757
QVQLVQSGAEVQKPGASVRVSCKASGYTFTDYYIH



WVRQAPGQGLEWMGWVNPNRGGTNNAQKFQGRVTM



TRDTSITTAYMELHSLRSDDTAVYYCARDRSYYHS



SGYHYYFDYWGQGSLVTVSS





758
QVQLVQSGAEVKKPGASVKVSCKASGYSFTGHYIH



WVRQAPGQGLEWMGWINPDSGGTNNAQKFQGRVTM



ARDTSISTAYMDLSTLTNDDTAVYYCVRDRIVGGY



SYGGDYWGQGTLVTVSS





759
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYGMS



WVRQAPGKGLEWVSAITGSGGSTHYADSVKGRFTI



SRDNSNNTLSLQMNSLRAEDTAVYYCAKGRLSPRL



GQGTLVTVSS





760
QLQLKESGSGLVKSSQTLSLTCAVSGGSISSDVYS



WSWIRQAPGKGLEYIGYVFHTGSAYYNPSLKSRVI



ISVDRSKNQVSLNVTSVTAADTAIYYCARVKVDNV



VFDLWGQGTMVTVSS





761
QVQLVQSGTEVKKPGSSVKVSCKASGDTFNSYAIS



WVRQAPGQGLEWMGRIIPILRLATYAQEFQGRVTI



TADKSTTTTYMEVTSLKSEDTAIYYCARDRGLAAR



PAGWVDLWGQGTLVTVSS





762
QTQLVESGGGVVQPGRSLRLSCAASGFTFSHYGMH



WVRQAPGKGLEWVALIWYDGSKKYYADSVKGRFTI



SRDISENTLYLQMNSLRAEDTAVYYCARENFHFSG



TPPLYWGQGTLVTVSS





763
EVQLVQSAAEQKKPGESLKLSCKGSGYSFPAHWID



WVRQMPGGGLEWVGSIFPGDSDTKYSPSFEGQVNI



SADRSINTAYLQWSSLKASDTAIYYCARKYTYDTS



GFFLSSSRNAFDVWGQGSMVFVSS





764
EVQLVQSGAEVKKPGESLKISCKGSGYNFDTYWIA



WVRQTPGKGLEWMGDIYPGDSDSRYSPSFQGRVTF



SADKSISVAYLQWSTLKASDTAMYFCARLGSNGYG



LWGQGTLITVSS





765
EVQLVQSGAEVKEPGESLKISCKGSGYSFSGYWIA



WVRQRPGKGLEWMGTIFPSDSDTRYSPSFEGQVTI



STDKSISTAYLQWSSLKASDTAMYYCARTYSYDSS



GFFLTSSREAFDIWGQGTMVIVSS





766
EVQLVQSGAEVKKPGESLKISCKASGYYFAAHWID



WVRQMPGRGLEWMGSIFPSDSDTEYGPSFQGQVNI



SADKSITTAYLQLKNLKASDTALYYCVRKYSFDVS



GFFLSSSRHAFDVWGQGTMVTVSS





767
EVHLVQSGPEQKKPGESLRISCKGSGYSFPAFWIV



WVRQMPGEGLEWMGSVFPGDSDTEYSPSFQGQVTI



SADKSISTAYLQWSSLKASDTAMYYCARKYSYDTS



GFFLTSSRDAFDVWGQGTMIAVSS





768
DVQLVQSGAEEKKPGEFLKISCKGSGYSFPAYWIG



WVRQMPGKGLEWMGSIFPGDSDTEYSPSFQGHVTI



SADKSISTAYLQWSSLKASDTAMYYCVRKFSYDIS



GFFLTSSRDAFDVWGQGTKVTISS





769
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATEGVWGQG



TTVTVSS





770
QVQLVQSGAEAKKPGASVKVSCKASGYTFTRYWMH



WVRQGPGQGLEWMGLMKPGDGKTIYAQKFQYRVTL



TRDTSTSTVYMELRSLTSADTAMYYCLLIEGMGAT



SGDWGQGTLVTVSS





771
EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMN



WVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCATTNDGYYY



GMDVWGQGTTVTVSS





772
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSMN



WVRQAPGKGLEWVSYISSSSSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCATNPHNTAM



VLDYYGMDVWGQGTTVTVSS





773
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCAGAYIAAA



GWGWELFQYYFDYWGQGTLVTVSS





774
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVG



VGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAHQAPFEW



FGVDYWGQGTLVTVSS





775
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMS



WVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRF



TISRDDSKNTLYLQMNSLKTEDTAVYYCTTDGLYC



SGGSCYYHSYYYYYGMDVWGQGTTVTVSS





776
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARDGLGNYD



ILTGYTERAFDIWGQGTMVTVSS





777
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARVKPILRV



VVVAATPCDYWGQGTLVTVSS





778
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARHARGYQ



LLSPRLGELSLYRSFDYWGQGTLVTVSS





779
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARATTTKM



IVVVINAFDIWGQGTMVTVSS





780
QLQLQESGPGLVKPSETLSLTCTVSGGSISSRSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARHWITMI



VVVIKGGWFDPWGQGTLVTVSS





781
QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMG



VSWIRQPPGKALEWLAHIFSNDEKSYSTSLKSRLT



ISKDTSKSQVVLTMTNMDPVDTATYYCARIRGQWL



VGKYYYGMDVWGQGTTVTVSS





782
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVG



VGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAHRGWGFS



SSFFDYWGQGTLVTVSS





783
QVQLVESGGGVVQPGRSLRLSCAASGFTISPYGMH



WVRQAPGKGLECVAIIWYDGSNKYYADSVKGRFTI



SRDSSKNTLYLQMDRLRAEDTAVYYCARMSSSLQH



YYGMDVWGQGTTVTVSS





784
QVQLVESGGGVVQPGRSLRLSCAASGFTISPYGMH



WVRQAPGKGLECVAIIWYDGSNKYYADSVKGRFTI



SRDSSKNTLYLQMDRLRAEDTAVYFCARMSSSLQH



YYGMDVWGQGTTVTVSS





785
QVQVVQSEGEVKKPGASVKVSCMASGYTFGDYGIS



WVRQAPGQGLEWMGWISGYNGDPKYAQKFQGRITL



TTDAATSSAYMELRSLRSDDTAVYFCARDVTLVRG



TASPRFDYWGQGTLITVSS





786
QVQVVQSEGEVKKPGASVKVSCMASGYTFGDYGIS



WVRQAPGQGLEWMGWISGYNGDPKYAQKFQGRITL



TTDAATSSAYMELRSLRSDDTAVYFCARDVTLVRG



TASPRFDYWGQGTLITVSS





787
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVG



VGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAQEGRNYD



RNWFDPWGQGTLVTVSS





788
QVRLQESGPGLVKPSETLSLTCTVSGGSISTYRWS



WIRQPPGKGLEWIGYIYYSGRTNYHPSLKSRVTMS



VDTSKNQFSLKLTFVSAADTAVYYCARLIPIDGRD



VWGRGTTVTVSS





789
EVQLVESGGGLVEPGGSLRLSCAASGFTFSNAWMC



WVRQAPGKGLEWVGRIKRIIDGGTINYAAPVKGRF



TISRDDSTNTVYLQMNSLRSEDTAVYYCTTYWDQY



TSTWTWGQGTLVTVSS





790
QVQLVQSGSELKKPGASVKVSCKASGYIFTNYAIN



WVRQAPGQGLEWMGWTNTNTGNPTYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAVYYCASIVKYDSS



GYNFDYWGQGTLVTVSS





791
QVQLVQSGAEVKKPGASVKLSCKTSGYAFTSYQVH



WVRQAPGQGLEWMGMINPSGSATHYAQKWQGRVSM



TADTSTTTVYMELSGLRSEDTAVYYCTRDPWHESE



HRFDPWGQGTLVTVSS





792
EVQLVESGGGLVQPGRSLRLSCAASGFTFGDYAMH



WVRQVPGKGLEWVSSITWNSGNIGYADSVKGRFTI



SRDNAKNSLYLQMNSLRIEDTALYYCAKDNKVSSW



YSFDIWGQGTMVTVSS





793
QVQLQQWGAGLLKPSETLSLTCAVSGASFSSYYWT



WIRQPPGKGLEWIGDISQSASTNYSPSLKSRVTIS



ADASRTQFSLNLISVTAADTAVYYCARGLGYYVAL



GQGTLVTVSS





794
EVQLVQSGVEVKEPGESLKISCKSSGYSFTKYWIG



WVRQMPGKGLEWLGIIYPDDSETRYSPSFRGQVTI



SADKSISTAYLAWDRLKASDTAIYYCVRGGQEVSL



RRLDWFVGYWGQGTLVTVSS





795
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS



WVRQAPGKGLEWVSSISGSGDKTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTALYYCAKERGGSGK



MYDYWGQGNLVTVSS





796
QVQLQQSGPGLLKPSQTLSLTCAISGDSVSSNTVA



WSWIRQSPSRGLEWLGRTYYRSNWYNDYAVSVKGR



ITLNSDTSKNQLSLQLNSVTPEDTAVYYCARRGAA



VAGTTGGSAFDIWGQGTMVTVSS





797
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYGMN



WVRQAPGKGLEWVSGISWNSNSVAYADSVNGRFTI



SRDNAKNSLYLQMNSLRIEDTAFYYCTKTSDLLYY



GSGSYLPYWGQGTLVVVSS





798
AVQLVESGGGFVQPGRSLRLSCAGSGFAFDDFAMH



WVRQAPGKGLEWVSGINWNSDNIAYAASVKGRFIV



SRDNGKNSLYLQMNSLRPEDTALYYCTRDGGAWDW



GRGTLVTVSS





799
EVQVVESGGGLVQPGGSLRLSCAASGFTVSSTFMS



WVRQAPGKGLEWVSVIYTVGDTFYADSVKGRFTIS



RHTSNNALYFQMNSLRTEDTAVYYCARGIPREYTT



RWENAFDIWGQGTMVTVSS





800
QVQLQESGSGLVKPSQTLSLTCSVSGGSIKRRGYY



WSWIRQHPGKGLEWIGYIYYSGTTYYNPSLQSRVN



ISVDTSKNQFSLNLRSVTAADTAVYYCARDRGADK



DSNSGDVFDIWGQGTMVTVSS





801
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSAYYWS



WIRQPPGKGLEWIGEINRRGNTNYNPSLKGRVTIS



IHTSKNQFSLNLSSMTAADTAVYYCVGPQGAYWGQ



GTLVTVSS





802
QLQLQESGPGLVKPSETLSLTCVVSGGSISSSDYY



WGWIRQPPGKGLEWIGTIYYSGNTFYNPSLKSRVT



MSVDPSKNQFSLKLSSVTAADTAVYYCARDPRGSS



TSCSYDYWGQGTLVTVSS





803
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMS



WVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRF



TISRDDSKNTLYLQMNSLKTEDTAVYYCTGQERIT



IFGVVIISSDYWGQGTLVTVSS





804
QVHLVQSGAEVKKPGSSVKVSCKASGGTFSTYAIS



WVRQAPGQGLEYMGGIIPSLRTANYAQRFQDRVSI



TADESTTTAYMELSSLRSDDTAVYYCARRLNDGAN



HSWGQGTRVTVSS





805
EVQLVQSGGGLVKPGESLRLSCAVSGLRFTDAWLN



WVRQAPGKGLEWVGRIKSRGSGGTIELAAPVKGRF



TISRDDSKSTLFLQMNSLRTEDTAIYYCSWDATVY



YDMAVWGQGTTVTVSS





806
QVQLVESGGGVVQPGGSLRLSCAASGFSFSSYALH



WVRQAPGKGLEWVALISYDGRNKYYADSVKGRFTI



SRDNSKKTLYLQMSTLTAEDTAVFYCARPSSGSYA



DPFDIWGQGTMVTVSS





807
QTVVESGGAVVQPGKSLTLSCEASGFSFSDFAMHW



VRQSPGKGLEWVAVVSYDSRQQYYADSVQGRFRIS



RDNSQYTVTLRMDTLSFEDTGIYFCVASRSSSLDY



WGQGTRVTVSS





808
QIQLVESGGGVVQPGRSLRLSCAASGFTFTTYGFH



WVRQAPGKGLEWVAVIWYDGSNEAYADSVKGRITI



SRDNSRNTVYLQMNSLRAEDTAIYHCARSRGYGGL



AGVDYWGQGTLVTVSS





809
DVQLVESGGGLVQPGGSLRLSCLATGFTFRSYSMN



WVRQAPGKGLEWISYLSNDDRTRKYADSVNGRFTI



SRDNDGSSLFLQMDSLRDEDTAIYYCARAYFDDSS



GGFDYWGQGALVIVSS





810
QVQLQESGPGLVKPAETLSLTCTVSGDSITSYYWS



WIRQPAGKGLEWIGRIYSSGDTNYDPSLKSRVTMS



VDTSKDQFSLRLSSVTAADTAIYYCAGSTYGDYVP



HFYFWGQGTLVTVSS





811
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGSYWS



WIRQSPGKGLEWIGEINPSGGSNYNPSLKSRVIIS



LDTSKNQFSLKLNSVTAADTAVYYCARGLSSFTTI



VVVFVGASFYFDSWGQGTLATVAS





812
QVQLQQWGAGLLKPSETLSLTCAVSGGSFTDHYWT



WIRQPPGKGLEWIGEINHSGRTNYSPSLKSRVTMS



LDTSKNQFSLKLRSVTAADTGIYYCARGTTSTTMI



VIVITAVSTWFDPWGQGTLVTVSS





813
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARHPLKVD



TIFGVVIIDPAPFDYWGQGTLVTVSS





814
QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMG



VSWIRQPPGKALEWLAHIFSNDEKSYSTSLKSRLT



ISKDTSKSQVVLTMTNMDPVDTATYYCARIASYYY



DSSGYYQTRPIGHAFDIWGQGTMVTVSS





815
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKDRAQLLW



FGQSRGMDVWGQGTTVTVSS





816
EVQLVESGGGLVKPGRSLRLSCTASGFTFGDYAMS



WFRQAPGKGLEWVGFIRSKAYGGTTEYAASVKGRF



TISRDDSKSIAYLQMNSLKTEDTAVYYCTSTSDWW



GQGTLVTVSS





817
EVQLVESGGGLVQPGGSLKLSCAASGFTFSGSAMH



WVRQASGKGLEWVGRIRSKANSYATAYAASVKGRF



TISRDDSKNTAYLQMNSLKTEDTAVYYCTRLRSGL



VGFDWLPLYGMDVWGQGTTVTVSs





818
EVQLVQSGAEVKKPGESLRISCKGSGYSFTSYWIS



WVRQMPGKGLEWMGRIDPSDSYTNYSPSFQGHVTI



SADKTISTAYLQWSSLKASDTAMYYCARRGVGILK



DLPVYAMDVWGQGTTVTVSs





819
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMH



WVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTM



TRDTSTSTVYMELSSLRSEDTAVYYCAREARQIFI



TMMTTKTSWFDPWGQGTLVTVSS





820
QVRLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGRIIPIFHIANSAQKFQGRVTI



TADKSTSTAYMELSSLRSEDTAVYYCARVSSTAVV



TGLDYYYGMDVWGQGTTVTVSS





821
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMS



WVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRF



TISRDDSKNTLYLQMNSLKTEDTAVYYCTTISVGL



LWFGLAVRDHYYFDYWGQGTLVTVSS





822
EVQLVESGGGSVRSGGSLRLSCAASGFTFRSYWMH



WVRQAPGKGLVWVSRIFSDWSTTTYADSVRGRFTI



SRDNAKNTLYLEMNRLKVEDTAVYYCARSYYDSST



GYYPDALDLWGQGTTVTVSS





823
EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMS



WVRQAPGKGLEWVAAISGSGGSTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKSGSVWGS



YHKTYYFDYWGQGTLVTVSS





824
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKNYADSVKGRFTI



SRENSKNTLYLQMNSLRAEDTAVYYCAKEILKGYS



SGWKYYYYGMDVWGQGTTVTVSS





825
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMN



WVRQAPGKGLEWVSVIYSGSSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARATTTMVRG



VIYHYYYYGMDVWGQGTTVTVSS





826
QVQLQESGPGLVKPSQTLSLTCTVSGGPISSGGYY



WSWIRQHPGKGLEWLGCIYYSGSTYYNPSLKSRVS



ISVDTSKSQFSLKLSSVTAADTAVYYCARERLGRM



VRGVNWFDPWGQGILVTVSS





827
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSYYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCASWTMVRG



VIRWFDPWGQGTLVTVSS





828
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARQFHYVG



IVVVVAPHYYYGMDVWGQGTTVTVSS





829
EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMN



WVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCASPRGYSYG



PFDYWGQGTLVTVSS





830
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARVLYYDIL



TGYWWYYYGMDVWGQGTTVTVSS





831
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMH



WVRQAPGKGLVWVSRINSDGSSTSYADSVKGRFTI



SRDNAKNTLYLQMNSLRAEDTAVYYCARGAPITIF



GVVISTWFDPWGQGTLVTVSS





832
QLQLQESGSGLVKPSQTLSLTCAVSGGSISSGGYS



WSWIRQPPGKGLEWIGYIYHSGSTYYNPSLKSRVT



ISVDRSKNQFSLKLSSVTAADTAVYYCARAHTDSL



ELGIWGQGTMVTVSS





833
EVQLLQSGGEVRRPGESLKISCKASGYSFPAHWIG



WVRQMPGRGLEWMGSIFPSDSDTEYSPSFEGQVKI



SADKSITTAYLQWSSLKASDTAFYYCVRKYTYDTS



GFFLTSTRSAFDVWGQGTMVTVSS





834
EVQLEQSGAEEKKPGESLKISCKGSGYSFPAFYIA



WMRQMPGKGLEWMGSIFPGDSETEYNPSFQGQVTI



SADKSITTAYLQWDNLKASDTALYYCARKHVYDTS



GFFLSSSRNAFDVWGQGTKVTVFS





835
EVQLVQSGAEQRKPGESLRISCKGSGYSFPAHWIA



WVRQMPGRGLEWMGSIFPGDSDTEYNPSFQGHVNI



SADRSINTAYLQWSSLKASDSAIYYCARKYSFDIS



GFFLSSSRYALDVWAQGTTVTVSS





836
DMQLVESGGGLVQPGGSLKLSCAASGFTFSASAIH



WVRQASGKGLEWVGHIRTRTNRYATAFSESVNGRF



TISRDDSKSTAYLQMNSLKAEDTAVYYCARDEGVT



FHDHWANEIRYGMDVWGRGTTVTVSS





837
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARARTTMI



VVVSQFDYWGQGTLVTVSS





838
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMH



WVRQAPGKGLVWVSRINSDGSSTSYADSVKGRFTI



SRDNAKNTLYLQMNSLRAEDTAVYYCARDRGGWLL



GSYYYYGMDVWGQGTTVTVSs





839
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARGQISHYG



FGESHWGQGTLVTVSS





840
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVS



VGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLT



ITKDTSKKQVVLTLTNMDPVDTASYYCAHSGIAVV



GNQLFHYYAMDVWGQGTTVTVSS





841
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKERSSGSQ



WGWTYYYYGMDVWGQGTTVTVSS





842
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARDPYGGNR



RFHGWVYYYYGMDVWGQGTTVTVSS





843
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARESTPDVR



GVMNYWGQGTLVTVSS





844
EVQLLESGGGLVLPGGSLRLSCAASGFTFSIYAMS



WVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKDAVASAG



SPDYWGQGTLVTVSS





845
QVQLVESGVGVVQPGKSLRLSCAASGFTFTSYGMH



WVRQAPGKGLEWVAVISFDGSNIYYADSVKGRFTI



SRDNFKNTLYLQMNSLRAEDTAVYYCARDKLLWFG



EPVVGYYYYYYMDVWGKGTTVTVSS





846
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARDGGGDYA



QIYFDYWGQGTLVTVSS





847
QVQLVESGGGVVHPGRSLRLSCAASGFAFNKYGIH



WVRQAPGKGLEWVALIWNDGNKQYYGDSVKGRFTV



SRDNSKNTVSLQMDTLRDEDTAVYYCARDRLMTTY



NYYSSMDVWGRGATVIVSS





848
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAREPGDCSG



GSCYYYGMDVWGQGTTVTVSS





849
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIFYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARATRGYS



YDDAFDIWGQGTMVTVSS





850
QVQLQESGPGLVKPSGTLSLTCSVSGGAITTSSYF



WGWIRQPPGRGLEWIGSISYSGDTFYNPSLNDRVT



ISVDSSKNQFFLKLRSVTAADSAVYYCASPSYTDL



LTGYYVPVDYWGQGILVIVSS





851
QVHLVESGGGVVQPGKSLTLSCAASGFTFSAYGMH



WVRQTPGKGLEWVALISFDGSNKYYRDSVKDRFTI



ARDNSKNTLSLQMNSLRPEDTAIYYCAKDPRVNEL



LWFGSLTQFYFDDWGQGTLVTVSS





852
QVQLVESGGGVVQPGRSLTLSCAASGFTFNNYGMH



WVRQAPGKGLEWLALISYEGSIRYYGDSVKGRFTI



SRDSSKNTVYLQMISLRAEDTAVYYCAKSGGPFHL



SLYYYMDVWGKGTTVTVSS





853
QVQLQESGPGLVKPSETLSLTCTVSGGSINSYYWS



WIRQTAGQGLEWIGRIYSGGSTNYNPSLKSRVTMS



VDTSQNQFSLNLNSVTAADTAVYYCARAFYGHAFD



FWGLGVLVIVSS





854
QVQLVESGGGVVHPGRSLRLSCAASGFTFSRFGMH



WVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAI



SRDNSKNTLYLQMNSLRPEDTAVYYCAKGLTIPFD



KWGHGTLVTVSS





855
QVQLVESGGGVVHPGRSLRLSCAASGFTFSRFGMH



WVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKGLTIPFD



KWGHGTLVTVSS





856
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSFWMT



WFRQTPGKGLEWVANIKEDGSEKQYVDSVKGRFNI



SRDNAHNSLYLEMNSLRSEDAAVYYCARRGKYCSG



GRCYSWWFDPWGQGTQVTVSS





857
QVQLVQSGGEMRKPGSSVKVSCKASGGTFSSYTIS



WVRQAPGQGLEWMGRIIPMLNKTYYAQKFQGRVTF



AADESTSTVYMELSSLRSEDTAMYYCARVASLIGD



DYWGQGSLVTVSS





858
QVQLVQSGGEMRKPGSSVKVSCKASGGSFSSYTIS



WVRQAPGHGLEWMGRIIPMLNKTYYAQKFQGRVTV



AADESTSTVYMELSSLSSEDTAIYYCARVASLIGD



DYWGQGSLVTVSS





859
QITLKESGPTLVKPTQTLTLTCTFSEFSLDSRGVG



VGWIRQPPGRALEWLALIYWNDNKRYNPSLRSRLT



ITKDTSKNQVVLTMSNMDPVDTATYYCAHKPSGWS



LRFDSWGQGTLVTVSS





860
QVQLQEAGPGLVKPSETLSLTCSVFGGSISSYYWS



WIRQPPGKGLEWIGYIYYRGSTNYNPSLKSRVTMS



VDTSKNQFSLNLTSVTAADTAVYFCARESLFNWFD



SWGHGTLVTVSS





861
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRYGMH



WVRQAPGKGLEWVALISYEGSTEQYSDSVKGRFAI



SRDNSKNTLYLQMNSLRHEDTAVYYCAKGLTIPFD



NWGQGTLVTVSS





862
EVQLVESGGGLVQTGGSLRLSCAASGFPFSGYALN



WVRQAPGKGLEWVSYISSSSSTVYYADSVKGRFTI



SRDNAKNSLYLQMNSLRDEDTAVYYCARVDYDSSR



NYWGQGTLVTVSS





863
EVQLVESGGGLVQPGGSLRLSCAASGFTFINYDMT



WVRQAPGKGLEWISYISSSSSTTHYSDSVKGRFTI



SRDNARNSLYLEMNSLRAEDTAVYYCARVERWLVL



GYYYYGMDVWGQGTTVTVSS





864
EVQLVESGGGLVQPGESLRLSCVASGFAFDKFWMA



WLRQAPGKGLEWVALLNKDESEKYYVDSVKGRFTI



SRDNAIDSVFLQMNSLRTEDTAVYYCGSIDYWGQG



ALVTVSS





865
QVQLQESGPGLVKPSQTLSVTCTVSGGSINRDGHY



WIWIRQHPEKGLEWLGYIYSGRNTFYNPSLRSRLS



ISADTSKSQFSLNLHSVTAADTAVYYCAKMYSDYD



DNYYGLDVWGRGTTVTVSS





866
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARDRYCSSTS



CGGYYYYMDVWGKGTTVTVSS





867
QVQLQESGPGLVKPSETLSLTCTVSGGSVSSGSYF



WSWIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVT



ISVDTSKNQFSLKLRSVTAADTAVYYCARAPNDFW



SGYPYYFDYWGQGTLVTVSS





868
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCTRDGSTAAI



FGNIDYWGQGTLVTVSS





869
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMH



WVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM



TRDTSISTAYMELSRLRSDDTAVYYCARGVVRNDY



GDPGFDYWGQGTLVTVSS





870
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATAPAYCSG



GSCPENNWFDPWGQGTLVTVSS





871
QVLLVQSGAEVKKPGASVKVSCKASGYRFTSYGIH



WVRQAPGQSLEWMGCINTDNEKTEYSQKFQGRVTI



TRDTSASTAYMELSTLRFEDTAVYYCAILWFGEFY



FYDLFYNAVDVWGQGTTVTVSS





872
QVLLVQSEAEVKKPGASVKVSCKASGYRFTSYGIH



WVRQAPGQGLEWMGSINTDNGKTEYSQKFQGRVTI



TRDTSAGTAYMELSTLRSEDTAVYYCAILWFGEFY



FYDLFYNAVDVWGQGTTVTVSS





873
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMH



WVRQAPGQRLEWMGWINAGNGNTRYSQKFQGRVTI



TRDTSASTAYMELSSLRSEDTAVYYCASRREQWLG



DLGYYYYGMDVWGQGTTVTVSS





874
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMH



WVRQAPEQGLEWMGIINPSGGSTSYAQKFQGRVTM



TRDTSTSTVYMELSSLRSEDTAVYYCARGGAHSED



YWGQGTLVTVSS





875
QVQMVQSGAEVKKPGASVKVSCKASGYTFTNYYVH



WVRQAPGQGLEWMGRINPSDGSTSYTQKFQGRVTM



TRDTSTSTVYMQLSSLRSEDTALYYCARHQDPLDI



VATVDWGGLDYWGQATLVTVSS





876
QVQLVQSGGELRKPGSSVKVSCKASGGTFSSYTIS



WVRQAPGQGLEWMGRIIPMLNKTYYAQKFQGRVTF



AADESTNTVYMELSSLRSEDTAMYYCARVASLIGD



DYWGQGSLVTVSS





877
QVQLVQSGAEVKKPGSAVKVSCKASGGTFNSYAFN



WVRQAPGQGLEWMGGIIPIFGPPNYAQNFQGRVTI



TADESTSTAYMELSSLTSEDTAVYYCATTGTDNYY



YYMDVWGKGTTVTVSS





878
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSSDIN



WVRQATGQGLEWMGWMNPNTGTTGYAQKFQDRVTM



TRDTSINTAYMELSSLRSEDTAVYYCARKNCSGGI



CYFHDYWGQGTRVTVSS





879
QITLKESGPTLVKPTQTLTLTCTFSEFSLDARGVG



VGWIRQPPGRALEWLALIYWNDYKRYSPSLQSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAHKPSGWS



LRFDSWGQGTLVTVSS





880
EVQLLESGGGLVQPGGSLRLSCAASGFTFISYATS



WVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKGQTIQLW



LFGALWGQGTLVTVSS





881
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS



WVRQAPGKGLEWVSAISGSGGTTYYADSVKGRFTI



SRDNSKNTLYLQMDSLRGDDTAVYSCALTVSSWYP



GIFENWGQGTLVTVSS





882
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKAFSGSYW



DAFDIWGQGTMVTVSs





883
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSHGMH



WVRQAPGKGLEWVAVISYDGINKYYADSVKGRFTI



SRDNSKNTLFLQLNSLRAEDTAVYYCAKAASGARG



YYGMDVWGQGTTVTVSS





884
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARSSSGHYV



SDLGYWGQGTLVTVSS





885
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARALNGYRY



NDYWGQGTLVTVSS





886
QVQLVESGGGVVQPGRSLRLSCAASGFTFSTYGMH



WVRQAPGKGLEWVAVMWFDGVDKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRDEDTAVYYCAREEGGGSS



THFDCWGQGTLVTVSS





887
QVQLVESGGGVVQPGRSLRLSCAASGFTFSTFAMH



WVRQAPGKGLEWVAIISYDEINKYYADSVKGRFTI



SRDNSKNMLYLQMNSLRAEDTAVYYCARTREGSYY



YGMDVWGQGTTVTVSS





888
EVKLVESGGHLVQPGRSLRLSCTASGFIFGDYAMG



WVRQAPGKGLEWVSFIRGRLVGATVEYAASVKGRF



TMSRDDSERVAYLQMNSLKIEDTGVYYCVRGGLQF



VVAVGPYGVDVWGQGTTVTVSS





889
EVKLVESGGHLVQPGGSLRLSCTASGFIFGDYAMG



WVRQAPGKGLEWVSFIRGRLVGATVEYAASVKGRF



TMSRDDSERVAYLQMSSLKIDDTGVYYCVRGGLQF



VVAVGPYGVDVWGQGTTVTVSS





890
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMS



WVRQAPGKGLEWVANIKQDGSEKYYVDSVKGRFTI



SRDNAKNSLYLQMNSLRVEDTAVYYCARDIGGGAP



DYWGQGTLVTVSS





891
QVLLQESGPGLVRPSQTLSLTCSVSGASISSGDYY



WTWVRQTPGKGLEWLGFIYYSGSTYYNPSLQRRVL



ISMDTAMNQFSLRLTSVTAADTAVYYCAIKPSIPG



YFDPWGQGTLVTVSS





892
QVQLQQWGAGLLKPSETLSLTCALNGGVLSDYYWS



WIRQPPGQGLEWIGAIHRSGSTSYTPSLKSRVTMS



VDTSKNQFSLRLSSVTAADTAVYYCARVGGWQRSP



RPNWGQGTRVTVSS





893
QVQLQQWGAGLLKPSETLSLTCALNGGVLSDYYWS



WIRQPPGQGLEWIGAIHRSGSTSYTPSLKGRVTMS



VDTSKNQFSLRLSSVTAADTAVYYCARVGGWQRSP



RPNWGQGTRVTVSS





894
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYYWN



WIRRPPGKGLEWIGEITHSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARGQGYGRVL



LWFGEWGQGTLVTVSS





895
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSDYFWY



WIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVSIS



VDTSKNQFSLKLSSVTAADTAVYYCARGQGYGRVL



LWFGEWGQGTLVTVSS





896
QVQLQESGPGLVKPSGTLSLTCDVSGDSISSNNWW



TWVRQPPGKGLEWIGDIYHSGTTNYNPSLKSRLTM



SVDKSKNHFSLKLTSVTAADTAVYYCARPSSGSRF



DYWGQGTLVTVSS





897
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPAGKGLEWIGHIYTSGSTNYNPSLKSRVTMS



VDTSKNQFSLKLSSVTAADTAVYYCARGFDYWGQG



TLVTVSS





898
QVQLQESGPGLVKPSETLSLTCTVSGDSISSYYWS



WIRQSPGKGLEWIGYIYHSGSADYNPSLKSRVSMS



LDASKNQFSLKMSSVTAADTALYYCAKARGVVLFD



YWGQGTLVTVSS





899
QVQLRESGPGLVKPSETLSLTCTVSGGSISGYYWS



WIRQPPGKGLEWIGYLHYSGRSNSSPSLNSRVSIS



VDTSQNRFSLKVTSLTAADTAVYYCARHSYGSGTY



LDPFDYWGQGTLVTVSS





900
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGSYY



WSWIRQPAGKGLEWIGRIYTSGSTNYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARQPHLAY



YYDSSGYNDAFDIWGQGTMVTVSS





901
QVQLQESGPGLVKPSQTLSLICTVSDDSISSGSYY



WSWIRQPAGKGLEWIGRIYAGESTNYNPSLKSRVI



ISVDTSKKQFSLRLSSVTAADTAVYYCARGAVVTP



FGLDSWGQGTLVTVSS





902
EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIG



WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI



SADKSISTAYLQWSSLKASDTAMYYCASEDYYDSS



GYYWYWGQGTLVTVSS





903
EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIG



WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI



SADKSISTAYLQWGSLKASDTAMYYCARLSAIAVV



GYYYYAMDVWGQGTTVTVSs





904
QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMN



WVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAVYYCARDFIAASP



FYYYYYMDVWGKGTTVTVSS





905
EVQLVQSGAEVKKPGESLKIFCKGSGYTFSFYWIG



WVRQTPGKGLEWMGIIYPGDFDTRYSPSFQGQVTI



SADKSINTAYLQWSSLKASDTAMYYCATSPGGYGV



RRTVLEDFRHWGQGTLVTVAS





906
QLQLQESGPGLVKPSETLSLTCTVSGGAFSSGRHY



WGWIRQPPGKGLEWIGSIYSGVITHYNAPLKSRVT



IAVDTSKNQFSLKLSSVTAADTAVYYCWTMEYDDY



SFVYDYWGQGTLVTVSS





907
QVHLQQWGAGLLKPSQTLSLTCAVYGGSFSSYYWS



WIRQTPGKGLEWIGEVTHSGSTNYKPSLKSRVTMS



VDTSRNQFSLNLTSVTAADTAVYYCARGGKQQLVR



NYYLDSWGQGTLVTVSS





908
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMD



WVRQAPGKGLEWMGGFDPEDGETIDAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATGFGGVIV



RGFDYWGQGTLVTVSS





909
QVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMS



WIRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARVYGDYSY



YMDVWGKGTTVTVSS





910
EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTDYADSVKGRFTIS



RDKSKNTLYLQMNSLRAEDTAVYYCARDLGEAGGM



DVWGQGTTVTVSS





911
EVQLVESGGGLVQPGGSLRLSCAASGFTFSRFWMT



WVRQAPGKGLEWVANIKEDGSVMFYVDSVKGRFSI



SRDNSKNSLYLEMNSLRAEDTAVYFCVREIESGVD



FWSGHYYWGQGTLVTVSS





912
EVQLVESGGGLVQPGGSQRLSCVASGFTFSNYWMS



WVRQAPGKGLHWVANIKSDGSETYYVDSLRGRFTI



SRDNAKNSLYLQLTSLTVEDTAVYYCARDSAYYDT



IGYYSGDYWGRGTLVTVSS





913
QVQLVESGGGAVQPGRSLRLSCEASAFSFHLHGMH



WVRQAPGKGLEWVALIWFDGSKKFYADAVKGRFTI



SRDNSKNTLYLQMNSLRVEDTAIYYCGRSFRGSCF



DYLGQGTLVTVSS





914
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS



WVRQAPGKGLEWVSAISSSGGGTYYADSVKGRFTI



SRDNSKNTLYVQMNSLRAEDTAVYYCALGTGSYYG



VNYWGQGTLVTVSS





915
EVQLVESGGGLVQPGRSLRLSCAAFGFIFDDYGMH



WVRQVPGKGLEWVSGITWNSGSIGYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTALYFCAKDMGGRYS



SGLYYYYYGMDVWGQGTTVTVSS





916
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARELRGYFDY



WGQGTLVTVSS





917
QMRLQESGPGLVKPSETLSLTCTVSGGSIGSSSYF



WGWIRQPPGKGLEWIGNIYYGGSTYYKPSLKSRVT



ISLDTSKNQLTLRLSSVTAADTAVYYCARDPNDFW



SGFPRGAFDIWGQGTMVTVSS





918
QLQLQESGPGLVKPSETLSLTCTVSGGSISSSSYY



WGWIRQPPGKGLEWIGSIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCASHARYEE



ETFDYWGQGTLVTVSS





919
EVQLVESGGGLAQPGGSLRLSCAASGFTFSSYDMH



WVRQAAGKGLEWVSTIGTAGDTYYPGSVKGRFTIS



RENDKNSLYLQMNSLRAGDTAVYYCVRDSYTSAWT



PAGYFDLWGRGTLVTVSS





920
QVQLVESGGGVVQPGRSLRLSCAASGFTFSRSAMH



WVRQGPGKGLEWVAMMSYDGSDIQYADSVKGRFTI



SRGNSKNTLFLQMNSLRLADTAMYYCAKDHYGSID



YWGQGTLVTVSS





921
QVQLVESGGGVVQPGRSLRLSCVASGFTFSSQSMH



WVRQAPGKGLEWVSIISYDGNNKQYADSVKGRFTI



SRDNSKSTLFLQINSLRPQDTAVYYCARPYTSRWF



WSNWGQGTLVTVSS





922
EVQLVESGGGLVQPGRSLRLSCAASGFTFEEYSIH



WVRQAPGKGLEWVSGVSWNSGTIAYADSVRGRFTI



SRDNAKNSLYLQMSRLRADDTALYYCALLPPNAYD



YGDGLLDHWGQGTLVTVSS





923
EVQVVQSGAEVKKPGESLKISCKGSGYTFGRYWIA



WVRQMPGKGLEWMGIINPADSDTRYSPTFQGQVTI



SVDQAISTAYLQWSSLKASDTAMYHCARHRAAGGN



YYYGMDVWGQGTTVTVSS





924
QVQLVQSGAEVKKPGASVKVSCKASGYTFSTYYMH



WVRQAPGQGLEWMGIINPSGDSTRYAQKFQGRVTM



TRDTSTSTVYMEVSSLRFEDTAVYYCARERVGPAA



GYMDVWGKGTTVTVSS





925
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTI



TADESTSTAYMELSSLRSEDTAVYYCARAAYYYDS



SGYGWFDPWGQGTLVTVSS





926
QVQLVQSGAEVKNPGSSVKVSCKTSGATFTTYAIN



WVRQAPGQGLEWIGGIFPIFTAAVYAQKFQGRVTI



TADESTTTAYLELSSLRSEDTAVYYCARGDYTEYS



YYYMDVWGKGTTVTVSS





927
EVQLLESGGGLVQPGGSLRLSCAASGFTLSSYAMS



WVRQAPGRGLEWVSAVSGSGGSTYYADSVKGRFTI



SRDNSKNMLYLQMNSLRAEDTAIYYCALPTGASSS



YSGPNYWGQGTLVTVSS





928
QVQLVESGGGVVQPGRSLRLSCVASGFTFSNYDMH



WVRQAPGKGLEWVTVISSDGNNRRYADSVKGRFTI



SRDNSKNMLYLQMNSLKAEDTAVYYCARDEVIAVA



TGEGMDVWGQGTTVTVSP





929
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMH



WVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTALYYCAKDMGYDIL



TGSGLGDYWGQGTLVTVSS





930
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMH



WVRQAPGKGLEWVSGISWNSGTIGYEDSVKGRFII



SRDNAKNSLYLQMNSLRAEDTALYYCAKEPLFGET



YGMDVWGQGTTVTVSS





931
EAQLVESGGGLVQPGRSLTVSCAVSGFTFDDYAMH



WVRQAPGKGLEWVSSISWNSEKIAYADSVKGRFTV



SRDNAKNSLYLQMTSLRPEDTALYYCARDKGSGSY



YSGAYYYYMDVWGKGTTVTVSS





932
EVQLVESGGGLVPPGGSLRLSCAASGFTFSSYTIN



WVRQAPGKGLEWVSYINSGSSIIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCATFNSGNDN



AYEYWGQGTLVTVSS





933
EVRLVESGGGWVQPGGSLRLSCEASTFIFSNSEMN



WVRQAPGKGLEWVSYISSSDNSVHYADSVKGRFTI



SKDSAKKTLYLQMNSLRAEDTGVYYCAREYPDFWS



GHYYYYMDVWGKGTTVTVSS





934
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARLPYGMDVW



GQGTTVTVSS





935
QVKLQQWGAGLVKPSETLSRTCAVYGGSFSGYFWS



WIRQSPGKGLEWIGEINHSGKTNYSPSLKSRVSIS



VDTSKNQFSLKLTSVTAADTAVYYCARGLYDKSGY



RSDGFDSWGQGAVVTVYS





936
QVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWT



WIRQPPGKGLEWIGEINHSGSTNYNPSLKSRITMS



VDTSKNQFSLELRSVSAADTAVYYCARGFEGYCSG



GRCYSYFDYWGQGTLVTVSS





937
QVQLQESGPGLVKPSETLSLTCTVSGGSLSSYYWN



WIRQPPGKGLEWIGYMYNSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARVKNWDYGL



YWGQGTLVIVSS





938
QVQLQESGPGLVKPSETLSLTCTVSGGSISTFYWN



WVRQPPGKGLEWIGFIYYSGRTNYNPSLKSRVTIS



VDTSKNQFSLKVSSVTAADTAVYYCARDGQSDWHF



DLWGRGTLVTVSS





939
QVQLQESGPGLVKPSETLSLTCTVSGGSVSSYFWS



WLRQPPGKGLEWIAYIFYTGTSNYNPSLKSRVTIS



LDTSKNQMSLNLSSVTTADTAVYYCARVYGDYLDH



WGQGTVVTVSS





940
QITLKESGPTLVKPTQTLTLTCTFSGFSFNTPGVG



VGWIRQPPGKAPECLALIYWDDEKLYNPSLKTRLT



ITKDPSKNQVVLTMTTMDPVDTATYYCAHRSFLYN



IFNGYSYAPFDYWGQGSMVTVSS





941
QVQLVESGGGVVQPGRSLRLSCAASGFSFSNHGMH



WVRQAPGKGLEWVAVIWYDGDNRFYADSVRGRFTI



SRDNSKNTLFLQMDSLRAEDTGIYYCAKDLFSGDR



DFWGQGTLVTVSS





942
QVQLVESGGGVVQPGRSLRLSCVASGFTFSNSAMH



WVRQAPGMGLEWVAVIYYDGSNEYYADSVKGRFTI



SRDNSKNTLYLQMNSLRADDTAVYYCAKDSGAVLL



WFGADFWGQGTLVTVSS





943
DVQLVESGGSLVQPGGSLRLSCAASEFTFSSYEMN



WVRQAPGKGLEWVSYIDSSSTTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCAREGAYDIW



RGSYMRAYDHWGQGTLVTVSS





944
QVQLVQSGSELKKPGASVKVSCKASGYTFTNFAIN



WVRQAPGQGLEWMGWINTKTGIPTYAQGFTGRFVF



SLDTSVSTAYLQISGLKAEDTAVYYCARYIEMFDP



WGQGTLVTVSS





945
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARQAYGDYG



WDYYYGMDVWGQGTTVTVSS





946
QVQLAEAGGGVVQPGTSLRLSCVVSGFSFSRYGMH



WVRQAPGKGLEWVAVISHDDSQKYYGDSVKGRFTI



SRDNSKDTLYLEMTSLRLEDTAVYYCLKDWDWEYE



DSRPTLRGSVYWGQGTLVIVSA





947
QVQLVESGGGAVQPGRSLRLSCVTSGFNFNSYTMH



WIRQAPGKGLEWVAVISYEGSKKYYADSLKGRFTI



SKDNSKNTVYLEMNSLTTEDTAVYYCARGSVFWFG



EGKNWFDPWGQGTLVTVSS





948
QVQLVESGGGAVQPGRSLRLSCVTSGFNFNSYTMH



WIRQAPGKGLEWVAVISYEGSKKYYADSLKGRFTI



SKDNSKNTVYLEMNSLTTEDTAVYYCARGSVFWFG



EGKNWFDPWGQGTLVIVSS





949
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCAREDSSGWS



RGDYWGQGTLVTVSS





950
QVQLVQSGSELKKPGASVKVSCKASGYIFTSYGMN



WVRQAPGQGLEWMGWINTNTGSPMYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAVYYCARRFVVREV



EYNWFDPWGQGTLVTVSS





951
QAQLVQSGSEVRKPGASVKVSCKASGYSFNDYGIT



WVRQAPGQGLEWMGWISAYNGETNYAQKFQDTVTM



TTDTSTNTAYLELRSLRFADTALYYCARDGYCNSM



RCYRYYHGMDVWGQGTTVTVSS





952
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATGPTAKPN



KQWGYWFDPWGQGTLVTVSS





953
QVQLVQSGAEVKKPGASVKVSCKASGNTFSTYYIH



WVRQAPGQGLEWMGIISPSGDDANYTQKFQDRVTM



TRDTPTNTVYLELSSLRSEDTAVYYCASPVSVEQD



FDIWGQGTMVTVSA





954
EVQLVESGGGSVKPGGSLRLSCAASGFTFSDVWMS



WVRQAPGKGLEWVGRIRSKSDGGTTDYAAPMKERF



SISRDDAKNTMYLQMNSLKTEDTGVYYCTTPVGDF



WGQGTMVTVSS





955
EVQLMESGGGLVKPGGSLRLSCAGSGLTFDNAWMS



WVRQAPGKGLEWVGRVKSKTDGGTTDYAAPVKGRF



TISRDDSKNTLFLQMNSLKTEDTAVYYCSTSHPPF



FDYWGQGTLVTVSS





956
QVQLVESGGGVVQPGRSLRLSCAASRFTFSSYAMH



WVRQAPGKGLEWVALISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMDSLRPEDTAVYYCARGLWQLVS



PVFDYWGQGTLVTVSS





957
EVQLVESGGVVVQPGGSLRLSCAASGFTFDDYAMH



WVRQAPGKGLEWVSLISWDGGSTYYADSVEGRFTI



SRDNSKNSLYLQMNSLRAEDSALYYCAKVTNRGVR



GLYFDYWGQGTLVTVSS





958
QVQLVQSGAEVKKPGASVKVSCKASGNTFTTYYIH



WVRQAPGQGLEWMGIISPSGDDANYTQKFQDRVTM



TRDTPTNTVYLELSSLRSEDTAVYYCASPVSVEQD



FDIWGQGTMVTVSA





959
QVQLVQSGAEVKKPGSSVNVSCKASGGTFNSYTLS



WVRQAPGQGLEWMGRIVPMLGITNYAQKFQDRVTI



TADESTATAYMDLSSLTSEDTAVYFCAINTLLVTA



WGQGTLVTVSS





960
QITLKESGPTLVKPTQTVTLTCTFSGFSLNTPGAG



VGWIRQPPGQALECLALIYWDDDKRYSPSLRSRLS



IAKDTAKNQVVLTVTNLDPVDTATYYCVHRSFLYD



IFSGYSYAPFDYWGQGMLVTVSS





961
QITLKESGPTLVKPTQTLTLTCTFSGFSFNTPGVG



VGWIRQPPGKAPECLGLIYWDDEKRYSPSLKSRLT



ITKDPSKNQVVLTMTTMDPVDTATYYCAHRSFLYN



IFDGYSYAPFDYWGQGSMVTVSS





962
QVQLVESGGGLVKPGGSLRLSCAASGFTFTFSDYY



MNWIRQAPGGGLEYIAYISSGGDAIYYADSVKGRF



IISRDNSESSVSLQMTSLRADDTAVYYCAGGADCR



RTSCHYLVSNREEYMGVWGKGTTVTVSS





963
EVQLVESGGGLVKPGGSLRLSCAASGFTFSDYYMN



WVRQAPGKGLEWVSSMSSDSDYIFYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARGLVLSGT



RYSYFYGMDVWGQGTTVTVSS





964
QVHLAEAGGGVVQPGRSLRLSCVVSGFSFSRYGMH



WVRQAPGKGLEWVAVISHDESQKYYGESVKGRFTI



SRDNSKDTVYLQMDSLRVEDTAVYYCVKDWDWEYE



DNRPTLRGSVYWGQGTLVIVSA





965
QVQLAEAGGGVVPPGRSLRLSCVVSGLSFSRYGMH



WVRQAPGKGLEWVAVISHDESQKYYGESVKGRFTI



SRDNSKDTLYLQMDGLRVEDTAMYYCVKDWDWEYE



ESRPTLRGSVYWGQGALVIVSA





966
QVQLVESGGGVVQPGRSLRLSCATSGFSFNNFGMH



WVRQAPGKGLEWLAVISYEGSKKYYADSLKGRFTI



SRDGSKDTLYLQLSSLGVEDTAVYHCAKGGPIFWL



GEGKNWFDAWGPGTPVIVSS





967
QVQLVESGGGVVQPGRSLRLSCAASGFTLSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYRDSVKGRFTI



SRDNSKNTLYLQINSLRVDDTAVYYCARDKGGILM



LRGADFWGQGTLATVSS





968
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYITSSGNTILYADSVKGRFTI



SRDNAKNSLYLRMNSLRAEDTALYYCARTLIAAAG



SAFDIWGQGTMVTVSS





969
EVQLVESGGGLGLPGGSLRLSCAASGFTFSSYAMN



WVRQAPGKGLEWISYISSSSGTIYYADSVKGRFTI



SRDNAKNSLFLQMNSLRDEDTAVYYCARGPTSITM



IVVVDDAFDIWGQGTMVTVSS





970
QVQLQESGPGLVKPSETLSLTCSVSGGSISPYSWS



WIRQPPGKGLEWIGYIYYTGKTNYNSSLKTRVTIS



LDTSKNQFSLRLTSVTTADTAIYYCARVMNSSWYT



RYYYNYMDVWGKGTSVTVSS





971
QLQLQESGPRLVKPSATLSLTCTVSGDSIRSSSFY



WGWIRQPPEKGLEWLGSVYNSGTAYYNPSLKSRVS



VSVDTSKNQFSLKVNSVTAADTAVYYCARRGGGCS



EGVCYNFDRWGQGTLVTVSS





972
QVQLVQSGSELKKPGASVKISCKAFGYSFTTYAMN



WVRQAPGRGLEWMGWIDTNTGKPTYARGFTGRFVF



SLDTSVRTSYMQINTLKAEDTAVYYCARGDPRDYW



GQGTLVTVSS





973
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTI



TADESTSTAYMELSSLRSEDTAVYYCARGSYYYDS



SGYYLDYWGQGTLVTVSS





974
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGRIIPIFGTANYAQKFQGRVTI



TADESTSTAYMELSSLRSEDTAVYYCARAAYYYDS



SGYGWFDPWGQGTLVTVSS





975
EVQLVESGGGLVKPGGSLRLSCAASGFTFSHAWMC



WVRQAPGKGLEWVGRIKSNTDGGTTDYAAPVKGRF



TISRHDSKNTLYLQLNSLKTEDTAVYYCTTDLGAT



GIYYYYYMDVWGKGTTVTVSS





976
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMN



WVRQAPGKGLEWVSYISSSGSTIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARFPRDYYD



SSGYLIQEGNFDYWGQGTLVTVSS





977
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARVTRAGAAG



DGGAFDIWGQGTMVTVSS





978
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTKYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARSVVPVAGT



DYWGQGTLVTVSS





979
QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDQHPGYP



ALVYYYYYMDVWGKGTTVTVSS





980
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGIT



WVRQAPGQGLEWMGWISTYSGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDNIQTFD



YWGQGTLVTVSS





981
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATSSPVAGY



NSWFDPWGQGTLVTVSS





982
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATGPAVIPL



RWFDPWGQGTLVTVSS





983
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCATAPAAAGP



TDWFDPWGQGTLVTVSS





984
QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMH



WVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM



TEDTSTDTAYMELSSLRSEDTAVYYCAISPSVHSL



WWFDPWGQGTLVTVSS





985
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMH



WVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTI



TRDTSASTSYMELSSLRSGDTAVYYCARDEIHYDI



LTGYYNRFWFHPWGQGTLVTVSS





986
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTI



TADESTSTAYMELSSLRSEDTAVYYCARDAETGYY



DSSGYPINWFDPWGQGTLVTVSS





987
QVTLKESGPVLVKPTETLTLTCTVSGFSLSNARMG



VSWIRQPPGKALEWLAHIFSNDKKSYSTSLKSRLT



ISKDTSKSQVVLTMTNMDPVDTATYYCARHYYDTG



AYYVPFDHWGQGTLVTVSS





988
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTTGVG



LAWIRQPPGKALEWLAFIYWDDDKRYSPSLQTRLT



ITKDTSKNQVVLTLTNMDPMDTATYYCAHFQGFGE



SEYFQHWGQGTLVTVSS





989
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVG



VGWIRQPPGKALEWLALIFWDDDKRYSPSLKSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAHRHPLTG



FDSWGQGTLVTVSS





990
EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMN



WVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCATPRGYSYG



PLDYWGQGTLVTVSS





991
EVQLVESGGGLVKPGGSLRLSCAASGFTFSSYSMN



WVRQAPGKGLEWVSSISSSSSYIYYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCASPRGYSYG



PFDYWGQGTLVTVSS





992
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARDRVDKGY



DFWSSWYFDLWGRGTLVTVSS





993
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCASGGGSYFD



AFDIWGQGTMVTVSS





994
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARDRSGSYY



GGFDYWGQGTLVTVSS





995
QVQLVESGGGVVQPGWSLRLSCAASGFTFGSYGMH



WVRQAPGKGLEWVALIWNDGSNKYYADSVKGRFTI



SRDKSKNTLYLQMNSLRAEDTAVYYCAKAVYGGNS



VYFDYWGQGTLVTVSS





996
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARIYGGNYE



NYFDYWGQGTLVTVSS





997
QVQLVESGGGVVQPGRSLRLSCAASGFTFSIYAMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCARESEAGTT



PSFDYWGQGTLVTVSS





998
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTNYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARSLVRGVIT



YFDYWGQGTLVTVSS





999
EVQLVESGGGLVQPGGSLRLSCAASGFTFSNYWMN



WVRQAPGKGLEWVANIKEDGSETYYVDSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTAVYYCARGLSMEVW



GQGTTVTVSS





1000
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWS



WIRQPPGKGLEWIGEIDHSGSTNDNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADAAVYYCARGGYSSSWY



GTKYYFDYWGQGTLVTVSS





1001
QVQLQQWGAGLLKPSETLSLTCAVYDGSFSGHYWS



WIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARGPTVTTFF



RRNAWFDPWGQGTLLTVSS





1002
QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWS



WIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARGRYSSGWY



GSRNWFDPWGQGTLVTVSS





1003
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARLSMGAARQ



SGFDPWGQGTLVTVSS





1004
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARDGGRDGYN



ELGARVYYYYGMDVWGQGTTVTVSS





1005
EVQLVQSGAEVKKPGESLRISCKGSGYNFTSYWIS



WVRQMPGKGLEWMGTIDPSDSYTNYRPSFQGHVTI



SADKSINTAYLQWSSLKASDTAMYYCARIGSYGIW



GQGTLVTVSS





1006
QVQLVQSGSELKKPGASVKVSCKASGYTFTSYAMN



WVRQAPGQGLEWMGWINTNTGNPTYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAVYYCAKLGCSGGS



CYYYYGMDVWGQGTTVTVSS





1007
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYVS



WVRQAPGTGLEWVSVVYSGGHAYYADSVKGRFTMS



RDNSENAVYLQMNSLRAEDTAVYYCARGDHYYDRS



GPHKFDYWGQGTLVTVSs





1008
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGLYH



WSWIRQPAGKGLEWIGRIFSSGSTAYSPSLKSRVI



ISADTSKNQFSLKLSSVTAADTAVYYCARDSPLKF



DSFGYPLYGMDVWGQGTTVTVSS





1009
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTIS



WVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTI



TADKSTSTAYMELSSLRSEDTAVYYCARGIVGATP



GYFDYWGQGTLVTVSS





1010
QVQLVQSGAEVKKPGASVKVSCKASGFTFGRHGIT



WVRQAPGQGLEWMGWISTYSGNTNYAQNLQGRVTM



TTDTSTNTAYMELRSLFFDDTAVYYCAKAVSGWPI



YFDAWGQGTLVTVSS





1011
QIQLVQSGAEVKKPGASVRVSCKASGFTFGRYGIT



WVRQVPGQGLEWMGWISTYSGNTNYAQNLQGRVTM



TTDTSTNTAYMELRSLFFDDTAMYYCAKAVSGWPI



YFDAWGQGTLVTVSS





1012
QITLEESGPTLVKPTQTLTLTCTFSGFSLTTRGEG



VAWIRQPPGKALEWLALIYWDDDQRYTPSLDSRLT



ITKDISKNHVVLTLTDVEPVDTATYFCAHTIHSGY



DRTFDSWGQGTLVIVSS





1013
QVQLVQSGSELKKPGASVKVSCKASGYTFTFYTIY



WVRQAPGQGLEWMGWINTNTGTPTYAQGFTGRFVF



SLDTSVSTAYLQISSLKAEDTAIYYCAREESYSSS



SPLDYWGPGTLVAVSS





1014
QMQLVQSGPEVKKPGTSVKVSCKASGFTFTSSAVQ



WVRQARGQRLEWIGWIVVGSGNTNYAQKFQERVTI



TRDMSTSTAYMELSSLRSEDTAVYYCAAGSDFWSG



YYVNYYMDVWGKGTTVTVSS





1015
QVTLRESGPALVKPTQTLTLTCTFSGFSLSTSGMC



VSWIRQPPGKALEWLARIDWDDDKYYSTSLKTRLT



ISKDTSKNQVVLTMTNMDPVDTATYYCARLTAAGV



YFDYWGQGTLVTVSS





1016
EVQLLESGGGVVQPGGSLRLSCAASGFTFTTYAMN



WVRQAPGRGLEWVSAISDSGGSAYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKTRGRGLY



DYVWGSKDYWGQGTLVTVSS





1017
EVQLLESGGGVVQPGGSLRLSCAASGFAFTTYAMN



WVRQAPGRGLEWVSAISDGGGSAYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKTRGRGLY



DYVWGSKDYWGQGTLVTVSS





1018
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDESGSYY



GDQAFDIWGQGTMVTVSS





1019
QAQLVQSGPEVKKPGASVKVSCEASGYTFSRYGIS



WVRQAPGQGLEWMGWISGYNGNTTSEQKVQGRVTM



TTDTSTNKVFLELRSLRSDDTAMYYCARDRRARAY



EIPFGSDHYYFGMDVWGQGTTVTVSS





1020
QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMH



WVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTM



TRDTSISTAYMELSRLRSDDTAVYYCARDYYGSGS



YPIGYMDVWGKGTTVTVSS





1021
EVQLVESGGGLAKPGGSLRVSCVVSGSGFTFRNAW



MSWVRQAPGKGLEWVGRIKSKNDGGTTDYAASVKG



RFTISRDDSKNSLDLQMQSLKTEDTAVYYCTTSYC



STKVCFDYWFDPWGQGTLVTVSS





1022
QVQLVESGGDVVQPGNSLRLSCAASGFTFNFYGMH



WVRQAPGKGLEWVAFISYDGNKRYYVDSVRGRFTA



SRDNSKNTLFLQMNGLRNDDSAVYYCASNLYATSP



YGGVKNWGRGTLVAVAS





1023
EVQLVESGGGLVQPGRSLRLSCAASGFTFDDYAMH



WVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTALYYCAKDIGSGSP



DAFDIWGQGTMVTVSS





1024
GVQLVESGGGLVQPGRSLRLSCAASGFIFDDYTMH



WVRQAPTKGLEWVSGITWNYATVGYADSVRGRFTI



SRDNVKNSLFLQIHSLRPDDTAFYYCVKDLEFRGG



TGGFDLWGQGTLVTVSS





1025
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDGHSAWG



AFDIWGQGTMVTVSS





1026
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDHPTLRR



AFDYWGQGTLVTVSS





1027
QVELVQSGAQVRKPGASVKVSCKASGDTFNDYHMH



WVRQAPGQGLEWMGWINPNSGETRYSQRFQGTVTM



TRDTSISTVYMELRSLPSDDTAVYFCARDRGSSSW



WGWLDPWGQGTLVTVSS





1028
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGGIIPIFGTANYAHKFQGRVTI



TADESTSTAYMELSSLRSEDTAVYYCATRRGYSGY



GAAYYFDYWGQGTLVTVSS





1029
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIS



WVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTI



TADKSTSTAYMELSSLRSEDTAVYYCAREVYVGGE



DDYSYYYGLDVWGQGTTVTVSS





1030
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNAWMS



WVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRF



TISRDDSKNTLYLQMNSLKTEDTAVYYCTTDLGEA



GPTEWLRSSLFDYWGQGTLVTVSS





1031
DIHMAESGGGLVKPGGSLRLSCAVSGLTFTKAWMS



WVRQAPGKGPEWVGRIKSRSDGGKIDYAAPVKGRF



IISRDDSKNTLYLQMHSLKTEDTALYYCTTSYCNP



KVCFDYWFDPWGQGTLVTVSS





1032
EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMS



WVRQAPGKGLEWVSVISGSGGSTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKEYYYDSS



GYYYREDAFDIWGQGTMVTVSS





1033
EVQLLESGGGLVQPGGSLRLSCAASGFTFSNYAMT



WVRQAPGKGLEWVSGISANGRSPYYADSVKGRFTI



SRDNSKNTMYVQMNSLRVEDTAVYYCAKDGGLTAY



LEYWGLGTLVTVSA





1034
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMS



WVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCATEKWEVVD



VCFDYWGQGTLVTVSS





1035
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKDIGWDVV



VVAATHGVFDYWGQGTLVTVSS





1036
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISYDGSNKYYVDSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKDPYYYGS



GSSNFFDYWGQGTLVTVSS





1037
QVQLVESGGGVVQPGWSLRLSCAASGFTFSSFAMY



WVRQAPGKGLEWVAVISYDGANKYYADSVKGRFTI



SRDNSKNTLYLQVNSLRVEDTAVYYCARGPDYYDT



GGYFDLWGRGTLVTVSs





1038
QVQLVESGGGVVQPGRSLRLSCAASGFTFSNYGMH



WVRQAPGKGLEWVAVMWHDGSNKYHSDSVKGRFTI



SRDNSKNTLYLQMKTLRADDTAVYYCARDGYKQIY



WYLDLWGRGTLVTVSS





1039
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKGEGVYGS



GSRYFLDYWGQGTLVTVSS





1040
QVQLVESGGGVVQPGRSLRLSCAASGFTFSSYATH



WVRQAPGKGLEWVAVISYDGSNKYHADSVKGRFTI



SRDNSKNTLYLQMNSLRAEDTAVYYCAREWSRGAV



AGTGYFDYWGQGTLVTVSS





1041
EVQLVESGGGLVQPGRSLRLSCAASGFTFHDYAMH



WVRQAPGKGLEWVSGISWNSGSIGYADSVKGRFTI



SRDNAKNSLYLQMNSLRAEDTALYYCAKVAKLPGD



YYGMDVWGQGTTVTVSS





1042
EVQLVESGGGLIQPGGSLRLSCAASGVIVSRNYMN



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARELRGAFDI



WGQGTMVTVSS





1043
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGTTYYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARDWGEYYFD



YWGQGTLVTVSS





1044
EVQLVESGGGLIQPGGSLRLSCAASEFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDYGDLYFD



YWGQGTLVTVSS





1045
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDRRVGSPY



YYYYMDVWGKGTTVTVSS





1046
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSILYSGGTTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLGDNAFD



IWGQGTMVTVSS





1047
EVQLVESGGGLVQPGGSLRLSCAASGITVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRITIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDRYSGYDF



WGQGTLVTVSS





1048
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARLSGTGYGG



DGGWFDPWGQGTLVTVSS





1049
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYWMH



WVRQAPGKGLVWVSRIKSDGSSTSYADSVKGRFTI



SRDNAKNTLYLQMNSLRAEDTAVYYCAGKKIYYGS



SFDPWGQGTLVTVSS





1050
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARGGSGSG



WYGGRFDYWGQGTLVTVSS





1051
QVQLQESGPGLVKPSQTLSLTCTVSGGSISSGGYY



WSWIRQHPGKGLEWIGYIYYSGSTYYNPSLKSRVT



ISVDTSKNQFSLKLSSVTAADTAVYYCARVWRETY



YYDSSGDSFDYWGQGTLVTVSS





1052
QVQLQQWGAGLLKPSETLSRTCAVYGGSFSGYYWT



WIRQSPGKRLEWIGEISHGGKTNYNIFFEGRVTLS



VDSSKSQFSLTLASVTAADTAIYYCARGRSITGIR



DVDFWGQGALVTVSS





1053
QVQLHQWGAGLLKPSETLSLTCAVSGGSFSDDFWN



WIRQPPGKGLEWIGEINHSGTTNYNPSLKSRITMS



VDTSKSQFSLKLNSVTAADSAMYFCARGRGNYMFR



WFDPWGQGTLVTVSS





1054
QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWS



WIRQPPGKGLEWIGYIYYSGSTNYNPSLKSRVTIS



VDTSKNQFSLKLSSVTAADTAVYYCARGGLWYDSI



NYYGMDVWGQGTTVTVSS





1055
EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIG



WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI



SADKSISTAYLQWSSLKASDTAMYYCARLILRWPT



TWDYFDYWGQGTLVTVSS





1056
QVQLVQSGTEVKEPGSSVKVSCKASGDTFSNYPIA



WVREAPGQGLEWMGRIIPIVGFANYAQKFQGRVTI



TADKSTSTAYMELSSLRFEDTAVYYCARVDGPFDY



WGQGTLVTVSS





1057
QVQLVESGGGVVQPGRSLRLSCAASGFTFSTSAMH



WVRQAPGKGLEWVAGISYDGSNEHLDSVKGRFTIS



RDNSKNTLYLQMSSLRPEDTAVYYCARCPFWNYGH



CYLDNWGQGTLVTVSS





1058
QVQLVESGGGVVQPGGSLRLSCAASGFTFSTYAMH



WLRQAPGRGLEWVAVISYDGSNKYNADSVKGRFTI



SRDNSKNTLSLHMNSLRPEDTAVYYCARPSVRWYY



HAMDVWGQGTTVTVTS





1059
EMQLLESGGGLVQPGGSLRLSCAASGFTFFSYALS



WVRQAPGKGLEWVSGISGISDSGGNTYYADSVKGR



FTISRDNSQNMLYLQMNSLRVEDTAVYYCAKERRP



VLRYFDWLPIEAPDYWGPGTLVTVSS





1060
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMN



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTLS



RDNSKNTLYLQMNSLRAEDTAVYYCARGQYDILTG



YQYGAFDIWGQGTMVTVSS





1061
QVQLQESGPGLVKPSQTLSLTCTVSAGSISSDTYY



WSWIRQPAGKGLEWIGRIYTTGSTIYNPSLNSRVL



ISADTSNNQFSLKLTSVTASDTAVYYCAAHYYSRT



DAFHIWGQGTMVTVSS





1062
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGIS



WVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM



TTDTSTSTAYMELRSLRSDDTAVYYCARDSVSGSG



SYYKGLWFDPWGQGTLVTVSS





1063
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMH



WMRQAPGQGLEWMGIINPSGGSTSYAHQFQGRVTM



TRDTSTSTVYMEMSSLRSEDTAVYFCVVGIGYCSS



PSCPPLRWFDYWGQGTLVTVSS





1064
QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTIS



WVRQAPGQGLEWMGRIIPILGIANYAQKFQGRVTI



TADKSTSTAYMELSSLRSEDTAVYYCARERGYSGS



GSLYYFDYWGQGTLVTVSS





1065
QITLKESGPTLVKPTQTLTLTCTFSGFSLSTSGVG



VGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLT



ITKDTSKNQVVLTMTNMDPVDTATYYCAHYSSSRP



PLFDYWGQGTLVTVSS





1066
EAQLLESGGGLVQPGGSLRLSCAVSGFTVSSYDMS



WVRQAPGKRLEWVSFISARGSVTYYADSVRGRFTI



SRDNFKNTLYVEMNNLRVEDTAVYYCAKGHWSTWG



QGTLVTVSS





1067
QVQLVESGGGVVQPGRSLRLSCAASGFTFRNYGMH



WVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTI



SRDNSKSTLYLQMNSLRAEDTAVYYCANGAYYYGS



GSYYNGAAYWGQGTLVTVSS





1068
QVQLVESGGGVVQPGKSLRLSCAASGFTFSSYGMH



WVRQAPGKGLEWVAVISNYGSNKYHADSVKGRITI



SRDNSKNTLYLQMNSLRAEDTAVYYCAKGGYYDIL



TGYFPFDYWGQGTLVTVSS





1069
EVQLVESGGGLIQPGGSLRLSCAASGFTVSRNYMS



WVRQAPGKGLEWVSLIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNTLRSEDTAVYYCARDLVVYGMD



VWGQGTTVTVSS





1070
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDPIRNGMD



VWGQGTTVTVSS





1071
EVQLVESGGGLVQPGGSLRLSCAASGFTVSRNYMS



WVRQAPGKGLEWVSVIYSGGTTHYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARDLVVYGMD



VWGQGTTVTVSS





1072
EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMT



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARDAMSYGMD



VWGQGTTVTVSS





1073
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDRVVYGMD



VWGQGTTVTVSS





1074
EVQLVESGGGLIQPGGSLRLSCAASGLIVSSNYMS



WVRQAPGKGLEWVSVLYAGGSTDYAGSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDAAVYGID



VWGQGTTVTVSS





1075
EVQLVESGGGLVQPGGSLRLSCAASGITVRSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLISRGMD



VWGQGTTVTVSS





1076
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMN



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDRVVYGMD



VWGQGTTVTVSS





1077
EVQLVESGGGLVQPGGSLRLSCAASGVTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTNYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLVSYGMD



VWGQGTTVTVSS





1078
EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMN



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNMVYLQMNSLRAEDTAVYYCARDLVVYGMD



VWGQGTTVTVSS





1079
EVQLVESGGGLVQPGGSLRLSCAASGFIVSSNYMT



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RHNSKNTLFLQMNSLRAEDTAVYYCARDAQNYGMD



VWGQGTTVTVSS





1080
EVQLVESGGGLVQPGGSLRLSCAASEFIVSRNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTGVYYCARDRGLVSDY



WGQGTLVTVSS





1081
DIEMTQSPSSLSASVGDRVTITCRASQSIASYAYW



YQQKPGKAPKLLISAASILQSGVPSRFSGSGSGGH



FTLTINSLQPEDVATYYCQQTYIIPYSFGQGTKLE



IK





1082
AIRMTQSPSSFSASTGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISCLQSEDFATYYCQQYYSYPYTFGQGTKLE



IK





1083
QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSG



NTASLTVSGLQAEDEADYYCSSYAGSNNLVFGGGT



KLTVL





1084
GIQMTQSPSTLSASVGDRVTITCRASQSISDWLAW



YQQKPGKIPKLLIYKASTLESGVPSRFSGSGSGTE



FTLTISSLQPDDFGTYYCQRYDSYRTFGQGTKVEI



K





1085
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKSPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLE



IK





1086
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKVLIYDASNLKTGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPLTFGQGTRLE



IK





1087
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASHRASGIPDRFSGSGSGT



DFTLTISRLEPGDFAMYYCQQYATSPWTFGQGTTV



EIK





1088
QSVLAQPPSASGTPGQSVTISCSGNNSNIGINNVY



WYQQFPGTAPKLLIHRSNQRPSGVPDRFSGSRSGT



SASLVISGLRSEDEAEYHCAAWDDSLSSWGFGGGT



KLTVL





1089
QLVLTQSPSASASLGASVKLTCTLSSGHSSYAIAW



HQQQPEKGPRYLMKLSSDGSHRKGDGIPDRFSGSS



SGAERYLTISSLQSEDEADYYCQTWGTGTVVFGGG



TKLTVL





1090
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLT



VL





1091
EIVLTQSPATLSLSPGERATLSCRASQSISSYLAW



YQQKPGQAPRLLIYEAANRATGIADRFSGSGSGTD



FTLTISSLEPEDFAIYYCQQRSDWTPTFGQGTKVE



IK





1092
AIQLTQSPSSLSASVGDRVTITCRASQGISSALAW



YQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQFNSYPRTFGGGTKVE



IK





1093
QSALTQPASVSGSPGQSITISCTATSSDFGTFHLV



SWYQQHPGKAPQLMIYEVNKRPSGVSDRFSASKSG



NTASLTISGLQPEDEADYYCCSYAGNTTFFGGGTK



LTVL





1094
QAVLTQPPSVSAAPGQRVSISCSGSAFNIGTNFVS



WYQHLPGAAPKLLIYGDQWRISGTPDRFSGSKSGT



SATLAITGLQSGDEAHYYCSTWDASLKEVLFGGGT



RLDVL





1095
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYYDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQGTHWPLTFGP



GTKVDIK





1096
DIQMTQSPSTLSASVGDSVTITCRPSQSISRWLAW



YQQKPGKAPKLLIYKASTLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYDSYPWTFGQGTKVE



IK





1097
DIQLTQSPSFLPASVGDRVTITCRASQHISNYVAW



YQQKPGKAPKLLIYAASTLESGVPSRFGGSGSGTE



FTLTINSLQPEDFATYYCQQLTTYPRTFGQGTKLE



IK





1098
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLT



VL





1099
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNN



NKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFS



GSGSGTDFTLTISSLQAEDVAVYFCQQFYSTPVTF



GPGTKVDIK





1100
NFMLTQPHSLSESPGKTVTISCTGSGASIASNYVQ



WYQQRPGSAPVTVIFEDTQRPSGVPDRFSGSIDRS



SNSASLTISGLRTEDEADYYCQSYDGSNVVFGGGT



KLTVL





1101
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNN



KNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFG



GGTKVEIK





1102
DIVMIQSPDSLAVSLGERATINCKSSHSVFFSKVN



KDYLAWYQQKPGLPPKLLIYWASTRQTGVPDRFSG



SGSGTDFSLTISNLQAEDVAVYYCQQYYDTPMYTF



GQGTKLEIK





1103
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYPYTFGQGTKLE



IK





1104
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTFVFGTGT



KVTVL





1105
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTYSNWVFGGGT



KLTVL





1106
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTVVFGGGT



KLTVL





1107
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKV



EIK





1108
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKV



EIK





1109
DFQMTQSPSSLSASVGDRVTISCQASEDIDNHLNW



YQQKPGKAPRLLIYDASNLETGVPSRFSGSGSGTD



FLFTITSLQPEDFATYYCQQYGAFGQGTKVEIK





1110
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKV



EIK





1111
QSVLTQPPSASGTPGQRVTISCSGSRSNIGSKNVH



WYQQLPGTAPKFLIYSNNQRPSGVPDRFSGSKSGT



SASLAISGLQSEDEADYYCAVWDDSLNGVVFGGGT



KLTVL





1112
QSALTQPPSASGSPGQSVTISCTGTSSDVGSYHYV



SWYQQHPGKAPKLIIYEVSKRPSGVPDRFSGSKSG



NTASLTVSGLQTDDEADYYCSSFAGSNNPYVFGTG



TKVTVL





1113
DIVMTQSPDSLAVSLGERATINCRSSQSVLYSANN



KYYLAWYQHKPGQPPKLLIHWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAIYYCQQYYSTPYTFG



QGTKLEIK





1114
EIVMTQSPATLSVSPGERATLSCRASQSVKSYLAW



YQQKAGQAPRLLIYGASSRATGIPARFSGSRSGTE



FTLTISSLQSEDFAVYFCHQYDSWPPTFGGGTKVE



IK





1115
DVVLTQSPATLSLSPGERATLSCRASKDINSYLAW



YQQKPGQAPRLLIYDASKRATGVPVRFSGSGSGTD



FTLTISSLEPEDSAIYFCQNRDDWPPLFTFGPGTK



VDFK





1116
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNN



KNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPRTFG



QGTKLEIK





1117
DMQMTQSPSSVSASVGDRVTITCRASQDISSSLAW



YQQKPGKPPKLLIYAASSLQRGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQAHSFLSLTFGGGTKV



EIK





1118
SCELTQPPSVSVSPGQTARITCSGDALSNQYTYWY



QQRPGQAPLLVIYKGTKRPSAIPERFSGSRSGTTV



TLTISGVQAEDEADYYCQSADTSGTYLWVFGGGTK



LTVL





1119
DIQMTQSPSSLSASVGDRVTITCQASQDISNFLNW



YQQKPGKAPELLIYDASNLETGVPSRISGSGSGTD



FTFTISSLQPEDIATYYCQQYDSLPITFGQGTRLE



IK





1120
DIQMTQSPSSLSAVLGDRVTITCRASQAISNSLAW



YQQKPGKAPKLLLYAASRLESGVPSRFSGSGSGTD



YTLTISSLRPEDFATYYCQQYYGIPTFGQGTRLEN



K





1121
DVQMTQSPSSLSASVGDRVTITCQASRDIHNLLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTITGLQPEDVATYYCQKCDNFPWTFGQGTKVE



IK





1122
QSVLTQSPSASGTPGQRVTISCSGSNSNIGSNYVF



WYHQLPGTTPKLLIYKNNQRPSGVPDRFSGSKSGT



SASLAISGLRSEDEADYYCAAWDDSLSVVVFGGGT



KLTVL





1123
DIHMTQSPSSLSASEGDRVTISCRASQGISTNYLN



WYQQKSGKAPRLLIYATSTLQSGVSSRFSGSGSGT



DFTLTINSVQPEDFATYYCQQSYSSPPTFGGGTKL



DIK





1124
QSVLTQPPSVSGAPGQRVTISCTGIGARYNVHWYQ



QVPGTAPKLLIYRNTNRPSGVPDRFSGSKSDTSAS



LAITGLQAEDEADYYCQSYDDTLTIFGGGTKLTVL


1125
DIQMTQSPSSLSASVGDRVTITCRASQSISNHFNW



YQHRPQKAPKLLIYSASNLQSGVPSRFSGSGSGRN



FTLTISSLQPEDFATYYCQQSYGAPPTFGGGTKVE



IK





1126
DIQMTQSPSSLSASEGDRVTITCRANQSISTNYLN



WYQQQSGKAPKLLIYASSTLQSGVPTRFSGSGSGT



DFALTINSLQPEDFAAYYCQQSYSTPPTFGGGTRV



DLR





1127
DIQMTQSPSSLSASEGDRVTILCRASQSISTNYLN



WYQQKSGKAPKLLIYSTSNLQSGVPSRFSGSGSGT



DFTLTIDSLQGEDFATYYCQQSFSTPPTFGGGTKV



DIK





1128
DIQMTQSPSSLSASEGDRVTITCRANQSISTNYLN



WYQQKSGKAPNLLIYATSSLERGVPSRFSGSGSGT



EFSLTINSLQPEDFVTYYCQQSYSSPPTFGGGTKV



EIKRMEIK





1129
SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWY



QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSTDSSGNHWVFGGGTKL



TVL





1130
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYP



YWFQQKPGQGPRTLIYDINNKYSWTPARFSGSLLG



GKAALTLFGAQPEDEADYYCLLSYSGVRIFGGGTK



LTVL





1131
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSKVFGGGT



KLTVL





1132
SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWY



QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTFYVFGTGTKVT



VL





1133
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGT



KLTVL





1134
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWPWTFGQGTKVE



IK





1135
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYP



YWFQQKPGQAPRTLIYDTSNKHSWTPARFSGSLLG



GKAALTLSGAQPEDEAEYYCLLSYSGARPVFGGGT



KLTVL





1136
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPPYTFGQGTKL



EIK





1137
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTRVVFGGG



TKLTVL





1138
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNN



KNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPITFG



QGTRLEIK





1139
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKV



EIK





1140
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSVVVFGGGT



KLTVL





1141
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTFAVFGGG



TQLTVL





1142
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGG



GTKVEIK





1143
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTVFTFGP



GTKVDIK





1144
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTVFTFGP



GTKVDIK





1145
DIEMTQSPSSLSASVGDRVTITCRASQSIASYAYW



YQQKPGKAPKLLISAASILQSGVPSRFSGSGSGGH



FTLTINSLQPEDVATYYCQQTYIIPYSFGQGTKLE



IK





1146
AIRMTQSPSSFSASTGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISCLQSEDFATYYCQQYYSYPYTFGQGTKLE



IK





1147
SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWY



QQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDSSSDHVVFGGGTKL



TVL





1148
SYELTQPPSVSVSPGQTASITCSRDKLGDEYACWY



QQKPGQSPILVIYQNNKRPAGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTSYVVFGGGTKL



TVL





1149
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRLSGIPDRFSGSKSGT



SATLDITGLQTGDEADYYCGTWDSSLSVGVFGGGT



KLTVL





1150
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCNSYTSNSTAVFGGGT



KLTVL





1151
EVVLTQSPATLSASPGERATLSCRASLSINTDLAW



YQQRPGQPPRLLIYGASTRATGIPARFSGSGSGTE



FTLTVSSLQSEDFALYYCQQSYNWPRTFGQGTRVE



IK





1152
DIQMTQSPSAMSASVGDRVTITCRASQGMSNYLAW



FQQKPGKVPKRLIYAASSLASGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCLQHNSYPYTFGQGTKLE



IK





1153
DIQMTQSPSTLSAPVGDRVTITCRASQSINSWLAW



YQQKPGKAPKLLIYKASNLESGVSSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNGYPHTFGQGTKLE



IK





1154
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASNLESGVPSRFSGSGSGTD



FTLTISSLQPDDFATYYCQQYSYYSAFGQGTQVEF



K





1155
EIVLTQSPGTLSLSPGERASLSCRASQTVSSTYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTITRLEPEDFAVYYCQQYGTFGQGTKLEIK





1156
QAGLTQPPSVSKGLRQTATLTCTGTSSNVGNQGAA



WLQQHQGHPPKLLSYRNDNRPSGISERLSASRSGN



TASLTITGLQPEDEADYYCSAWDSSLSAWVFGGGT



KLTVL





1157
DIVMTQSPDSLAVSLGERATINCKSSQSVLYNSNN



KDYLAWYQQKPGQPPKLLFSWASTRQSGVPARFSG



GGSGTDFTLTISSLQAEDVAVYYCQQYYSTPITFG



GGTKVEIK





1158
DFVLTQPHSVSESPGKTVTISCTRSSGSIASYFVH



WYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSS



SNSASLIISGLKTEDEADYYCQSFDDNDQVFGGGT



KLTVL





1159
QTVVTQEPSFSVSPGGTVTLTCGLTSGSVSTTYYP



SWYQQTPGQPPRTLIYSTNIRSSGVPDRFSGSILG



NKAALTITGAQADDESNYYCLLYVGGGIWVFGGGT



KLTVL





1160
EIVMTQSPATLAVSPGERATLSCRASQSVSDNLAW



YQQRPGQPPRLLIYAASTRATGIPPRFSGSGSGTE



FTLTIASLQSEDFALYYCQQYNIWLTFGGGTKVEI



K





1161
AVVMTQSPLSLPVTLGQPASISCRSSQSLVHSDGN



TYLNWFQQRPGQSPRRLIYKVSDRDSGVPDRFSGS



GSGTDFTLKINRVEAEDVGVYYCMQGTLLLTFGGG



TKVEIK





1162
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGVPDRFSGSKSGT



SATLGITGLQTGDEADYYCETWDSSLDAVIFGGGT



KLTVL





1163
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVY



WYQQLPGTAPKVLIYRNNQRPSGVPDRFSGSKSGT



SASLAISGLRSEDEADYYCAAWDDSLSGRVFGGGT



KLTVL





1164
DVVVTQSPLSLSVTLGQPASISCRSSQSLVHSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLKISRVEADDVGVYYCMQGTHWPHPTFG



QGTRVEIK





1165
AVVVTQSPLSLPVTLGQPASISCRSSQSLVYSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLQISKVEAEDVGVYYCMQGTPWPTFGQG



TKVEIK





1166
EIVLTQSPGTLSLSPGERATLSCRASQSVRSNYLA



WYQLKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQSGSSYTFGQGTKLE



IK





1167
AIVMTQSPLSLPVTPGEPASISCRSSQSLRQSQRF



SYLDWYVQKPGQSPQLLIYLNSRRAPGVPDRFSAS



GSGTDFTLKISRVEAEDVGVYYCMQSLPSGFTFGP



GTNVHIK





1168
DIVMTQAPLSLSVTPGQPASISCKSSQSLLHSIGK



THLYWYLQKPGQPPQLLIYEVSNRFSGVPERVSGS



GSGTDFTLTISRVEAEDVGVYYCMQSLDLPPTFGQ



GTKVDIK





1169
DIQMTQSPSFVSASVGDRVTITCRASHDIRTWLSW



YQQKPGKAPKLLIYTAFRLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYFCQQGSSFPLTFGGGTTVD



IR





1170
DIQMTQSPSSLSASVGDSVTVTCRASQDIGNWLAW



YQLKPEKAPRSLIFAASILRSGVPSRFSGSGSGTE



FTLTISSLQPEDFGVFYCQQYDSSPITFGQGTRLE



IK





1171
SSQLTQDPAVSVALGQTVRITCQGDSLETYYATWY



QQKPGQAPLLVIYGKNSRPSGIPDRFSGSSSGNTA



SLTITGAQAEDEADYYCNSRDSSGQLHVVVFGGGT



KLTVL





1172
SSELTQDPAVSVALGQTVRITCQGDSLRTSYASWY



QQKPGQAPMLVIYEKNNRPSGVPDRFSGSTSFNTA



SLTITGAQAEDEAEYYCNSRDNNDDLPLFGGGTRL



TVL





1173
QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSG



NTASLTVSGLQAEDEADYYCSSYAGSNNLGVFGTG



TKVTVL





1174
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGVVFGGG



TKLTVL





1175
DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNN



KNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPFTFG



PGTKVDIK





1176
DVVMTQSPLSLPVTLGQPASISCRSSQSLVHSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQGTHWPITFGQ



GTRLEIK





1177
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTLVVFGGG



TKLTVL





1178
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLE



IK





1179
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSYVVFGGGTK



LTVL





1180
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTLHTFGQGTKVE



IK





1181
SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWY



QQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTA



SLTITGAQAEDEADYYCNSRDSSGNHLVFGGGTKL



TVL





1182
SYELTQPPSVSVSPGQTATITCSGDELGDTDIAWY



QQKPGQSPVLVILQDTKRPSGIPERFSGSNSGTTA



TLTIGGTQAMDEAEYYCQAWDTITHEEVFGGGTKL



TVL





1183
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNYYPVAFGQGTKVE



IK





1184
DIVMTQTPLSSPVTLGQPASISCRSSQSLVHSDGN



TYLSWLQQRPGQPPRLLIYKISNRFSGVPDRFSGS



GAGTDFTLKISRVEAEDVGVYYCTQATQFPLTFGG



GTKVEIK





1185
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDLATYYCQQSYSTPPYTFGQGTKL



EIK





1186
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGIAPKLLIYGNNNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSSPVVFGG



GTKLTVL





1187
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNYVY



WYQQLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGT



SASLAISGLRSEDEADYYCAAWDDSLSGPVFGGGT



KLTVL





1188
SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWY



QQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTA



SLTITGAQAEDEADYYCNSRDSSGNHLVFGGGTKL



TVL





1189
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLE



IK





1190
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGT



KLTVL





1191
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWPPWTFGQGTKV



EIK





1192
SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWY



QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTYVVFGGGTKLT



VL





1193
DIQMTQSPSSLSASEGDRVTITCRASQSISTNYLN



WYQQKSGRAPTLLIYATSTLQSGVPSRFSGSGSGT



DFTLTISSLQPEDFATYYCQQSYSSPPTFGGGTTV



DVK





1194
DIQMTQSPSSVYASEGDRVTITCRASHSISTNYLN



WYQQNSGKAPKLLIYATSSLQSGVPFRFSGSGSGT



DFTLTISSLQPEDFATYYCQQSYSSPPTFGGGTKV



EIK





1195
DIQMTQSPSSLSASEGDRVTISCRASQTISTNYLN



WYQQKSGKAPRLLIYATSTLESGVPSRFSGSGSGT



DFTLTINTLQPDDFATYYCQQSYSSPPTFGGGTKV



DIK





1196
EIVLTQSPATLSLSPGERAALSCRASQTINSGYLA



WYQQKPGQAPRLLIYAASHRATGIPNRFSGSGSAT



DFTLTITRLEPEDVAVYYCHHYGTSPPFTFGPGTK



VDIK





1197
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKV



EIK





1198
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTYYVFGTGTKV



TVL





1199
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPRTFGQGTKVE



IK





1200
SYELTQPPSVSVSPGQTASISCSGDKLGDTYASWY



QQKPGQSPVLVMYQDNKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTV



L





1201
DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGK



TYLYWYLQKPGQSPQLLIYEVSNRFSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQSIQLPLTFGG



GTKVEIK





1202
DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGK



TYLYWYLQKPGQSPQLLIYEVSNRFSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQSIQLPFTFGQ



GTRLEIK





1203
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTYTFGQG



TKLEIK





1204
SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWY



QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSTDSSGNHRRVFGGGTK



LTVL





1205
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKWPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTLVFGGGT



KLTVL





1206
SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWY



QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSTDSSGNHRGVFGGGTK



LTVL





1207
DIQMTQSPDTLSASVGDRVTITCRASESISNWLAW



YQKKVGQAPNLLIDKASNLHRGVPSRFSGSGSGTE



FTLTITSLQPDDSASYYCQQYNSFPYTFGQGTTLE



IK





1208
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWPVTFGQGTKVE



IK





1209
DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGW



YQQKPGKAPKRLIYAASSLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCLQHNSYPLTFGGGTKVE



IK





1210
DIQMTQSPSSLSASVGDRVTITCRASQGIGNDLGW



FQQKPGKAPKRLIYGASNLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCLQHNSYPFTFGGGTKVE



IK





1211
ETVLTQSPGTLSLSPGERATLSCRASQSVSGSYLA



WYQQKPGQAPRLLIYGASRRATGIADRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGTSAGTFGQGTKV



EIK





1212
EIVLTQSPGTLSLSPGERGTLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASTRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGNLPPFTFGPGTK



VDIK





1213
DIVVTQSPDSLAVSLGERATINCKSSQSLLYNFNN



ENYLGWYQQKPGQPPKLLIYWASTRESGVPDRFNG



SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPLTFG



GGTKVEIK





1214
GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGK



TYMCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGS



GSGTDFTLKISRVETEDVGVYYCMQNRHLYTFGQG



TKLEIK





1215
GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGK



TYMCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGS



GSGTDFTLKISRVEAEDVGVYYCMQNRHLYTFGQG



TKLEIK





1216
NIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQTLQTSITFGQ



GTRLEIK





1217
EIVLTQSPGTLSLSPGERATLSCRASQSVSTYLAW



YQQRPGQAPRLLIYGSSSRAAGIPDRFSGSGSGTD



FTLTISRLEPEDFAVYYCQQYGSSQYSFGQGTKLE



IK





1218
EIVLTQSPGTLSLSPGERATLSCRASQSVSSYLAW



YQQRPGQAPRLLIYGASSRAAGIPDRFSGSGSGTD



FTLTISRLEPEDFAVYYCQQYGSSQYTFGQGTKLE



IK





1219
DIQMTQSPSSLSASVGDRVTITCQASQDSSKYLNW



YQQKPGKAPKLLIYDASTLETGVPSRFSGSGSGTD



FTFTISGLQPEDVATYYCQHYDTLLTFGPGTKVEI



K





1220
DIVMTQSPDSLAVSLGERATINCKSSQSVSFTSNN



KNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVALYLCQQYFDTPWTFG



QGTKVEIK





1221
GIVMTQSPLSLSVTPGQPASISCKSSQSLLDSDGK



TYLCWYLQKPGQPPQLLIYEVSNRFSGVPERFSGS



GSGTDFTLKISRVEAEDVGVYYCMQNRQLYTFGQG



TKLEIK





1222
DIQMTQSPSSLSASVGDRVTITCQASQDISTYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQFDNLPPFTFGPGTRV



HIT





1223
DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNW



YQQKPGRAPKVLIYGASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSARMSTFGQGTKL



EIK





1224
DVVMTQSPLSLPVTLGQPASISCRSSQSVVHSDGK



TYLNWYHQRPGQSPRRLIYEVSNRDSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQGTQWPWTFGQ



GTKVEIK





1225
EIVLTQSPGTLSLSPGERATLSCRASHTISSSYLA



WYQQKAGQAPRLLIYAASSRATGIPARFSGSGSGT



DFTLTISRLEPEDFAVYYCQQFDNSPPWTFGRGTK



VEMR





1226
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTYVVFGGGTKL



TVL





1227
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVPDRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSYTLVFGGGT



KLTVL





1228
DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNW



YQQKPGKAPKLLIYAASGLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVD



IK





1229
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQGTHSYTFGQG



TKLEIK





1230
SYELTQPPSVSVSPGQTASITCSGDKLGDKYACWY



QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTASYVFGTGTKV



TVL





1231
QSALTQPASVSGSPGQAITISCTGTSSDVGGHDYV



SWYQQHPGKVPKLVVYDVTNRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSASTVVFGGGT



KLTVL





1232
QSALTQPASVSGSPGQAITISCTGTSSDVGGHDYV



SWYQQHPGKVPKLVVYDVTNRPSGISNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSASTVVFGGGT



KLTVL





1233
DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQGTHSPWTFGQ



GTKVEIK





1234
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYHCGTWDSSLSAWVFGGGT



KLTVL





1235
SYELTQPPSVSVSPGQTASITCSGDALPKQYGYWY



QQKPGQAPVMVIYKDNERPSGIPERFSGSSSGTTV



TLTISGAQAEDEADYYCQSADGRGDWVFGGGTKLT



VL





1236
EIVLTQSPGTLSLSPGERATLSCRASQSVSTYLAW



YQQRPGQAPRLLIYGSSSRAAGIPDRFSGSGSGTD



FTLTISRLEPEDFAVYFCQQYGSSQYSFGQGTKLD



IK





1237
DIQMTQSPSTLSASIGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYETSSLEPGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYDSYSGTFGQGTKVE



IK





1238
QPVLTQSSSASASLGSSVKLTCTLSVGHDYFTIAW



HQQQPGKAPRFLMKLEGSGSYYKGSGVPDRFSGSS



SGADRYLIISNLQSEDEADYFCETWDSPYVVFGGG



TKLTVL





1239
DIQMTQYPSSLSASVGDTVTITCQASQDSNTYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISGLQPEDIATYYCQHYDSLLTFGPGTKVDI



K





1240
QSALTQPASVSGSPGQSITISCNGTNSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDDADYYCSSYTSSSTVVFGGGT



KLTVL





1241
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTLTFGPG



TKVDIK





1242
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYPLFTFGPGTKV



DIK





1243
DVVLTQSPLSLPVTLGQPASISCRSSQSLIYSDGN



TYLNWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGS



GSGTDFTLRISRVEAEDVGVYYCMQGTHWPMTFGQ



GTKVEIK





1244
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPMYTFGQGTK



LEIK





1245
DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQANSFPAFGGGTKVEI



K





1246
SYEVTQSPSVSVSPGQTASITCSGDKLGDKYACWY



QQRPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSHTVVFGGGTKLTV



L





1247
DIQMTQSPSTLSASVGDRVTITCRASQSISTWLAW



YQQRPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYSWTFGQGTKVE



IK





1248
ETMMTQSPVALSVSPGDRATLSCEASQYVGDNLAW



YQQKPGQAPRLLIYGAFTRATGVPARFSASGSGAG



FTLTISSLQSEDFAVYYCQQYTSWPLTFGGGTKVE



IK





1249
ETMMTQSPVALSVSPGDRATLSCKASQYIGDNLAW



YQQKPGQTPRLLIYGASTRATGVPARFSASGSGAG



FTLTISSLQSEDFAVYYCQQYTSWPLTFGGGTKVE



IK





1250
SYELTQPPSVSVSPGQTARITCSGDALPKKYAYWY



QQKSGQAPVLVIYEDSKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSPKVFGGGTKLTVL





1251
DIQMTQSPSSLSASVGDRVTVACQASQDVSIYLNW



YQQKPGRAPKLLIYDAYNLQTGVPSRFSGSGSGTH



FTLTISSLQPEDVATYHCQQYNILPHTFGGGTKVE



LT





1252
DIVMTQSPDSLAVSLGERATIKCKSSQSVYDSSNS



KNYLAWFQQKPGQPPQLLIFWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYNAPLSFG



GGTKVEIK





1253
DIVMTQSPDSLPVSLGERATIKCKSSQSVYDTSNS



KNYLAWFQQKPGQPPQLLIFWASTRESGVPDRFSG



SGSGTDFTLTISSLQAEDVAVYYCQQYYNAPLSFG



GGTKVEIK





1254
EIVLTQSPATLSLSPGERATLSCRASQSVSTYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWITFGQGTRLEI



K





1255
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWITFGQGTRLEI



K





1256
QSVLTQPPSASGTPGQGVTISCSGGSSNIGAYTVS



WYQQLPGTAPKLLIYSTDQRPSGVPDRFSGSKSGT



SASLAVTGLQSEDEADYYCAAWDDSLNGPVFGGGT



KLTVL





1257
EIVLTQSPGTLSLSPGERATLSCRASQSVSSIYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPQTFGQGTKL



EIK





1258
EIVMTQSPATLSVSPGERATLSCRASQSVTSYLAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWPPLTFGGGTKV



EIK





1259
DIQMTQSPSTLSASVGDRVTITCRASQSITNWLAW



YQQRPGKAPKLLLSKASSLESGVPSRFSGSGSGTD



FTLTISSLQPDDFATYYCQQYYSYSLTFGGGTKVE



SK





1260
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSTFYVFGTG



TKVTVL





1261
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKTGQAPVLVIYKDSERPSGIPERVSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTWVFGGGTKLT



VL





1262
EIVLTQSPGTLSLSPGERATLSCRASQSVSSRYLA



WYQQKPGQAPRLLIYGASRRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPEMYTFGQGT



KLEIK





1263
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCHQYGSGLGTFGPGTKV



DIK





1264
DIVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGK



TYLYWYLQKPGQTPQLLIYEVSDRFSGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQSIQLRTFGQG



TKVEIK





1265
EIVLTQSPATLSLSPGERATLSCRASQRVGSSLAW



YQQKPGQAPRLLIYGASNRATGIPARFSGSGSGTD



FTLTITRLEPEDFAVYYCQQCSSWPLSLTFGGGTK



VEIR





1266
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRL



DIK





1267
DIQMTQSPSSVSASVGDRVTITCRASQGIRFWLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSNSFPPTFGGGTKVE



IK





1268
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNTNRPSGVPDRFSGSKSG



TSPSLAITGLQAEDEAGYYCQSYDISLSAYVFGGG



TKLTVL





1269
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTE



FTLTISSLLPADFATYYCQQYNTYSLTFGQGTRLE



IK





1270
AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNSYPPAFGGGTKVE



IK





1271
EIVMTQSPDSLAVSLGERATINCKSSQSVLYSASN



KNYLAWYQQKQGQSPKLLIYWASTRESGVPDRFSG



SGSGTDFTLTINGLQAEDVAVYYCQQYYRTPLTFG



GGTKVEIK





1272
DIQMTQSPSAMSASVGDRVTITCRASQDISNYLAW



FQQRPGKVPKRLIYAASSLQSGVPSRFSGTGSGTE



FTLTISSLQPEDFATYYCLQHHTYPLTFGGGTKVE



IR





1273
EIVLTQTPLSLSVTPGQPASISCKSSHSLLHSDGK



TYVYWYLQRPGQPPQLLIYELFNRFSGVPDRFSGS



GSGTDFTLKISRVEAEDVGTYYCMQSIQLWSFGQG



TKVEIK





1274
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYP



YWFQQKPGQAPRTLIYDTNNKHSWTPARFSGSLLG



GKAALTLSGAQPEDEAEYYCLLSYSGPWVFGGGTK



LTVL





1275
QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSG



NTASLTVSGLQAEDEADYYCSSYAGSNNYVFGTGT



KVTVL





1276
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPSFTFGPGTKV



DIK





1277
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVNKRPSGVPDRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSYTLVFGGGT



KLSVL





1278
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSTVVFGGGT



KLTVL





1279
DIQMTQSPSSLSASVGDRVTISCRASQSIGKYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTINNLQPEDFATYYCQQSYNVPPWTFGQGTKV



EIK





1280
DVVMTQSPVSLTVTLGQPASISCRPSQSIEHSDGN



IYLNWFQQRPGQSPRRLIYKISNRDSGVPDRISGS



GSGTDFTLKISRVEAEDVGVYYCMQGTHWPWTFGQ



GTKVEIK





1281
QSVLTQPPSVSGAPGQRVIIPCTGSSSNTGAGYDV



HWYQQLPGTAPKLVIYDNSHRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDINLSAVFGGGT



KLTVL





1282
EIVLTQSPGTLSLSPGERATLSCRATQSLTSSSLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLKPEDFAVYYCHQYHNSPWTFGQGTKV



EIK





1283
DFVMTQSPLSLPVTPGEPASISCRSSQSLLHGNGY



TYLDWYLQKPGQSPQLLIYLGSTRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQ



GTKLEIK





1284
SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWY



QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDSSSDHYVFGTGTKV



TVL





1285
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





1286
QIVMTQSPATLSVSPGGGATLSCRASQSVSSKVAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDSAVYYCQQYDNWLPYTFGQGTKL



EIK





1287
QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGHYP



YWFQQKPGQAPRTLIYDTSNKHSWTPARFSGSLLG



GKAALTLSGAQPEDEAEYYCLLSYSGAYVLFGGGT



KLTVL





1288
EIVMTQSPAILSVSPGERATLSCRASQSVTRNLAW



YQQKPGQAPRLLIYGASTRATNIPARFSGSGFGTE



FTLIISSLQSEDFAVYYCQQYSNWPLYTFGQGTKL



EIK





1289
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVN



WYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGT



SASLAISGLQSEDEADYYCAAWDDSLNGPYVFGTG



TKVTVL





1290
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQHHPGKAPKLMIYEVSNRPSGVSNRFSGSKSA



NTASLTISGLQTEDEADYYCSSYTSISTVLFGGGT



KLTVL





1291
SDALTQPPSVSVAPGKTAAITCGGDNIGSKNVHWY



QQKPGQAPLLVVFDDGDRPSGIPERFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDGGSDDRGYVFGTGT



KVTVL





1292
QSALTQPASVSGSPGQSITISCTGTSSDVGAYNYV



SWYQQHPGKAPKLMIYDVTKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSFTSNGAWVFGGGT



KVTVL





1293
DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNW



YQQKPGKAPKFLIYAASTLHTGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQNYIRPYTFGQGTKLE



IK





1294
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPITFGGGTKVE



IK





1295
QSVLTQPPSTSGAPGQRVTISCSGSSSNVALNAVS



WYQQLPRMAPKLLIYRDNQRPSGVPERFSGSRSGT



SASLAITGLQSDDEADYYCATWDDSLNGVFGGGTK



LTVL





1296
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAW



YQQKPGQAPRLLIYGASSRATGIPARFSGSGSGTE



FTLTISSLQSEDFGVYYCQQYNNWPYTFGQGTKLE



IK





1297
QPVLTQPPSASASLGASVTLTCTLSSGYSNYKVDW



YQQRPGKGPRFVMRVGTGGIVGSKGDGIPDRFSVL



GSGLNRYLTIKNIQEEDESDYHCGADHGSGSNFVY



VFGTGTKVTVL





1298
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSTLVFGGGT



KVTVL





1299
DIKMTQSPSTLSASVGDRVTITCRASQHINRWLAW



YQQKPGKAPKLLIYEASSLKSGVPSRFSGSGSGTE



FTLTITSLQLDDFATYSCQQHDSAPYTFGQGTKLE



IK





1300
DIQMTQSPSTLSASLGDRVMITCRASQNISRWLAW



YQQKPGKAPKFLIYKASALETGVPSRFSGSGSGTE



FTLTITGLQPDDFATYYCQQYNSYVTFGGGTKVEM



K





1301
DIVMTQTPLSLSVTPGQPASISCKSSQSLLHSDGK



TYLYWFLLKPGQSPQFLIYEVSSRFSGVPDRFRGS



GSGTDFTLKISRVEAEDVGVYYCMQGKHLRWTFGQ



GTKVEIK





1302
SYELAQPPSVSVSPGQTARITCSGDALPIKYAYWY



QQKSGQAPVLVISEDSKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSTDYSGNHGVFGGGTKL



TVV





1303
EIVLTQSPATLSLSPGERATLSCRASQSVSTYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQCSNWPNTFGQGTKLE



IK





1304
SYELTQPPSVSVSPGQTARITCSGDELPKQYSYWF



QQRPGQAPVLVIYKDRERPSGIPERFSGSHSGTTV



TLTISGVQAEDEADYYCQSADSNDSWVFGGGTKLT



VL





1305
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGT



KLTVL





1306
GIQLTQSPSSVSASLGDTVTITCRASQNINVFLAW



YQQRPGSAPSLLIYAASNLQSGVPSRFVGSGSGTD



FTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVE



VK





1307
EIVLTQSPGTLSLSPGDRATLSCRASQSLNNNQLA



WYQQKLGQAPRLLIYGASSRATGIPDKISGSGSGT



VFTLTISRLEPEDFAVYYCQQYGSLPLTFGGGTKV



EIK





1308
EIVLTQSPGTLSLSPGDRATLSCRASQSLNNNQLA



WYQQKLGQAPRLLIYGASSRATGIPDKISGSGSGT



VFTLTISRLEPEDFAVYYCQQYGSLPLTFGGGTKV



EIK





1309
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGG



TKLTVL





1310
EIVLTQSPATLSLSPGERATLSCRASQSISSHLGW



YQQKPGQAPRLLIYDASNRAPGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRRNWPLTFGGGTKVE



IK





1311
EIVLTQSPATLSLSPGEGATLSCRASQSVASYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQHRSNWPYTFGQGTKLE



IK





1312
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVN



WYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGT



SASLAISGLQSEDEADYYCAAWDDSLNGVVFGGGT



KLTVL





1313
DIVMTQTPLSSPVILGQSASISCRSSHSLLHNNGN



TYLSWLHQRPGQPPRLLIYEISNRFSGVPDRFSGS



GAGTDFTLKISRVEAEDVGIYYCMQTTQFPRTFGQ



GTKVEIR





1314
SYELTQPPSVSVSPGQTAKITCSGDALPKEFAYWY



QQKPGQAPVLIIYKDKERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSQDSSATYVVFGGGTKL



TVL





1315
SSDLTQPPSVSVSPGQTASIACSGDKLGDKYVSWY



QQKPRQSPVLVIYQDNKRPSGIPERFAGSNSGNTA



TLTISGTQTMDEADYYCQAWDSSIEVFGTGTKVTV



L





1316
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPPWTFGQGTK



VEIK





1317
SYELTQPPSVSVSPGQTARITCSADALSKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSNSGTTV



TLTISGVQAEDEAEYYCQSGDSSGTYVVFGGGTKL



TVL





1318
DIVMTQTPLSSPVILGQSASISCRSSQSLLHNNGN



TYLSWLHQRPGQPPRLLIYEISNRFSGVPDRFSGS



GAGTDFTLKISRVEAEDVGIYYCMQTTQFPRTFGQ



GTKVEIR





1319
DIQMTQSPSAMSASVGDRVTITCRASQGIRNSLAW



FQQKPGKVPKRLIYDASNLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCLQYNTYSYSFGQGTKLE



IK





1320
DIQMTQSPSILSASVGDRVTITCRASQNISRWLAW



YQQKPGKAPKFLIYKASGLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYITFGGGTKIEI



K





1321
DIQMTQSPSTLSASVGDRVIITCRASQNISRWLAW



YQQKPGTAPKFLIYKASALESGVPSRFSGSGSGTE



FTLTITSLQPDDFATYYCQQYNSYVTFGGGTKVEM



K





1322
SYELTQPPSVSVSPGQTARITCSGDALPQRYAYWY



QQKSGQAPVLVIYEDTKRPSGIPERFSGFSLGTLA



TLTISGAQVEDEADYYCYSTDSSDNQRVFGGGTKL



TVL





1323
AIQLTQSPSSLSASVGDRVTITCRASQGVASYLAW



YQQKPGKAPNLLIYAASTLQGGVPSRFSGSGSGTD



FTLTISNLQPEDFATYYCQHLKSYPLTFGGGTKVE



IK





1324
DIQMTQSPPSVSASIGDTVTITCRATQNINVFLAW



YQQKPGSAPTLLIYGASSLQSGVPSRFVGSGSGTD



FTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVE



VK





1325
DIQMTQSPSSVSASIGDTVTITCRATQNINVFLAW



YQQKPGSAPTLLIYGASSLQSGVPSRFVGSGSGTD



FTLTISGLQPEDFATYYCQQGHNFPWTFGRGTKVE



VK





1326
EIVMTQSPATLSVSPGERATLSCRASQSLNSNLAW



YQQKPGQAPRLVIYGASTRAAGFPARFSGSGSETE



FTLTISSLQSEDFAIYFCQQYHNFPLTFGQGTEVE



VR





1327
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQLLPGTAPKLLIYGNNNRPSGVPDRFSGSKSG



TSASLAIIGLQAEDEATYYCQSYDSSLSVVFGGGT



KVTVL





1328
SYELTQPPSVSVSPGQTAIITCSGDKLGEKYASWY



QQRPGQSPMLVIYQDTKRPSGIPERFSGSNSGNTA



TLTISGTQAVDEADYFCQAWDSNTGVFGTGTKVTV



L





1329
QSVLTQPPSLSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGDSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGSVFGGG



TKLTVL





1330
SYELTQPPSVSVSPGQTARISCSADALPKQNAYWY



QCKPGQAPILLIYKDTERPSGIPERFSGSSSGTTV



TLTISGVQPEDDADYYCQSVDNTGASPHVVFGGGT



KLTVL





1331
DIQMTQSPSTLSASVGDSVTITCRANETIASWVAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSESGTE



FTLTISSLQPDDFATYYCQQYHTYWTFGQGTKVEV



K





1332
SYELTQPPSVSVSPGQTASIACSGDKLGDKYTCWY



QQKPGQSPVLVMYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQVMDEADYYCQAWDSGTVVFGGGTKLTV



L





1333
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





1334
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





1335
DIVLTQSPGTLSLSPGERATLSCRASQSISSSYLA



WYQQKPGQAPRLVIHGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQHYGTSPYTFGQGTKL



EIK





1336
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSTLVTFGQGTK



VEIK





1337
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSLWVFGGGT



KLTVL





1338
NFMLTQPHSVSESPGKTVTISCTGSSGSIASNYVQ



WYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSS



SNSASLTISGLKTEDEADYYCQSYDSSFWVFGGGT



KLTVL





1339
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGT



KLTVL





1340
SYELTQPPSVSVSPGQTARITCSGDALPEKYAYWF



QQKSGQAPVLVIYEDNKRPSGIPERFSGSSSGTMA



TLTISGAQVEDEADYYCYSTDRSGNHRGVFGTGTK



VTVL





1341
SSELTQDPAVSVALGQTVRITCQGDSLRSYYASWY



QQKPGQAPVLVIYGKNNRPSGIPDRFSGSSSGNTA



SLTITGAQAEDEADYYCNSRDSSGNHLYWVFGGGT



KLTVL





1342
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGHVVFGG



GTKLTVL





1343
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAGGVFGTG



TKVTVL





1344
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSTFVVFGGG



TKLTVL





1345
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQFPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAVVFGGGT



KLTVL





1346
AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNSYPPTFGQGTKVE



IK





1347
DIQMTQSPSSLSASVGDRVTITCRASQSIRFYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTLWTFGQGTKVE



IK





1348
EIVLTQSPGTLSLSPGERATLSCRASQSVSSTYLA



WYQQKPGQAPRLLIYDASSRATGIPDRFSGGGSGT



DFTLTISRLEPEDFAVYYCQQYGDSPETFGQGTKV



EIK





1349
SYELTQPPSVSVSPGQTASITCSGDKLGDNYASWY



QQKSGQSPVLVIYQDTKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTVVFGGGTKLTV



L





1350
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLE



IK





1351
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPYTFGQGTKLE



IK





1352
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWPSITFGQGTRL



EIK





1353
DIQMTQSPSSVSASVGDRVTITCRASQGISNWLAW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQANSFPLAFGGGTKVE



IK





1354
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPFGFGPGTKVD



IK





1355
QSVLTQPPSVSGAPGQRVTISCTGSRSNIGAGFDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEAVYYCLSYDSSLSGSVFGGG



TKLTVL





1356
AIQLTQSPSSLSASVGDRVTITCRASQGISSALAW



YQQKPGKAPKVLIYDASSLESGVPPRFSGSGSGTD



FTLTISSLQPEDFATYYCQQFNNYPLTFGGGTKVE



IK





1357
DIQMTQSPSSLSASVGDRVTITCQASQDMSNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPFTFGPGTKVD



IK





1358
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSNRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSAYVFGTGT



KVTVL





1359
SSELTQDPAVSVALGQTVRITCQGDSLRSYSASWY



QQKPGQAPVLVIYVKNNRPSGIPDRFSGSSSGNTA



SLTITGAQAEDEADYYCNSRDSSGNHVVFGGGTRL



TVL





1360
QSALTQPRSVSGSPGQSVTISCTGTSSDVGDYDYV



SWYQHHPGKAPKLMIYDVSKRPSGVPDRFSGSKSG



NTASLTISGLQAEDDADYYCCSYAGSYPVVFGGGT



KLTVL





1361
QSALTQPPSASGSPGQSVTISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYEVSKRPSGVPDRFSGSKSG



NTASLTVSGLQAEDEADYYCSSYAGSNKVFGGGTK



LTVL





1362
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSGGYTFGQGTK



LEIK





1363
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLE



IK





1364
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSSWTFGQGTKV



EIK





1365
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLE



IK





1366
SYELTQPPSVSVSPGQTASITCSGDKLGNKYACWY



QQKPGQSPVLVIYQDSKRPSGIPERFSGSNSGNTA



TLTISGTQAMDEADYYCQAWDSSTANWVFGGGTKL



TVL





1367
QSALTQPASVSGSPGQSITISCTATSGDVGGYNYV



SWYQQHPGKAPKLMIFDVYNRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSFTDSSTLVVFGGG



TKLTVL





1368
DIQMTQSPSSLSASVRDKVTITCRASQSISSCLNW



YQQKPGKAPKVLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSVQPEDFATYYCQQSYSVPHTFGQGTKVE



IK





1369
EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAW



YQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWLTFGGGTKVEI



K





1370
EIVMTQSPATLSVSPGERVTLSCRASQSINRNLAW



YQQKPGQAPRLLVYDASTRAPGIPTRVSGSGSGTD



FTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRL



EIQ





1371
EIVMTQSPATLSVSPGERVTLSCRASQSVNRNLAW



YQQKPGQAPRLLVYDASTRAPGIPTRVRGSGSGTD



FTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRL



EIQ





1372
QTALTQPPSASGSPGQSVTISCTGSSGDVGGYNYV



SWYQQYPGKAPKLILSEVSQRPSGVPDRFFGSKSG



NTASLTVFGLQAEDEADYYCSSYAGTNKILFGGGT



KLTVL





1373
DIQMTQSPSSLSASVGDRVTITCRASQSISSFLNW



FQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTD



FTLTINSLQPEDFATYYCQQSYSTPLTFGGGTKVE



IK





1374
QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYV



SWYQQHPGKAPKLMIYDVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCSSYTSSSTWVFGGGT



KLTVL





1375
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLE



IK





1376
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTPGTFGQ



GTRLEIK





1377
DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGY



NYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGS



GSGTDFTLKISRVEAEDVGVYYCMQALQTPGTFGQ



GTRLEIK





1378
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYSAFGQGTKLEI



K





1379
PYDLTQPPSVSVSPGQTATITCSGDKLGKKYACWY



QQKPGQSPVLLIYQDVKRPSGIPERFSGSNSGTTA



TLTISETQTMDEADYYCQAWDRTTATFGGGTRLTV



L





1380
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGWVFGGG



TKLTVL





1381
QSALTQPASVSGSPGQSITISCTGTTFDVGVYDFV



SWYQQLPGKAPKLIIHDDTHRPSGVSDRFSGSRSG



TTASLTISGLQADDEADYYCSSYTSLNTLEVVFGG



GTKLTVL





1382
DIVMTQSPLSLPVTPGEPASMSCKSTQSLLHSNGN



YYVTWYLQKPGQSPHLLIYLASNRASGVPDRFSGS



GSGTDFTLKISSVEAEDVGVYYCMQALQTPYSFGQ



GTKLEIK





1383
SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWY



QQKPGQAPVLVIYYDSDRPSGIPERFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDSSSDRTVVFGGGTK



LTVL





1384
QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVY



WYQHLPGTAPKLLIYRNNQRPSGVPDRFSGSKSGT



SASLAISGLRSENEADYYCASWDDKVRGWVFGGGT



KLTVL





1385
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKV



EIK





1386
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYSRTFGQGTKVE



IK





1387
DIQMTQSPSTLSASVGDRVTITCRASQSISDWLAW



YQQKPGKAPKLLIYKASTLEGGVPSRFSGSESGTE



FTLTISSLQPDDFATYYCQQYNTSPLTFGGGTKVE



IK





1388
QSVLTQPPSVSGAPGQRVTISCTGSSSNIGAGYDV



HWYQQLPGTAPKLLIYGNSNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEADYYCQSYDSSLSGSLFGGG



TKLTVL





1389
SYELTQPPSVSVSPGQTARITCSGDALPKQYAYWY



QQKPGQAPVLVIYKDSERPSGIPERFSGSSSGTTV



TLTISGVQAEDEADYYCQSADSSGTYRVFGGGTKL



TVL





1390
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGRTFGQGTKVEIK


1391
QSALTQPASVAGSPGQTITISCTGPNSDINSYDYV



SWYQQRPGKAPKLIIHDVDHRPSGVSDRFSGFMSD



NTASLTISGLQAEDEAHYYCSSYTNIDTLEIVFGA



GTKLTVL





1392
DIQMTQSPSAMSASVGDRVTITCRASQGISNYLAW



FQQKPGKVPKRLIYAASSLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCLQHNSYPRTFGQGTKVE



IK





1393
SYELTQPPSVSVAPGKAASITCGGINIGSKSVHWY



QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTA



TLTISRVESGDEADYYCQVWHSSFDPWVFGGGTKL



TVL





1394
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPPTTFGPGTKV



DIK





1395
DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYNSYFPTFGQGTKVE



IK





1396
SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWY



QQKPGQAPVLVVYDDNDRPSGIPDRFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDSSSDHYWVFGGGTK



LTVL





1397
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGT



KLTVL





1398
QLVVTQSPSASASLGASVKLTCTLSSGHSSYVIAW



HQQQPEKGPRFLMKLNSDGSHNKGDGIPDRFSGSS



SGAERYLTISNLQSEDEADYYCQTWGTGPQVLFGG



GTKLTVL





1399
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGRAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLLTFGGGTKVEI



K





1400
SYVLTQPPSVSVAPGKTARITCGGNNIGSKSVHWY



QQKPGQAPVLVVYDDSDRPSGIPERFSGSNSGNTA



TLTISRVEAGDEADYYCQVWDSSGDHWVFGGGTKL



TVL





1401
EIVLTQSPATLSLSPGERATLSCRASQSVSNYLAW



YQQKPGQVPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWLTFGGGTKVEI



K





1402
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLISDASLLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQHDNLPSFTFGPGTKV



DIK





1403
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





1404
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQTPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





1405
QTVVTQEPSLTVSPGGTVTLTCASSTGAVTSGYYP



NWFQQKPGQAPRALIYSTSNKHSWTPARFSGSLLG



GKAALTLSGVQPEDEAEYYCLLYYGGAPVFGGGTK



LTVL





1406
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPPAFGQGTKVE



IK





1407
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPQTFGPGTKVD



IK





1408
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSLWVFGGGT



KLTVL





1409
NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQ



WYQQRPGSAPTTVIYEDNQRPSGVPDRFSGSIDSS



SNSASLTISGLKTEDEADYYCQSYDSSNQVFGGGT



KLTVL





1410
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW



YQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRSNWLFTFGPGTKVD



IK





1411
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAGVFGGGT



KLTVL





1412
VIVLTQTPLSSPVTLGQPASISCRSRRSLVHTNGN



TYLSWLHQRPGQTPRLLIHNVSNRFSGVPDRFSGS



GAGTDFTLNISRVEADDVGIYYCMQASQFPLTFGG



GTKLEIK





1413
QSALTQPASVSGSPGQSITISCTGTFSDIGNYDLV



SWYQQHPGKAPKVIIYEGYKRPSGVSDRFSGSKSG



NTASLTISGLQAEDEADYFCCSFAGSNREFGGGTK



LTVL





1414
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPWTFGQGTKV



EIK





1415
QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVS



WYQQLPGTAPKLLIYDNNKRPSGIPDRFSGSKSGT



SATLGITGLQTGDEADYYCGTWDSSLSAWVFGGGT



KLTVL





1416
EIVLTQSPGTLSLSPGERATLSCRASQSVSNYLAW



YQHKPGQAPRLLIYGASNGATGIPDRFSGSGSGTD



FTLTISRLEPEDFAVYYCQHYSSSAPITFGQGTRL



EIK





1417
EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAW



YQQKPGQAPRLLIFDASNRATGIPARFSGSGSGTD



FTLTISSLEPEDFAVYYCQQRNKWPGTFGQGTKVE



IK





1418
ETVLTQSPGTLSLSPGERATLSCRASQSVNSNYLA



WYQQKPGQAPRLLIYGASSRATGIPDNFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGDSPYTFGQGTNL



EIK





1419
AIQLTQSPSSLSASVGDRVTITCRASQGISSSLAW



YQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTD



FTLTITSLQPEDFATYYCQQLNSYPLTFGGGTKVE



IK





1420
QSALTQPASVSGSPGQSITISCTGTSSDVGTYNLV



SWYQQHPGKAPKLMIYEVSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCTYAGSSTWVFGGGT



KLTVL





1421
DIQMTQSPSSLSASVGDRVTITCRASQSIAKFLNW



YQKKPGKAPNLLISTASSFQSGVPSRFSGSGSGTD



YTLTISGLQPEDFATYYCQQSYSSPYTFGQGTNLE



IK





1422
DIQMTQSPSSVSASVGDRVTITCRASQGISSWLAW



YQQKPGKAPKLLIYAASSLQSGIPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQANSFPRTFGQGTKVE



IK





1423
AIQLTQSPSSLSASVGDRVTITCRASQGISSALAW



YQQKPGKAPKVLIYDASGLQSGVPSRFSGGGSGTD



FTLTISSLQPEDFATYYCQQFNDYPLTFGGGTKVE



IK





1424
QSVLTQPPSVSGAPGQRVTISCTGSNSNIGAGYDV



HWYQQLPGTAPKLLIYVNTNRPSGVPDRFSGSKSG



TSASLAITGLQAEDEAHYYCQSYDSSLSGSVFGGG



TKLTVL





1425
DIQMTQSPSTLSASVGDRVTITCRASQIISSWLAW



YQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTE



FTLTISSLQPDDFATYYCQQYSTYYTFGQGTKLEI



K





1426
DVVLTQSPLSLPVTLGQPASISCRSSHSLVYSDGY



THLHWIQERPGQSPRRLIYSVSHRDSGVPDRFSGS



GSATDFTLQISRVEAEDVGVYYCMQGSHWPWTFGQ



GTKVEIK





1427
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVN



WYQQLPGTAPKLLIYSNNQRPSGVPDRFSGSKSGT



SASLAISGLQSEDEADYYCAAWDDSLNGPWVFGGG



TKLTVL





1428
QSALTQPRSVSGSPGQSVTISCTGTSSDVGGYNYV



SWYQQYPGKAPKLMIYEVSKRPSGVPDRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSYTWVFGTGT



KVTVL





1429
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQVGVPSRFSGSGSGTE



FTLTISSLQPEDFATYFCQQLNSYPFTFGPGTKVD



IK





1430
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPRTFGQGTKVE



IK





1431
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSSFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVE



IK





1432
DIQMTQSPSSLSASVGDRVTITCRASQSISNFLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTG



FTLTISSLQPEDFATYYCQQSYSTPPDTFGQGTRL



EIK





1433
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPPTFGGGTKVE



IK





1434
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYTTPLFTFGPGTKV



DIK





1435
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNGYPHSAFGPGTKV



DIK





1436
DIQMTQSPSSLSASVGDRVTITCQASQDIINYLNW



YQQKPGKAPKLLIYGASNLETGVPSRFSGGGSGTD



FTFTISSLQPEDIATYYCHQYDNLPPTFGQGTRLE



IK





1437
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVE



IK





1438
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDVATYYCQQLNSNPPITFGPGTKV



DIK





1439
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIFAASSLQTGAPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQSYSTPPYTFGQGTKL



EIK





1440
DIQMTQSPSSLSASVGDRVTITCQASQDINKYLNW



YQQKPGKAPKLLIFDASHLETGVPSRFSASGSGTD



FTFTISSLQPEDIATYYCHQYDNLPRTFGQGTRLE



IK





1441
GGSFSDYY





1442
GGSFSDYF





1443
GITVSSNY





1444
GYTFTSYA





1445
ITHSGST





1446
INHSGST





1447
IYSGGST





1448
INTNTGNP





1449
QSVSTY





1450
QSVSSY





1451
QGISSY





1452
QSISSW





1453
DAS





1454
DAS





1455
AAS





1456
KAS





1457
ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE



PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVT



VPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDK



THTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTP



EVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR



EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA



LPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ



VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV



LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL



HNHYTQKSLSLSPGK





1458
RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR



EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSS



TLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRG



EC





1459
RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAW



NRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLN



DLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNY



KLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRK



SNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQ



SYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPK



KSTNLVKNKCVNF





1460
MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRG



VYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHV



SGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWI



FGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPF



LGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPF



LMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPI



NLVRDLPQGFSALEPLVDLPIGINITRFQTLLALH



RSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYN



ENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQT



SNFRVQPTESIVRFPNITNLCPFGEVFNATRFASV



YAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPT



KLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIAD



YNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRL



FRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYF



PLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVC



GPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFL



PFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGV



SVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLT



PTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIP



IGAGICASYQTQTNSPRRARSVASQSIIAYTMSLG



AENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTS



VDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGI



AVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQI



LPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDC



LGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTS



ALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIG



VTQNVLYENQKLIANQFNSAIGKIQDSLSSTASAL



GKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDI



LSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRA



AEIRASANLAATKMSECVLGQSKRVDFCGKGYHLM



SFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDG



KAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNT



FVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKY



FKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVA



KNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLI



AIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDD



SEPVLKGVKLHYT





1461
GFTFSSYG





1462
GFTFSSYG





1463
GYSFTSYW





1464
GYSFTSYW





1465
GYSFTSYW





1466
GYSFTSYW





1467
GYSFTSYW





1468
GGSINRNHF





1469
GGSINRNHF





1470
GYTFTSYG





1471
GFTFSYFE





1472
GFTFSYFE





1473
GYKFSNYY





1474
GYIFTNFY





1475
GFNFSSYA





1476
GIIVSRNE





1477
GGTFSTYA





1478
GFTFSSYG





1479
GFTFNNYA





1480
GFVFSNYW





1481
GGSISSGGYY





1482
GYNFNNYW





1483
GYTFTSYA





1484
GYTLTELS





1485
GFTFSSYG





1486
GFTFSSYP





1487
GGSISSGGYY





1488
GGSISSGGYY





1489
GFTVSSNY





1490
GGSISSYY





1491
gytftgyf





1492
GFTASSNY





1493
GGTFSSYG





1494
GGRFGSFA





1495
GFTFTDYA





1496
GGSISSYY





1497
gytftdyy





1498
GYSFTGHY





1499
GFTFSNYG





1500
GGSISSDVYS





1501
GDTFNSYA





1502
GFTFSHYG





1503
GYSFPAHW





1504
GYNFDTYW





1505
GYSFSGYW





1506
GYYFAAHW





1507
GYSFPAFW





1508
GYSFPAYW





1509
GYTLTELS





1510
gytftryw





1511
GFTFSSYS





1512
GFTFSSYS





1513
GGSISSSSYY





1514
GFSLSTSGVG





1515
GFTFSNAW





1516
GFTFSSYE





1517
GFTFSSYE





1518
GGSISSSSYY





1519
GGSISSGGYY





1520
GGSISSRSYY





1521
GFSLSNARMG





1522
GFSLSTSGVG





1523
GFTISPYG





1524
GFTISPYG





1525
GYTFGDYG





1526
GYTFGDYG





1527
GFSLSTSGVG





1528
GGSISTYR





1529
GFTFSNAW





1530
GYIFTNYA





1531
GYAFTSYQ





1532
GFTFGDYA





1533
GASFSSYY





1534
GYSFTKYW





1535
GFTFSSYA





1536
GDSVSSNTVA





1537
GFTFDDYG





1538
GFAFDDFA





1539
GFTVSSTF





1540
GGSIKRRGYY





1541
GGSFSAYY





1542
GGSISSSDYY





1543
GFTFSNAW





1544
GGTFSTYA





1545
GLRFTDAW





1546
GFSFSSYA





1547
GFSFSDFA





1548
GFTFTTYG





1549
GFTFRSYS





1550
GDSITSYY





1551
GGSFSGSY





1552
GGSFTDHY





1553
GGSISSSSYY





1554
GFSLSNARMG





1555
GFTFSSYG





1556
GFTFGDYA





1557
GFTFSGSA





1558
GYSFTSYW





1559
gytftsyy





1560
GGTFSSYA





1561
GFTFSNAW





1562

GFTFRSYW






1563
GFTFSTYA





1564
GFTFSSYG





1565
GFTVSSNY





1566
GGPISSGGYY





1567
GGSISSSYYY





1568
GGSISSSSYY





1569
GFTFSSYS





1570
GYTFTSYG





1571
GFTFSSYW





1572
GGSISSGGYS





1573
GYSFPAHW





1574
GYSFPAFY





1575
GYSFPAHW





1576

GFTFSASA






1577
GGSISSGGYY





1578
GFTFSSYW





1579
GYTFTSYG





1580
GFSLSTSGVS





1581
GFTFSSYG





1582
GFTFSSYA





1583
GFTFSSYE





1584
GFTFSIYA





1585
GFTFTSYG





1586
GFTFSSYG





1587
GFAFNKYG





1588
GFTFSSYG





1589
GGSISSSSYY





1590
GGAITTSSYF





1591
GFTFSAYG





1592
GFTFNNYG





1593
GGSINSYY





1594
GFTFSRFG





1595
GFTFSRFG





1596
GFTFSSFW





1597
GGTFSSYT





1598
GGSFSSYT





1599
EFSLDSRGVG





1600
GGSISSYY





1601
GFTFSRYG





1602
GFPFSGYA





1603
GFTFINYD





1604
GFAFDKFW





1605
GGSINRDGHY





1606
GGSISSYY





1607
GGSVSSGSYF





1608
GYTFTSYG





1609
GYTFTGYY





1610
GYTLTELS





1611
GYRFTSYG





1612
GYRFTSYG





1613
GYTFTSYA





1614
gytftsyy





1615
GYTFTNYY





1616
GGTFSSYT





1617
GGTFNSYA





1618
GYTFTSSD





1619
EFSLDARGVG





1620
GFTFISYA





1621
GFTFSSYA





1622
GFTFSSYG





1623
GFTFSSHG





1624
GFTFSSYA





1625
GFTFSSYA





1626
GFTFSTYG





1627
GFTFSTFA





1628
GFIFGDYA





1629
GFIFGDYA





1630
GFTFSSYW





1631
GASISSGDYY





1632
GGVLSDYY





1633
GGVLSDYY





1634
GGSFSDYY





1635
GGSFSDYF





1636
GDSISSNNW





1637
GGSISSYY





1638
GDSISSYY





1639
GGSISGYY





1640
GGSISSGSYY





1641
DDSISSGSYY





1642
GYSFTSYW





1643
GYSFTSYW





1644
GYTFTSYA





1645
GYTFSFYW





1646
GGAFSSGRHY





1647
GGSFSSYY





1648
GYTLTELS





1649
GFTFSDYY





1650
GITVSSNY





1651
GFTFSRFW





1652
GFTFSNYW





1653
AFSFHLHG





1654
GFTFSSYA





1655
GFIFDDYG





1656
GFTVSSNY





1657
GGSIGSSSYF





1658
GGSISSSSYY





1659
GFTFSSYD





1660
GFTFSRSA





1661
GFTFSSQS





1662
GFTFEEYS





1663
GYTFGRYW





1664
gytfstyy





1665
GGTFSSYA





1666
GATFTTYA





1667
GFTLSSYA





1668
GFTFSNYD





1669
GFTFDDYA





1670
GFTFDDYA





1671
GFTFDDYA





1672
GFTFSSYT





1673
TFIFSNSE





1674
GFTVSSNY





1675
GGSFSGYF





1676
GGSFSGYY





1677
GGSLSSYY





1678
GGSISTFY





1679
GGSVSSYF





1680
GFSFNTPGVG





1681
GFSFSNHG





1682
GFTFSNSA





1683
EFTFSSYE





1684
gytftnfa





1685
GYTFTSYG





1686
GFSFSRYG





1687
GFNFNSYT





1688
GFNFNSYT





1689
GFTFSSYE





1690
GYIFTSYG





1691
GYSFNDYG





1692
GYTLTELS





1693
GNTFSTYY





1694
GFTFSDVW





1695
GLTFDNAW





1696
RFTFSSYA





1697
GFTFDDYA





1698
GNTFTTYY





1699
GGTFNSYT





1700
GFSLNTPGAG





1701
GFSFNTPGVG





1702
GFTFTFSDYY





1703
GFTFSDYY





1704
GFSFSRYG





1705
GLSFSRYG





1706
GFSFNNFG





1707
GFTLSSYA





1708
GFTFSSYE





1709
GFTFSSYA





1710
GGSISPYS





1711
GDSIRSSSFY





1712
GYSFTTYA





1713
GGTFSSYA





1714
GGTFSSYA





1715
GFTFSHAW





1716
GFTFSSYE





1717
GFTVSSNY





1718
GGSISSYY





1719
GYTFTTYG





1720
GYTFTNYG





1721
GYTLTELS





1722
GYTLTELS





1723
GYTLTELS





1724
GYTLTELS





1725
GYTFTSYA





1726
GGTFSSYA





1727
GFSLSNARMG





1728
GFSLSTTGVG





1729
GFSLSTSGVG





1730
GFTFSSYS





1731
GFTFSSYS





1732
GFTFSSYA





1733
GFTFSSYA





1734
GFTFSSYA





1735
GFTFGSYG





1736
GFTFSSYA





1737
GFTFSIYA





1738
GFTVSSNY





1739
GFTFSNYW





1740
GGSFSGYY





1741
DGSFSGHY





1742
GGSFSGYY





1743
GGSISSYY





1744
GGSISSYY





1745
GYNFTSYW





1746
GYTFTSYA





1747
GFTVSSNY





1748
GGSISSGLYH





1749
GGTFSSYT





1750
GFTFGRHG





1751
GFTFGRYG





1752
GFSLTTRGEG





1753
GYTFTFYT





1754
GFTFTSSA





1755
GFSLSTSGMC





1756
GFTFTTYA





1757
GFAFTTYA





1758
GYTFTSYG





1759
GYTFSRYG





1760
GYTFTGYY





1761
GSGFTFRNAW





1762
GFTFNFYG





1763
GFTFDDYA





1764
GFIFDDYT





1765
GYTFTSYG





1766
GYTFTSYG





1767
GDTFNDYH





1768
GGTFSSYA





1769
GGTFSSYA





1770
GFTFSNAW





1771
GLTFTKAW





1772
GFTFSTYA





1773
GFTFSNYA





1774
GFTFSSYA





1775
GFTFSSYG





1776
GFTFSSYG





1777
GFTFSSFA





1778
GFTFSNYG





1779
GFTFSSYG





1780
GFTFSSYA





1781
GFTFHDYA





1782
GVIVSRNY





1783
GFTVSSNY





1784
EFTVSSNY





1785
GFTVSSNY





1786
GFTVSSNY





1787
GITVSSNY





1788
GFTVSSNY





1789
GFTFSSYW





1790
GGSISSGGYY





1791
GGSISSGGYY





1792
GGSFSGYY





1793
GGSFSDDF





1794
GGSISSYY





1795
GYSFTSYW





1796
GDTFSNYP





1797
GFTFSTSA





1798
GFTFSTYA





1799
GFTFFSYA





1800
GFTVSSNY





1801
AGSISSDTYY





1802
GYTFTSYG





1803
GYTFTNYY





1804
GGTFSSYT





1805
GFSLSTSGVG





1806
GFTVSSYD





1807
GFTFRNYG





1808
GFTFSSYG





1809
GFTVSRNY





1810
GFTVSSNY





1811
GFTVSRNY





1812
GLTVSSNY





1813
GFTVSSNY





1814
GLIVSSNY





1815
GITVRSNY





1816
GFTVSSNY





1817
GVTVSSNY





1818
GLTVSSNY





1819
GFIVSSNY





1820
EFIVSRNY





1821
IWYDGSNK





1822
IWYDGSNK





1823
IDPSDSYT





1824
IDPSDSYT





1825
IDPSDSYT





1826
IDPSDSYT





1827
IDPSDSYT





1828
ASYTGTT





1829
ASYTGTT





1830
ISAYNGNT





1831
ISSSGTNI





1832
ISSSGTNI





1833
INPYSGET





1834
VNPNDGSS





1835
ISATGGTT





1836
ISSSGTGV





1837
IIPIFGTP





1838
ISYDGSNK





1839
ISSYGDNT





1840
IKQDESEE





1841
IYYSGST





1842
IYGGDSDT





1843
INTNTGNP





1844
FDPEDGET





1845
ISYDGSNK





1846
ISYDGSNK





1847
IYYSGST





1848
IYYSGST





1849
LYSGGNE





1850
IYYSGST





1851
INPSSGVA





1852
IYAGGGT





1853
ILPVLDTT





1854
VTPIVGVP





1855
ISYDGNDK





1856
IYYSGST





1857
VNPNRGGT





1858
INPDSGGT





1859
ITGSGGST





1860
VFHTGSA





1861
IIPILRLA





1862
IWYDGSKK





1863
IFPGDSDT





1864
IYPGDSDS





1865
IFPSDSDT





1866
IFPSDSDT





1867
VFPGDSDT





1868
IFPGDSDT





1869
FDPEDGET





1870
MKPGDGKT





1871
ISSSSSYI





1872
ISSSSSTI





1873
IYYSGST





1874
IYWDDDK





1875
IKSKTDGGTT





1876
ISSSGSTI





1877
ISSSGSTI





1878
IYYSGST





1879
IYYSGST





1880
IYYSGST





1881
IFSNDEK





1882
IYWDDDK





1883
IWYDGSNK





1884
IWYDGSNK





1885
ISGYNGDP





1886
ISGYNGDP





1887
IYWDDDK





1888
IYYSGRT





1889
IKRIIDGGTI





1890
TNTNTGNP





1891
INPSGSAT





1892
ITWNSGNI





1893
ISQSAST





1894
IYPDDSET





1895
ISGSGDKT





1896
TYYRSNWYN





1897
ISWNSNSV





1898
INWNSDNI





1899
IYTVGDT





1900
IYYSGTT





1901
INRRGNT





1902
IYYSGNT





1903
IKSKTDGGTT





1904
IIPSLRTA





1905
IKSRGSGGTI





1906
ISYDGRNK





1907
VSYDSRQQ





1908
IWYDGSNE





1909
LSNDDRTR





1910
IYSSGDT





1911
INPSGGS





1912
INHSGRT





1913
IYYSGST





1914
IFSNDEK





1915
ISYDGSNK





1916
IRSKAYGGTT





1917
IRSKANSYAT





1918
IDPSDSYT





1919
INPSGGST





1920
IIPIFHIA





1921
IKSKTDGGTT





1922
IFSDWSTT





1923
ISGSGGST





1924
ISYDGSNK





1925
IYSGSST





1926
IYYSGST





1927
IYYSGST





1928
IYYSGST





1929
ISSSSSYI





1930
ISAYNGNT





1931
INSDGSST





1932
IYHSGST





1933
IFPSDSDT





1934
IFPGDSET





1935
IFPGDSDT





1936
IRTRTNRYAT





1937
IYYSGST





1938
INSDGSST





1939
ISAYNGNT





1940
IYWDDDK





1941
ISYDGSNK





1942
ISYDGSNK





1943
ISSSGSTI





1944
ISGSGGST





1945
ISFDGSNI





1946
ISYDGSNK





1947
IWNDGNKQ





1948
IWYDGSNK





1949
IFYSGST





1950
ISYSGDT





1951
ISFDGSNK





1952
ISYEGSIR





1953
IYSGGST





1954
ISYEGSTE





1955
ISYEGSTE





1956
IKEDGSEK





1957
IIPMLNKT





1958
IIPMLNKT





1959
IYWNDNK





1960
IYYRGST





1961
ISYEGSTE





1962
ISSSSSTV





1963
ISSSSSTT





1964
LNKDESEK





1965
IYSGRNT





1966
IYYSGST





1967
IYYSGST





1968
ISAYNGNT





1969
INPNSGGT





1970
FDPEDGET





1971
INTDNEKT





1972
INTDNGKT





1973
INAGNGNT





1974
INPSGGST





1975
INPSDGST





1976
IIPMLNKT





1977
IIPIFGPP





1978
MNPNTGTT





1979
IYWNDYK





1980
ISGSGGST





1981
ISGSGGTT





1982
ISYDGSNK





1983
ISYDGINK





1984
ISYDGSNK





1985
ISYDGSNK





1986
MWFDGVDK





1987
ISYDEINK





1988
IRGRLVGATV





1989
IRGRLVGATV





1990
IKQDGSEK





1991
IYYSGST





1992
IHRSGST





1993
IHRSGST





1994
ITHSGST





1995
INHSGST





1996
IYHSGTT





1997
IYTSGST





1998
IYHSGSA





1999
LHYSGRS





2000
IYTSGST





2001
IYAGEST





2002
IYPGDSDT





2003
IYPGDSDT





2004
INTNTGNP





2005
IYPGDFDT





2006
IYSGVIT





2007
VTHSGST





2008
FDPEDGET





2009
ISSSGSTI





2010
IYSGGST





2011
IKEDGSVM





2012
IKSDGSET





2013
IWFDGSKK





2014
ISSSGGGT





2015
ITWNSGSI





2016
IYSGGST





2017
IYYGGST





2018
IYYSGST





2019
IGTAGDT





2020
MSYDGSDI





2021
ISYDGNNK





2022
VSWNSGTI





2023
INPADSDT





2024
INPSGDST





2025
IIPIFGTA





2026
IFPIFTAA





2027
VSGSGGST





2028
ISSDGNNR





2029
ISWNSGSI





2030
ISWNSGTI





2031
ISWNSEKI





2032
INSGSSII





2033
ISSSDNSV





2034
IYSGGST





2035
INHSGKT





2036
INHSGST





2037
MYNSGST





2038
IYYSGRT





2039
IFYTGTS





2040
IYWDDEK





2041
IWYDGDNR





2042
IYYDGSNE





2043
IDSSSTTI





2044
INTKTGIP





2045
ISAYNGNT





2046
ISHDDSQK





2047
ISYEGSKK





2048
ISYEGSKK





2049
ISSSGSTI





2050
INTNTGSP





2051
ISAYNGET





2052
FDPEDGET





2053
ISPSGDDA





2054
IRSKSDGGTT





2055
VKSKTDGGTT





2056
ISYDGSNK





2057
ISWDGGST





2058
ISPSGDDA





2059
IVPMLGIT





2060
IYWDDDK





2061
IYWDDEK





2062
ISSGGDAI





2063
MSSDSDYI





2064
ISHDESQK





2065
ISHDESQK





2066
ISYEGSKK





2067
ISYDGSNK





2068
ITSSGNTI





2069
ISSSSGTI





2070
IYYTGKT





2071
VYNSGTA





2072
IDTNTGKP





2073
IIPIFGTA





2074
IIPIFGTA





2075
IKSNTDGGTT





2076
ISSSGSTI





2077
IYSGGST





2078
IYYSGST





2079
ISAYNGNT





2080
ISTYSGNT





2081
FDPEDGET





2082
FDPEDGET





2083
FDPEDGET





2084
FDPEDGET





2085
INAGNGNT





2086
IIPIFGTA





2087
IFSNDKK





2088
IYWDDDK





2089
IFWDDDK





2090
ISSSSSYI





2091
ISSSSSYI





2092
ISYDGSNK





2093
ISYDGSNK





2094
ISYDGSNK





2095
IWNDGSNK





2096
ISYDGSNK





2097
ISYDGSNK





2098
IYSGGST





2099
IKEDGSET





2100
IDHSGST





2101
INHSGST





2102
INHSGST





2103
IYYSGST





2104
IYYSGST





2105
IDPSDSYT





2106
INTNTGNP





2107
VYSGGHA





2108
IFSSGST





2109
IIPILGIA





2110
ISTYSGNT





2111
ISTYSGNT





2112
IYWDDDQ





2113
INTNTGTP





2114
IWGSGNT





2115
IDWDDDK





2116
ISDSGGSA





2117
ISDGGGSA





2118
ISAYNGNT





2119
ISGYNGNT





2120
INPNSGGT





2121
IKSKNDGGTT





2122
ISYDGNKR





2123
ISWNSGSI





2124
ITWNYATV





2125
ISAYNGNT





2126
ISAYNGNT





2127
INPNSGET





2128
IIPIFGTA





2129
IIPILGIA





2130
IKSKTDGGTT





2131
IKSRSDGGKI





2132
ISGSGGST





2133
ISANGRSP





2134
ISGSGGST





2135
ISYDGSNK





2136
ISYDGSNK





2137
ISYDGANK





2138
MWHDGSNK





2139
IWYDGSNK





2140
ISYDGSNK





2141
ISWNSGSI





2142
IYSGGST





2143
IYSGGTT





2144
IYSGGST





2145
IYSGGST





2146
LYSGGTT





2147
IYSGGST





2148
IYSGGST





2149
IKSDGSST





2150
IYYSGST





2151
IYYSGST





2152
ISHGGKT





2153
INHSGTT





2154
IYYSGST





2155
IYPGDSDT





2156
IIPIVGFA





2157
ISYDGSN





2158
ISYDGSNK





2159
ISGISDSGGNT





2160
IYSGGST





2161
IYTTGST





2162
ISAYNGNT





2163
INPSGGST





2164
IIPILGIA





2165
IYWDDDK





2166
ISARGSVT





2167
ISYDGSNK





2168
ISNYGSNK





2169
IYSGGST





2170
IYSGGST





2171
IYSGGTT





2172
IYSGGST





2173
IYSGGST





2174
LYAGGST





2175
IYSGGST





2176
IYSGGST





2177
IYSGGST





2178
IYSGGST





2179
IYSGGST





2180
IYSGGST





2181
QSIASY





2182
QGISSY





2183
SSDVGGYNY





2184
QSISDW





2185
QSISSY





2186
QDISNY





2187
QSVSSSY





2188
NSNIGINN





2189
SGHSSYA





2190
ALPKQY





2191
QSISSY





2192
QGISSA





2193
SSDFGTFHL





2194
AFNIGTNF





2195
QSLVYYDGNTY





2196
QSISRW





2197
QHISNY





2198
ALPKQY





2199
QSVLYSSNNNKNY





2200
GASIASNY





2201
QSVLYSSNNKNY





2202
HSVFFSKVNKDY





2203
QSISSW





2204
SSDVGGYNY





2205
ALPKQY





2206
SSDVGGYNY





2207
QSVSSSY





2208
QSVSSSY





2209
EDIDNH





2210
QSVSSSY





2211
RSNIGSKN





2212
SSDVGSYHY





2213
QSVLYSANNKYY





2214
QSVKSY





2215
KDINSY





2216
QSVLYSSNNKNY





2217
QDISSS





2218
ALSNQY





2219
QDISNF





2220
QAISNS





2221
RDIHNL





2222
NSNIGSNY





2223
QGISTNY





2224
GARYN





2225
QSISNH





2226
QSISTNY





2227
QSISTNY





2228
QSISTNY





2229
ALPKKY





2230
TGAVTSGHY





2231
SSNIGAGYD





2232
KLGDKY





2233
SSNIGNNY





2234
QSVSSN





2235
TGAVTSGHY





2236
QSISSY





2237
SSDVGGYNY





2238
QSVLYSSNNKNY





2239
QSVSSSY





2240
SSNIGNNY





2241
SSDVGGYNY





2242
QSLLHSNGYNY





2243
QSLLHSNGYNY





2244
QSLLHSNGYNY





2245
QSIASY





2246
QGISSY





2247
NIGSKS





2248
KLGDEY





2249
SSNIGNNY





2250
SSDVGGYNY





2251
LSINTD





2252
QGMSNY





2253
QSINSW





2254
QSISSW





2255
QTVSSTY





2256
SSNVGNQG





2257
QSVLYNSNNKDY





2258
SGSIASYF





2259
SGSVSTTYY





2260
QSVSDN





2261
QSLVHSDGNTY





2262
SSNIGNNY





2263
SSNIGSNY





2264
QSLVHSDGNTY





2265
QSLVYSDGNTY





2266
QSVRSNY





2267
QSLRQSQRFSY





2268
QSLLHSIGKTH





2269
HDIRTW





2270
QDIGNW





2271
SLETYY





2272
SLRTSY





2273
SSDVGGYNY





2274
SSNIGAGYD





2275
QSVLYSSNNKNY





2276
QSLVHSDGNTY





2277
SSDVGGYNY





2278
QSISSY





2279
SSDVGGYNY





2280
QSISSY





2281
SLRSYY





2282

ELGDTD






2283
QSISSW





2284
QSLVHSDGNTY





2285
QSISSY





2286
SSNIGAGYD





2287
SSNIGSNY





2288
SLRSYY





2289
QDISNY





2290
SSNIGNNY





2291
QSVSSN





2292
KLGDKY





2293
QSISTNY





2294
HSISTNY





2295
QTISTNY





2296

QTINSGY






2297
QSVSSSY





2298
ALPKQY





2299
QSISSY





2300
KLGDTY





2301
QSLLHSDGKTY





2302
QSLLHSDGKTY





2303
QSLLHSNGYNY





2304
ALPKKY





2305
SSDVGGYNY





2306
ALPKKY





2307
ESISNW





2308
QSVSSY





2309
QGIRND





2310
QGIGND





2311
QSVSGSY





2312
QSVSSSY





2313
QSLLYNFNNENY





2314
QSLLDSDGKTY





2315
QSLLDSDGKTY





2316
QSLLHSNGYNY





2317
QSVSTY





2318
QSVSSY





2319
QDSSKY





2320
QSVSFTSNNKNY





2321
QSLLDSDGKTY





2322
QDISTY





2323
QSISNY





2324
QSVVHSDGKTY





2325
HTISSSY





2326
ALPKQY





2327
SSDVGGYNY





2328
QSISNY





2329
QSLVYSDGNTY





2330
KLGDKY





2331
SSDVGGHDY





2332
SSDVGGHDY





2333
QSLVYSDGNTY





2334
SSNIGNNY





2335
ALPKQY





2336
QSVSTY





2337
QSISSW





2338
VGHDYFT





2339
QDSNTY





2340
NSDVGGYNY





2341
QSLLHSNGYNY





2342
QSISSW





2343
QSLIYSDGNTY





2344
QSVSSSY





2345
QGISSW





2346
KLGDKY





2347
QSISTW





2348
QYVGDN





2349
QYIGDN





2350
ALPKKY





2351
QDVSIY





2352
QSVYDSSNSKNY





2353
QSVYDTSNSKNY





2354
QSVSTY





2355
QSVSSY





2356
SSNIGAYT





2357
QSVSSIY





2358
QSVTSY





2359
QSITNW





2360
SSDVGSYNL





2361
ALPKQY





2362
QSVSSRY





2363
QSVSSSY





2364
QSLLDSDGKTY





2365
QRVGSS





2366
QSVSSN





2367
QGIRFW





2368
SSNIGAGYD





2369
QSISSW





2370
QGISSY





2371
QSVLYSASNKNY





2372
QDISNY





2373
HSLLHSDGKTY





2374
TGAVTSGHY





2375
SSDVGGYNY





2376
QDISNY





2377
SSDVGGYNY





2378
SSDVGSYNL





2379
QSIGKY





2380
QSIEHSDGNIY





2381
SSNTGAGYD





2382
QSLTSSS





2383
QSLLHGNGYTY





2384
NIGSKS





2385
QSVSSSY





2386
QSVSSK





2387
TGAVTSGHY





2388
QSVTRN





2389
SSNIGSNT





2390
SSDVGGYNY





2391
NIGSKN





2392
SSDVGAYNY





2393
QSISNY





2394
QDISNY





2395
SSNVALNA





2396
QSVSSN





2397
SGYSNYK





2398
SSDVGSYNL





2399
QHINRW





2400
QNISRW





2401
QSLLHSDGKTY





2402
ALPIKY





2403
QSVSTY





2404
ELPKQY





2405
SSNIGNNY





2406
QNINVF





2407
QSLNNNQ





2408
QSLNNNQ





2409
SSNIGAGYD





2410
QSISSH





2411
QSVASY





2412
SSNIGSNT





2413
HSLLHNNGNTY





2414
ALPKEF





2415
KLGDKY





2416
QSVSSSY





2417
ALSKQY





2418
QSLLHNNGNTY





2419
QGIRNS





2420
QNISRW





2421
QNISRW





2422
ALPQRY





2423
QGVASY





2424
QNINVF





2425
QNINVF





2426
QSLNSN





2427
SSNIGAGYD





2428
KLGEKY





2429
SSNIGAGYD





2430
ALPKQN





2431
ETIASW





2432
KLGDKY





2433
QSVSSSY





2434
QSVSSSY





2435
QSISSSY





2436
QSVSSSY





2437
SSDVGSYNL





2438
SGSIASNY





2439
SSNIGNNY





2440
ALPEKY





2441
SLRSYY





2442
SSNIGAGYD





2443
SSNIGNNY





2444
SSDVGSYNL





2445
SSNIGNNY





2446
QGISSY





2447
QSIRFY





2448
QSVSSTY





2449
KLGDNY





2450
QDISNY





2451
QDISNY





2452
QSVSSY





2453
QGISNW





2454
QSISSY





2455
RSNIGAGFD





2456
QGISSA





2457
QDMSNY





2458
SSDVGGYNY





2459
SLRSYS





2460
SSDVGDYDY





2461
SSDVGGYNY





2462
QSVSSSY





2463
QSISSY





2464
QSVSSSY





2465
QSISSY





2466
KLGNKY





2467
SGDVGGYNY





2468
QSISSC





2469
QSVSSN





2470
QSINRN





2471
QSVNRN





2472
SGDVGGYNY





2473
QSISSF





2474
SSDVGGYNY





2475
QSISSY





2476
QSLLHSNGYNY





2477
QSLLHSNGYNY





2478
QSISSW





2479
KLGKKY





2480
SSNIGAGYD





2481
TFDVGVYDF





2482
QSLLHSNGNYY





2483
NIGSKS





2484
SSNIGNNY





2485
QSVSSSY





2486
QSISSW





2487
QSISDW





2488
SSNIGAGYD





2489
ALPKQY





2490
QSVSSSY





2491
NSDINSYDY





2492
QGISNY





2493
NIGSKS





2494
QSISSY





2495
QSISSW





2496
NIGSKS





2497
SSNIGNNY





2498
SGHSSYV





2499
QDISNY





2500
NIGSKS





2501
QSVSNY





2502
QDISNY





2503
QSVSSSY





2504
QSVSSSY





2505
TGAVTSGYY





2506
QGISSY





2507
QDISNY





2508
SSDVGSYNL





2509
SGSIASNY





2510
QSVSSY





2511
SSNIGNNY





2512
RSLVHTNGNTY





2513
FSDIGNYDL





2514
QSVSSSY





2515
SSNIGNNY





2516
QSVSNY





2517
QSVSSY





2518
QSVNSNY





2519
QGISSS





2520
SSDVGTYNL





2521
QSIAKF





2522
QGISSW





2523
QGISSA





2524
NSNIGAGYD





2525
QIISSW





2526
HSLVYSDGYTH





2527
SSNIGSNT





2528
SSDVGGYNY





2529
QGISSY





2530
QDISNY





2531
QGISSY





2532
QSISNF





2533
QDISNY





2534
QSISSY





2535
QGISSY





2536
QDIINY





2537
QGISSY





2538
QGISSY





2539
QSISSY





2540
QDINKY





2541
AAS





2542
AAS





2543
EVS





2544
KAS





2545
AAS





2546
DAS





2547
GAS





2548
RSN





2549
LSSDGSH





2550
KDS





2551
EAA





2552
DAS





2553
EVN





2554
GDQ





2555
KVS





2556
KAS





2557
AAS





2558
KDS





2559
WAS





2560
EDT





2561
WAS





2562
WAS





2563
KAS





2564
DVS





2565
KDS





2566
DVS





2567
GAS





2568
GAS





2569
DAS





2570
GAS





2571
SNN





2572
EVS





2573
WAS





2574
GAS





2575
DAS





2576
WAS





2577
AAS





2578
KGT





2579
DAS





2580
AAS





2581
DAS





2582
KNN





2583
ATS





2584
RNT





2585
SAS





2586
ASS





2587
STS





2588
ATS





2589
EDS





2590
DIN





2591
GNS





2592
QDS





2593
DNN





2594
GAS





2595
DTS





2596
AAS





2597
DVS





2598
WAS





2599
GAS





2600
DNN





2601
DVS





2602
LGS





2603
LGS





2604
LGS





2605
AAS





2606
AAS





2607
YDS





2608
QNN





2609
DNN





2610
DVS





2611
GAS





2612
AAS





2613
KAS





2614
KAS





2615
GAS





2616
RND





2617
WAS





2618
EDN





2619
STN





2620
AAS





2621
KVS





2622
DNN





2623
RNN





2624
KVS





2625
KVS





2626
GAS





2627
LNS





2628
EVS





2629
TAF





2630
AAS





2631
GKN





2632
EKN





2633
EVS





2634
GNS





2635
WAS





2636
KVS





2637
DVS





2638
AAS





2639
DVS





2640
AAS





2641
GKN





2642
QDT





2643
KAS





2644
KIS





2645
AAS





2646
GNN





2647
RNN





2648
GKN





2649
DAS





2650
DNN





2651
GAS





2652
QDS





2653
ATS





2654
ATS





2655
ATS





2656
AAS





2657
GAS





2658
KDS





2659
AAS





2660
QDN





2661
EVS





2662
EVS





2663
LGS





2664
EDS





2665
DVS





2666
EDS





2667
KAS





2668
DAS





2669
AAS





2670
GAS





2671
GAS





2672
GAS





2673
WAS





2674
EVS





2675
EVS





2676
LGS





2677
GSS





2678
GAS





2679
DAS





2680
WAS





2681
EVS





2682
DAS





2683
GAS





2684
EVS





2685
AAS





2686
KDS





2687
DVS





2688
AAS





2689
KVS





2690
QDS





2691
DVT





2692
DVT





2693
KVS





2694
DNN





2695
KDN





2696
GSS





2697
ETS





2698
LEGSGSY





2699
DAS





2700
DVS





2701
LGS





2702
KAS





2703
KVS





2704
GAS





2705
AAS





2706
QDS





2707
KAS





2708
GAF





2709
GAS





2710
EDS





2711
DAY





2712
WAS





2713
WAS





2714
DAS





2715
DAS





2716
STD





2717
GAS





2718
GAS





2719
KAS





2720
EVS





2721
KDS





2722
GAS





2723
GAS





2724
EVS





2725
GAS





2726
GAS





2727
AAS





2728
GNT





2729
DAS





2730
AAS





2731
WAS





2732
AAS





2733
ELF





2734
DTN





2735
EVS





2736
DAS





2737
DVN





2738
EVS





2739
AAS





2740
KIS





2741
DNS





2742
GAS





2743
LGS





2744
DDS





2745
GAS





2746
GAS





2747
DTS





2748
GAS





2749
SNN





2750
EVS





2751
DDG





2752
DVT





2753
AAS





2754
DAS





2755
RDN





2756
GAS





2757
VGTGGIVG





2758
EVS





2759
EAS





2760
KAS





2761
EVS





2762
EDS





2763
DAS





2764
KDR





2765
DNN





2766
AAS





2767
GAS





2768
GAS





2769
GNS





2770
DAS





2771
DAS





2772
SNN





2773
EIS





2774
KDK





2775
QDN





2776
GAS





2777
KDS





2778
EIS





2779
DAS





2780
KAS





2781
KAS





2782
EDT





2783
AAS





2784
GAS





2785
GAS





2786
GAS





2787
GNN





2788
QDT





2789
GDS





2790
KDT





2791
KAS





2792
QDS





2793
GAS





2794
GAS





2795
GAS





2796
GAS





2797
EVS





2798
EDN





2799
DNN





2800
EDN





2801
GKN





2802
GNS





2803
DNN





2804
EGS





2805
DNN





2806
AAS





2807
AAS





2808
DAS





2809
QDT





2810
DAS





2811
DAS





2812
DAS





2813
AAS





2814
AAS





2815
GNS





2816
DAS





2817
DAS





2818
DVS





2819
VKN





2820
DVS





2821
EVS





2822
GAS





2823
AAS





2824
GAS





2825
AAS





2826
QDS





2827
DVY





2828
AAS





2829
GAS





2830
DAS





2831
DAS





2832
EVS





2833
AAS





2834
DVS





2835
AAS





2836
LGS





2837
LGS





2838
KAS





2839
QDV





2840
GNS





2841
DDT





2842
LAS





2843
YDS





2844
RNN





2845
GAS





2846
KAS





2847
KAS





2848
GNS





2849
KDS





2850
GAS





2851
DVD





2852
AAS





2853
DDS





2854
AAS





2855
KAS





2856
DDN





2857
DNN





2858
LNSDGSH





2859
DAS





2860
DDS





2861
DAS





2862
DAS





2863
GAS





2864
GAS





2865
STS





2866
AAS





2867
DAS





2868
EVS





2869
EDN





2870
DAS





2871
DNN





2872
NVS





2873
EGY





2874
GAS





2875
DNN





2876
GAS





2877
DAS





2878
GAS





2879
SAS





2880
EVS





2881
TAS





2882
AAS





2883
DAS





2884
VNT





2885
KAS





2886
SVS





2887
SNN





2888
EVS





2889
AAS





2890
DAS





2891
AAS





2892
AAS





2893
DAS





2894
AAS





2895
AAS





2896
GAS





2897
AAS





2898
AAS





2899
AAS





2900
DAS





2901
GLTVSSNY





2902
GFTVSRNY





2903
GVIVSSNY





2904
GFTVSSNY





2905
GVTVSSNY





2906
GIIVSSNY





2907
GIIVSSNY





2908
GFTVSSNY





2909
GLTVSSNY





2910
GLTVSSNY





2911
GIIVSSNY





2912
GVTVSRNY





2913
GITVSSNY





2914
GFTVSSNY





2915
GLTVSSNY





2916
GLTVSSNY





2917
GLIVSSNY





2918
GFTVSSNY





2919
GFIVSSNY





2920
GFTVSSNY





2921
GFIVSRNY





2922
GITVSSNY





2923
GFTVSSNY





2924
GFTVSSNY





2925
GFTVSSNY





2926
GVTVSSNY





2927
GFTVSSNY





2928
GYTFSSYG





2929
GYSFTYYG





2930
GFTFSSYD





2931
GFIVSSNY





2932
EFIVSRNY





2933
GFTVSSNY





2934
GFTVSSNY





2935
GFTVSFNY





2936
IYSGGST





2937
IYSGGTT





2938
IYSGGTT





2939
IYSGGST





2940
IYSGGST





2941
IYSGGST





2942
IYSGGST





2943
IYSGGST





2944
IYSGGST





2945
IYSGGST





2946
IYSGGST





2947
IYSGGST





2948
IYSGGST





2949
IYSGGST





2950
IYSGGST





2951
IYSGGST





2952
IYSGGST





2953
IYRGGST





2954
IYSGGST





2955
IYPGGST





2956
IYSGGST





2957
IYSGGST





2958
IYSGGST





2959
IYSGGST





2960
IYSGGST





2961
VYSGGST





2962
IYSGGST





2963
ISGYNGHT





2964
ISPYNGDT





2965
IGTAGDT





2966
IYSGGST





2967
IYSGGST





2968
IYSGGST





2969
IYSGGST





2970
IYPGGST





2971
ARDLDYYGMDV





2972
ARDLVVYGMDV





2973
ARDLDYYGMDV





2974
ARDLDYGGGMDV





2975
ARPIVGARSGMDV





2976
ARDLGTYGMDV





2977
ARDLGPYGMDV





2978
ARDLGAYGMDV





2979
ARDLYYYGMDV





2980
ARDLDYYGMDV





2981
ARDLDYYGMDV





2982
ARDGYGMDV





2983
ARGGAYYYGMDV





2984
ARDLDYMDV





2985
ARLPYGMDV





2986
ARLPYGMDV





2987
ARARIYTYGPDY





2988
ARVGDSRSWPFEY





2989
ARAPYSSRSET





2990
AREIRVITPVEV





2991
ARGPYPRFDY





2992
ARERGGRFDY





2993
ARDRPAAAIRF





2994
ARDYAGRV





2995
ARELSYSSSSGVGPKY





2996
ARLINHYYDSSGDGGAFDI





2997
ARIGGVAAAGTADGAFDI





2998
ARERFGISHDY





2999
AKGVVALTGTLLRLDP





3000
ARDRDNGSGSYLGWAFDI





3001
ARDYGDYYFDY





3002
ARDYGDYYFDY





3003
ARDYGDYWFDP





3004
ARSYGDYYFDY





3005
ARDYGDFYFDY





3006
QGISSY





3007
QGISSY





3008
QGISSY





3009
QGISSY





3010
QDINNY





3011
QGISSY





3012
QGISSD





3013
QGISSY





3014
QGISSY





3015
QGISSY





3016
QGISSY





3017
QGISSY





3018
QGISSY





3019
QGISSY





3020
QDVSKY





3021
QDIRNY





3022
QDINNY





3023
QDISNY





3024
QDIRNY





3025
QDINKY





3026
QDIRNY





3027
QDISNY





3028
QDISNY





3029
QDIRSY





3030
QDISNY





3031
SSDVGSYNL





3032
SSDVGSYNL





3033
QSVGSN





3034
QSVRTN





3035
QSISSY





3036
QSVSSSY





3037
QGVSSF





3038
QSVSSSY





3039
QGISSY





3040
QSVSSSY





3041
AAS





3042
AAS





3043
AAS





3044
AAS





3045
DAS





3046
AAS





3047
AAS





3048
AAS





3049
AAS





3050
AAS





3051
AAS





3052
AAS





3053
AAS





3054
AAS





3055
DAS





3056
DAS





3057
DAS





3058
DAS





3059
DAS





3060
DAS





3061
DAS





3062
DAS





3063
DAS





3064
DAS





3065
DAS





3066
EVT





3067
EGS





3068
GAF





3069
EAS





3070
AAS





3071
GAS





3072
GAS





3073
GTS





3074
AAS





3075
GAS





3076
QHLNSYPPIT





3077
QQLNSYPLT





3078
QQLNSYGLT





3079
QQLNSYPHRFT





3080
QQHDNLPVT





3081
QQLNSYLYT





3082
QQLNSDLYT





3083
QQLNSDLYT





3084
QQLDSYPL





3085
QQLNSYLAIT





3086
QQLNSYPPFT





3087
QQLNSYPPA





3088
QQLNTYPPFG





3089
QQLNSYPPMYT





3090
QQYDNLPVT





3091
QQYDNLPIT





3092
QQYDNLPPV





3093
QQYDNLPLFT





3094
QQYDNLPIT





3095
HQYDNLPRT





3096
QQYDNLPVT





3097
QQHDNLPSFT





3098
QQYDNLPPA





3099
QQYDNLPQT





3100
QQYDNLPPT





3101
CSYAGSSTWV





3102
CSYAGSSTWV





3103
QQYNNWYT





3104
QQYNNWPPIT





3105
QQSYSMPPVT





3106
QQYGSTPRT





3107
QQYGSSPRT





3108
QQYGSSPRT





3109
QQLNS





3110
QQYDSSPRT





3111
EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSTNTLYLQMNSLRAEDTAVYYCARDLDYYGMD



VWGQGTTVTVSS





3112
EVQLVESGGGLVQPGGSLRLSCAASGFTVSRNYMS



WVRQAPGKGLEWVSVIYSGGTTHYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARDLVVYGMD



VWGQGTTVTVSS





3113
EVQLVESGGGLVQPGGSLRLSCAASGVIVSSNYMR



WVRQAPGKGLEWVSVIYSGGTTYYADSVKGRFTIS



RHNSKNTLYLQMNSLRTEDTAVYYCARDLDYYGMD



VWGQGTTVTVSS





3114
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RHNSKNTLYLQMNSLRAEDTAVYYCARDLDYGGGM



DVWGQGTTVTVSS





3115
EVQLVESGGGLIQPGGSLRLSCAASGVTVSSNYMS



WVRQAPGKGLEWVSLIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARPIVGARSG



MDVWGQGTTVTVSS





3116
EVQLVESGGGLIQPGGSLRLSCAASGIIVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNTMRAEDTAVYYCARDLGTYGMD



VWGQGTTVTVS





3117
EVQLVESGGGLIQPGGSLRLSCAASGIIVSSNYMT



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMSSLRAEDTAVYYCARDLGPYGMD



VWGQGTTVTVSS





3118
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLGAYGMD



VWGQGTTVTVSS





3119
EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLYYYGMD



VWGQGTTVTVSS





3120
EVQLVESGGGLIQPGGSLRLSCAASGLTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLDYYGMD



VWGQGTTVTVSS





3121
EVQLVESGGGLVQPGGSLRLSCAASGIIVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLDYYGMD



VWGQGTTVTVSS





3122
EVQLVESGGGLVQPGGSLRLSCAASGVTVSRNYMS



WVRQAPGKGLEWVSVIYSGGSTDYADSVKGRFTIS



RHNSKNTLYLQMNSLRVEDTAVYYCARDGYGMDVW



GQGTTVTVSS





3123
EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARGGAYYYGM



DVWGQGTTVTVSS





3124
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDLDYMDVW



GKGTTVTVSS





3125
EVQLVESGGGLVQPGGSLRLSCAASGLTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYADSVKGRFTIS



RDNSKNTLYLQMNSVRAEDTAVYYCARLPYGMDVW



GQGTTVTVSS





3126
EVQLVESGGGLVQPGGSLRLSCAASGLTVSSNYMS



WVRQAPGKGLNWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLEMNSLKPEDTAVYYCARLPYGMDVW



GQGTTVTVSS





3127
QVQLVESGGGLVQPGGSLRLSCAASGLIVSSNYMS



WVRQAPGEGLEWVSVIYSGGSTYYADSVKGRFTIS



RDTSKNTLYLQMNSLRAEDTAVYYCARARIYTYGP



DYWGQGTLVTVSS





3128
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGRGLEWVSVIYRGGSTYYADSVKGRFSIS



RDNSKNTLYLQMNSLRVEDTAVYYCARVGDSRSWP



FEYWGQGTLVTVSS





3129
EVQLVESGGGLVQPGGSLRLSCAASGFIVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLRMNSLRAEDTAVYYCARAPYCSSRS



CETWGQGTLVTVSS





3130
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSLIYPGGSTYYADSVEGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCAREIRVITPV



EVWGQGTLVTVSS





3131
EVQLVESGGGLVQPGGSLRLSCAVSGFIVSRNYMT



WVRQAPGKGLEWVSLIYSGGSTFYTNSVKGRFTIS



RDNSKNTLYLQMDSLRAEDTAVYYCARGPYPRFDY



WGQGTLVTVSS





3132
EVQLVESGGGLIQPGGSLRLSCAASGITVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTFYSDSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARERGGRFDY



WGQGTLVTVSS





3133
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSLIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDRPAAAIR



FGQGTLVTVSS





3134
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSIIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDYAGRVWG



QGTLVTVSS





3135
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARELSYSSSS



GVGPKYWGQGTLVTVSS





3136
EVQLVESGGGLVQPGGSLRLSCAASGVTVSSNYMS



WVRQAPGKGLEWVSAVYSGGSTYYADSVKGRFTIS



RHNSKNTLYLQMKSLRPEDTAIYYCARLINHYYDS



SGDGGAFDIWGQGTMVTVSS





3137
EVQLVESGGGLVQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARIGGVAAAG



TADGAFDIWGQGTMVTVSS





3138
QVQLVQSGAEVKKPGASVKVSCKTSGYTFSSYGLS



WVRQAPGQGLEWMGWISGYNGHTVNAQNFQDRVTM



TTDTSTDTAYMELRSLRSDDTALYFCARERFGISH



DYWGQGTLVIVSS





3139
QIQLVQSGPEVKRPGASVKVSCKASGYSFTYYGIS



WVRQAPGQGLEWMGWISPYNGDTKFAQKFQDRVIL



TTDTSTSTAYMELKSLRSDDTAVYYCAKGVVALTG



TLLRLDPWGQGTLVTVSS





3140
EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYDMH



WVRQATGKGLEWVSVIGTAGDTYYPGSVKGRFTIS



RENAKNSLYLQMNSLRAGDTAVYYCARDRDNGSGS



YLGWAFDIWGQGTMVTVSS





3141
EVQLVESGGGLIQPGGSLRLSCAASGFIVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDYGDYYFD



YWGQGTLVTVSS





3142
EVQLVESGGGLIQPGGSLRLSCAASEFIVSRNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLNLQMNSLRAEDTAVYYCARDYGDYYFD



YWGQGTLVTVSS





3143
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARDYGDYWFD



PWGQGTLVTVSS





3144
EVQLVESGGGLIQPGGSLRLSCAASGFTVSSNYMS



WVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTIS



RDNSKNTLYLQMNSLRAEDTAVYYCARSYGDYYFD



YWGQGTLVTVSS





3145
EVQVVESGGGLVQPGGSLRLSCAASGFTVSFNYMS



WVRQAPGKGLEWVSVIYPGGSTYYADSVKGRFTIS



RHNSKNTVYLQMNSLRAEDTAVYYCARDYGDFYFD



YWGQGTLVTVSS





3146
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQHLNSYPPITFGQGTRL



EIK





3147
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSSFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVE



IK





3148
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQRGVPSRFSGSGSGTD



FNLTISSLQPEDFGTYYCQQLNSYGLTFGGGTKVE



IK





3149
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPHRFTFGPGTK



VDIK





3150
DIQMTQSPSSLSASVGDRVTITCQASQDINNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFIISSLQPEDIATYYCQQHDNLPVTFGGGTKVE



IK





3151
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YEQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISTLQPGDFATYYCQQLNSYLYTFGQGTKLE



IK





3152
DIQLTQSPSFLSASVGDRVTITCRASQGISSDLAW



YQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSDLYTFGQGTKLE



IK





3153
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSDLYTFGQGTKLE



IK





3154
AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIFAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLDSYPLFGGGTKVEI



K





3155
AIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNSYLAITFGQGTRL



EIK





3156
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPPFTFGPGTKV



DIK





3157
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPNLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNSYPPAFGPGTKVD



IK





3158
DIQLTQSPSFLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTE



FTLTISSLQPEDFATYYCQQLNTYPPFGFGPGTKV



DIK





3159
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNSYPPMYTFGQGTK



LEIK





3160
DIQMTQSPSSLSASVGDRVTITCQASQDVSKYLNW



YQQKPGKAPKLLIHDASNLQTGVPSRFSGGGSGTD



FTFTISSLQPEDIATYYCQQYDNLPVTFGGGTKVE



IK





3161
DIQMTQSPSSLSASVGDRVTITCQASQDIRNYLNW



YQQKPGKAPKLLIHDASNLETGVPSRFIGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPITFGQGTRLE



IK





3162
DIQMTQSPSSLSASVGDRVTITCQASQDINNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPPVFGPGTKVD



IK





3163
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPLFTFGPGTKV



DIK





3164
DIQMTQSPSSLSASVGDRVTITCQASQDIRNYLNW



YQQKPGKAPNLLIYDASNLETGVPSRFSGSGSGTD



FTFTINSLQPEDIATYYCQQYDNLPITFGQGTRLE



IK





3165
DIQMTQSPSSLSASVGDRVTITCQASQDINKYLNW



YQLKPGKAPNLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCHQYDNLPRTFGQGTKVE



IK





3166
DIQMTQSPSSLSASLGDRVTITCQASQDIRNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPVTFGGGTKVE



IK





3167
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASTLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQHDNLPSFTFGPGTKV



DIK





3168
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPPAFGGGTKVE



IK





3169
DIQMTQSPSSLSASVGDRVTITCQASQDIRSYLNW



YQQKPGKAPKLLIYDASNLETGVASRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPQTFGQGTKLE



IK





3170
DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNW



YQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTD



FTFTISSLQPEDIATYYCQQYDNLPPTFGGGTKVE



IK





3171
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQRPGKAPKLILYEVTKRPSGVSNRFSGSKSG



NTASLAISGLQAEDEADYYCCSYAGSSTWVFGGGT



KLTVL





3172
QSALTQPASVSGSPGQSITISCTGTSSDVGSYNLV



SWYQQHPGKAPKLMIYEGSKRPSGVSNRFSGSKSG



NTASLTISGLQAEDEADYYCCSYAGSSTWVFGGGT



KLTVL





3173
EIVMTQFPATLSVSPGERATLFCRASQSVGSNLAW



YQQKPGQAPRLLIYGAFTRATGVPARFSGSGSGSE



FSLTISSLQSEDFAVYYCQQYNNWYTFGQGTKLEI



K





3174
EIVMTQSPATLSVSPGERATLSCRASQSVRTNLAW



YQQKRGQAPRLLIYEASTRATGVPDRFSGSGSGTE



FTLTISSLQSEDFAVYYCQQYNNWPPITFGQGTRL



DIK





3175
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNW



YQQKPGKAPKLLIYAASSLQSGVPSRFSASGSGTD



FTLTISSLQPEDFATYYCQQSYSMPPVTFGQGTKV



EIK





3176
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPERFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSTPRTFGQGTKV



EIK





3177
EIVLTQSPGTLSLSPGERATLSCRASQGVSSFLAW



YQQKPGQAPRLLIHGASSRATGIPDRFSGSGSGTD



FTLTITRLEPEDFAVYYCQQYGSSPRTFGQGTKVE



IK





3178
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGTSSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAVYYCQQYGSSPRTFGQGTKV



EIK





3179
DIQLTQSPSSLSASVGDRVTITCRASQGISSYLAW



YQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTD



FTLTISSLQPEDFATYYCQQLNSFGPGTKVDIK





3180
EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLA



WYQQKPGQAPRLLIYGASSRATGIPDRFSGSGSGT



DFTLTISRLEPEDFAMYYCQQYDSSPRTFGQGTKV



EIK









Although the specific embodiments described herein have been described in detail, a person skilled in the art would understand that: Various modifications and changes in the details can be made according to all the teachings disclosed and these changes are within the scope of the protection of the present invention. All of the present invention are given by the appended claims and any equivalents thereof

Claims
  • 1. An antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, and/or wherein the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110.
  • 2. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.
  • 3. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.
  • 4. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935.
  • 5. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935.
  • 6. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR1 comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935.
  • 7. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR1 comprises the same sequence as CDR1 contained in SEQ ID NOs: 721-1080 and 3111-3145.
  • 8. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970.
  • 9. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970.
  • 10. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR2 comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970.
  • 11. The antigen-binding unit of any one of the preceding claims, wherein the VH CDR2 comprises the same sequence as CDR2 contained in SEQ ID NOs: 721-1080 and 3111-3145.
  • 12. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040.
  • 13. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040.
  • 14. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR1 comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040.
  • 15. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR1 comprises the same sequence as CDR1 contained in SEQ ID NOs: 1081-1440 and 3146-3180.
  • 16. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075.
  • 17. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075.
  • 18. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR2 comprises a sequence comprising 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075.
  • 19. The antigen-binding unit of any one of the preceding claims, wherein the VL CDR2 comprises the same sequence as CDR2 contained in SEQ ID NOs: 1081-1440 and 3146-3180.
  • 20. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145.
  • 21. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.
  • 22. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145.
  • 23. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.
  • 24. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180.
  • 25. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.
  • 26. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180.
  • 27. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.
  • 28. An antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935, or the same sequence as CDR1 contained in SEQ ID NOs: 721-1080 and 3111-3145, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970, or the same sequence as CDR2 contained in SEQ ID NOs: 721-1080 and 3111-3145, and wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, or the same sequence as CDR3 contained in SEQ ID NOs: 721-1080 and 3111-3145, and/or wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040, or the same sequence as CDR1 contained in SEQ ID NOs: 1081-1440 and 3146-3180, the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075, or the same sequence as CDR2 contained in SEQ ID NOs: 1081-1440 and 3146-3180, and the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110, a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110, or the same sequence as CDR3 contained in SEQ ID NOs: 1081-1440 and 3146-3180.
  • 29. An antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the heavy chain variable region comprises VH CDR1, VH CDR2 and VH CDR3, and the light chain variable region comprises VL CDR1, VL CDR2 and VL CDR3, wherein the VH CDR1 comprises a sequence selected from SEQ ID NOs: 1461-1820 and 2901-2935 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1461-1820 and 2901-2935, wherein the VH CDR2 comprises a sequence selected from SEQ ID NOs: 1821-2180 and 2936-2970 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1821-2180 and 2936-2970, and wherein the VH CDR3 comprises a sequence selected from SEQ ID NOs: 1-360 and 2971-3005 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1-360 and 2971-3005, and/or wherein the VL CDR1 comprises a sequence selected from SEQ ID NOs: 2181-2540 and 3006-3040 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2181-2540 and 3006-3040, the VL CDR2 comprises a sequence selected from SEQ ID NOs: 2541-2900 and 3041-3075 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 2541-2900 and 3041-3075, and the VL CDR3 comprises a sequence selected from SEQ ID NOs: 361-720 and 3076-3110 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 361-720 and 3076-3110.
  • 30. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145.
  • 31. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.
  • 32. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 721-1080 and 3111-3145.
  • 33. The antigen-binding unit of any one of the preceding claims, wherein the VH comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145.
  • 34. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180 or a sequence comprising one or more amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180.
  • 35. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.
  • 36. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence comprising 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid additions, deletions, or substitutions compared with SEQ ID NOs: 1081-1440 and 3146-3180.
  • 37. The antigen-binding unit of any one of the preceding claims, wherein the VL comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.
  • 38. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.
  • 39. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.
  • 40. An antigen-binding unit comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 721-1080 and 3111-3145, and/or wherein the VL comprises a sequence having at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99% identity to a sequence selected from SEQ ID NOs: 1081-1440 and 3146-3180.
  • 41. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit binds to a receptor binding domain (RBD) of an S protein of a novel coronavirus (SARS-CoV-2) with an equilibrium dissociation constant (KD) of less than 100 nM, less than 50 nM, less than 20 nM, less than 15 nM, less than 10 nM, less than 5 nM, less than 4 nM, less than 3 nM, less than 2 nM, less than 1 nM, less than 0.5 nM, less than 0.1 nM, less than 0.05 nM, or less than 0.01 nM.
  • 42. The antigen-binding unit of any one of the preceding claims, wherein the antigen-binding unit neutralizes the novel coronavirus (SARS-CoV-2) with an IC50 of less than 20 μg/ml, less than 10 μg/ml, less than 9 μg/ml, less than 8 μg/ml, less than 7 μg/ml, less than 6 μg/ml, less than 5 μg/ml, less than 4 μg/ml, less than 3 μg/ml, less than 2 μg/ml, less than 1 μg/ml, less than 0.5 μg/ml, less than 0.25 μg/ml, less than 0.2 μg/ml, less than 0.1 μg/ml, less than 0.05 μg/ml, or less than 0.001 μg/ml.
  • 43. A pharmaceutical composition comprising the antigen-binding unit of any one of claims 1 to 42 and a pharmaceutically acceptable excipient.
  • 44. An isolated nucleic acid encoding the antigen-binding unit of any one of claims 1 to 42.
  • 45. A vector comprising a nucleic acid sequence encoding the antigen-binding unit of any one of claims 1 to 42.
  • 46. A host cell expressing the antigen-binding unit of any one of claims 1 to 42.
  • 47. A host cell comprising a nucleic acid encoding the antigen-binding unit of any one of claims 1 to 42.
  • 48. A method for producing the antigen-binding unit of any one of claims 1 to 42, comprising: culturing the host cell of claim 46 or 47 under conditions suitable for the expression of the antigen-binding unit; and isolating the antigen-binding unit expressed by the host cell.
  • 49. A conjugate comprising the antigen-binding unit of any one of claims 1 to 42, wherein the antigen-binding unit is conjugated to a chemically functional moiety.
  • 50. The conjugate of claim 49, wherein the chemically functional moiety is selected from a radioisotope, an enzyme, a fluorescent compound, a chemiluminescent compound, a bioluminescent compound, a substrate, a cofactor and an inhibitor.
  • 51. A method for preventing and/or treating SARS-CoV-2 infection in a patient in need thereof, comprising administering the antigen-binding unit of any one of claims 1 to 42 or a nucleic acid encoding the antigen-binding unit to the patient.
  • 52. A kit for detecting SARS-CoV-2, comprising the antigen-binding unit of any one of claims 1 to 42.
Priority Claims (1)
Number Date Country Kind
202010352448.5 Apr 2020 CN national
PCT Information
Filing Document Filing Date Country Kind
PCT/CN2021/090146 4/27/2021 WO