Anti-HIV Antibody 10-1074 Variants

Abstract

The present disclosure provides optimized broadly-neutralizing anti-HIV antibodies, having modified light chain variable regions and/or heavy chain variable regions leading to improved biophysical characteristics. The present disclosure also provides methods for producing these anti-HIV antibodies and methods of use thereof.

Description

FIELD OF THE INVENTION

This invention relates generally to broad and potent antibodies against Human Immunodeficiency Virus (“HIV”) and more specifically to anti-HIV antibody 10-1074 variants and the use thereof.

BACKGROUND OF THE INVENTION

HIV causes acquired immunodeficiency syndrome (AIDS), a condition in humans characterized by clinical features including wasting syndromes, central nervous system degeneration and profound immunosuppression that results in life-threatening opportunistic infections and malignancies. Since its discovery in 1981, HIV type 1 (HIV-1) has led to the death of at least 25 million people worldwide. It is predicted that 20-60 million people will become infected over the next two decades even if there is a 2.5% annual decrease in HIV infections. There is a need for therapeutic agents and methods for treatment or inhibition of HIV infection.

Some HIV infected individuals show broadly neutralizing IgG antibodies in their serum. Yet, little is known regarding the specificity and activity of these antibodies, despite their potential importance in designing effective vaccines. In animal models, passive transfer of neutralizing antibodies can contribute to protection against virus challenge. Neutralizing antibody responses also can be developed in HIV-infected individuals, but the detailed composition of the serologic response is yet to be fully uncovered.

SUMMARY OF INVENTION

The present disclosure relates to a new category of broadly-neutralizing anti-HIV antibodies, having modified light chain variable regions and/or heavy chain variable regions leading to improved biophysical characteristics, as well as methods of production and methods of use thereof.

Accordingly, in a first aspect, the present disclosure provides an isolated anti-HIV antibody, or antigen-binding portion thereof, including a light chain variable region having a light chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the light chain variable regions of SEQ ID NOs: 3-13, 22, 24-28, 35-39, 43-45, and 47. The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more light chain substitutions at one or more residues located within or outside the light chain variable region. The one or more residues are selected from the group consisting of LmdV:Y2, LmdV:R7, LmdV:P9, LmdV:E17, LmdV:H46, LmdV:P81.1, LmdV:I81.3, LmdV:N82, LmdV:R88, LmdV:D110, and LmdV:A142.

In another aspect, the present disclosure provides an isolated anti-HIV antibody, or antigen-binding portion thereof, including a heavy chain variable region having a heavy chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94. The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more heavy chain substitutions at one or more residues located within or outside of the heavy chain variable region. The one or more residues are selected from the group consisting of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

In another aspect, the present disclosure provides an isolated anti-HIV antibody, or antigen-binding portion thereof, including a light chain variable region having a light chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the light chain variable regions of SEQ ID NOs: 3-13, 22, 24-28, 35-39, 43-45, and 47. The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more light chain substitutions at one or more residues selected from the group consisting of LmdV:Y2, LmdV:R7, LmdV:P9, LmdV:E17, LmdV:H46, LmdV:P81.1, LmdV:I81.3, LmdV:N82, LmdV:R88, LmdV:D110, and LmdV:A142. The anti-HIV antibody, or antigen-binding portion thereof, further includes a heavy chain variable region having a heavy chain amino acid sequence is at least 75% identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94. The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more heavy chain substitutions at one or more residues selected from the group consisting of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes the one or more light chain substitutions selected from the group consisting of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof (i.e., LmdV:P9C, LmdV:P9T, LmdV:E17N, LmdV:H46N, LmdV:P81.1Q, LmdV:R88C, LmdV:R88S).

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes the one or more heavy chain substitutions selected from the group consisting of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof (i.e., HV:L89W, HV:L89Y, HV:T108H, HV:T108K, HV:K141N).

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof, includes the one or more light chain substitutions selected from the group consisting of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof (i.e., LmdV:P9C, LmdV:P9T, LmdV:E17N, LmdV:H46N, LmdV:P81.1Q, LmdV:R88C, LmdV:R88S) and the one or more heavy chain substitutions selected from the group consisting of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof (i.e., HV:L89W, HV:L89Y, HV:T108H, HV:T108K, HV:K141N).

In some embodiments, the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 3 and includes a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2.

In some embodiments, the heavy chain amino acid sequence is at least 75% identical to to the heavy chain variable region of SEQ ID NO.: 63 and includes an HV:V79T substitution or a conservative substitution of threonine at HV:V79.

In some embodiments, the heavy chain amino acid sequence is at least 75% identical to to the heavy chain variable region of SEQ ID NO.: 64 and includes an HV:R82V substitution or a conservative substitution of valine at HV:R82.

In some embodiments, the heavy chain amino acid sequence is at least 75% identical to to the heavy chain variable region of SEQ ID NO.: 65 and includes an HV:L89F substitution or a conservative substitution of phenylalanine of HV:L89.

In some embodiments, the heavy chain amino acid sequence is at least 75% identical to to the heavy chain variable region of SEQ ID NO.: 66 and includes an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 22 and includes a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 69 and includes an HV:R82V substitution or a conservative substitution of valine at HV:R82, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 70 and includes an HV:V79T substitution or a conservative substitutions of threonine at HV:V79, an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 24 and comprises a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 71 and includes an HV:V79T substitution or a conservative substitution of threonine at HV:V79, an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes SEQ NO.: 3. In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes SEQ NO.: 63, 64, 65, 66, or 70. In some embodiments, the light chain variable region includes the light chain variable region of SEQ NO.: 22 and the heavy chain variable region includes the heavy chain variable region of SEQ No.: 69. In some embodiments, the light chain variable region includes the light chain variable region of SEQ NO.: 24 and the heavy chain variable region includes the heavy chain variable region of SEQ No.: 71.

In another aspect, the present disclosure also provides a pharmaceutical composition having the above-presented anti-HIV antibody or antigen-binding portion and a pharmaceutically acceptable carrier or excipient. In some embodiments, the pharmaceutical composition further includes a second therapeutic agent. In some embodiments, the second therapeutic agent is an anti-HIV-1 broadly neutralizing antibody, such as 3BNC117.

In another aspect, the present disclosure additionally provides a nucleic acid, or a codon-optimized nucleic acid, encoding the above-presented anti-HIV antibody or antigen-binding portion thereof. Also provided is a vector or vector system having at least one above-presented nucleic acid and a cell having at least one above-presented nucleic acid.

In another aspect, the present disclosure provides a method of making recombinant anti-HIV antibody, or antigen-binding portion thereof. The method includes, among others, obtaining the cultured cell mentioned above, culturing the cell in a medium under conditions permitting expression of a polypeptide encoded by the vector and assembling of an antibody or fragment thereof, and purifying the antibody or fragment from the cultured cell or the medium of the cell.

In another aspect, the present disclosure provides a method of preventing or treating an HIV infection or an HIV-related disease. The method includes, among others, identifying a patient in need of such prevention or treatment, and administering to said patient a first therapeutic agent having a therapeutically effective amount of at least one above presented anti-HIV antibody of or an antigen-binding portion thereof. The method can further include administering a second therapeutic agent. The second therapeutic agent can be administered before, concurrently with or after the administration of the anti-HIV antibody or antigen-binding portion thereof. In some embodiments, the second therapeutic agent is an anti-HIV-1 broadly neutralizing antibody, such as 3BNC117.

In another aspect, the present disclosure further provides a kit having a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of at least one isolated anti-HIV antibody presented above or antigen-binding portion thereof. The kit can further include a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of an anti-HIV agent. The two pharmaceutically acceptable dose units can optionally take the form of a single pharmaceutically acceptable dose unit. An exemplary anti-HIV agent can be selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor. In some embodiments, the anti-HIV agent is an anti-HIV broadly neutralizing antibody, such as 3BNC117.

The foregoing summary is not intended to define every aspect of the disclosure, and additional aspects are described in other sections, such as the following detailed description. The entire document is intended to be related as a unified disclosure, and it should be understood that all combinations of features described herein are contemplated, even if the combination of features are not found together in the same sentence, or paragraph, or section of this document. Other features and advantages of the invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the disclosure, are given by way of illustration only, because various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B (collectively “FIG. 1”) show the characterization of anti-HIV antibody 10-1074 variants MS-194 (FIG. 1A) and MS-203 (FIG. 1B) by high-performance size exclusion chromatography (“HP-SEC”) before and after viral neutralization. Peaks in the HP-SEC profiles corresponding to the oligomeric species formed during viral inactivation are indicated by arrows.

FIG. 2 shows quantification of the degree of aggregation represented by the level of high molecular weight (“HMW”) and oligomeric species following each of the purification steps for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203.

FIG. 3 shows the level of HMW during incubation at 40° C. for up to 13 weeks for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203.

FIG. 4 shows the level of sub-visible particle formation during 6 weeks and 13 weeks for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203.

FIGS. 5A, 5B, and 5C (collectively “FIG. 5”) show delayed viral rebound with 3BNC117 and 10-1074 combination therapy during analytical treatment interruption (ATI). FIG. 5A shows the study design of the Phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during ATI. Red and blue triangles represent 3BNC117 and 10-1074 infusions, respectively. FIG. 5B shows plasma HIV-1 RNA levels (black; left y-axis) and bNAb serum concentrations (3BNC117, red; 10-1074, blue; right y-axis) in the 9 bNAb-sensitive participants (left) and the 2 participants with pre-existing resistance against one of the antibodies (right). Red and blue triangles indicate 3BNC117 and 10-1074 infusions, respectively. Serum antibody concentrations were determined by TZM-bl assay. Grey shaded areas indicate time on ART. Lower limit of detection of HIV-1 RNA was 20 copies/ml. FIG. 5C shows Kaplan-Meier plots summarizing time to viral rebound for the participants with HIV-1 RNA<20 copies/ml 2 weeks before and at the start of ATI (n=11, left), for the participants sensitive to both antibodies (n=9, center), and for the participants that showed pre-existing resistance to one of the antibodies (n=2, right). Y-axis indicates percentage of participants that maintain viral suppression. X-axis indicates weeks after start of ATI. Participants receiving the combination of 3BNC117+10-1074 are indicated by the blue line. Dotted red lines indicate a cohort of individuals receiving 3BNC117 alone during ATI (n=13) and dotted black lines indicate a cohort of participants who underwent ATI without intervention (n=52).

FIGS. 6A, 6B, 6C, 6D, 6E, and 6F (collectively “FIG. 6”) show demographics, CD4⁺ T cells during study period in participants and pharamacokinetics of 3BNC117 and 10-1074. FIG. 6A is a table showing baseline participant demographics. *NNRTI—Non-nucleoside reverse transcriptase inhibitor. FIG. 6B shows absolute CD4⁺ T cell counts and percentage of CD4⁺ T cells among CD3⁺ T cells at screening (n=15), day 0 (n=15), at the time of viral rebound (n=13) and at the end of the study are shown (n=15) (see also Supplementary Table 2). The last available time point after resuppression was used as end of the study time point for the participants that reinitiated ART. Red lines indicate mean, and error bars indicate standard deviation. P values were obtained using a two-tailed paired t-test comparing CD4⁺ T cell counts between day 0 and the time of viral rebound. FIGS. 6C and 6D show 3BNC117 (red) and 10-1074 (blue) levels in serum (n=15) as determined by TZM-bl assay (FIG. 6C) and ELISA (FIG. 6D). Curves indicate mean serum antibody concentrations and error bars represent standard deviation. Red and blue triangles indicate 3BNC117 and 10-1074 infusions, respectively. In the TZM-bl assay, lower limits of detection were 0.46 μg/ml and 0.01 μg/ml for 3BNC117 and 10-1074, respectively (FIG. 6C). In the ELISA, lower limits of detection were 0.78 μg/ml and 0.41 μg/ml, respectively (FIG. 6D). In cases where participants only received 2 infusions due to early viral rebound (9245, 9249 and 9253), only antibody concentrations up to the second infusion were included. The half-life of each bNAb is indicated in days. FIGS. 6E and 6F show half-lives of both antibodies as measured by TZM-bl assay (FIG. 6E) and ELISA (FIG. 6F). Each dot represents a single participant. The half-lives of both antibodies from the 15 participants enrolled in the study are represented. Black lines indicate the mean value and standard deviation (n=15). P values were obtained using a two-tailed unpaired t-test comparing the two antibodies.

FIGS. 7A, 7B, and 7C (collectively “FIG. 7”) show amino acid variants at 10-1074 contact sites and bNAb sensitivity of reactivated latent and rebound viruses. FIG. 7A is a set of charts showing Env contact sites of 10-1074 at the G(D/N)IR motif (positions 324-327, according to HXB2 numbering) and the glycan at the potential N-linked glycosylation site at position 332 (N×S/T motif at positions 332-334). The diagram shows the 7 bNAb-sensitive participants that rebounded before week 30 (left) and the 2 individuals with preexisting resistance to one of the 2 antibodies (right). LR indicates latent reservoir viruses isolated by Q²VOA, and RB indicates rebound viruses isolated by SGA (plasma) or viral outgrowth (PBMCs). Each amino acid is represented by a color, and the frequency of each amino acid is indicated by the height of the rectangle. Shaded rectangles indicate the lack of variation between latent reservoir virus and rebound virus at the indicated position. Full-color rectangles represent amino acid residues with changes in distribution between reservoir and rebound viruses. FIGS. 7B and 7C are dot plots indicating IC80 (μg/ml) of 3BNC117 (FIG. 7B, left panel) and 10-1074 (FIG. 7C, right panel) against latent and rebound viruses determined by TZM-bl neutralization assay. Q²VOA-derived latent viruses from week −2 and week 12 are shown as black and grey circles, respectively. For outgrowth culture-derived rebound viruses, the highest IC80 determined is shown as red circle. For 9246, 9252, 9245 and 9251 viruses could not be obtained from rebound outgrowth cultures and pseudoviruses were made from env sequences from Q²VOA and plasma SGA.

FIG. 8 shows a comparison of the circulating latent reservoir and rebound viruses. Maximum likelihood phylogenetic trees of full-length env sequences of viruses isolated from Q²VOA, rebound plasma SGA, and rebound PBMC outgrowth cultures from 3 out of 7 participants (9242, 9243 and 9252) that rebounded before week 30. Open and closed black rectangles indicate Q²VOA-derived viruses from week −2 and week 12, respectively. Viruses obtained at the time of rebound are indicated by red rectangles (plasma SGA) and red stars (rebound PBMC outgrowth cultures). Asterisks indicate nodes with significant bootstrap values (bootstrap support ≥70%). Boxes indicate IC80s (μg/ml) of 3BNC117 and 10-1074 against representative viruses throughout the phylogenetic tree and clones, when possible. Asterisks in boxes indicate IC100 values of >50 μg/ml.

FIGS. 9A and 9B (collectively “FIG. 9”) show distribution of the circulating latent reservoir and rebound viruses. FIG. 9A is a set of Venn diagrams showing sequence identity between env sequences obtained from Q²VOA at week −2 (blue) and week 12 (grey), and plasma SGA or rebound PBMC outgrowth culture at the time of viral rebound (red). Area of overlap is proportional to the number of identical sequences. Number of sequences obtained is indicated. FIG. 9B shows infectious units per million (IUPM) CD4⁺ T cells at weeks −2 and 12 as determined by Q²VOA. Participants with IUPMs higher and lower than 0.1 are shown on the top and bottom, respectively. The 2 time points were not statistically different (P=0.078 (paired t-test)).

DETAILED DESCRIPTION OF THE INVENTION

This disclosure is based, at least in part, on an unexpected discovery of a new category of broadly neutralizing antibodies (bNAbs) against HIV that can recognize carbohydrate-dependent epitopes, including complex-type N-glycan, on gp120.

Antibodies are essential for the success of most vaccines, and antibodies against HIV appear to be the only correlate of protection in the recent RV144 anti-HIV vaccine trial. Some HIV-1 infected patients develop broadly neutralizing serologic activity against the gp160 viral spike 2-4 years after infection, but these antibodies do not generally protect infected humans because autologous viruses escape through mutation. Nevertheless, broadly neutralizing activity puts selective pressure on the virus and passive transfer of broadly neutralizing antibodies (bNAbs) to macaques protects against SHIV infection. It has therefore been proposed that vaccines that elicit such antibodies may be protective against HIV infection in humans.

The development of single cell antibody cloning techniques revealed that bNAbs target several different epitopes on the HIV-1 gp160 spike. The most potent HIV-1 bNAbs recognize the CD4 binding site (CD4bs) (Science 333(6049):1633-1637; Nature 477(7365):466-470; Science 334(6060):1289-1293) and carbohydrate-dependent epitopes associated with the variable loops (Nature 477(7365):466-470; Science 326(5950):285-289; Science 334(6059):1097-1103; Nature 480(7377):336-343), including the V1/V2 (PG9/PG16) (Science 326(5950):285-289) and V3 loops (PGTs) (Nature 477(7365):466-470). Less is known about carbohydrate-dependent epitopes because the antibodies studied to date are either unique examples or members of small clonal families.

To better understand the neutralizing antibody response to HIV-1 and the epitope targeted by PGT antibodies, members of a large clonal family dominating the gp160-specific IgG memory response from the clade A-infected patient who produced PGT121 have been isolated. The isolation of PGT121 is described in greater details in PCT/US13/65696. PGT121 antibodies can be divided into two groups, a PGT121-like and a 10-1074-like group, according to sequence, binding affinity, neutralizing activity and recognition of carbohydrates and the V3 loop. 10-1074 and related family members exhibit unusual potent neutralization, including broad reactivity against newly-transmitted viruses. Unlike previously-characterized carbohydrate-dependent bNAbs, PGT121 binds to complex-type, rather than high-mannose, N-glycans in glycan microarray experiments. The 10-1074 group exhibits remarkable potency and breadth despite not binding detectably to protein-free glycans. Crystal structures of un-liganded PGT121, 10-1074, and their germline precursor reveal that differential carbohydrate recognition maps to a cleft between CDRH2 and CDRH3, which was occupied by a complex-type N-glycan in a separate PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed the importance of these residues in neutralizing activities.

Because the biophysical stability of monoclonal antibodies is an important determinant of their usefulness and commercial value, this disclosure presents the processes to optimize biophysical characteristics of the 10-1074 broadly neutralizing antibody. For example, a series of substitutions were carried out to identify potentially destabilizing residues in the Fv region of the 10-1074 broadly neutralizing antibody. These residues may, by themselves or in combination, lead to instability at low pH, increase susceptibility to chemical degradation, or lead to aggregation during production or long-term storage. Based on this analysis, a series of variants are designed for maintaining potency while optimizing desired characteristics using combinatorial residue replacement techniques. The optimization process is divided into different stages with the first being identification of single residues in the framework region which are potentially responsible for destabilization. Specifically, anti-HIV 10-1074 antibody variants (shown in Tables 2-7 and 9) were produced by transient expression, each containing a single residue modification of the identified amino acids. The variants were characterized for retention of neutralization activity and for desired biophysical characteristics as shown in Tables 8-16. Five distinct amino acid residues, LmdV:Y2, HV:V79, HV:R82, HV:L89, and HV:T108, were identified that showed an increase in desirable biophysical characteristics and did not impact neutralization. The residues were used to produce a library of variants (shown in Tables 2-7 and 12) encompassing all possible combinations of the five amino acids. The variants were again produced by transient expression, and the purified combinatorial variants were analyzed for retention of neutralization activity and desired biophysical characteristics. From the combinatorial library three variants, MS-200, MS-201, and MS-202 were identified for more in-depth analysis including expression, purification, and storage stability to identify combinatorial variants with optimized characteristics which included increased thermal stability, increased resistance to chemical unfolding, increased solubility, and increased resistance to aggregation during storage.

Isolated Anti-HIV Antibodies, Pharmaceutical Compositions, and Kits

Accordingly, in one aspect, this disclosure provides an isolated anti-HIV antibody, or antigen-binding portion thereof, including a light chain variable region having a light chain amino acid sequence that is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to a polypeptide sequence selected from the group consisting of the light chain variable regions of SEQ ID NOs: 3-13, 22, 24-28, 35-39, 43-45, and 47 (Table 2). The isolated anti-HIV antibody, or antigen-binding portion thereof may include one or more light chain substitutions at one or more residues located within or outside the light chain variable region. The residues for substitution are can be one or more of LmdV:Y2, LmdV:R7, LmdV:P9, LmdV:E17, LmdV:H46, LmdV:P81.1, LmdV:I81.3, LmdV:N82, LmdV:R88, LmdV:D110, and LmdV:A142.

Also provided is an isolated anti-HIV antibody, or antigen-binding portion thereof, including a heavy chain variable region having a heavy chain amino acid sequence that is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94 (Table 3). The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more heavy chain substitutions at one or more residues located within or outside of the heavy chain variable region. The residues for substitution can be one or more of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

In another aspect, the present disclosure provides an isolated anti-HIV antibody, or antigen-binding portion thereof, including a light chain variable region having a light chain amino acid sequence that is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to a polypeptide sequence selected from the group consisting of the light chain variable regions of SEQ ID NOs: 3-13, 22, 24-28, 35-39, 43-45, and 47 (Table 2). The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more light chain substitutions at one or more residues of LmdV:Y2, LmdV:R7, LmdV:P9, LmdV:E17, LmdV:H46, LmdV:P81.1, LmdV:I81.3, LmdV:N82, LmdV:R88, LmdV:D110, and LmdV:A142. The anti-HIV antibody, or antigen-binding portion thereof, further includes a heavy chain variable region having a heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94 (Table 3). The isolated anti-HIV antibody, or antigen-binding portion thereof includes one or more heavy chain substitutions at one or more residues of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes the one or more light chain substitutions of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof (i.e., LmdV:P9C, LmdV:P9T, LmdV:E17N, LmdV:H46N, LmdV:P81.1Q, LmdV:R88C, LmdV:R88S).

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes the one or more heavy chain substitutions of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof (i.e., HV:L89W, HV:L89Y, HV:T108H, HV:T108K, HV:K141N).

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof, includes the one or more light chain substitutions of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof (i.e., LmdV:P9C, LmdV:P9T, LmdV:E17N, LmdV:H46N, LmdV:P81.1Q, LmdV:R88C, LmdV:R88S) and the one or more heavy chain substitutions of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof (i.e., HV:L89W, HV:L89Y, HV:T108H, HV:T108K, HV:K141N).

In some embodiments, the light chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the light chain variable region of SEQ ID NO.: 3 and includes a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2.

In some embodiments, the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 63 and includes an HV:V79T substitution or a conservative substitution of threonine at HV:V79.

In some embodiments, the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 64 and includes an HV:R82V substitution or a conservative substitution of valine at HV:R82.

In some embodiments, the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 65 and includes an HV:L89F substitution or a conservative substitution of phenylalanine of HV:L89.

In some embodiments, the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 66 and includes an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the light chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the light chain variable region of SEQ ID NO.: 22 and includes a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 69 and includes an HV:R82V substitution or a conservative substitution of valine at HV:R82, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 70 and includes an HV:V79T substitution or a conservative substitutions of threonine at HV:V79, an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the light chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the light chain variable region of SEQ ID NO.: 24 and comprises a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and the heavy chain amino acid sequence is at least 75% (i.e., 80%, 85%, 90%, 95%, 97%, 98%, 99%) identical to the heavy chain variable region of SEQ ID NO.: 71 and includes an HV:V79T substitution or a conservative substitution of threonine at HV:V79, an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes SEQ NO.: 3. In some embodiments, the isolated anti-HIV antibody, or antigen-binding portion thereof includes SEQ NO.: 63, 64, 65, 66, or 70. In some embodiments, the light chain variable region includes the light chain variable region of SEQ NO.: 22 and the heavy chain variable region includes the heavy chain variable region of SEQ No.: 69. In some embodiments, the light chain variable region includes the light chain variable region of SEQ NO.: 24 and the heavy chain variable region includes the heavy chain variable region of SEQ No.: 71.

Variable domain residue positions are numbered according to the AHo (Honegger, A., & Plückthun, A. (2001). Journal of Molecular Biology, 309(3), 657-70.) structure-based numbering system. An exemplary residue numbering of variable domains of MS-194 is shown in Table 1. The abbreviations used in Table 1 are described as follows. “Ldr” refers leader sequence (e.g., AKA signal sequence or signal peptide). “Mat. Linear” refers to the linear number of the mature form of protein chains. “LmdV” refers variable regions in light chains which are of the lambda type.

The term “antibody” (Ab) as used herein includes monoclonal antibodies, polyclonal antibodies, multispecific antibodies (for example, bispecific antibodies and polyreactive antibodies), and antibody fragments. Thus, the term “antibody” as used in any context within this specification is meant to include, but not be limited to, any specific binding member, immunoglobulin class and/or isotype (e.g., IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD, IgE and IgM); and biologically relevant fragment or specific binding member thereof, including but not limited to Fab, F(ab′)2, Fv, and scFv (single chain or related entity). It is understood in the art that an antibody is a glycoprotein having at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, or an antigen-binding portion thereof. A heavy chain is comprised of a heavy chain variable region (VH) and a heavy chain constant region (CH1, CH2, and CH3). A light chain is comprised of a light chain variable region (VL) and a light chain constant region (CL). The variable regions of both the heavy and light chains comprise framework regions (FWR) and complementarity determining regions (CDR). The four FWR regions are relatively conserved while CDR regions (CDR1, CDR2, and CDR3) represent hypervariable regions and are arranged from NH2 terminus to the COOH terminus as follows: FWR1, CDR1, FWR2, CDR2, FWR3, CDR3, and FWR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen while, depending on the isotype, the constant region(s) may mediate the binding of the immunoglobulin to host tissues or factors.

Also included in the definition of “antibody” as used herein are chimeric antibodies, humanized antibodies, and recombinant antibodies, human antibodies generated from a transgenic non-human animal, as well as antibodies selected from libraries using enrichment technologies available to the artisan.

The term “variable” refers to the fact that certain segments of the variable (V) domains differ extensively in sequence among antibodies. The V domain mediates antigen-binding and defines specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the amino acid span of the variable regions. Instead, the V regions consist of relatively invariant stretches called framework regions (FRs) of 15-30 amino acids separated by shorter regions of extreme variability called “hypervariable regions” that may be 9-12 amino acids long. The variable regions of native heavy and light chains each comprise four FRs, largely adopting a beta-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the beta-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see, for example, Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)).

The term “hypervariable region” as used herein refers to the amino acid residues of an antibody that are responsible for antigen binding. The hypervariable region generally comprises amino acid residues from a “complementarity determining region” (“CDR”).

The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. The term “polyclonal antibody” refers to preparations that include different antibodies directed against different determinants (“epitopes”).

The monoclonal antibodies herein include “chimeric” antibodies in which a portion of the heavy and/or light chain is identical with, or homologous to, corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with, or homologous to, corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see, for example, U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). The described invention provides variable region antigen-binding sequences derived from human antibodies. Accordingly, chimeric antibodies of primary interest herein include antibodies having one or more human antigen-binding sequences (for example, CDRs) and containing one or more sequences derived from a non-human antibody, for example, an FR or C region sequence. In addition, chimeric antibodies included herein are those comprising a human variable region antigen-binding sequence of one antibody class or subclass and another sequence, for example, FR or C region sequence, derived from another antibody class or subclass.

A “humanized antibody” generally is considered to be a human antibody that has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues often are referred to as “import” residues, which typically are taken from an “import” variable region. Humanization may be performed following the method of Winter and co-workers (see, for example, Jones et al., Nature, 321:522-525 (1986); Reichmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting import hypervariable region sequences for the corresponding sequences of a human antibody. Accordingly, such “humanized” antibodies are chimeric antibodies (see, for example, U.S. Pat. No. 4,816,567), where substantially less than an intact human variable region has been substituted by the corresponding sequence from a non-human species.

An “antibody fragment” comprises a portion of an intact antibody, such as the antigen-binding or variable region of the intact antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments; diabodies; linear antibodies (see, for example, U.S. Pat. No. 5,641,870; Zapata et al., Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

“Fv” is the minimum antibody fragment that contains a complete antigen-recognition and antigen-binding site. This fragment contains a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable regions (three loops each from the H and L chain) that contribute the amino acid residues for antigen-binding and confer antigen-binding specificity to the antibody. However, even a single variable region (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

“Single-chain Fv” (“sFv” or “scFv”) are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain. The sFv polypeptide can further comprise a polypeptide linker between the VH and VL domains that enables the sFv to form the desired structure for antigen binding. For a review of sFv, see, for example, Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994); Borrebaeck 1995, infra.

The term “diabodies” refers to small antibody fragments prepared by constructing sFv fragments with short linkers (about 5-10 residues) between the VH and VL domains such that inter-chain but not the intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, i.e., fragment having two antigen-binding sites. Bispecific diabodies are heterodimers of two “crossover” sFv fragments in which the VH and VL domains of the two antibodies are present on different polypeptide chains. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

Domain antibodies (dAbs), which can be produced in fully human form, are the smallest known antigen-binding fragments of antibodies, ranging from about 11 kDa to about 15 kDa. DAbs are the robust variable regions of the heavy and light chains of immunoglobulins (VH and VL, respectively). They are highly expressed in microbial cell culture, show favorable biophysical properties including, for example, but not limited to, solubility and temperature stability, and are well suited to selection and affinity maturation by in vitro selection systems such as, for example, phage display. DAbs are bioactive as monomers and, owing to their small size and inherent stability, can be formatted into larger molecules to create drugs with prolonged serum half-lives or other pharmacological activities. Examples of this technology have been described in, for example, WO9425591 for antibodies derived from Camelidae heavy chain Ig, as well in US20030130496 describing the isolation of single domain fully human antibodies from phage libraries.

Fv and sFv are the only species with intact combining sites that are devoid of constant regions. Thus, they are suitable for reduced nonspecific binding during in vivo use. sFv fusion proteins can be constructed to yield fusion of an effector protein at either the amino or the carboxy terminus of an sFv. See, for example, Antibody Engineering, ed. Borrebaeck, supra. The antibody fragment also can be a “linear antibody,” for example, as described in U.S. Pat. No. 5,641,870 for example. Such linear antibody fragments can be monospecific or bispecific.

In certain embodiments, antibodies of the described invention are bispecific or multispecific. Bispecific antibodies are antibodies that have binding specificities for at least two different epitopes. Exemplary bispecific antibodies can bind to two different epitopes of a single antigen. Other such antibodies can combine a first antigen-binding site with a binding site for a second antigen. Alternatively, an anti-HIV arm can be combined with an arm that binds to a triggering molecule on a leukocyte, such as a T-cell receptor molecule (for example, CD3), or Fc receptors for IgG (Fc gamma R), such as Fc gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16), so as to focus and localize cellular defense mechanisms to the infected cell. Bispecific antibodies also can be used to localize cytotoxic agents to infected cells. Bispecific antibodies can be prepared as full-length antibodies or antibody fragments (for example, F(ab′)2 bispecific antibodies). For example, WO 96/16673 describes a bispecific anti-ErbB2/anti-Fc gamma RIII antibody and U.S. Pat. No. 5,837,234 discloses a bispecific anti-ErbB2/anti-Fc gamma RI antibody. For example, a bispecific anti-ErbB2/Fc alpha antibody is reported in WO98/02463; U.S. Pat. No. 5,821,337 teaches a bispecific anti-ErbB2/anti-CD3 antibody. See also, for example, Mouquet et al., Polyreactivity Increases The Apparent Affinity Of Anti-HIV Antibodies By Heteroligation. Nature. 467, 591-5 (2010), and Mouquet et al., Enhanced HIV-1 neutralization by antibody heteroligation” Proc Natl Acad Sci USA. 2012 Jan. 17; 109(3):875-80.

Methods for making bispecific antibodies are known in the art. Traditional production of full-length bispecific antibodies is based on the co-expression of two immunoglobulin heavy chain-light chain pairs, where the two chains have different specificities (see, for example, Millstein et al., Nature, 305:537-539 (1983)). Similar procedures are disclosed in, for example, WO 93/08829, Traunecker et al., EMBO J., 10:3655-3659 (1991) and see also Mouquet et al., Enhanced HIV-1 neutralization by antibody heteroligation” Proc Natl Acad Sci USA. 2012 Jan. 17; 109(3):875-80.

Alternatively, antibody variable regions with the desired binding specificities (antibody-antigen combining sites) are fused to immunoglobulin constant domain sequences. The fusion is with an Ig heavy chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. According to some embodiments, the first heavy-chain constant region (CH1) containing the site necessary for light chain bonding, is present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors and are co-transfected into a suitable host cell. This provides for greater flexibility in adjusting the mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in the construction provide the optimum yield of the desired bispecific antibody. It is, however, possible to insert the coding sequences for two or all three polypeptide chains into a single expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios have no significant effect on the yield of the desired chain combination.

Techniques for generating bispecific antibodies from antibody fragments also have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. For example, Brennan et al., Science, 229: 81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′)2 fragments. These fragments are reduced in the presence of the dithiol complexing agent, sodium arsenite, to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated then are converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives then is reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

Other modifications of the antibody are contemplated herein. For example, the antibody can be linked to one of a variety of nonproteinaceous polymers, for example, polyethylene glycol, polypropylene glycol, polyoxyalkylenes, or copolymers of polyethylene glycol and polypropylene glycol. The antibody also can be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization (for example, hydroxymethyl cellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively), in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules), or in macroemulsions. Such techniques are disclosed in, for example, Remington's Pharmaceutical Sciences, 16th edition, Oslo, A., Ed., (1980).

Typically, the antibodies of the described invention are produced recombinantly, using vectors and methods available in the art. Human antibodies also can be generated by in vitro activated B cells (see, for example, U.S. Pat. Nos. 5,567,610 and 5,229,275). General methods in molecular genetics and genetic engineering useful in the present disclosure are described in the current editions of Molecular Cloning: A Laboratory Manual (Sambrook, et al., 1989, Cold Spring Harbor Laboratory Press), Gene Expression Technology (Methods in Enzymology, Vol. 185, edited by D. Goeddel, 1991. Academic Press, San Diego, Calif.), “Guide to Protein Purification” in Methods in Enzymology (M. P. Deutscher, ed., (1990) Academic Press, Inc.); PCR Protocols: A Guide to Methods and Applications (Innis et al. 1990. Academic Press, San Diego, Calif.), Culture of Animal Cells: A Manual of Basic Technique, 2nd Ed. (R. I. Freshney. 1987. Liss, Inc. New York, N.Y.), and Gene Transfer and Expression Protocols, pp. 109-128, ed. E. J. Murray, The Humana Press Inc., Clifton, N.J.). Reagents, cloning vectors, and kits for genetic manipulation are available from commercial vendors such as BioRad, Stratagene, Invitrogen, ClonTech and Sigma-Aldrich Co.

Human antibodies also can be produced in transgenic animals (for example, mice) that are capable of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described that the homozygous deletion of the antibody heavy-chain joining region (JH) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array into such germ-line mutant mice results in the production of human antibodies upon antigen challenge. See, for example, Jakobovits et al., Proc. Natl. Acad. Sci. USA, 90:2551 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immuno., 7:33 (1993); U.S. Pat. Nos. 5,545,806, 5,569,825, 5,591,669 (all of GenPharm); U.S. Pat. No. 5,545,807; and WO 97/17852. Such animals can be genetically engineered to produce human antibodies comprising a polypeptide of the described invention.

Various techniques have been developed for the production of antibody fragments. Traditionally, these fragments were derived via proteolytic digestion of intact antibodies (see, for example, Morimoto et al., Journal of Biochemical and Biophysical Methods 24:107-117 (1992); and Brennan et al., Science, 229:81 (1985)). However, these fragments can now be produced directly by recombinant host cells. Fab, Fv and ScFv antibody fragments can all be expressed in and secreted from E. coli, thus allowing the facile production of large amounts of these fragments. Fab′-SH fragments can be directly recovered from E. coli and chemically coupled to form F(ab′)2 fragments (see, for example, Carter et al., Bio/Technology 10:163-167 (1992)). According to another approach, F(ab′)2 fragments can be isolated directly from recombinant host cell culture. Fab and F(ab′)2 fragment with increased in vivo half-life comprising a salvage receptor binding epitope residues are described in U.S. Pat. No. 5,869,046. Other techniques for the production of antibody fragments will be apparent to the skilled practitioner.

Other techniques that are known in the art for the selection of antibody fragments from libraries using enrichment technologies, including but not limited to phage display, ribosome display (Hanes and Pluckthun, 1997, Proc. Nat. Acad. Sci. 94: 4937-4942), bacterial display (Georgiou, et al., 1997, Nature Biotechnology 15: 29-34) and/or yeast display (Kieke, et al., 1997, Protein Engineering 10: 1303-1310) may be utilized as alternatives to previously discussed technologies to select single chain antibodies. Single-chain antibodies are selected from a library of single chain antibodies produced directly utilizing filamentous phage technology. Phage display technology is known in the art (e.g., see technology from Cambridge Antibody Technology (CAT)) as disclosed in U.S. Pat. Nos. 5,565,332; 5,733,743; 5,871,907; 5,872,215; 5,885,793; 5,962,255; 6,140,471; 6,225,447; 6,291650; 6,492,160; 6,521,404; 6,544,731; 6,555,313; 6,582,915; 6,593,081, as well as other U.S. family members, or applications which rely on priority filing GB 9206318, filed 24 May 1992; see also Vaughn, et al. 1996, Nature Biotechnology 14: 309-314). Single chain antibodies may also be designed and constructed using available recombinant DNA technology, such as a DNA amplification method (e.g., PCR), or possibly by using a respective hybridoma cDNA as a template.

Variant antibodies also are included within the scope of the invention. Thus, variants of the sequences recited in the application also are included within the scope of the invention. Further variants of the antibody sequences having improved affinity can be obtained using methods known in the art and are included within the scope of the invention. For example, amino acid substitutions can be used to obtain antibodies with further improved affinity. Alternatively, codon optimization of the nucleotide sequence can be used to improve the efficiency of translation in expression systems for the production of the antibody.

Such variant antibody sequences will share 70% or more (i.e., 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or greater) sequence identity with the sequences disclosed in the application. Such sequence identity is calculated with regard to the full length of the reference sequence (i.e., the sequence recited in the application). Percentage identity, as referred to herein, is as determined using BLAST version 2.1.3 using the default parameters specified by the NCBI (the National Center for Biotechnology Information) [Blosum 62 matrix; gap open penalty=11 and gap extension penalty=1]. For example, peptide sequences provided by this disclosure include at least about 5, 10, 15, 20, 30, 40, 50, 75, 100, 150, or more contiguous peptides of one or more of the sequences disclosed herein as well as all intermediate lengths therebetween. As used herein, the term “intermediate lengths” is meant to describe any length between the quoted values, such as 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, etc.; 21, 22, 23, etc.; 30, 31, 32, etc.; 50, 51, 52, 53, etc.; 100, 101, 102, 103, etc.; 150, 151, 152, 153, etc.

The present disclosure provides for antibodies, either alone or in combination with other antibodies, such as, but not limited to, VRC01, anti-V3 loop, CD4bs, and CD4i antibodies as well as PG9/PG16-like antibodies, that have broad neutralizing activity in serum.

According to another embodiment, the present disclosure provides methods for the preparation and administration of an HIV antibody composition that is suitable for administration to a human or non-human primate patient having HIV infection, or at risk of HIV infection, in an amount and according to a schedule sufficient to induce a protective immune response against HIV, or reduction of the HIV virus, in a human.

According to another embodiment, the present disclosure provides a vaccine comprising at least one antibody of the disclosure and a pharmaceutically acceptable carrier. According to one embodiment, the vaccine is a vaccine comprising at least one antibody described herein and a pharmaceutically acceptable carrier. The vaccine can include a plurality of the antibodies having the characteristics described herein in any combination and can further include antibodies neutralizing to HIV as are known in the art.

It is to be understood that compositions can be a single or a combination of antibodies disclosed herein, which can be the same or different, in order to prophylactically or therapeutically treat the progression of various subtypes of HIV infection after vaccination. Such combinations can be selected according to the desired immunity. When an antibody is administered to an animal or a human, it can be combined with one or more pharmaceutically acceptable carriers, excipients or adjuvants as are known to one of ordinary skilled in the art. The composition can further include broadly neutralizing antibodies known in the art, including but not limited to, VRC01, b12, anti-V3 loop, CD4bs, and CD4i antibodies as well as PG9/PG16-like antibodies.

Further, with respect to determining the effective level in a patient for treatment of HIV, in particular, suitable animal models are available and have been widely implemented for evaluating the in vivo efficacy against HIV of various gene therapy protocols (Sarver et al. (1993b), supra). These models include mice, monkeys, and cats. Even though these animals are not naturally susceptible to HIV disease, chimeric mice models (for example, SCID, bg/nu/xid, NOD/SCID, SCID-hu, immunocompetent SCID-hu, bone marrow-ablated BALB/c) reconstituted with human peripheral blood mononuclear cells (PBMCs), lymph nodes, fetal liver/thymus or other tissues can be infected with lentiviral vector or HIV, and employed as models for HIV pathogenesis. Similarly, the simian immune deficiency virus (SIV)/monkey model can be employed, as can the feline immune deficiency virus (FIV)/cat model. The pharmaceutical composition can contain other pharmaceuticals, in conjunction with a vector according to the invention, when used to therapeutically treat AIDS. These other pharmaceuticals can be used in their traditional fashion (i.e., as agents to treat HIV infection).

According to another embodiment, the present disclosure provides an antibody-based pharmaceutical composition comprising an effective amount of an isolated HIV antibody, or an affinity matured version, which provides a prophylactic or therapeutic treatment choice to reduce infection of the HIV virus. The pharmaceutical composition may further include a second therapeutic agent. In some embodiments, the second therapeutic agent can be an anti-HIV-1 broadly neutralizing antibody. The anti-HIV-1 broadly neutralizing antibody can be one of 10-259, 10-303, 10-410, 10-847, 10-996, 10-1121, 10-1130, 10-1146, 10-1341, 10-1369, 10-1074GM, GL, 10E8, 12A12, 12A21, 2F5, 2G12, 35022, 3BC176, 3BNC117, 3BNC55, 3BNC60, 3BNC62, 447-52D, 4E10, 5H/11-BMV-D5, 8ANC195, b12, CAP256-VRC26.01, CAP256-VRC26.02, CAP256-VRC26.03, CAP256-VRC26.04, CAP256-VRC26.05, CAP256-VRC26.06, CAP256-VRC26.07, CAP256-VRC26.08, CAP256-VRC26.09, CAP256-VRC26.10, CAP256-VRC26.11, CAP256-VRC26.12, CH01, CH02, CH03, CH04, CH103, HGN194, HJ16, HK20, M66.6, NIH45-46, PCDN-33A, PCDN-33B, PCDN-38A, PG9, PG16, PGDM1400, PGDM1401, PGDM1402, PGDM1403, PGDM1404, PGDM1405, PGDM1406, PGDM1407, PGDM1408, PGDM1409, PGDM1410, PGDM1411, PGDM1412, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT145, PGT151, PGT152, VRC-CH30, VRC-CH31, VRC-CH32, VRC-CH33, VRC-CH34, VRC-PG04, VRC-CH04b, VRC-PG20, VRC01, VRC02, VRC03, VRC07, VRC23, and Z13. In some embodiments, the anti-HIV-1 broadly neutralizing antibody is 3BNC117. 3BNC117 is a next-generation bNAb that targets the CD4 binding site on HIV envelope gp160. It is a recombinant human IgG1 kappa monoclonal antibody cloned from an HIV-infected viremic controller. A long-acting version of 3BNC117 is known as 3BNC117-LS. 3BNC117 was described in US patent U.S. Pat. No. 9,783,594.

The antibody-based pharmaceutical composition of the present disclosure may be formulated by any number of strategies known in the art (e.g., see McGoff and Scher, 2000, Solution Formulation of Proteins/Peptides: In McNally, E. J., ed. Protein Formulation and Delivery. New York, N.Y.: Marcel Dekker; pp. 139-158; Akers and Defilippis, 2000, Peptides and Proteins as Parenteral Solutions. In: Pharmaceutical Formulation Development of Peptides and Proteins. Philadelphia, Pa.: Talyor and Francis; pp. 145-177; Akers et al., 2002, Pharm. Biotechnol. 14:47-127). A pharmaceutically acceptable composition suitable for patient administration will contain an effective amount of the antibody in a formulation which both retains biological activity while also promoting maximal stability during storage within an acceptable temperature range. The pharmaceutical compositions can also include, depending on the formulation desired, pharmaceutically acceptable diluents, pharmaceutically acceptable carriers and/or pharmaceutically acceptable excipients, or any such vehicle commonly used to formulate pharmaceutical compositions for animal or human administration. The diluent is selected so as not to affect the biological activity of the combination. Examples of such diluents are distilled water, physiological phosphate-buffered saline, Ringer's solutions, dextrose solution, and Hank's solution. The amount of an excipient that is useful in the pharmaceutical composition or formulation of this disclosure is an amount that serves to uniformly distribute the antibody throughout the composition so that it can be uniformly dispersed when it is to be delivered to a subject in need thereof. It may serve to dilute the antibody to a concentration which provides the desired beneficial palliative or curative results while at the same time minimizing any adverse side effects that might occur from too high a concentration. It may also have a preservative effect. Thus, for the antibody having high physiological activity, more of the excipient will be employed. On the other hand, for any active ingredient(s) that exhibit a lower physiological activity, a lesser quantity of the excipient will be employed.

The above-described antibodies and antibody compositions or vaccine compositions, comprising at least one or a combination of the antibodies described herein, can be administered for the prophylactic and therapeutic treatment of HIV viral infection.

The present disclosure also relates to isolated polypeptides comprising the novel amino acid sequences of the light chain regions and heavy chain variable regions, listed in Tables 2-3. In other related embodiments, this disclosure provides polypeptide variants having the amino acid sequences of the light chain regions and heavy chain variable regions of the HIV antibodies that share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or greater sequence identity compared to a polypeptide sequence, listed in Tables 2-3, as determined using the methods described herein (i.e., BLAST analysis using standard parameters). One skilled in this art will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by taking into amino acid similarity and the like. In other related embodiments, this disclosure provides polypeptide variants having the amino acid sequences of the light chain regions and heavy chain variable regions of the HIV antibodies that share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or greater sequence identity compared to a polypeptide sequence, listed in Tables 2-3, and having the amino acid sequences of the CDR regions identical or substantially identical to those listed in Table 4 or to the amino acid sequences of the CDR regions of the unmodified 10-1074-LS antibody (or MS-193). In other related embodiments, this disclosure provides polypeptide variants having the amino acid sequences of the light chain regions and heavy chain variable regions of the HIV antibodies that share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or greater sequence identity compared to a polypeptide sequence, listed in Tables 2-3, and having the amino acid sequences of the CDR regions identical or substantially identical to those listed in Table 4 or to the amino acid sequences of the CDR regions of the unmodified 10-1074-LS antibody (or MS-193), such that polypeptide variants retain 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%, or greater binding affinity to the HIV virus. The term “substantially identical” refers to the identity of a sequence to another sequence greater than about 85%.

The term “polypeptide” is used in its conventional meaning, i.e., as a sequence of amino acids. The polypeptides are not limited to a specific length of the product. Peptides, oligopeptides, and proteins are included within the definition of polypeptide, and such terms can be used interchangeably herein unless specifically indicated otherwise. This term also includes post-expression modifications of the polypeptide, for example, glycosylations, acetylations, phosphorylations and the like, as well as other modifications known in the art, both naturally occurring and non-naturally occurring. A polypeptide can be an entire protein or a subsequence thereof. Particular polypeptides of interest in the context of this disclosure are amino acid subsequences comprising CDRs, VH, and VL, being capable of binding an antigen or HIV-infected cell.

A polypeptide “variant,” as the term is used herein, is a polypeptide that typically differs from a polypeptide specifically disclosed herein in one or more substitutions, deletions, additions and/or insertions. Such variants can be naturally occurring or can be synthetically generated, for example, by modifying one or more of the above polypeptide sequences of the disclosure and evaluating one or more biological activities of the polypeptide as described herein and/or using any of some techniques well known in the art.

For example, certain amino acids can be substituted for other amino acids in a protein structure without appreciable loss of its ability to bind other polypeptides (for example, antigens) or cells. Since it is the binding capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid sequence substitutions can be made in a protein sequence, and, accordingly, its underlying DNA coding sequence, whereby a protein with like properties is obtained. It is thus contemplated that various changes can be made in the peptide sequences of the disclosed compositions, or corresponding DNA sequences that encode said peptides without appreciable loss of their biological utility or activity.

Variant antibody sequences include those wherein conservative substitutions have been introduced by modification of polynucleotides encoding polypeptides of the invention. Amino acids can be classified according to physical properties and contribution to secondary and tertiary protein structure. A “conservative substitution” is recognized in the art as a substitution of one amino acid for another amino acid that has similar properties. Exemplary conservative substitutions are set out below:

CONSERVATIVE SUBSTITUTION I
Side chain characteristic Amino acid
Aliphatic
Non-polar                 G A P I L V
Polar - uncharged         C S T M N Q
Polar - charged           D E K R
Aromatic                  H F W Y
Other                     N Q D E

Alternatively, conservative amino acids can be grouped as described in Lehninger, [Biochemistry, Second Edition; Worth Publishers, Inc. NY, N.Y. (1975), pp. 71-77] as set out below:

CONSERVATIVE SUBSTITUTION II
Side chain characteristic    Amino acid
Non-polar (hydrophobic)
A. Aliphatic:                A L I V P
B. Aromatic:                 F W
C. Sulfur-containing:        M
D. Borderline:               G
Uncharged-polar
A. Hydroxyl:                 S T Y
B. Amides:                   N Q
C. Sulfhydryl:               C
D. Borderline:               G
Positively Charged (Basic):  K R H
Negatively Charged (Acidic): D E

As still another alternative, exemplary conservative substitutions are set out below:

CONSERVATIVE SUBSTITUTIONS III
Original residue Exemplary substitution
Ala (A)          Val, Leu, Ile
Arg (R)          Lys, Gln, Asn
Asn (N)          Gln, His, Lys, Arg
Asp (D)          Glu
Cys (C)          Ser
Gln (Q)          Asn
Glu (E)          Asp
His (H)          Asn, Gln, Lys, Arg
Ile (I)          Leu, Val, Met, Ala, Phe,
Leu (L)          Ile, Val, Met, Ala, Phe
Lys (K)          Arg, Gln, Asn
Met (M)          Leu, Phe, Ile
Phe (F)          Leu, Val, Ile, Ala
Pro (P)          Gly
Ser (S)          Thr
Thr (T)          Ser
Trp (W)          Tyr
Tyr (Y)          Trp, Phe, Thr, Ser
Val (V)          Ile, Leu, Met, Phe, Ala

A conservative substitution of an existing substitution refers to a conservative substitution of the substituting residue. For example, a conservative substitution of LmdV:Y2P refers to a conservative substitution (i.e., glycine (G)) of proline (P) at position LmdV:Y2. In another example, a conservative substitution of HV:V79T refers to a conservative substitution (i.e., serine (S), cysteine (C)) of threonine (T) at position HV:V79.

“Homology” or “sequence identity” refers to the percentage of residues in the polynucleotide or polypeptide sequence variant that are identical to the non-variant sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. In particular embodiments, polynucleotide and polypeptide variants have at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% polynucleotide or polypeptide homology with a polynucleotide or polypeptide described herein.

Such variant polypeptide sequences will share 70% or more (i.e. 80%, 85%, 90%, 95%, 97%, 98%, 99% or more) sequence identity with the sequences recited in the application. In additional embodiments, the described invention provides polypeptide fragments comprising various lengths of contiguous stretches of amino acid sequences disclosed herein. For example, peptide sequences provided by this disclosure include at least about 5, 10, 15, 20, 30, 40, 50, 75, 100, 150, or more contiguous peptides of one or more of the sequences disclosed herein as well as all intermediate lengths therebetween.

The disclosure also includes nucleic acid sequences encoding part or all of the light and heavy chains of the described inventive antibodies, and fragments thereof. Due to the redundancy of the genetic code, variants of these sequences will exist that encode the same amino acid sequences.

The present disclosure also includes isolated nucleic acid sequences encoding the polypeptides for the light and heavy chains of the HIV antibodies listed in Tables 2-3. In other related embodiments, the described invention provides polynucleotide variants that encode the peptide sequences of the heavy and light chains of the HIV antibodies listed in Tables 5-6. These polynucleotide variants have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, or greater, sequence identity compared to a polynucleotide sequence of this disclosure, as determined using the methods described herein (i.e., BLAST analysis using standard parameters). One skilled in this art will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning, and the like.

The terms “nucleic acid” and “polynucleotide” are used interchangeably herein to refer to single-stranded or double-stranded RNA, DNA, or mixed polymers. Polynucleotides can include genomic sequences, extra-genomic and plasmid sequences, and smaller engineered gene segments that express, or can be adapted to express polypeptides.

An “isolated nucleic acid” is a nucleic acid that is substantially separated from other genome DNA sequences as well as proteins or complexes such as ribosomes and polymerases, which naturally accompany a native sequence. The term encompasses a nucleic acid sequence that has been removed from its naturally occurring environment and includes recombinant or cloned DNA isolates and chemically synthesized analogs or analogs biologically synthesized by heterologous systems. A substantially pure nucleic acid includes isolated forms of the nucleic acid. Accordingly, this refers to the nucleic acid as originally isolated and does not exclude genes or sequences later added to the isolated nucleic acid by the hand of man.

A polynucleotide “variant,” as the term is used herein, is a polynucleotide that typically differs from a polynucleotide specifically disclosed herein in one or more substitutions, deletions, additions and/or insertions. Such variants can be naturally occurring or can be synthetically generated, for example, by modifying one or more of the polynucleotide sequences of the disclosure and evaluating one or more biological activities of the encoded polypeptide as described herein and/or using any of some techniques well known in the art.

Modifications can be made in the structure of the polynucleotides of the described invention and still obtain a functional molecule that encodes a variant or derivative polypeptide with desirable characteristics. When it is desired to alter the amino acid sequence of a polypeptide to create an equivalent or even an improved, variant or portion of a polypeptide of the invention, one skilled in the art typically will change one or more of the codons of the encoding DNA sequence.

Typically, polynucleotide variants contain one or more substitutions, additions, deletions and/or insertions, such that the immunogenic binding properties of the polypeptide encoded by the variant polynucleotide is not substantially diminished relative to a polypeptide encoded by a polynucleotide sequence specifically set forth herein.

In additional embodiments, the described invention provides polynucleotide fragments comprising various lengths of contiguous stretches of sequence identical to or complementary to one or more of the sequences disclosed herein. For example, polynucleotides are provided by this disclosure that comprise at least about 10, 15, 20, 30, 40, 50, 75, 100, 150, 200, 300, 400, 500 or 1000 or more contiguous nucleotides of one or more of the sequences disclosed herein as well as all intermediate lengths therebetween and encompass any length between the quoted values, such as 16, 17, 18, 19, etc.; 21, 22, 23, etc.; 30, 31, 32, etc.; 50, 51, 52, 53, etc.; 100, 101, 102, 103, etc.; 150, 151, 152, 153, etc.; and including all integers through 200-500; 500-1,000.

In another embodiment of the invention, polynucleotide compositions are provided that are capable of hybridizing under moderate to high stringency conditions to a polynucleotide sequence provided herein, or a fragment thereof, or a complementary sequence thereof. Hybridization techniques are well known in the art of molecular biology. For purposes of illustration, suitable moderately stringent conditions for testing the hybridization of a polynucleotide of this disclosure with other polynucleotides include prewashing in a solution of 5×SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50-60° C., 5×SSC, overnight; followed by washing twice at 65° C. for 20 minutes with each of 2×, 0.5×, and 0.2×SSC containing 0.1% SDS. One skilled in the art will understand that the stringency of hybridization can be readily manipulated, such as by altering the salt content of the hybridization solution and/or the temperature at which the hybridization is performed. For example, in another embodiment, suitable highly stringent hybridization conditions include those described above, with the exception that the temperature of hybridization is increased, for example, to 60-65° C. or 65-70° C.

In some embodiments, the polypeptide encoded by the polynucleotide variant or fragment has the same binding specificity (i.e., specifically or preferentially binds to the same epitope or HIV strain) as the polypeptide encoded by the native polynucleotide. In some embodiments, the described polynucleotides, polynucleotide variants, fragments, and hybridizing sequences, encode polypeptides that have a level of binding activity of at least about 50%, at least about 70%, and at least about 90% of that for a polypeptide sequence specifically set forth herein.

The polynucleotides of the described invention, or fragments thereof, regardless of the length of the coding sequence itself, can be combined with other DNA sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length can vary considerably. A nucleic acid fragment of almost any length is employed. For example, illustrative polynucleotide segments with total lengths of about 10000, about 5000, about 3000, about 2000, about 1000, about 500, about 200, about 100, about 50 base pairs in length, and the like, (including all intermediate lengths) are included in many implementations of this invention.

Further included within the scope of the invention are vectors such as expression vectors, comprising a nucleic acid sequence according to the invention. Cells transformed with such vectors also are included within the scope of the invention.

The present disclosure also provides vectors and host cells comprising a nucleic acid of the invention, as well as recombinant techniques for the production of a polypeptide of the invention. Vectors of the invention include those capable of replication in any type of cell or organism, including, for example, plasmids, phage, cosmids, and minichromosomes. In some embodiments, vectors comprising a polynucleotide of the described invention are vectors suitable for propagation or replication of the polynucleotide, or vectors suitable for expressing a polypeptide of the described invention. Such vectors are known in the art and commercially available.

“Vector” includes shuttle and expression vectors. Typically, the plasmid construct also will include an origin of replication (for example, the ColE1 origin of replication) and a selectable marker (for example, ampicillin or tetracycline resistance), for replication and selection, respectively, of the plasmids in bacteria. An “expression vector” refers to a vector that contains the necessary control sequences or regulatory elements for expression of the antibodies including antibody fragment of the invention, in bacterial or eukaryotic cells.

As used herein, the term “cell” can be any cell, including, but not limited to, that of a eukaryotic, multicellular species (for example, as opposed to a unicellular yeast cell), such as, but not limited to, a mammalian cell or a human cell. A cell can be present as a single entity or can be part of a larger collection of cells. Such a “larger collection of cells” can comprise, for example, a cell culture (either mixed or pure), a tissue (for example, endothelial, epithelial, mucosa or other tissue), an organ (for example, lung, liver, muscle and other organs), an organ system (for example, circulatory system, respiratory system, gastrointestinal system, urinary system, nervous system, integumentary system or other organ system), or an organism (e.g., a bird, mammal, or the like).

Polynucleotides of the invention may be synthesized, in whole or in parts that are then combined, and inserted into a vector using routine molecular and cell biology techniques, including, for example, subcloning the polynucleotide into a linearized vector using appropriate restriction sites and restriction enzymes. Polynucleotides of the described invention are amplified by polymerase chain reaction using oligonucleotide primers complementary to each strand of the polynucleotide. These primers also include restriction enzyme cleavage sites to facilitate subcloning into a vector. The replicable vector components generally include but are not limited to, one or more of the following: a signal sequence, an origin of replication, and one or more marker or selectable genes.

In order to express a polypeptide of the invention, the nucleotide sequences encoding the polypeptide, or functional equivalents, may be inserted into an appropriate expression vector, i.e., a vector that contains the necessary elements for the transcription and translation of the inserted coding sequence. Methods well known to those skilled in the art may be used to construct expression vectors containing sequences encoding a polypeptide of interest and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. Such techniques are described, for example, in Sambrook, J. et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Plainview, N.Y., and Ausubel, F. M. et al. (1989) Current Protocols in Molecular Biology, John Wiley & Sons, New York. N.Y.

The present disclosure also provides kits useful in performing diagnostic and prognostic assays using the antibodies, polypeptides and nucleic acids of the present invention. Kits of the present invention include a suitable container comprising an HIV antibody, a polypeptide or a nucleic acid of the invention in either labeled or unlabeled form. In addition, when the antibody, polypeptide or nucleic acid is supplied in a labeled form suitable for an indirect binding assay, the kit further includes reagents for performing the appropriate indirect assay. For example, the kit may include one or more suitable containers including enzyme substrates or derivatizing agents, depending on the nature of the label. Control samples and/or instructions may also be included. The present disclosure also provides kits for detecting the presence of the HIV antibodies or the nucleotide sequence of the HIV antibody of the present disclosure in a biological sample by PCR or mass spectrometry.

In some embodiments, the kit includes a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of at least one isolated anti-HIV antibody described herein or antigen-binding portion thereof. The kit can further include a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of an anti-HIV agent. The two pharmaceutically acceptable dose units can optionally take the form of a single pharmaceutically acceptable dose unit. An exemplary anti-HIV agent can be selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor. In some embodiments, the anti-HIV agent is an anti-HIV broadly neutralizing antibody, such as 3BNC117.

“Label” as used herein refers to a detectable compound or composition that is conjugated directly or indirectly to the antibody so as to generate a “labeled” antibody. A label can also be conjugated to a polypeptide and/or a nucleic acid sequence disclosed herein. The label can be detectable by itself (for example, radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, can catalyze chemical alteration of a substrate compound or composition that is detectable. Antibodies and polypeptides of the described invention also can be modified to include an epitope tag or label, for example, for use in purification or diagnostic applications. Suitable detection means include the use of labels such as, but not limited to, radionucleotides, enzymes, coenzymes, fluorescers, chemiluminescers, chromogens, enzyme substrates or co-factors, enzyme inhibitors, prosthetic group complexes, free radicals, particles, dyes, and the like.

According to another embodiment, the present disclosure provides diagnostic methods. Diagnostic methods generally involve contacting a biological sample obtained from a patient, such as, for example, blood, serum, saliva, urine, sputum, a cell swab sample, or a tissue biopsy, with an HIV antibody and determining whether the antibody preferentially binds to the sample as compared to a control sample or predetermined cut-off value, thereby indicating the presence of the HIV virus.

According to another embodiment, the present disclosure provides methods to detect the presence of the HIV antibodies of the present disclosure in a biological sample from a patient. Detection methods generally involve obtaining a biological sample from a patient, such as, for example, blood, serum, saliva, urine, sputum, a cell swab sample, or a tissue biopsy and isolating HIV antibodies or fragments thereof, or the nucleic acids that encode an HIV antibody, and assaying for the presence of an HIV antibody in the biological sample. Also, the present disclosure provides methods to detect the nucleotide sequence of an HIV antibody in a cell. The nucleotide sequence of an HIV antibody may also be detected using the primers disclosed herein. The presence of the HIV antibody in a biological sample from a patient may be determined by utilizing known recombinant techniques and/or the use of a mass spectrometer.

In another embodiment, the present disclosure provides a method for detecting an HIV antibody comprising a heavy chain comprising a highly conserved consensus sequence and a light chain comprising a highly conserved consensus sequence in a biological sample, comprising obtaining an immunoglobulin-containing biological sample from a mammalian subject, isolating an HIV antibody from said sample, and identifying the highly conserved consensus sequences of the heavy chain and the light chain. The biological sample may be blood, serum, saliva, urine, sputum, a cell swab sample, or a tissue biopsy. The amino acid sequences may be determined by methods known in the art including, for example, PCR and mass spectrometry.

The term “assessing” includes any form of measurement, and includes determining if an element is present or not. The terms “determining,” “measuring,” “evaluating,” “assessing” and “assaying” are used interchangeably and include quantitative and qualitative determinations. Assessing may be relative or absolute. “Assessing the presence of” includes determining the amount of something present, and/or determining whether it is present or absent. As used herein, the terms “determining,” “measuring,” and “assessing,” and “assaying” are used interchangeably and include both quantitative and qualitative determinations.

Method of Reducing Viral Replication

Methods for reducing an increase in HIV virus titer, virus replication, virus proliferation or an amount of an HIV viral protein in a subject are further provided. According to another aspect, a method includes administering to the subject an amount of an HIV antibody effective to reduce an increase in HIV titer, virus replication or an amount of an HIV protein of one or more HIV strains or isolates in the subject.

According to another embodiment, the present disclosure provides a method of reducing viral replication or spread of HIV infection to additional host cells or tissues comprising contacting a mammalian cell with the antibody, or a portion thereof, which binds to an antigenic epitope on gp120.

Method of Treatment

According to another embodiment, the present disclosure provides a method for treating a mammal infected with a virus infection, such as, for example, HIV, comprising administering to said mammal a pharmaceutical composition comprising the HIV antibodies disclosed herein. According to one embodiment, the method for treating a mammal infected with HIV comprises administering to said mammal a pharmaceutical composition that comprises an antibody of the present disclosure, or a fragment thereof. The compositions of the disclosure can include more than one antibody having the characteristics disclosed (for example, a plurality or pool of antibodies). It also can include other HIV neutralizing antibodies as are known in the art, for example, but not limited to, 10-259, 10-303, 10-410, 10-847, 10-996, 10-1121, 10-1130, 10-1146, 10-1341, 10-1369, 10-1074GM, GL, 10E8, 12A12, 12A21, 2F5, 2G12, 35022, 3BC176, 3BNC117, 3BNC55, 3BNC60, 3BNC62, 447-52D, 4E10, 5H/11-BMV-D5, 8ANC195, b12, CAP256-VRC26.01, CAP256-VRC26.02, CAP256-VRC26.03, CAP256-VRC26.04, CAP256-VRC26.05, CAP256-VRC26.06, CAP256-VRC26.07, CAP256-VRC26.08, CAP256-VRC26.09, CAP256-VRC26.10, CAP256-VRC26.11, CAP256-VRC26.12, CH01, CH02, CH03, CH04, CH103, HGN194, HJ16, HK20, M66.6, NIH45-46, PCDN-33A, PCDN-33B, PCDN-38A, PG9, PG16, PGDM1400, PGDM1401, PGDM1402, PGDM1403, PGDM1404, PGDM1405, PGDM1406, PGDM1407, PGDM1408, PGDM1409, PGDM1410, PGDM1411, PGDM1412, PGT121, PGT122, PGT123, PGT125, PGT126, PGT127, PGT128, PGT130, PGT131, PGT135, PGT136, PGT137, PGT141, PGT142, PGT143, PGT145, PGT151, PGT152, VRC-CH30, VRC-CH31, VRC-CH32, VRC-CH33, VRC-CH34, VRC-PG04, VRC-CH04b, VRC-PG20, VRC01, VRC02, VRC03, VRC07, VRC23, and Z13.

The method can further include administering a second therapeutic agent, such as a therapeutically effective amount of the second therapeutic agent. The second therapeutic agent can be administered before, concurrently with or after the administration of the anti-HIV antibody or antigen-binding portion thereof. In some embodiments, the second therapeutic agent is an anti-HIV-1 broadly neutralizing antibody. Examples of anti-HIV-1 broadly neutralizing antibodies are provided above. In some embodiments, the anti-HIV-1 broadly neutralizing antibody is 3BNC117.

Passive immunization has proven to be an effective and safe strategy for the prevention and treatment of viral diseases. (See, for example, Keller et al., Clin. Microbiol. Rev. 13:602-14 (2000); Casadevall, Nat. Biotechnol. 20:114 (2002); Shibata et al., Nat. Med. 5:204-10 (1999); and Igarashi et al., Nat. Med. 5:211-16 (1999). Passive immunization using human monoclonal antibodies provides an immediate treatment strategy for emergency prophylaxis and treatment of HIV.

Subjects at risk for HIV-related diseases or disorders include patients who have come into contact with an infected person or who have been exposed to HIV in some other way. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of HIV-related disease or disorder, such that a disease or disorder is prevented or, alternatively, delayed in its progression.

For in vivo treatment of human and non-human patients, the patient is administered or provided a pharmaceutical formulation including an HIV antibody of this disclosure. When used for in vivo therapy, the antibodies of this disclosure are administered to the patient in therapeutically effective amounts (i.e., amounts that eliminate or reduce the patient's viral burden). The antibodies are administered to a human patient, in accord with known methods, such as intravenous administration, for example, as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intracerobrospinal, subcutaneous, intraarticular, intrasynovial, intrathecal, oral, topical, or inhalation routes. The antibodies can be administered parenterally, when possible, at the target cell site, or intravenously. In some embodiments, the antibody is administered by an intravenous or subcutaneous administration. Therapeutic compositions of the disclosure may be administered to a patient or subject systemically, parenterally, or locally. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician.

For parenteral administration, the antibodies may be formulated in a unit dosage injectable form (solution, suspension, emulsion) in association with a pharmaceutically acceptable, parenteral vehicle. Examples of such vehicles include, but are not limited, water, saline, Ringer's solution, dextrose solution, and 5% human serum albumin. Nonaqueous vehicles include, but are not limited to, fixed oils and ethyl oleate. Liposomes can be used as carriers. The vehicle may contain minor amounts of additives such as substances that enhance isotonicity and chemical stability, such as, for example, buffers and preservatives. The antibodies can be formulated in such vehicles at concentrations of about 1 mg/ml to 150 mg/ml.

The dose and dosage regimen depends upon a variety of factors readily determined by a physician, such as the nature of the infection, for example, its therapeutic index, the patient, and the patient's history. Generally, a therapeutically effective amount of an antibody is administered to a patient. In some embodiments, the amount of antibody administered is in the range of about 0.1 mg/kg to about 50 mg/kg of patient body weight. Depending on the type and severity of the infection, about 0.1 mg/kg to about 50 mg/kg body weight (for example, about 0.1-15 mg/kg/dose) of antibody is an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion. The progress of this therapy is readily monitored by conventional methods and assays and based on criteria known to the physician or other persons of skill in the art. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician.

Other therapeutic regimens may be combined with the administration of the HIV antibody of the present disclosure. The combined administration includes co-administration, using separate formulations or a single pharmaceutical formulation, and consecutive administration in either order, wherein preferably there is a time period while both (or all) active agents simultaneously exert their biological activities. Such combined therapy can result in a synergistic therapeutic effect. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician.

The terms “treating” or “treatment” or “alleviation” are used interchangeably and refer to both therapeutic treatment and prophylactic or preventative measures; wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented. A subject or mammal is successfully “treated” for an infection if, after receiving a therapeutic amount of an antibody according to the methods of the present disclosure, the patient shows observable and/or measurable reduction in or absence of one or more of the following: reduction in the number of infected cells or absence of the infected cells; reduction in the percent of total cells that are infected; and/or relief to some extent, one or more of the symptoms associated with the specific infection; reduced morbidity and mortality, and improvement in quality of life issues. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician.

The term “effective amount,” “effective dose,” or “effective dosage” is defined as an amount sufficient to achieve or at least partially achieve a desired effect. A “therapeutically effective amount” or “therapeutically effective dosage” of a drug or therapeutic agent is any amount of the drug that, when used alone or in combination with another therapeutic agent, promotes disease regression evidenced by a decrease in severity of disease symptoms, an increase in frequency and duration of disease symptom-free periods, or a prevention of impairment or disability due to the disease affliction. A “prophylactically effective amount” or a “prophylactically effective dosage” of a drug is an amount of the drug that, when administered alone or in combination with another therapeutic agent to a subject at risk of developing a disease or of suffering a recurrence of disease, inhibits the development or recurrence of the disease. The ability of a therapeutic or prophylactic agent to promote disease regression or inhibit the development or recurrence of the disease can be evaluated using a variety of methods known to the skilled practitioner, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by assaying the activity of the agent in in vitro assays.

Administration “in combination with” one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order.

“Carriers” as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers that are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable carriers include, but not limited to, buffers such as phosphate, citrate, acetate and other organic acids; antioxidants including, but not limited to, ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as, but not limited to, serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as, but not limited to, polyvinylpyrrolidone; amino acids such as, but not limited to, glycine, glutamine, asparagine, arginine, proline or lysine; monosaccharides, disaccharides, and other carbohydrates including, but not limited to, glucose, mannose, or dextrins; chelating agents such as, but not limited to, EDTA; sugar alcohols such as, but not limited to, mannitol, sorbitol, sucrose or trehalose; salt-forming counterions such as, but not limited to, sodium; and/or nonionic surfactants such as, but not limited to, TWEEN; polyethylene glycol (PEG), poloxamers, i.e. Pluronic F-68 and polysorbates, i.e. polysorbate 20 or polysorbate 80

Definitions

To aid in understanding the detailed description of the compositions and methods according to the disclosure, a few express definitions are provided to facilitate an unambiguous disclosure of the various aspects of the disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

The term “recombinant” when made in reference to a nucleic acid molecule refers to a nucleic acid molecule which is comprised of segments of nucleic acid joined together by means of molecular biological techniques. The term “recombinant,” when made in reference to a protein or a polypeptide, refers to a protein molecule which is expressed using a recombinant nucleic acid molecule.

The term “operably linked” refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.

As used herein, the term “in vitro” refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, etc., rather than within a multi-cellular organism.

As used herein, the term “in vivo” refers to events that occur within a multi-cellular organism such as a non-human animal.

The terms “prevent,” “preventing,” “prevention,” “prophylactic treatment” and the like refer to reducing the probability of developing a disorder or condition in a subject, who does not have, but is at risk of or susceptible to developing a disorder or condition.

As used herein, “administering” refers to the physical introduction of a composition comprising a therapeutic agent to a subject, using any of the various methods and delivery systems known to those skilled in the art. Routes of administration described herein include intravenous, intraperitoneal, intramuscular, subcutaneous, spinal or other parenteral routes of administration, for example by injection or infusion. The phrase “parenteral administration” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intraperitoneal, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion, as well as in vivo electroporation. Alternatively, a composition described herein can be administered via a non-parenteral route, such as a topical, epidermal or mucosal route of administration, for example, intranasally, orally, vaginally, rectally, sublingually or topically. Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.

The term “agent” is used herein to denote a chemical compound, a mixture of chemical compounds, a biological macromolecule (such as a nucleic acid, an antibody, a protein or portion thereof, e.g., a peptide), or an extract made from biological materials such as bacteria, plants, fungi, or animal (particularly mammalian) cells or tissues. The activity of such agents may render it suitable as a “therapeutic agent,” which is a biologically, physiologically, or pharmacologically active substance (or substances) that acts locally or systemically in a subject.

The terms “therapeutic agent,” “therapeutic capable agent,” or “treatment agent” are used interchangeably and refer to a molecule or compound that confers some beneficial effect upon administration to a subject. The beneficial effect includes enablement of diagnostic determinations; amelioration of a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder or condition; and generally counteracting a disease, symptom, disorder or pathological condition.

“Combination” therapy, as used herein, unless otherwise clear from the context, is meant to encompass administration of two or more therapeutic agents in a coordinated fashion, and includes, but is not limited to, concurrent dosing. Specifically, combination therapy encompasses both co-administration (e.g., administration of a co-formulation or simultaneous administration of separate therapeutic compositions) and serial or sequential administration, provided that administration of one therapeutic agent is conditioned in some way on administration of another therapeutic agent. For example, one therapeutic agent may be administered only after a different therapeutic agent has been administered and allowed to act for a prescribed period of time. See, e.g., Kohrt et al. (2011) Blood 117:2423.

Where a value of ranges is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges which may independently be included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either both of those included limits are also included in the disclosure.

It is noted here that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise.

The terms “including,” “comprising,” “containing,” or “having” and variations thereof are meant to encompass the items listed thereafter and equivalents thereof as well as additional subject matter unless otherwise noted.

The phrases “in one embodiment,” “in various embodiments,” “in some embodiments,” and the like are used repeatedly. Such phrases do not necessarily refer to the same embodiment, but they may unless the context dictates otherwise.

The terms “and/or” or “/” means any one of the items, any combination of the items, or all of the items with which this term is associated.

The word “substantially” does not exclude “completely,” e.g., a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the definition of the invention.

As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In some embodiments, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). Unless indicated otherwise herein, the term “about” is intended to include values, e.g., weight percents, proximate to the recited range that are equivalent in terms of the functionality of the individual ingredient, the composition, or the embodiment.

As used herein, the term “each,” when used in reference to a collection of items, is intended to identify an individual item in the collection but does not necessarily refer to every item in the collection. Exceptions can occur if explicit disclosure or context clearly dictates otherwise.

The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.

All methods described herein are performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. In regard to any of the methods provided, the steps of the method may occur simultaneously or sequentially. When the steps of the method occur sequentially, the steps may occur in any order, unless noted otherwise.

In cases in which a method comprises a combination of steps, each and every combination or sub-combination of the steps is encompassed within the scope of the disclosure, unless otherwise noted herein.

Each publication, patent application, patent, and other reference cited herein is incorporated by reference in its entirety to the extent that it is not inconsistent with the present disclosure. Publications disclosed herein are provided solely for their disclosure prior to the filing date of the present invention. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates, which may need to be independently confirmed.

It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.

EXAMPLES

Example 1

Identification and Characterization of the Variants of the 10-1074 Broadly Neutralizing Antibody—Round 1

The first round variants, including MS-203, MS-204, MS-205, MS-206, MS-207, MS-208, MS-209, MS-210, MS-211, MS-212, MS-213, MS-214, MS-215, MS-216, MS-217, MS-218, MS-219, MS-220, and MS-224, as shown in Table 9, were produced using transient expression in HEK293 cells and purified by protein A chromatography. The characterization methods used to analyze the variants are listed in Table 8, including size exclusion chromatography (SEC), differential scanning fluorimetry (DSF), low pH stability, and relative solubility assay (RSA). The antibodies were buffer exchanged into phosphate-buffered saline and used for analysis. Assays used for analysis of the first round variants included SEC to quantify monomer and high molecular weight species following purification, DSF to characterize stability of the CH2 and Fab domains during thermal ramping, and retention of neutralization capacity.

The monomer content of the variants ranged from a low of 60.8% to a high of 96.3%. The monomer content of the unmodified 10-1074-LS (or MS-194) was 91.5% with the remainder of material for all variants being high molecular weight species (HMW). Variants with less than 10% HMW were considered for the second round combinatorial variants. In addition to SEC analysis, differential scanning fluorimetry was used to define molecules with increased thermodynamic stability. For the 10-1074-LS (or MS-194) parental molecule, only a single Tm was measured indicating that the CH2 and Fab domains unfolded at the same temperature. Similar results were observed for some of the variants. A few, though, also showed the presence of both a Tm1 and a second melting transition termed Tm2, because modifications that help to stabilize the Fab domain were made in the Fv domain of the antibodies, resulting in the increased thermal transition. Antibodies that did not show a consistent Tm2 for both replicates of the DSF analysis were not considered for Round 2 combinations.

Neutralization activity was also measured to ensure retention of activity of the bnAb variants. Results are shown in Table 10 for neutralization against six pseudoviruses of HIV (e.g., Du156.12, WIT04160.33, CNE17, CNE30, CAAN5342.A2, Du172.17), which are representative of the broader set of viruses against which 10-1074 is active. Antibodies with more than a 3-fold increase in the IC50 or IC80 value for a particular pseudovirus were considered inactive and discarded from further consideration. As evidenced by the data, only one variant, MS-208, lost neutralization activity and was not selected for further development.

The final set of amino acids for further development was based on the combination of amount purified, percent high molecular weight, increase in thermodynamic stability by DSF, and retention of neutralization activity. An example of the reasoning for the selection of residues for combinatorial analysis is described in Table 11. Five amino acid residues selected for further development are MS-203 (LmdV: Y2P), MS-216 (HV: V79T), MS-217 (HV: R82V), MS-218 (HV: L89F) and MS-219 (HV: T108R).

Example 2

Identification and Characterization of the Variants of the 10-1074 Broadly Neutralizing Antibody—Round 2

The second round combinatorial variants were designed based on the first round variants as described in the prior section. The combinatorial variants tested in the second round of optimization are shown in Table 12 and consist of ten double combinations, ten triple combinations, five quadruples and one quintuple combination consisting of all five amino acid modifications. These variants include MS-200, MS-201, MS-202, MS-225, MS-226, MS-227, MS-228, MS-229, MS-230, MS-231, MS-232, MS-233, MS-234, MS-235, MS-236, MS-237, MS-238, MS-239, MS-240, MS-241, MS-242, MS-243, MS-244, and MS-245. The combinatorial variants were produced using transient expression in HEK293 cells and purified by protein A chromatography. The antibodies were buffer exchanged into phosphate-buffered saline before being used for analysis. Assays used for analysis of the second round variants included SEC to quantify monomer and high molecular weight species following purification, differential scanning fluorimetry to characterize stability of the CH2 and Fab domains during thermal ramping, chemical unfolding, low pH stability, solubility, and retention of neutralization capacity.

Results of the initial screening consisting of SEC analysis for dimer and oligomer content and DSF for increased thermodynamic stability are shown in Table 13. For example, MS-200 has lower HMW than the control variant MS-194. MS-200 also has a Tm1=70.15° C. and a Tm2=74.62° C., suggesting it has improved thermal stability. Separation of the HMW species into dimer and oligomer species, with HMW species eluting earlier than dimer, provides a more refined view of the data. The data show that the dimer content was relatively unchanged from 10-1074-LS (or MS-194), while the oligomer content of the variants both increased up to 2-fold for a few variants and decreased up to approximately 7-fold for others. The variants were also characterized by DSF to identify those with increased thermodynamic stability as evidenced by the presence of distinct Tm2 unfolding temperatures.

To better differentiate the variants by DSF, an alternative analysis of the data was devised which took advantage of the change between Tm1 and Tm2 and the area under the thermal unfolding curves. As indicated by the data in Table 14 termed DSF Shoulder Score, the variants may have similar Tm2 values, but different shoulder score values with the increased values indicative of greater stability. For example, the DSF Shoulder Score values for MS-200, MS-201, and MS-202 are 16.12, 29.39, and 22.49, respectively, which are significantly larger than the Shoulder Score value, 7.65, of the control antibody variant MS-194, suggesting the variants MS-200, MS-201, and MS-203 are more stable than the control antibody variant MS-194. Thermodynamic stability was also assessed by chemical unfolding which asses the intrinsic resistance of the native state against unfolding as measured by the mid-point of the denaturation curve. The higher the value, the greater the stability. Together with the DSF shoulder score, a much finer differentiation of the intrinsic thermodynamic stability of the antibodies was obtained. In addition to the intrinsic stability, the resistance to aggregation during low pH incubation, neutralization, and solubility of the variants was also analyzed. While the parental 10-1074-LS (or MS-194) aggregated with up to 40% HMW formation, some variants showed only 2-3% HMW formation. Solubility was also increased for some variants, with up to a 42% increase in solubility over the parental molecule.

The neutralization capacity of a subset of the combinatorial variants was also examined to ensure no loss in neutralization occurred. As shown in Table 15, a reduced set of variants were tested against a representative set of 12 pseudoviruses, including SC422661.8, WITO4160.33, CAAN5342.A2, DU156.12, DU172.17, CNE17, CNE30, CNE53, 235-47, X1193_c1, X1254_c3, and 3301.v1.c24. Variants with a Tm2 were selected for the testing. Of the variants that were tested they all retained neutralization activity against the set of pseudoviruses examined.

The final set of variants for in-depth biophysical analysis was defined based on the biophysical attributes since the reduced set of antibodies defined in Table 15 all retained neutralization activity. The specific reasons for exclusion of bnAbs from the set for in-depth analysis are described in Table 16, and the final set is shown below.

		LIGHT CHAIN	HEAVY CHAIN
	ORIGINAL NAME	MODIFICATIONS	MODIFICATIONS
MS-200	10-1074_ROUND2_XTEND.015	LMDV: Y2P	HV: R82V, HV: T108R
MS-201	10-1074_ROUND2_XTEND.019		HV: V79T, HV: L89F,
			HV: T108R
MS-202	10-1074_ROUND2_XTEND.023	LMDV: Y2P	HV: V79T, HV: L89F,
			HV: T108R

In-Depth Analysis of the Final Variant Set

The final optimized variant was based on the final variant set defined above. Analysis performed was downstream purification (FIGS. 1-2), accelerated stability (FIGS. 3-4). For the downstream purification analysis and accelerated stability, molecules were produced using transient expression in a CHO-S cell line.

The results from the in-depth analysis indicate that MS-202 was the best performing molecule of the optimized variants. While both MS-200, MS-201, and MS-202 have similar rates of dimer formation at 40° C., MS-202 shows better resistance to sub-visible particle formation over a 13 week period.

Production of Antibodies

Antibody materials were cloned and produced as previously described (Durocher, Y., Perret, S., & Kamen, A. (2002). Nucleic Acids Research, 30(2), E9). bNAbs antibody materials were generated from transient expression of two suspension cell lines, Human Embryonic Kidney 293 (HEK293) and Chinese Hamster Ovary (CHO). The pTT5 mammalian expression vectors containing either a light chain (LC) or heavy chain (HC) coding region were co-transfected into HEK293 cells at a viable cell density (VCD) of 1*10{circumflex over ( )}6 cells/mL using polyethyleneimine (PEI) (Durocher, Perret, & Kamen, 2002) then two-fold diluted with pre-warmed medium to ⅕ shake flask volume. Expression duration was 5-7 days at 37° C., 5% CO₂, and 85% humidity at a shaking speed of 130 RPM with an orbit of 19 mm. The ExpiCHO-S™ “max titer” method was followed essentially as described by ThermoFisher (catalog number A29133, document part number A29518). The pcDNA3.4 expression vectors containing either LC or HC coding regions were co-transfected into CHO-S cells at a VCD of 6*10{circumflex over ( )}6 using expifectamine. The expression duration was 12 days at 32° C., 5% CO₂, and 85% humidity at a shaking speed of 130 RPM with an orbit of 19 mm. All clarified supernatants were produced by pelleting the cells at 3000 g for 20 minutes followed by 0.22 m filtration. Antibodies were purified from the clarified supernatants using Mab Select SuRe protein A resin. A sodium phosphate, sodium chloride buffer system with an arginine wash and an acetate pH 3.5 elution was utilized. Protein A elutions were neutralized with tris and buffer exchanged into 20 mM sodium phosphate, 150 mM NaCl, pH 7.4.

Neutralization Assays

Virus neutralization was evaluated using a luciferase-based assayin TZM.bl cells (J Virol 79(16):10108-10125). The HIV-1 pseudoviruses tested contained mostly tier-2 and tier-3 viruses (Journal of Virology 84(3):1439-1452). High-mannose-only pseudoviruses were produced in wild-type cells treated with 25 μM kifunensine (Enzo Life Sciences) or in HEK 293S GnTI^−/− cells. Non-linear regression analysis was used to calculate concentrations at which half-maximal inhibition was observed (IC₅₀ values). Neutralization activities were also evaluated with a previously characterized PBMC-based assay using infection with primary HIV-1 variants (n=95) isolated from clade B-infected donors with known seroconversion dates either between 1985 and 1989 (“historical seroconverters”, n=14) or between 2003 and 2006 (“contemporary seroconverters”, n=21) (Journal of Virology 85(14):7236-7245; Nat Med 16(9):995-997). Neutralization activity for each antibody was calculated using GraphPad Prism software (v5.0b) as the area under the best-fit curve, which fits the proportion of viruses neutralized over IC₅₀ values ranging from 0.001 to 50 μg/ml.

HP-SEC

High-Performance Size Exclusion Chromatography (“HP-SEC”) separates proteins based on differences in their hydrodynamic volumes. Molecules with larger hydrodynamic protein volumes elute earlier than molecules with smaller volumes. Undiluted samples were loaded onto a Waters XBridge Protein BEH SEC 200 Å column (3.5 μm, 7.8×300 mm), separated isocratically with a 100 mM sodium phosphate, 250 mM sodium chloride, pH 6.8 running buffer, and the eluent was monitored by UV absorbance at 280 nm. Purity was determined by calculating the percentage of each separated component as compared to the total integrated area.

DSF

The DSF technique consists of measuring the fluorescence intensity of a hydrophobic probe at gradually increasing temperatures to determine the transition temperature and exposure of the hydrophobic regions of a protein. The measurements from this technique, reported as transition temperatures, correlate well with data obtained from differential scanning calorimetry (DSC). DSF is a high throughput technique that is used to estimate a protein's relative thermodynamic stability and by ranking the results, can be used as a tool to select candidates with more favorable stability properties. Thermal transition temperature(s) by DSF were measured according to the method previously described (Feng H, et al. J Pharm Sci, 2010; 99:4, 1707-1720). The analysis was carried out in PBS buffer (20 mM sodium phosphate and 150 mM sodium chloride pH 7.1) at a final protein concentration of 0.15 mg/mL and a final Sypro Orange concentration of 3×. Protein and Sypro Orange were mixed at a 1:1 volumetric ratio in a 96 well PCR plate and analyzed using a Roche Light Cycler 480 instrument equipped with Thermal Shift Analysis Software. Thermal curves were generated by heating the samples from 20-95° C. at a ramp rate of 4.4° C./s and 10 acquisitions per ° C., at Ex=465 nm Em=580 nm. Transition temperatures and shoulder scores were determined using the first derivative of the melting curve.

Low pH Stability

The pH of protein samples at 1 mg/mL in 20 mM PBS was lowered to approximately pH 3.3 using 2 M acetic acid. After a 30 minute incubation, samples were neutralized to approximately pH 5 using 2 M Tris base. Samples were measured for high molecular weight species using the SE-HPLC method and measured in duplicate. As a control, protein samples had PBS added that was the same volume of the 2 M acetic acid and 2 M Tris base and measured for high molecular weight species.

Relative Solubility

Solubility was assessed according to the method previously described (Vishal M. Toprani, Sangeeta B. Joshi, Lisa A. Kueltzo, Richard M. Schwartz, C. Russell Middaugh, David B. Volkin). A micro-polyethylene glycol precipitation assay as a relative solubility screening tool for monoclonal antibody design and formulation development (J. Pharm. Sci 2016; 105:8: 2319-2327). Analysis was done in PBS buffer (20 mM sodium phosphate and 150 mM sodium chloride pH 7.1) and a final PEG 10,000 concentration of 7.9%. Protein at 1 mg/mL was diluted into the PEG solution at a 1:4 ratio and incubated at room temperature overnight in a 96 well 0.22 m filter plate. After PEG incubation, samples are passed through the filter by centrifugation and the remaining soluble protein is measured by a protein A titer assay.

Chemical Unfolding

Thirty-two guanidine hydrochloride (GND) concentrations in PBS ranging from 0 to 6 M GND were prepared using a liquid handling robot. Then, the protein samples at 1 mg/mL in 20 mM PBS were transferred to each GND concentration to achieve a final protein concentration of 0.05 mg/mL. After a 24 hr incubation, the samples were measured on a SpectraMax M5 plate reader (excitation: 280 nm, emission: 300-450 nm). The measured fluorescence intensity at 373 nm was corrected for scattering and stray light by subtraction of a small amount of the summed intensity measured between 300 and 320 nm (used as a surrogate for signal due to scattering) and then ratioed to the total intensity measured between 320 and 440 nm to correct for total intensity fluctuations. Then, the chemical unfolding curve was generated by graphing each corrected intensity against the GND concentration. The inflection point of the curve was calculated and reported for each protein sample from this curve. Samples were completed in triplicate.

Sub-Visible Particle Analysis

Sub-visible particles were measured using a Flowcam 8100 benchtop microflow imaging system equipped with an 80 μm flow cell and a 10× magnification lens and controlled by the Visual Spreadsheet software. Samples were equilibrated to room temperature and gently swirled to mix thoroughly. Single readings of 100 μl per sample were collected, and total particle concentration above 2 μm was recorded.

Example 3

Characterization for the Formation of Oligomeric Species and HMW of the 10-1074 Variants During Viral Inactivation and the Purification Steps

FIG. 1 shows the characterization of anti-HIV antibody 10-1074 variants MS-194 (FIG. 1A) and MS-203 (FIG. 1B) by high-performance size exclusion chromatography (“HP-SEC”) before and after viral neutralization. Peaks in the HP-SEC profiles corresponding to the oligomeric species formed during viral inactivation are indicated by arrows. FIG. 2 shows quantification of the degree of aggregation represented by the level of high molecular weight (“HMW”) and oligomeric species following each of the purification steps for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203.

Molecules MS-194, MS-200, MS-201, and MS-203, were produced using the ExpiCHO-S™ “max titer” method essentially as described by ThermoFisher (catalog number A29133, document part number A29518). The pcDNA3.4 expression vectors containing either light chain or heavy chain coding regions were co-transfected into CHO-S cells at a VCD of 6*10{circumflex over ( )}6 using expifectamine. The expression duration was 12 days at 32° C., 5% CO₂ and 85% humidity at a shaking speed of 130 RPM with an orbit of 19 mm. All clarified supernatants were produced by pelleting the cells at 3000 g for 20 minutes followed by 0.22 μm filtration.

Antibodies were purified from the clarified supernatants using MabSelect SuRe protein A resin. Equilibrated with a Tris and sodium chloride buffer. Following loading of the column, the column was washed with a Tris buffer containing 0.5M sodium chloride. Bound mAb was eluted with a 0.1 M acetate buffer at pH 3.6 and neutralized. The stability of each molecule during viral inactivation was ascertained by titrating the eluate to pH 3.5, followed by incubating for 1 hour followed by neutralization with Tris buffer. The remainder of the Protein A elutions were also neutralized with a tris buffer system immediately following elution. Further purification was achieved by loading the neutralized eluent onto a Fractogel SO₃⁻ cation-exchange resin (EMD Millipore Corporation) and eluting with a sodium chloride gradient. The peak containing the mAb was collected, concentrated to 20 mg/mL, and buffer exchanged into 10 mM acetate, 9% sucrose, pH 5.2.

The percent high molecular weight and oligomer were determined for each sample using HP-SEC analysis as previously described. As shown in FIGS. 1A and 1B and quantified in FIG. 2 the MS-194 antibody shows a significant increase in oligomer during the low pH viral inactivation while molecules MS-200, MS-201, and MS-203 showed no increase in HMW or oligomer content during the viral inactivation process.

Example 4

Characterization of Stability of the 10-1074 Variants

FIG. 3 shows the level of HMW during incubation at 40° C. for up to 13 weeks for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203. The figure shows a similar rate of dimer formation during incubation at 40° C. for up to 13 weeks. FIG. 4 shows the level of sub-visible particle formation during 6 weeks and 13 weeks for the 10-1074 antibody variants MS-194, MS-200, MS-201, and MS-203. The figure shows that antibodies MS-200, MS-201 and MS-203 particulated to a much smaller degree than MS-194. After 6 weeks, MS-194 showed 6× more particles than MS-200, MS-201, and MS-203, while after 13 weeks MS-200 and MS-203 had approximately 2× less than MS-194 and MS-203 showed 4× less particle formation.

Monoclonal antibodies MS-194, MS-200, MS-201 and MS-203 purified by cation-exchange chromatography and buffer exchanged as previously described were buffer exchanged into 20 mM acetate, 9% sucrose and concentrated to 100 mg/mL at a final pH of 5.2. A 500 μL aliquot of each sample was placed in a 4 mL Type I glass vial, sealed with a rubber stopper and aluminum crimp seal. The samples were incubated for up to 13 weeks at 40° C. Samples were removed at the indicated time points and the vials resealed and placed back in the incubator. The % HMW was determined using HP-SEC and sub-visible particles determined using the FlowCam instrument as described above.

Example 5

Combination Therapy with Anti-HIV-1 Antibodies

Although anti-HIV-1 antibodies constitute a potential alternative to ARTS, treatment of viremic individuals with a single antibody also results in emergence of resistant viral variants ((Caskey, M. et al. Nature 522, 487-491 (2015); Caskey, M. et al. Nat. Med. 23, 185-191 (2017); Lynch, R. M. et al. Sci. Transl. Med. 7, 319ra206 (2015)). Moreover, combinations of first-generation anti-HIV-1 broadly neutralizing antibodies (bNAbs) had little measurable effect on the infection. This disclosure presents the results from a phase 1b clinical trial (NCT02825797) in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption (ATI) (Mendoza et al., Nature. 2018 September; 561(7724): 479-484; Bar-On et al., Nature Medicine 24:1701-1707 (2018)). Participants received three infusions of 30 mg/kg of each antibody at 0, 3, and 6 weeks. Infusions of the two antibodies were generally well tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for 15 to >30 weeks (median=21 weeks). In the four individuals with dual antibody-sensitive viruses, immunotherapy resulted in an average reduction in HIV-1 viral load of 2.05 log₁₀ copies per ml that remained significantly reduced for three months following the first of up to three infusions. In addition, none developed viruses resistant to both antibodies. It was concluded that the combination of anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 could maintain long-term suppression in the absence of ART in individuals with antibody-sensitive viral reservoirs.

Study Design

An open-label phase 1b study was conducted in HIV-1-infected participants who were virologically suppressed on antiretroviral therapy (ART) (http://www.clinicaltrials.gov; NCT02825797; EudraCT: 2016-002803-25) (Mendoza et al., Nature. 2018 September; 561(7724): 479-484; Bar-On et al., Nature Medicine 24:1701-1707 (2018)). Study participants were enrolled sequentially according to eligibility criteria. Participants received 3BNC117 and 10-1074 intravenously at a dose of 30 mg/kg body weight of each antibody, at weeks 0, 3, and 6, unless viral rebound occurred. ART was discontinued 2 days after the first infusion of antibodies (day 2). Plasma HIV-1 viral RNA levels were monitored weekly and ART was resumed if viral load increased to ≥200 copies/ml or CD4⁺ T cell counts decreased to <350 cells/μl in two consecutive measurements. Time of viral rebound was determined by the first viral load >200 copies/ml. Study participants were followed for 30 weeks after the first infusion. Safety data are reported until the end of study follow-up. All participants provided written informed consent before participation in the study, and the study was conducted in accordance with Good Clinical Practice (GCP). The protocol was approved by the Federal Drug Administration (FDA) in the USA, the Paul-Ehrlich-Institute in Germany, and the Institutional Review Boards (IRBs) at the Rockefeller University and the University of Cologne.

Study Participants

Study participants were recruited at the Rockefeller University Hospital, New York, USA, and the University Hospital Cologne, Cologne, Germany. Eligible participants were adults aged 18-65 years, HIV-1-infected, on ART for a minimum of 24 months, with plasma HIV-1 RNA levels of <50 copies/ml for at least 18 months (one viral blip of >50 but <500 copies/ml during this 18-month period was allowed), plasma HIV-1 RNA levels <20 copies/ml at the screening visit, and a current CD4⁺ T cell count >500 cells/μl. In addition, participants were pre-screened for sensitivity of latent proviruses against 3BNC117 and 10-1074 by bulk PBMC viral outgrowth culture as described below. Sensitivity was defined as an IC50<2 μg/ml for both 3BNC117 and 10-1074 against outgrowth virus. Participants on an NNRTI-based ART regimen were switched to an integrase inhibitor-based regimen (dolutegravir plus tenofovir disoproxil fumarate/emtricitabine) 4 weeks before treatment interruption due to the prolonged half-life of NNRTIs. Exclusion criteria included reported CD4⁺ T cell nadir of <200 cells/μl, concomitant hepatitis B or C infection, previous receipt of monoclonal antibodies of any kind, clinically relevant physical findings, medical conditions or laboratory abnormalities, and pregnancy or lactation.

Study Procedures

3BNC117 and 10-1074 were administered intravenously at a dose level of 30 mg/kg (Mendoza et al., Nature. 2018 September; 561(7724): 479-484; Bar-On et al., Nature Medicine 24:1701-1707 (2018)). The appropriate stock volume of 3BNC117 and 10-1074 was calculated according to body weight and diluted in sterile normal saline to a total volume of 250 ml per antibody. Monoclonal antibody infusions were administered sequentially and intravenously over 60 minutes. Study participants were observed at the Rockefeller University Hospital or the University Hospital Cologne for one hour after the last antibody infusion. Participants returned for weekly follow-up visits during the ATI period for safety assessments, which included physical examination and measurements of clinical laboratory parameters such as hematology, chemistries, urinalysis, and pregnancy tests (for women). Plasma HIV-1 RNA levels were monitored weekly during the ATI period, and CD4⁺ T cell counts were measured every 1 to 2 weeks. After ART was re-initiated, participants returned for follow up every 2 weeks until viral re-suppression was achieved, and every 8 weeks thereafter. Study investigators evaluated and graded adverse events according to the DAIDS AE Grading Table (version 2.0, November 2014) and determined causality. Leukapheresis was performed at the Rockefeller University Hospital or at the University Hospital Cologne at week −2 and week 12. Blood samples were collected before and at multiple times after 3BNC117 and 10-1074 infusions. Samples were processed within 4 h of collection, and serum and plasma samples were stored at −80° C. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. The absolute number of PBMCs was determined by an automated cell counter (Vi-Cell XR; Beckman Coulter) or manually, and cells were cryopreserved in fetal bovine serum plus 10% DMSO.

Plasma HIV-1 RNA Levels

HIV-1 RNA levels in plasma were measured at the time of screening, at week −2, day 0 (before infusion), weekly during ATI, and every two weeks to every eight weeks after viral rebound had occurred. HIV-1 RNA levels were determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Assay (version 2.0) or the Roche COBAS HIV-1 quantitative nucleic acid test (COBAS 6800), which quantitate HIV-1 RNA over a range of 2×10¹ to 1×10⁷ copies/ml. These assays were performed at LabCorp or at the University Hospital Cologne.

CD4⁺ T Cells

CD4⁺ T-cell counts were determined by a clinical flow cytometry assay, performed at LabCorp or at the University Hospital Cologne, at screening, week 0 (before infusion), weeks 2, 3, 5, 6, 8, 10, and weekly thereafter, while participants remained off ART.

Determination of Baseline Neutralizing Antibody Activity

Purified IgG (Protein G Sepharose 4 Fast Flow, GE Life Sciences) obtained before antibody infusions was tested against a panel of 12 HIV-1 pseudoviruses as described previously (Schoofs T et al. Science 352, 997-1001 (2016)).

Measurement of 3BNC117 and 10-1074 Serum Levels

Blood samples were collected before, at the end of each 3BNC117 infusion and at the end of each 10-1074 infusion at weeks 0, 3, and 6, and weekly during the ATI period, up to week 30. Serum levels of 3BNC117 and 10-1074 were determined by a TZM-bl assay and by ELISA from samples obtained before and after each antibody infusion, and approximately every three weeks during follow up as well as at the time of viral rebound.

3BNC117 and 10-1074 serum concentrations were measured by a validated sandwich ELISA. High bind polystyrene plates were coated with 4 μg/ml of an anti-idiotypic antibody specifically recognizing 3BNC117 (anti-ID 1F1-2E3 mAb) or 2 μg/ml of an anti-idiotypic antibody specifically recognizing 10-1074 (anti-ID 3A1-4E11 mAb), and incubated overnight at 2-8° C. After washing, plates were blocked with 5% Milk Blotto (w/v), 5% NGS (v/v), and 0.05% Tween 20 (v/v) in PBS. Serum samples, QCs and standards were added (1:50 minimum dilution in 5% Milk Blotto (w/v), 5% NGS (v/v), and 0.05% Tween 20 (v/v) in PBS) and incubated at room temperature. 3BNC117 or 10-1074 were detected using a horseradish peroxidase (HRP)-conjugated mouse anti-human IgG kappa-chain-specific antibody (Abcam) for 3BNC117 or an HRP-conjugated goat antihuman IgG Fc-specific antibody for 10-1074 (Jackson ImmunoResearch) and the HRP substrate tetra-methylbenzidine. 3BNC117 and 10-1074 concentrations were then calculated from a standard curve of 3BNC117 or 10-1074 run on the same plate using a 5-PL curve-fitting algorithm (Softmax Pro, v5.4.5). Standard curves and positive controls were created from the drug product lots of 3BNC117 and 10-1074 used in the clinical study. The capture anti-idiotypic mAbs were produced using a stable hybridoma cell line (Duke Protein Production Facility). The lower limit of quantitation for the 3BNC117 ELISA is 0.78 μg/ml and for the 10-1074 ELISA is 0.41 μg/ml. The lower limit of detection was determined to be 0.51 μg/ml and 0.14 μg/ml in HIV-1 seropositive serum for the 3BNC117 and 10-1074 ELISA, respectively. For values that were detectable (i.e., positive for mAb) but were below the lower limit of quantitation, values are reported as <0.78 μg/ml and <0.41 μg/ml for 3BNC117 and 10-1074 ELISA, respectively. If day 0 baseline samples had measurable levels of antibody by the respective assays, the background measured antibody level was subtracted from subsequent results. In addition, samples with antibody levels measured to be within 3-fold from background were excluded from the analysis of PK parameters.

Serum concentrations of active 3BNC117 and 10-1074 were also measured using a validated luciferase-based neutralization assay in TZM-bl cells as previously described (Sarzotti-Kelsoe M et al. J Immunol Methods 409, 131-146 (2014)). Briefly, serum samples were tested using a primary 1:20 dilution with a 5-fold titration series against HIV-1 Env pseudoviruses Q769.d22 and X2088_c9, which are highly sensitive to neutralization by 3BNC117 and 10-1074, respectively, while fully resistant against the other administered antibody. In the case of the post-infusion time points of 10-1074, instances where serum ID50 titers against X2088_c9 were >100,000, serum samples were also tested against a less sensitive strain, Du422. To generate standard curves, 3BNC117 and 10-1074 clinical drug products were included in every assay set-up using a primary concentration of 10 μg/ml with a 5-fold titration series. Serum concentrations of 3BNC117 and 10-1074 for each sample were calculated as follows: serum ID50 titer (dilution)×3BNC117_IC50 or 10-1074 IC50 titer (μg/ml)=serum concentration of 3BNC117 or 10-1074 (μg/ml). Env pseudoviruses were produced using an ART-resistant backbone vector that reduces background inhibitory activity of antiretroviral drugs if present in the serum sample (SG3ΔEnv/K101P.Q148H.Y181C). Virus pseudotyped with the envelope protein of murine leukemia virus (MuLV) was utilized as a negative control. Antibody concentrations were calculated using the serum ID80 titer and monoclonal antibody IC80 if non-specific activity against MuLV was detected (ID50>20; 9246, week 30; 9248, baseline, d0, wk 18). All assays were performed in a laboratory meeting GCLP standards.

Pre-Screening Bulk PBMC Culture

To test HIV-1 viral strains for sensitivity to 3BNC117 and 10-1074, bulk viral outgrowth cultures were performed by co-culturing isolated CD4⁺ T cells with MOLT-4/CCR-5 cells or CD8⁺ T cell-depleted donor lymphoblasts. PBMCs for pre-screening were obtained up to 72 weeks (range 54-505 days) before enrollment under separate protocols approved by the IRBs of The Rockefeller University and the University of Cologne. Sensitivity was determined by TZM-bl neutralization assay as described below. Culture supernatants with IC50<2 μg/ml were deemed sensitive.

Quantitative and Qualitative Viral Outgrowth Assay (Q²VOA)

The quantitative and qualitative viral outgrowth assay (Q²VOA) was performed using isolated PBMCs from leukapheresis at week −2 and week 12 as previously described (Lorenzi J C et al. PNAS 113, E7908-E7916 (2016)). Briefly, isolated CD4⁺ T cells were activated with 1 μg/ml phytohemagglutinin (Life Technologies) and 100 U/ml IL-2 (Peprotech) and co-cultured with 1×10⁶ irradiated PBMCs from a healthy donor in 24-well plates. A total of 6×10⁷-6.2×10⁸ cells were assayed for each individual at each of the 2 time points. After 24 hours, PHA was removed and 0.1×10⁶ MOLT-4/CCR5 cells were added to each well. Cultures were maintained for 2 weeks, splitting by half the MOLT-4/CCR5 cells 7 days after the initiation of the culture and every other day after that. Positive wells were detected by measuring p24 by ELISA. The frequency of latently infected cells was calculated through the infectious units per million (IUPM) algorithm developed by the Siliciano lab (http://silicianolab.johnshopkins.edu).

Rebound Outgrowth Cultures

CD4⁺ T cells isolated from PBMCs from the rebound time points were cultured at limiting dilution exactly as described for Q²VOA. CD4⁺ T cells were activated with T cell activation beads (Miltenyi) at a concentration of 0.5×10⁶ beads per 10⁶ CD4⁺ T cells and 20 U/ml of IL-2. Rebound outgrowth was performed using PBMCS from the highest viral load sample (usually the repeat measurement ≥200 copies/ml). Viruses whose sequences matched the SGA env sequences, and therefore were identical to those present in plasma, as opposed to potentially reactivated PBMC-derived latent reservoir viruses, were selected to test for neutralization.

Viral Sensitivity Testing

Supernatants from p24-positive bulk PBMC cultures, rebound PBMC outgrowth cultures and Q²VOA wells were tested for sensitivity to 3BNC117 and 10-1074 by TZM-bl neutralization assay as previously described (Sarzotti-Kelsoe M et al. J Immunol Methods 409, 131-146 (2014)).

Sequencing

HIV-1 RNA extraction and single genome amplification were performed as previously described (Salazar-Gonzalez J F et al. J Virol 82, 3952-3970 (2008)). In brief, HIV-1 RNA was extracted from plasma samples or Q²VOA-derived virus supernatants using the MinElute Virus Spin kit (Qiagen) followed by first strand cDNA synthesis using SuperScript III reverse transcriptase (Invitrogen). cDNA synthesis for plasma-derived HIV-1 RNA was performed using the antisense primer envB3out Fidelity Platinum Taq (Invitrogen) and run at 94° C. for 2 min; 35 cycles of 94° C. for 15 s, 55° C. for 30 s, and 68° C. for 4 min; and 68° C. for 15 min. Second round PCR was performed with 1 μl of first PCR product as template and High Fidelity Platinum Taq at 94° C. for 2 min; 45 cycles of 94° C. for 15 s, 55° C. for 30 s, and 68° C. for 4 min; and 68° C. for 15 min. cDNA synthesis for Q²VOA-derived HIV-1 RNA was performed using the antisense primer R3B6R

Study Outcomes

Combination bNab Infusion is Well Tolerated

To evaluate the effects of the combination of 3BNC117 and 10-1074 on maintaining HIV-1 suppression during ATI, a Phase 1b clinical trial was conducted (FIG. 5A) (Mendoza et al., Nature. 2018 September; 561(7724): 479-484). HIV-1-infected individuals on ART were pre-screened for 3BNC117 and 10-1074 sensitivity of bulk outgrowth culture-derived viruses using the TZM-bl neutralization assay. Consistent with previous results, 64% and 71% of the outgrowth viruses were sensitive to 3BNC117 and 10-1074, respectively, and 48% were sensitive to both (IC50≤2 μg/ml).

Study eligibility criteria included ongoing ART for at least 24 months with plasma HIV-1 RNA levels of <50 copies/ml for at least 18 months (with one blip <500 copies/ml allowed) and <20 copies/ml at screening, as well as CD4⁺ T cell counts >500 cells/μl. Enrolled participants received 3 infusions of 30 mg/kg each of 3BNC117+10-1074 at 3-week intervals beginning 2 days before treatment interruption (FIG. 5A). Individuals whose regimens contained non-nucleoside reverse transcriptase inhibitors were switched to an integrase inhibitor-based regimen 4 weeks before discontinuing ART (FIG. 6A). Viral load and CD4⁺ T cell counts were monitored every 1-2 weeks. ART was reinitiated, and antibody infusions were discontinued if viremia of >200 copies/ml was confirmed. Time of viral rebound was defined as the first of two consecutive viral loads >200 copies/ml. Fifteen individuals were enrolled, but four of them showed viral loads of >20 copies/ml two weeks before or at the time of the first bNAb infusion, and they were excluded from efficacy analyses.

Antibody infusions were generally safe and well-tolerated with no reported serious adverse events or antibody-related adverse events except for mild fatigue in two participants. The mean CD4⁺ T cell count was 685 and 559 cells/μl at the time of first antibody infusion and at rebound, respectively (FIG. 6B). Re-initiation of ART after viral rebound resulted in resuppression of viremia. It was concluded that combination therapy with 3BNC117+10-1074 is generally safe and well-tolerated.

Combination bNAbs Maintain Viral Suppression

For the 11 individuals who had complete viral suppression (HIV-1 RNA<20 copies/ml) during the screening period and at day 0, combination antibody therapy was associated with maintenance of viral suppression for 5 to >30 weeks (FIGS. 5B and 5C) (Mendoza et al., Nature. 2018 September; 561(7724): 479-484). The median time to rebound was 21 weeks compared to 2.3 weeks for historical controls who participated in non-interventional ATI studies and 6-10 weeks for monotherapy with 3BNC117 (FIG. 5C). Altogether, 9 of the 11 participants maintained viral suppression for over 15 weeks, while 2 rebounded at weeks 5 and 7 (FIGS. 5B and 5C).

Quantitative and qualitative viral outgrowth assays (Q²VOA) were used to retrospectively analyze the replication-competent latent viral reservoir in all individuals. Phylogenetic analysis showed that the trial participants were infected with epidemiologically distinct clade B viruses. Q²VOA analysis revealed that the pre-infusion latent reservoir in the two individuals rebounding early, 9245 and 9251, harbored 10-1074- or 3BNC117-resistant viruses, respectively (FIG. 7). Therefore, these two individuals were effectively subjected to antibody monotherapy because there was pre-existing resistance in the reservoir to one of the two bNAbs. Consistent with this idea, the delay in rebound in these two participants was within the range anticipated for antibody monotherapy (FIG. 5C). In addition, all four of the individuals excluded from the analysis due to incomplete viral suppression showed pre-existing resistance or viruses that were not fully neutralized by one or both of the antibodies and these individuals rebounded before week 12.

To examine the viruses arising in the early rebounding individuals, single genome analysis (SGA) on rebound plasma was performed. Pseudoviruses constructed from plasma SGA were tested for bNAb sensitivity in the TZM-bl assay. In addition to the pre-existing sequences associated with resistance in the 10-1074 target site (N332T+S334N, FIG. 7A), rebound viruses in 9245 also carried an extended V5 loop and potential N-linked glycosylation sites that could interfere with 3BNC117 binding. Conversely, genetic features associated with resistance to 3BNC117 were found in the pre-infusion reservoir of 9251 and were accompanied by mutations in the 10-1074 target site in the rebounding viruses (S334N, FIG. 7A). For both individuals, resistance of rebound viruses to both antibodies was confirmed by the TZM-bl neutralization assay (FIGS. 7B and 7C). Thus, bulk outgrowth cultures used for screening failed to detect pre-existing resistance in the reservoir of 2 of the 11 individuals studied. This result is not surprising given that bulk cultures are dominated by a limited number of rapidly growing viral species which may not be representative of the diversity in the latent reservoir.

Similarly, participant 91C33, who failed to respond to antibody infusions, had preexisting circulating viruses that were resistant to both antibodies (Bar-On et al., Nature Medicine 24:1701-1707 (2018)). These viruses carried mutations in 3BNC117 contact sites (N280S and A281H) and in 10-1074 contact sites (N332T and S334N). Two individuals, 91C35 and 9341, responded to antibody therapy with a decrease in viremia of −1.58 and −1.32 log₁₀ copies per ml but HIV-1 RNA levels returned to baseline within 3 and 4 weeks, respectively. 91C35 was found to have pre-infusion circulating viruses with reduced sensitivity to 3BNC117, and carried a CD4 contact residue mutation (A281T) that was associated with viral escape from 3BNC11720. Pre-infusion viruses derived from bulk CD4⁺ T cell outgrowth cultures of 9341 showed a 10-1074 IC80 that was 1.3 log₁₀ higher than the geometric mean IC80 of all other enrolled viremic individuals. In both of these cases, rebounding viruses were resistant to both antibodies and carried mutations resulting in the loss of the potential N-linked glycosylation site at position 332 that is critical for 10-1074 binding. In addition, rebound viruses from 91C35 and 9341 contained G471E and N276D mutations, respectively, that are associated with increased resistance to 3BNC117. These mutations were not found in the pre-infusion circulating viruses described above or in the additional 113 pre-infusion env sequences that were analyzed from these two participants. Thus, 91C35 and 9341 were infected with viruses with reduced sensitivity to one of the two antibodies and resemble individuals that received antibody monotherapy, both in the magnitude of the drop in viremia and time required to return to baseline viremia. It was concluded that the bulk outgrowth cultures used for initial screening failed to detect partial or complete preexisting resistance against one or both of the antibodies in three of the seven individuals studied.

The four remaining individuals showed no detectable pre-existing resistant viruses in circulation and experienced significantly suppressed viremia until day 94 after the first antibody infusion with an average maximum drop in viral load of −2.05 log₁₀ copies per ml (Bar-On et al., Nature Medicine 24:1701-1707 (2018)). The individual in this group with the highest initial viral load (97,800 copies per ml; patient 9343) was the first to rebound at eight weeks. The two individuals with the lowest initial viral loads, 91C22 and 9342 (750 and 2,550 copies per ml, respectively), demonstrated suppression to near or below the limit of detection for 12 and 16 weeks, respectively. Finally, viremia in participant 91C34 was reduced for a period of 12 weeks, however it never dropped below 810 copies per ml. Despite the persistent viremia, no resistance against both antibodies developed in this individual for as long as bNAb serum levels were above 10 μg/ml. In three of the four initially sensitive individuals, rebound viremia was associated with the appearance of viruses that were resistant to 10-1074, but these individuals remained sensitive to 3BNC117. This is consistent with the relatively shorter half-life of 3BNC117, which means that participants were effectively exposed to 10-1074 monotherapy at the end of the observation period. In accordance with the increased resistance to 10-1074, rebound viruses carried mutations in 10-1074 contact sites. By contrast, there was no accumulation of de novo mutations in 3BNC117 contact sites. 91C22, the participant with the lowest initial viral load, only returned to baseline viremia after both antibodies were below the limit of detection, and rebound viruses remained sensitive to both antibodies. Overall none of the four participants that were initially sensitive to the two antibodies developed de novo resistance to 3BNC117 over a cumulative observation period of over one year (56 weeks), despite the residual viremia observed in three of these participants and frequent recombination events between circulating viruses.

The median time to rebound in the 7 individuals that had no detectable resistant viruses in the pre-infusion latent reservoir, and rebounded during the study period, was also 21 weeks and different from 6-10 weeks for monotherapy with 3BNC117 (FIG. 5C) (Mendoza et al., Nature. 2018 September; 561(7724): 479-484). In these participants, viral suppression was maintained for 15 to 26 weeks after ART discontinuation. The two remaining participants (9254 and 9255) completed the study follow-up at 30 weeks without experiencing rebound. Notably, viral rebound never occurred when the concentration of both administered antibodies was above 10 μg/ml. The average 3BNC117 serum concentration (determined by TZM-bl assay) at the time of rebound in sensitive individuals that rebounded during study follow-up was 1.9 μg/ml (FIG. 5B). In contrast, the average serum concentration of 10-1074 at rebound was 14.8 μg/ml (FIG. 5B). The difference in the antibody concentrations at the time of rebound is consistent with the longer half-life of 10-1074 which resulted in a period of 10-1074 monotherapy (FIG. 5B). Finally, these 9 individuals showed little or no preexisting neutralizing antibodies against a diagnostic panel of viruses before bNAb infusion.

Rebound and Latent Viruses

To examine the relationship between rebound viruses and the circulating latent reservoir, env sequences obtained from plasma rebound viruses were compared by SGA with sequences obtained by Q²VOA from both pre-infusion and week 12 samples. In addition, sensitivity of rebound outgrowth viruses and/or pseudoviruses to 3BNC117 and 10-1074 was measured by the TZM-bl neutralization assay (FIGS. 7B and 7C). A total of 154 viral env sequences obtained by plasma SGA were analyzed and compared to 408 sequences obtained from the latent reservoir by Q²VOA. Although rebound and reservoir viruses clustered together for each individual, no identical sequences between the two compartments in any of the individuals studied were found (FIGS. 8 and 9A). The difference could be accounted for by distinct requirements for HIV-1 reactivation in vitro and in vivo, compartmentalization of reservoir viruses, HIV-1 mutation during the course of the trial, and/or by viral recombination in some individuals. Whether or not bNAb therapy influences selection for recombination events remains to be determined.

Similar to 3BNC117 monotherapy, the vast majority of rebounding viruses clustered within low diversity lineages consistent with expansion of 1-2 recrudescent viruses (FIG. 8). In contrast, rebound viruses are consistently polyclonal during ATI in the absence of antibody therapy. Thus, the antibodies restrict the outgrowth of latent viruses in vivo.

The emerging viruses in 6 of the 7 individuals that rebounded when the mean 3BNC117 and 10-1074 concentrations were 1.9 and 14.8 μg/ml, respectively, carried resistance-associated mutations in the 10-1074 target site (FIGS. 5B and 8A). Consistent with the sequence data, these rebound viruses were generally resistant to 10-1074 by the TZM-bl neutralization assay but remained sensitive to 3BNC117 (FIGS. 7B and 7C). The level of sensitivity to 3BNC117 in these emerging viruses was similar to that found in the reservoir viruses in each of the individuals (FIG. 7B). One individual, 9244, showed rebound viruses that remained sensitive to both antibodies in TZM-bl neutralization assays. Rebound occurred when 3BNC117 and 10-1074 concentrations in serum of this individual were undetectable and 11.6 μg/ml, respectively (FIG. 5B). The sensitivity of the plasma rebound viruses was similar to that of latent pre-infusion and week 12 viruses obtained in viral outgrowth cultures (FIGS. 7B and 7C). Therefore, this individual did not develop resistance to either of the antibodies despite prolonged exposure to both. In conclusion, none of the 9 individuals with pre-infusion reservoirs containing viruses that were sensitive to both antibodies developed double resistance during the observation period.

The Latent Reservoir

To determine whether there were changes in the circulating reservoir during the observation period, the results of Q²VOA assays performed at entry and 12 weeks after the start of ATI for 8 of the 9 individuals that remained suppressed for at least 12 weeks were compared (FIG. 9). Similar to previous reports, 63% of all viruses obtained by Q²VOA belonged to expanded clones. Comparison of the env sequences of the viruses that emerged in outgrowth cultures revealed that 60% of the sequences could be found at both time points. However, there were numerous examples of clones that appeared or disappeared between the time points, and some of these changes were significant. To determine the number of infectious units per million (IUPM, http://silicianolab.johnshopkins.edu/), 6.0×10⁷-6.2×10⁸ CD4⁺ T cells were assayed by Q²VOA for each time point for each individual (FIG. 9B). The difference between the 2 time points was never greater than 6.5-fold for any individual, and the 2 time points were not statistically different (P=0.078). Moreover, time to rebound was not directly correlated with IUPM. Additional time points would be required to calculate the half-life of the reservoir in individuals receiving immunotherapy.

Discussion

First generation anti-HIV-1 bNAbs were generally ineffective in suppressing viremia in animal models and humans leading to the conclusion that this approach should not be pursued. bNAb monotherapy with 3BNC117 or VRC01 was not enough to maintain control during ATI in HIV-1-infected humans. In contrast, the combination of 3BNC117 and 10-1074 was sufficient to maintain viral suppression in sensitive individuals when the concentration of both antibodies remains above a certain level in serum, for example, above 10 μg/ml. Rebound occurred when 3BNC117 levels dropped below 10 μg/ml effectively leading to 10-1074 monotherapy, from which nearly all individuals rapidly escaped by mutations in the 10-1074 contact site. The observation that 9 individuals infected with distinct viruses were unable to develop double resistant viruses over a median 21 week period suggests that viral replication was severely limited by this antibody combination.

In human studies, monotherapy with 3BNC117 is associated with enhanced humoral immunity and accelerated clearance of HIV-1-infected cells. In addition, when administered early to SHIVAD8-infected macaques, combined 3BNC117+10-1074 immunotherapy induced host CD8⁺ T cell responses that contributed to the control of viremia in nearly 50% of the animals. However, virus-specific CD8⁺ T cells responsible for control of viremia in these macaques were not detected in the circulation, and their contribution to viral suppression was only documented after CD8⁺ T cell depletion. In most controller macaques, complete viral suppression was only established after rebound viremia that followed antibody clearance.

Two individuals in this study remained suppressed for over 30 weeks after ATI, 9254 and 9255. Neither one had detectable levels of ART in the blood or carried the B*27 and B*57 HLA alleles that are most frequently associated with elite control (Walker B D & Yu X G. Nat Rev Immunol 13, 487-498 (2013)). The first, 9254, reports starting ART within 4-5 months after probable exposure to the virus with an initial viral load of 860,000 copies/ml. Despite relatively early therapy and excellent virological control for 21 years on therapy, this individual had an IUPM of 0.68 by Q²VOA at the 12-week time point. The second individual, 9255, showed several viral blips that were spontaneously controlled beginning 15 weeks after ATI when antibody levels were waning. This individual was infected for at least 7 months before starting ART with an initial viral load of 85,800 copies/ml and had an IUPM of 1.4 at the 12-week time point. A small fraction of individuals on ART show spontaneous prolonged virologic control after ART was discontinued, and this number appears to increase when ART treatment was initiated during the acute phase of infection.

A significant fraction of the circulating latent reservoir is composed of expanded clones of infected T cells. These T cell clones appear to be dynamic in that the specific contribution of individual clones of circulating latently infected CD4⁺ T cells to the reservoir of individuals receiving ART fluctuates over time. Individuals that maintain viral suppression by antibody therapy appear to show similar fluctuations in reservoir clones that do not appear to be associated with antibody sensitivity. Whether the apparent differences observed in the reservoir during immunotherapy lead to changes in the reservoir half-life cannot be determined from the available data and will require reservoir assessments in additional individuals at multiple time points over an extended observation period.

Individuals harboring viruses sensitive to 3BNC117 and 10-1074 maintained viral suppression during ATI for a median of almost 4 months after the final antibody administration. In macaques, the therapeutic efficacy of anti-HIV-1 antibodies is directly related to their half-life, which can be extended by mutations that enhance Fc domain interactions with the neonatal Fc receptor. The mutations can increase the half-life of antibodies in humans by 2-4-fold. The data suggest that a single administration of combinations of bNAbs with extended half-lives could maintain suppression for 6-12 months in individuals harboring sensitive viruses.

TABLE 1
Residue numbering of anti-HIV antibody 10-1074 variant MS-194
MS-194_LC	MS-194_HC
		Mat.				Mat.
Residue	Linear #	Linear #	ASN #	Residue	Linear #	Linear #	ASN #
M	1		Ldr: −19	M	1		Ldr: −19
G	2		Ldr: −18	G	2		Ldr: −18
W	3		Ldr: −17	W	3		Ldr: −17
S	4		Ldr: −16	S	4		Ldr: −16
C	5		Ldr: −15	C	5		Ldr: −15
I	6		Ldr: −14	I	6		Ldr: −14
I	7		Ldr: −13	I	7		Ldr: −13
L	8		Ldr: −12	L	8		Ldr: −12
F	9		Ldr: −11	F	9		Ldr: −11
L	10		Ldr: −10	L	10		Ldr: −10
V	11		Ldr: −9	V	11		Ldr: −9
A	12		Ldr: −8	A	12		Ldr: −8
T	13		Ldr: −7	T	13		Ldr: −7
A	14		Ldr: −6	A	14		Ldr: −6
T	15		Ldr: −5	T	15		Ldr: −5
G	16		Ldr: −4	G	16		Ldr: −4
V	17		Ldr: −3	V	17		Ldr: −3
H	18		Ldr: −2	H	18		Ldr: −2
S	19		Ldr: −1	S	19		Ldr: −1
S	20	1	LmdV: 1	Q	20	1	HV: 1
Y	21	2	LmdV: 2	V	21	2	HV: 2
V	22	3	LmdV: 3	Q	22	3	HV: 3
—	22.1	3.1	LmdV: 4	L	23	4	HV: 4
—	22.2	3.2	LmdV: 5	Q	24	5	HV: 5
—	22.3	3.3	LmdV: 6	E	25	6	HV: 6
R	23	4	LmdV: 7	S	26	7	HV: 7
—	23.1	4.1	LmdV: 8	—	26.1	7.1	HV: 8
P	24	5	LmdV: 9	G	27	8	HV: 9
—	24.1	5.1	LmdV: 10	P	28	9	HV: 10
L	25	6	LmdV: 111	G	29	10	HV: 11
S	26	7	LmdV: 12	L	30	11	HV: 12
V	27	8	LmdV: 13	V	31	12	HV: 13
A	28	9	LmdV: 14	K	32	13	HV: 14
L	29	10	LmdV: 15	P	33	14	HV: 15
G	30	11	LmdV: 16	S	34	15	HV: 16
E	31	12	LmdV: 17	E	35	16	HV: 17
T	32	13	LmdV: 18	T	36	17	HV: 18
A	33	14	LmdV: 19	L	37	18	HV: 19
R	34	15	LmdV: 20	S	38	19	HV: 20
I	35	16	LmdV: 21	V	39	20	HV: 21
S	36	17	LmdV: 22	T	40	21	HV: 22
C	37	18	LmdV: 23	C	41	22	HV: 23
G	38	19	LmdV: 24	S	42	23	HV: 24
R	39	20	LmdV: 25	V	43	24	HV: 25
Q	40	21	LmdV: 26	S	44	25	HV: 26
—	40.1	21.1	LmdV: 27	G	45	26	HV: 27
—	40.2	21.2	LmdV: 28	—	45.1	26.1	HV: 28
—	40.3	21.3	LmdV: 29	D	46	27	HV: 29
A	41	22	LmdV: 30	S	47	28	HV: 30
L	42	23	LmdV: 31	M	48	29	HV: 31
G	43	24	LmdV: 32	N	49	30	HV: 32
S	44	25	LmdV: 33	N	50	31	HV: 33
—	44.1	25.1	LmdV: 34	—	50.1	31.1	HV: 34
—	44.2	25.2	LmdV: 35	—	50.2	31.2	HV: 35
—	44.3	25.3	LmdV: 36	—	50.3	31.3	HV: 36
—	44.4	25.4	LmdV: 37	—	50.4	31.4	HV: 37
—	44.5	25.5	LmdV: 38	—	50.5	31.5	HV: 38
R	45	26	LmdV: 39	Y	51	32	HV: 39
A	46	27	LmdV: 40	Y	52	33	HV: 40
V	47	28	LmdV: 41	W	53	34	HV: 41
Q	48	29	LmdV: 42	T	54	35	HV: 42
W	49	30	LmdV: 43	W	55	36	HV: 43
Y	50	31	LmdV: 44	I	56	37	HV: 44
Q	51	32	LmdV: 45	R	57	38	HV: 45
H	52	33	LmdV: 46	Q	58	39	HV: 46
R	53	34	LmdV: 47	S	59	40	HV: 47
P	54	35	LmdV: 48	P	60	41	HV: 48
G	55	36	LmdV: 49	G	61	42	HV: 49
Q	56	37	LmdV: 50	K	62	43	HV: 50
A	57	38	LmdV: 51	G	63	44	HV: 51
P	58	39	LmdV: 52	L	64	45	HV: 52
I	59	40	LmdV: 53	E	65	46	HV: 53
L	60	41	LmdV: 54	W	66	47	HV: 54
L	61	42	LmdV: 55	I	67	48	HV: 55
I	62	43	LmdV: 56	G	68	49	HV: 56
Y	63	44	LmdV: 57	Y	69	50	HV: 57
N	64	45	LmdV: 58	I	70	51	HV: 58
—	64.1	45.1	LmdV: 59	S	71	52	HV: 59
—	64.2	45.2	LmdV: 60	D	72	53	HV: 60
—	64.3	45.3	LmdV: 61	—	72.1	53.1	HV: 61
—	64.4	45.4	LmdV: 62	—	72.2	53.2	HV: 62
—	64.5	45.5	LmdV: 63	—	72.3	53.3	HV: 63
—	64.6	45.6	LmdV: 64	—	72.4	53.4	HV: 64
—	64.7	45.7	LmdV: 65	R	73	54	HV: 65
—	64.8	45.8	LmdV: 66	E	74	55	HV: 66
N	65	46	LmdV: 67	S	75	56	HV: 67
Q	66	47	LmdV: 68	A	76	57	HV: 68
D	67	48	LmdV: 69	T	77	58	HV: 69
R	68	49	LmdV: 70	Y	78	59	HV: 70
P	69	50	LmdV: 71	N	79	60	HV: 71
S	70	51	LmdV: 72	P	80	61	HV: 72
G	71	52	LmdV: 73	S	81	62	HV: 73
I	72	53	LmdV: 74	L	82	63	HV: 74
P	73	54	LmdV: 75	N	83	64	HV: 75
E	74	55	LmdV: 76	S	84	65	HV: 76
R	75	56	LmdV: 77	R	85	66	HV: 77
F	76	57	LmdV: 78	V	86	67	HV: 78
S	77	58	LmdV: 79	V	87	68	HV: 79
G	78	59	LmdV: 80	I	88	69	HV: 80
T	79	60	LmdV: 81	S	89	70	HV: 81
P	80	61	LmdV: 81.1	R	90	71	HV: 82
D	81	62	LmdV: 81.2	D	91	72	HV: 83
I	82	63	LmdV: 81.3	T	92	73	HV: 84
N	83	64	LmdV: 82	S	93	74	HV: 85
F	84	65	LmdV: 83	K	94	75	HV: 86
G	85	66	LmdV: 84	N	95	76	HV: 87
—	85.1	66.1	LmdV: 85	Q	96	77	HV: 88
—	85.2	66.2	LmdV: 86	L	97	78	HV: 89
T	86	67	LmdV: 87	S	98	79	HV: 90
R	87	68	LmdV: 88	L	99	80	HV: 91
A	88	69	LmdV: 89	K	100	81	HV: 92
T	89	70	LmdV: 90	L	101	82	HV: 93
L	90	71	LmdV: 91	N	102	83	HV: 94
T	91	72	LmdV: 92	S	103	84	HV: 95
I	92	73	LmdV: 93	V	104	85	HV: 96
S	93	74	LmdV: 94	T	105	86	HV: 97
G	94	75	LmdV: 95	P	106	87	HV: 98
V	95	76	LmdV: 96	A	107	88	HV: 99
E	96	77	LmdV: 97	D	108	89	HV: 100
A	97	78	LmdV: 98	T	109	90	HV: 101
G	98	79	LmdV: 99	A	110	91	HV: 102
D	99	80	LmdV: 100	V	111	92	HV: 103
E	100	81	LmdV: 101	Y	112	93	HV: 104
A	101	82	LmdV: 102	Y	113	94	HV: 105
D	102	83	LmdV: 103	C	114	95	HV: 106
Y	103	84	LmdV: 104	A	115	96	HV: 107
Y	104	85	LmdV: 105	T	116	97	HV: 108
C	105	86	LmdV: 106	A	117	98	HV: 109
H	106	87	LmdV: 107	R	118	99	HV: 110
M	107	88	LmdV: 108	R	119	100	HV: 111
W	108	89	LmdV: 109	G	120	101	HV: 112
D	109	90	LmdV: 110	Q	121	102	HV: 113
S	110	91	LmdV: 111	R	122	103	HV: 114
R	111	92	LmdV: 112	I	123	104	HV: 115
—	111.1	92.1	LmdV: 113	Y	124	105	HV: 116
—	111.2	92.2	LmdV: 114	G	125	106	HV: 117
—	111.3	92.3	LmdV: 115	V	126	107	HV: 118
—	111.4	92.4	LmdV: 116	V	127	108	HV: 119
—	111.5	92.5	LmdV: 117	—	127.1	108.1	HV: 120
—	111.6	92.6	LmdV: 118	—	127.2	108.2	HV: 121
—	111.7	92.7	LmdV: 119	—	127.3	108.3	HV: 122
—	111.8	92.8	LmdV: 120	—	127.4	108.4	HV: 123
—	111.9	92.9	LmdV: 121	—	127.5	108.5	HV: 124
—	111.10	92.10	LmdV: 122	—	127.6	108.6	HV: 125
—	111.11	92.11	LmdV: 123	S	128	109	HV: 126
—	111.12	92.12	LmdV: 124	F	129	110	HV: 127
—	111.13	92.13	LmdV: 125	G	130	111	HV: 128
—	111.14	92.14	LmdV: 126	E	131	112	HV: 129
—	111.15	92.15	LmdV: 127	F	132	113	HV: 130
—	111.16	92.16	LmdV: 128	F	133	114	HV: 131
—	111.17	92.17	LmdV: 129	Y	134	115	HV: 132
—	111.18	92.18	LmdV: 130	Y	135	116	HV: 133
—	111.19	92.19	LmdV: 131	Y	136	117	HV: 134
—	111.20	92.20	LmdV: 132	S	137	118	HV: 135
S	112	93	LmdV: 133	M	138	119	HV: 136
G	113	94	LmdV: 134	D	139	120	HV: 137
F	114	95	LmdV: 135	V	140	121	HV: 138
S	115	96	LmdV: 136	W	141	122	HV: 139
W	116	97	LmdV: 137	G	142	123	HV: 140
S	117	98	LmdV: 138	K	143	124	HV: 141
F	118	99	LmdV: 139	G	144	125	HV: 142
G	119	100	LmdV: 140	T	145	126	HV: 143
G	120	101	LmdV: 141	T	146	127	HV: 144
A	121	102	LmdV: 142	V	147	128	HV: 145
T	122	103	LmdV: 143	T	148	129	HV: 146
R	123	104	LmdV: 144	V	149	130	HV: 147
L	124	105	LmdV: 145	S	150	131	HV: 148
T	125	106	LmdV: 146	S	151	132	HV: 149
V	126	107	LmdV: 147	—	151.1	132.1	HCnst-Ig: 1
L	127	108	LmdV: 148	—	151.2	132.2	HCnst-Ig: 2
G	128	109	LmdV: 149	A	152	133	HCnst-Ig: 3
Q	129	110	LmdCnst-Ig: 1	S	153	134	HCnst-Ig: 4
P	130	111	LmdCnst-Ig: 2	T	154	135	HCnst-Ig: 5
K	131	112	LmdCnst-Ig: 3	K	155	136	HCnst-Ig: 6
A	132	113	LmdCnst-Ig: 4	G	156	137	HCnst-Ig: 7
A	133	114	LmdCnst-Ig: 5	P	157	138	HCnst-Ig: 8
P	134	115	LmdCnst-Ig: 6	S	158	139	HCnst-Ig: 9
S	135	116	LmdCnst-Ig: 7	V	159	140	HCnst-Ig: 10
V	136	117	LmdCnst-Ig: 8	F	160	141	HCnst-Ig: 11
T	137	118	LmdCnst-Ig: 9	P	161	142	HCnst-Ig: 12
L	138	119	LmdCnst-Ig: 10	L	162	143	HCnst-Ig: 13
F	139	120	LmdCnst-Ig: 11	A	163	144	HCnst-Ig: 14
P	140	121	LmdCnst-Ig: 12	P	164	145	HCnst-Ig: 15
P	141	122	LmdCnst-Ig: 13	—	164.1	145.1	HCnst-Ig: 16
S	142	123	LmdCnst-Ig: 14	S	165	146	HCnst-Ig: 17
S	143	124	LmdCnst-Ig: 15	—	165.1	146.1	HCnst-Ig: 18
E	144	125	LmdCnst-Ig: 16	S	166	147	HCnst-Ig: 19
—	144.1	125.1	LmdCnst-Ig: 17	K	167	148	HCnst-Ig: 20
—	144.2	125.2	LmdCnst-Ig: 18	S	168	149	HCnst-Ig: 21
E	145	126	LmdCnst-Ig: 19	T	169	150	HCnst-Ig: 22
L	146	127	LmdCnst-Ig: 20	S	170	151	HCnst-Ig: 23
—	146.1	127.1	LmdCnst-Ig: 21	G	171	152	HCnst-Ig: 24
—	146.2	127.2	LmdCnst-Ig: 22	G	172	153	HCnst-Ig: 25
Q	147	128	LmdCnst-Ig: 23	T	173	154	HCnst-Ig: 26
A	148	129	LmdCnst-Ig: 24	A	174	155	HCnst-Ig: 27
N	149	130	LmdCnst-Ig: 25	A	175	156	HCnst-Ig: 28
K	150	131	LmdCnst-Ig: 26	L	176	157	HCnst-Ig: 29
A	151	132	LmdCnst-Ig: 27	G	177	158	HCnst-Ig: 30
T	152	133	LmdCnst-Ig: 28	C	178	159	HCnst-Ig: 31
L	153	134	LmdCnst-Ig: 29	L	179	160	HCnst-Ig: 32
V	154	135	LmdCnst-Ig: 30	V	180	161	HCnst-Ig: 33
C	155	136	LmdCnst-Ig: 31	K	181	162	HCnst-Ig: 34
L	156	137	LmdCnst-Ig: 32	D	182	163	HCnst-Ig: 35
I	157	138	LmdCnst-Ig: 33	Y	183	164	HCnst-Ig: 36
S	158	139	LmdCnst-Ig: 34	F	184	165	HCnst-Ig: 37
D	159	140	LmdCnst-Ig: 35	P	185	166	HCnst-Ig: 38
F	160	141	LmdCnst-Ig: 36	—	185.1	166.1	HCnst-Ig: 39
Y	161	142	LmdCnst-Ig: 37	—	185.2	166.2	HCnst-Ig: 40
P	162	143	LmdCnst-Ig: 38	E	186	167	HCnst-Ig: 41
—	162.1	143.1	LmdCnst-Ig: 39	P	187	168	HCnst-Ig: 42
—	162.2	143.2	LmdCnst-Ig: 40	V	188	169	HCnst-Ig: 43
G	163	144	LmdCnst-Ig: 41	T	189	170	HCnst-Ig: 44
A	164	145	LmdCnst-Ig: 42	V	190	171	HCnst-Ig: 45
V	165	146	LmdCnst-Ig: 43	S	191	172	HCnst-Ig: 46
T	166	147	LmdCnst-Ig: 44	W	192	173	HCnst-Ig: 47
V	167	148	LmdCnst-Ig: 45	—	192.1	173.1	HCnst-Ig: 48
A	168	149	LmdCnst-Ig: 46	N	193	174	HCnst-Ig: 49
W	169	150	LmdCnst-Ig: 47	S	194	175	HCnst-Ig: 50
—	169.1	150.1	LmdCnst-Ig: 48	G	195	176	HCnst-Ig: 51
K	170	151	LmdCnst-Ig: 49	A	196	177	HCnst-Ig: 52
A	171	152	LmdCnst-Ig: 50	L	197	178	HCnst-Ig: 53
D	172	153	LmdCnst-Ig: 51	T	198	179	HCnst-Ig: 54
S	173	154	LmdCnst-Ig: 52	S	199	180	HCnst-Ig: 55
S	174	155	LmdCnst-Ig: 53	G	200	181	HCnst-Ig: 56
P	175	156	LmdCnst-Ig: 54	V	201	182	HCnst-Ig: 57
V	176	157	LmdCnst-Ig: 55	H	202	183	HCnst-Ig: 58
K	177	158	LmdCnst-Ig: 56	T	203	184	HCnst-Ig: 59
A	178	159	LmdCnst-Ig: 57	—	203.1	184.1	HCnst-Ig: 60
G	179	160	LmdCnst-Ig: 58	—	203.2	184.2	HCnst-Ig: 61
V	180	161	LmdCnst-Ig: 59	F	204	185	HCnst-Ig: 62
E	181	162	LmdCnst-Ig: 60	P	205	186	HCnst-Ig: 63
T	182	163	LmdCnst-Ig: 61	A	206	187	HCnst-Ig: 64
T	183	164	LmdCnst-Ig: 62	V	207	188	HCnst-Ig: 65
T	184	165	LmdCnst-Ig: 63	L	208	189	HCnst-Ig: 66
P	185	166	LmdCnst-Ig: 64	Q	209	190	HCnst-Ig: 67
S	186	167	LmdCnst-Ig: 65	—	209.1	190.1	HCnst-Ig: 68
K	187	168	LmdCnst-Ig: 66	—	209.2	190.2	HCnst-Ig: 69
Q	188	169	LmdCnst-Ig: 67	—	209.3	190.3	HCnst-Ig: 70
—	188.1	169.1	LmdCnst-Ig: 68	—	209.4	190.4	HCnst-Ig: 71
—	188.2	169.2	LmdCnst-Ig: 69	—	209.5	190.5	HCnst-Ig: 72
—	188.3	169.3	LmdCnst-Ig: 70	S	210	191	HCnst-Ig: 73
—	188.4	169.4	LmdCnst-Ig: 71	S	211	192	HCnst-Ig: 74
—	188.5	169.5	LmdCnst-Ig: 72	G	212	193	HCnst-Ig: 75
S	189	170	LmdCnst-Ig: 73	L	213	194	HCnst-Ig: 76
N	190	171	LmdCnst-Ig: 74	Y	214	195	HCnst-Ig: 77
N	191	172	LmdCnst-Ig: 75	S	215	196	HCnst-Ig: 78
K	192	173	LmdCnst-Ig: 76	L	216	197	HCnst-Ig: 79
Y	193	174	LmdCnst-Ig: 77	S	217	198	HCnst-Ig: 80
A	194	175	LmdCnst-Ig: 78	S	218	199	HCnst-Ig: 81
A	195	176	LmdCnst-Ig: 79	V	219	200	HCnst-Ig: 82
S	196	177	LmdCnst-Ig: 80	V	220	201	HCnst-Ig: 83
S	197	178	LmdCnst-Ig: 81	T	221	202	HCnst-Ig: 84
Y	198	179	LmdCnst-Ig: 82	V	222	203	HCnst-Ig: 85
L	199	180	LmdCnst-Ig: 83	P	223	204	HCnst-Ig: 86
S	200	181	LmdCnst-Ig: 84	S	224	205	HCnst-Ig: 87
L	201	182	LmdCnst-Ig: 85	S	225	206	HCnst-Ig: 88
T	202	183	LmdCnst-Ig: 86	S	226	207	HCnst-Ig: 89
P	203	184	LmdCnst-Ig: 87	L	227	208	HCnst-Ig: 90
E	204	185	LmdCnst-Ig: 88	—	227.1	208.1	HCnst-Ig: 91
Q	205	186	LmdCnst-Ig: 89	G	228	209	HCnst-Ig: 92
W	206	187	LmdCnst-Ig: 90	T	229	210	HCnst-Ig: 93
—	206.1	187.1	LmdCnst-Ig: 91	Q	230	211	HCnst-Ig: 94
K	207	188	LmdCnst-Ig: 92	T	231	212	HCnst-Ig: 95
S	208	189	LmdCnst-Ig: 93	—	231.1	212.1	HCnst-Ig: 96
H	209	190	LmdCnst-Ig: 94	—	231.2	212.2	HCnst-Ig: 97
R	210	191	LmdCnst-Ig: 95	—	231.3	212.3	HCnst-Ig: 98
S	211	192	LmdCnst-Ig: 96	Y	232	213	HCnst-Ig: 99
—	211.1	192.1	LmdCnst-Ig: 97	I	233	214	HCnst-Ig: 100
—	211.2	192.2	LmdCnst-Ig: 98	C	234	215	HCnst-Ig: 101
Y	212	193	LmdCnst-Ig: 99	N	235	216	HCnst-Ig: 102
S	213	194	LmdCnst-Ig: 100	V	236	217	HCnst-Ig: 103
C	214	195	LmdCnst-Ig: 101	N	237	218	HCnst-Ig: 104
Q	215	196	LmdCnst-Ig: 102	H	238	219	HCnst-Ig: 105
V	216	197	LmdCnst-Ig: 103	K	239	220	HCnst-Ig: 106
T	217	198	LmdCnst-Ig: 104	P	240	221	HCnst-Ig: 107
H	218	199	LmdCnst-Ig: 105	S	241	222	HCnst-Ig: 108
E	219	200	LmdCnst-Ig: 106	N	242	223	HCnst-Ig: 109
G	220	201	LmdCnst-Ig: 107	—	242.1	223.1	HCnst-Ig: 110
S	221	202	LmdCnst-Ig: 108	—	242.2	223.2	HCnst-Ig: 111
T	222	203	LmdCnst-Ig: 109	T	243	224	HCnst-Ig: 112
—	222.1	203.1	LmdCnst-Ig: 110	K	244	225	HCnst-Ig: 113
—	222.2	203.2	LmdCnst-Ig: 111	V	245	226	HCnst-Ig: 114
V	223	204	LmdCnst-Ig: 112	D	246	227	HCnst-Ig: 115
E	224	205	LmdCnst-Ig: 113	K	247	228	HCnst-Ig: 116
K	225	206	LmdCnst-Ig: 114	—	247.1	228.1	HCnst-Ig: 117
T	226	207	LmdCnst-Ig: 115	K	248	229	HCnst-Ig: 118
V	227	208	LmdCnst-Ig: 116	V	249	230	HCnst-Ig: 119
—	227.1	208.1	LmdCnst-Ig: 117	—	249.1	230.1	HCnst-Ig: 120
A	228	209	LmdCnst-Ig: 118	—	249.2	230.2	HCnst-Ig: 121
P	229	210	LmdCnst-Ig: 119	—	249.3	230.3	HCnst-Ig: 122
T	230	211	LmdCnst-Ig: 120	—	249.4	230.4	HCnst-Ig: 123
E	231	212	LmdCnst-Ig: 121	—	249.5	230.5	Hinge: 1
C	232	213	LmdCnst-Ig: 122	—	249.6	230.6	Hinge: 2
S	233	214	LmdCnst-Ig: 123	—	249.7	230.7	Hinge: 3
				—	249.8	230.8	Hinge: 4
				—	249.9	230.9	Hinge: 5
				—	249.10	230.10	Hinge: 6
				—	249.11	230.11	Hinge: 7
				—	249.12	230.12	Hinge: 8
				—	249.13	230.13	Hinge: 9
				—	249.14	230.14	Hinge: 10
				—	249.15	230.15	Hinge: 11
				—	249.16	230.16	Hinge: 12
				—	249.17	230.17	Hinge: 13
				—	249.18	230.18	Hinge: 14
				—	249.19	230.19	Hinge: 15
				—	249.20	230.20	Hinge: 16
				—	249.21	230.21	Hinge: 17
				—	249.22	230.22	Hinge: 18
				—	249.23	230.23	Hinge: 19
				—	249.24	230.24	Hinge: 20
				—	249.25	230.25	Hinge: 21
				—	249.26	230.26	Hinge: 22
				—	249.27	230.27	Hinge: 23
				—	249.28	230.28	Hinge: 24
				—	249.29	230.29	Hinge: 25
				—	249.29	230.29	Hinge: 25
				—	249.30	230.30	Hinge: 26
				—	249.31	230.31	Hinge: 27
				—	249.32	230.32	Hinge: 28
				—	249.33	230.33	Hinge: 29
				—	249.34	230.34	Hinge: 30
				—	249.35	230.35	Hinge: 31
				—	249.36	230.36	Hinge: 32
				—	249.37	230.37	Hinge: 33
				—	249.38	230.38	Hinge: 34
				—	249.39	230.39	Hinge: 35
				—	249.40	230.40	Hinge: 36
				—	249.41	230.41	Hinge: 37
				—	249.42	230.42	Hinge: 38
				—	249.43	230.43	Hinge: 39
				—	249.44	230.44	Hinge: 40
				—	249.45	230.45	Hinge: 41
				—	249.46	230.46	Hinge: 42
				—	249.47	230.47	Hinge: 43
				—	249.48	230.48	Hinge: 44
				—	249.49	230.49	Hinge: 45
				—	249.50	230.50	Hinge: 46
				—	249.51	230.51	Hinge: 47
				—	249.52	230.52	Hinge: 48
				—	249.53	230.53	Hinge: 49
				—	249.54	230.54	Hinge: 50
				—	249.55	230.55	Hinge: 51
				—	249.56	230.56	Hinge: 52
				—	249.57	230.57	Hinge: 53
				—	249.58	230.58	Hinge: 54
				—	249.59	230.59	Hinge: 55
				—	249.60	230.60	Hinge: 56
				—	249.61	230.61	Hinge: 57
				—	249.62	230.62	Hinge: 58
				—	249.63	230.63	Hinge: 59
				—	249.64	230.64	Hinge: 60
				—	249.65	230.65	Hinge: 61
				—	249.66	230.66	Hinge: 62
				—	249.67	230.67	Hinge: 63
				—	249.68	230.68	Hinge: 64
				—	249.69	230.69	Hinge: 65
				—	249.70	230.70	Hinge: 66
				—	249.71	230.71	Hinge: 67
				—	249.72	230.72	Hinge: 68
				—	249.73	230.73	Hinge: 69
				—	249.74	230.74	Hinge: 70
				—	249.75	230.75	Hinge: 71
				—	249.76	230.76	Hinge: 72
				—	249.77	230.77	Hinge: 73
				—	249.78	230.78	Hinge: 74
				—	249.79	230.79	Hinge: 75
				—	249.80	230.80	Hinge: 76
				—	249.81	230.81	Hinge: 77
				—	249.82	230.82	Hinge: 78
				—	249.83	230.83	Hinge: 79
				—	249.84	230.84	Hinge: 80
				—	249.85	230.85	Hinge: 81
				—	249.86	230.86	Hinge: 82
				—	249.87	230.87	Hinge: 83
				—	249.88	230.88	Hinge: 84
				—	249.89	230.89	Hinge: 85
				—	249.90	230.90	Hinge: 86
				—	249.91	230.91	Hinge: 87
				—	249.92	230.92	Hinge: 88
				—	249.93	230.93	Hinge: 89
				—	249.94	230.94	Hinge: 90
				—	249.95	230.95	Hinge: 91
				—	249.96	230.96	Hinge: 92
				—	249.97	230.97	Hinge: 93
				—	249.98	230.98	Hinge: 94
				—	249.99	230.99	Hinge: 95
				E	250	231	Hinge: 96
				P	251	232	Hinge: 97
				K	252	233	Hinge: 98
				S	253	234	Hinge: 99
				—	253.1	234.1	Hinge: 100
				—	253.2	234.2	Hinge: 101
				—	253.3	234.3	Hinge: 102
				—	253.4	234.4	Hinge: 103
				—	253.5	234.5	Hinge: 104
				—	253.6	234.6	Hinge: 105
				—	253.7	234.7	Hinge: 106
				C	254	235	Hinge: 107
				D	255	236	Hinge: 108
				K	256	237	Hinge: 109
				T	257	238	Hinge: 110
				H	258	239	Hinge: 111
				T	259	240	Hinge: 112
				C	260	241	Hinge: 113
				P	261	242	Hinge: 114
				P	262	243	Hinge: 115
				C	263	244	Hinge: 116
				P	264	245	Hinge: 117
				A	265	246	Hinge: 118
				P	266	247	Hinge: 119
				E	267	248	Hinge: 120
				L	268	249	Hinge: 121
				L	269	250	Hinge: 122
				G	270	251	Hinge: 123
				—	270.1	251.1	Fc-N: 1
				—	270.2	251.2	Fc-N: 2
				—	270.3	251.3	Fc-N: 3
				—	270.4	251.4	Fc-N: 4
				G	271	252	Fc-N: 5
				P	272	253	Fc-N: 6
				S	273	254	Fc-N: 7
				V	274	255	Fc-N: 8
				F	275	256	Fc-N: 9
				L	276	257	Fc-N: 10
				F	277	258	Fc-N: 11
				P	278	259	Fc-N: 12
				P	279	260	Fc-N: 13
				—	279.1	260.1	Fc-N: 14
				K	280	261	Fc-N: 15
				P	281	262	Fc-N: 16
				K	282	263	Fc-N: 17
				—	282.1	263.1	Fc-N: 18
				D	283	264	Fc-N: 19
				T	284	265	Fc-N: 20
				L	285	266	Fc-N: 21
				M	286	267	Fc-N: 22
				I	287	268	Fc-N: 23
				S	288	269	Fc-N: 24
				R	289	270	Fc-N: 25
				T	290	271	Fc-N: 26
				P	291	272	Fc-N: 27
				E	292	273	Fc-N: 28
				V	293	274	Fc-N: 29
				T	294	275	Fc-N: 30
				C	295	276	Fc-N: 31
				V	296	277	Fc-N: 32
				V	297	278	Fc-N: 33
				V	298	279	Fc-N: 34
				D	299	280	Fc-N: 35
				V	300	281	Fc-N: 36
				S	301	282	Fc-N: 37
				H	302	283	Fc-N: 38
				E	303	284	Fc-N: 39
				D	304	285	Fc-N: 40
				P	305	286	Fc-N: 41
				E	306	287	Fc-N: 42
				V	307	288	Fc-N: 43
				K	308	289	Fc-N: 44
				F	309	290	Fc-N: 45
				N	310	291	Fc-N: 46
				W	311	292	Fc-N: 47
				—	311.1	292.1	Fc-N: 48
				Y	312	293	Fc-N: 49
				V	313	294	Fc-N: 50
				D	314	295	Fc-N: 51
				G	315	296	Fc-N: 52
				V	316	297	Fc-N: 53
				E	317	298	Fc-N: 54
				—	317.1	298.1	Fc-N: 55
				—	317.2	298.2	Fc-N: 56
				V	318	299	Fc-N: 57
				H	319	300	Fc-N: 58
				N	320	301	Fc-N: 59
				A	321	302	Fc-N: 60
				K	322	303	Fc-N: 61
				T	323	304	Fc-N: 62
				K	324	305	Fc-N: 63
				P	325	306	Fc-N: 64
				R	326	307	Fc-N: 65
				E	327	308	Fc-N: 66
				E	328	309	Fc-N: 67
				Q	329	310	Fc-N: 68
				—	329.1	310.1	Fc-N: 69
				—	329.2	310.2	Fc-N: 70
				—	329.3	310.3	Fc-N: 71
				—	329.4	310.4	Fc-N: 72
				Y	330	311	Fc-N: 73
				N	331	312	Fc-N: 74
				S	332	313	Fc-N: 75
				T	333	314	Fc-N: 76
				Y	334	315	Fc-N: 77
				R	335	316	Fc-N: 78
				V	336	317	Fc-N: 79
				V	337	318	Fc-N: 80
				S	338	319	Fc-N: 81
				V	339	320	Fc-N: 82
				L	340	321	Fc-N: 83
				T	341	322	Fc-N: 84
				V	342	323	Fc-N: 85
				L	343	324	Fc-N: 86
				H	344	325	Fc-N: 87
				Q	345	326	Fc-N: 88
				D	346	327	Fc-N: 89
				W	347	328	Fc-N: 90
				—	347.1	328.1	Fc-N: 91
				L	348	329	Fc-N: 92
				N	349	330	Fc-N: 93
				G	350	331	Fc-N: 94
				K	351	332	Fc-N: 95
				E	352	333	Fc-N: 96
				—	352.1	333.1	Fc-N: 97
				—	352.2	333.2	Fc-N: 98
				Y	353	334	Fc-N: 99
				K	354	335	Fc-N: 100
				C	355	336	Fc-N: 101
				K	356	337	Fc-N: 102
				V	357	338	Fc-N: 103
				S	358	339	Fc-N: 104
				N	359	340	Fc-N: 105
				K	360	341	Fc-N: 106
				A	361	342	Fc-N: 107
				L	362	343	Fc-N: 108
				P	363	344	Fc-N: 109
				—	363.1	344.1	Fc-N: 110
				—	363.2	344.2	Fc-N: 111
				A	364	345	Fc-N: 112
				P	365	346	Fc-N: 113
				I	366	347	Fc-N: 114
				E	367	348	Fc-N: 115
				K	368	349	Fc-N: 116
				T	369	350	Fc-N: 117
				I	370	351	Fc-N: 118
				S	371	352	Fc-N: 119
				K	372	353	Fc-N: 120
				A	373	354	Fc-N: 121
				K	374	355	Fc-N: 122
				G	375	356	Fc-N: 123
				—	375.1	356.1	Fc-C: 1
				Q	376	357	Fc-C: 2
				P	377	358	Fc-C: 3
				R	378	359	Fc-C: 4
				E	379	360	Fc-C: 5
				P	380	361	Fc-C: 6
				Q	381	362	Fc-C: 7
				V	382	363	Fc-C: 8
				Y	383	364	Fc-C: 9
				T	384	365	Fc-C: 10
				L	385	366	Fc-C: 11
				P	386	367	Fc-C: 12
				P	387	368	Fc-C: 13
				—	387.1	368.1	Fc-C: 14
				S	388	369	Fc-C: 15
				R	389	370	Fc-C: 16
				D	390	371	Fc-C: 17
				—	390.1	371.1	Fc-C: 18
				E	391	372	Fc-C: 19
				L	392	373	Fc-C: 20
				—	392.1	373.1	Fc-C: 21
				—	392.2	373.2	Fc-C: 22
				T	393	374	Fc-C: 23
				K	394	375	Fc-C: 24
				N	395	376	Fc-C: 25
				Q	396	377	Fc-C: 26
				V	397	378	Fc-C: 27
				S	398	379	Fc-C: 28
				L	399	380	Fc-C: 29
				T	400	381	Fc-C: 30
				C	401	382	Fc-C: 31
				L	402	383	Fc-C: 32
				V	403	384	Fc-C: 33
				K	404	385	Fc-C: 34
				G	405	386	Fc-C: 35
				F	406	387	Fc-C: 36
				Y	407	388	Fc-C: 37
				P	408	389	Fc-C: 38
				—	408.1	389.1	Fc-C: 39
				—	408.2	389.2	Fc-C: 40
				S	409	390	Fc-C: 41
				D	410	391	Fc-C: 42
				I	411	392	Fc-C: 43
				A	412	393	Fc-C: 44
				V	413	394	Fc-C: 45
				E	414	395	Fc-C: 46
				W	415	396	Fc-C: 47
				—	415.1	396.1	Fc-C: 48
				E	416	397	Fc-C: 49
				S	417	398	Fc-C: 50
				N	418	399	Fc-C: 51
				G	419	400	Fc-C: 52
				Q	420	401	Fc-C: 53
				P	421	402	Fc-C: 54
				—	421.1	402.1	Fc-C: 55
				—	421.2	402.2	Fc-C: 56
				E	422	403	Fc-C: 57
				N	423	404	Fc-C: 58
				N	424	405	Fc-C: 59
				Y	425	406	Fc-C: 60
				K	426	407	Fc-C: 61
				T	427	408	Fc-C: 62
				T	428	409	Fc-C: 63
				P	429	410	Fc-C: 64
				P	430	411	Fc-C: 65
				V	431	412	Fc-C: 66
				L	432	413	Fc-C: 67
				D	433	414	Fc-C: 68
				—	433.1	414.1	Fc-C: 69
				—	433.2	414.2	Fc-C: 70
				—	433.3	414.3	Fc-C: 71
				—	433.4	414.4	Fc-C: 72
				S	434	415	Fc-C: 73
				D	435	416	Fc-C: 74
				G	436	417	Fc-C: 75
				S	437	418	Fc-C: 76
				F	438	419	Fc-C: 77
				F	439	420	Fc-C: 78
				L	440	421	Fc-C: 79
				Y	441	422	Fc-C: 80
				S	442	423	Fc-C: 81
				K	443	424	Fc-C: 82
				L	444	425	Fc-C: 83
				T	445	426	Fc-C: 84
				V	446	427	Fc-C: 85
				D	447	428	Fc-C: 86
				K	448	429	Fc-C: 87
				S	449	430	Fc-C: 88
				R	450	431	Fc-C: 89
				W	451	432	Fc-C: 90
				—	451.1	432.1	Fc-C: 91
				Q	452	433	Fc-C: 92
				Q	453	434	Fc-C: 93
				G	454	435	Fc-C: 94
				N	455	436	Fc-C: 95
				V	456	437	Fc-C: 96
				—	456.1	437.1	Fc-C: 97
				—	456.2	437.2	Fc-C: 98
				F	457	438	Fc-C: 99
				S	458	439	Fc-C: 100
				C	459	440	Fc-C: 101
				S	460	441	Fc-C: 102
				V	461	442	Fc-C: 103
				L	462	443	Fc-C: 104
				H	463	444	Fc-C: 105
				E	464	445	Fc-C: 106
				A	465	446	Fc-C: 107
				L	466	447	Fc-C: 108
				H	467	448	Fc-C: 109
				—	467.1	448.1	Fc-C: 110
				—	467.2	448.2	Fc-C: 111
				S	468	449	Fc-C: 112
				H	469	450	Fc-C: 113
				Y	470	451	Fc-C: 114
				T	471	452	Fc-C: 115
				—	471.1	452.1	Fc-C: 116
				Q	472	453	Fc-C: 117
				K	473	454	Fc-C: 118
				S	474	455	Fc-C: 119
				L	475	456	Fc-C: 120
				S	476	457	Fc-C: 121
				L	477	458	Fc-C: 122
				S	478	459	Fc-C: 123
				P	479	460	HCnst-Po: 1
				G	480	461	HCnst-Po: 2
				K	481	462	HCnst-Po: 3
				—	481.1	462.1	HCnst-Po: 4
				—	481.2	462.2	HCnst-Po: 5
				—	481.3	462.3	HCnst-Po: 6
				—	481.4	462.4	HCnst-Po: 7
				—	481.5	462.5	HCnst-Po: 8
				—	481.6	462.6	HCnst-Po: 9
				—	481.7	462.7	HCnst-Po: 10
				—	481.8	462.8	HCnst-Po: 11
				—	481.9	462.9	HCnst-Po: 12
				—	481.10	462.10	HCnst-Po: 13
				—	481.11	462.11	HCnst-Po: 14
				—	481.12	462.12	HCnst-Po: 15
				—	481.13	462.13	HCnst-Po: 16
				—	481.14	462.14	HCnst-Po: 17
				—	481.15	462.15	HCnst-Po: 18
				—	481.16	462.16	HCnst-Po: 19
				—	481.17	462.17	HCnst-Po: 20
				—	481.18	462.18	HCnst-Po: 21
				—	481.19	462.19	HCnst-Po: 22
				—	481.20	462.20	HCnst-Po: 23
				—	481.21	462.21	HCnst-Po: 24
				—	481.22	462.22	HCnst-Po: 25
				—	481.23	462.23	HCnst-Po: 26
				—	481.24	462.24	HCnst-Po: 27
				—	481.25	462.25	HCnst-Po: 28
				—	481.26	462.26	HCnst-Po: 29
				—	481.27	462.27	HCnst-Po: 30
				—	481.28	462.28	HCnst-Po: 31
				—	481.29	462.29	HCnst-Po: 32
				—	481.30	462.30	HCnst-Po: 33
				—	481.31	462.31	HCnst-Po: 34
				—	481.32	462.32	HCnst-Po: 35
				—	481.33	462.33	HCnst-Po: 36
				—	481.34	462.34	HCnst-Po: 37
				—	481.35	462.35	HCnst-Po: 38
				—	481.36	462.36	HCnst-Po: 39
				—	481.37	462.37	HCnst-Po: 40
				—	481.38	462.38	HCnst-Po: 41
				—	481.39	462.39	HCnst-Po: 42
				—	481.40	462.40	HCnst-Po: 43
				—	481.41	462.41	HCnst-Po: 44
				—	481.42	462.42	HCnst-Po: 45
				—	481.43	462.43	HCnst-Po: 46
				—	481.44	462.44	HCnst-Po: 47
				—	481.45	462.45	HCnst-Po: 48
				—	481.46	462.46	HCnst-Po: 49
				—	481.47	462.47	HCnst-Po: 50
				—	481.48	462.48	HCnst-Po: 51
				—	481.49	462.49	HCnst-Po: 52
				—	481.50	462.50	HCnst-Po: 53
				—	481.51	462.51	HCnst-Po: 54
				—	481.52	462.52	HCnst-Po: 55
				—	481.53	462.53	HCnst-Po: 56
				—	481.54	462.54	HCnst-Po: 57
				—	481.55	462.55	HCnst-Po: 58
				—	481.56	462.56	HCnst-Po: 59
				—	481.57	462.57	HCnst-Po: 60
				—	481.58	462.58	HCnst-Po: 61
				—	481.59	462.59	HCnst-Po: 62
				—	481.60	462.60	HCnst-Po: 63
				—	481.61	462.61	HCnst-Po: 64
				—	481.62	462.62	HCnst-Po: 65
				—	481.63	462.63	HCnst-Po: 66
				—	481.64	462.64	HCnst-Po: 67
				—	481.65	462.65	HCnst-Po: 68
				—	481.66	462.66	HCnst-Po: 69
				—	481.67	462.67	HCnst-Po: 70
				—	481.68	462.68	HCnst-Po: 71
				—	481.69	462.69	HCnst-Po: 72
				—	481.70	462.70	HCnst-Po: 73
				—	481.71	462.71	HCnst-Po: 74
				—	481.72	462.72	HCnst-Po: 75
				—	481.73	462.73	HCnst-Po: 76
				—	481.74	462.74	HCnst-Po: 77
				—	481.75	462.75	HCnst-Po: 78
				—	481.76	462.76	HCnst-Po: 79
				—	481.77	462.77	HCnst-Po: 80
				—	481.78	462.78	HCnst-Po: 81
				—	481.79	462.79	HCnst-Po: 82
				—	481.80	462.80	HCnst-Po: 83
				—	481.81	462.81	HCnst-Po: 84
				—	481.82	462.82	HCnst-Po: 85
				—	481.83	462.83	HCnst-Po: 86
				—	481.84	462.84	HCnst-Po: 87
				—	481.85	462.85	HCnst-Po: 88
				—	481.86	462.86	HCnst-Po: 89
				—	481.87	462.87	HCnst-Po: 90
				—	481.88	462.88	HCnst-Po: 91
				—	481.89	462.89	HCnst-Po: 92
				—	481.90	462.90	HCnst-Po: 93
				—	481.91	462.91	HCnst-Po: 94
				—	481.92	462.92	HCnst-Po: 95
				—	481.93	462.93	HCnst-Po: 96
				—	481.94	462.94	HCnst-Po: 97
				—	481.95	462.95	HCnst-Po: 98
				—	481.96	462.96	HCnst-Po: 99
				—	481.97	462.97	HCnst-Po: 100
				—	481.98	462.98	HCnst-Po: 101
				—	481.99	462.99	HCnst-Po: 102
				—	481.100	462.100	HCnst-Po: 103
				—	481.101	462.101	HCnst-Po: 104
				—	481.102	462.102	HCnst-Po: 105
				—	481.103	462.103	HCnst-Po: 106
				—	481.104	462.104	HCnst-Po: 107
				—	481.105	462.105	HCnst-Po: 108
				—	481.106	462.106	HCnst-Po: 109
				—	481.107	462.107	HCnst-Po: 110
				—	481.108	462.108	HCnst-Po: 111
				—	481.109	462.109	HCnst-Po: 112
				—	481.110	462.110	HCnst-Po: 113
				—	481.111	462.111	HCnst-Po: 114
				—	481.112	462.112	HCnst-Po: 115
				—	481.113	462.113	HCnst-Po: 116
				—	481.114	462.114	HCnst-Po: 117
				—	481.115	462.115	HCnst-Po: 118
				—	481.116	462.116	HCnst-Po: 119
				—	481.117	462.117	HCnst-Po: 120
				—	481.118	462.118	HCnst-Po: 121
				—	481.119	462.119	HCnst-Po: 122
				—	481.120	462.120	HCnst-Po: 123

TABLE 2
Amino acid sequences of light chain variable
regions (hightlighted in bold) of the
10-1074 antibody variants
SEQ ID		OTHER
NO.	SEQUENCE	INFORMATION
SEQ ID	MGWSCIILFLVATATGVHSS	MS-193_LC
NO: 1	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-194_LC
NO: 2	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-203_LC
NO: 3	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-204_LC
NO: 4	YVPPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-205_LC
NO: 5	YVRSLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-206_LC
NO: 6	YVRPLSVALGQTARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-207_LC
NO: 7	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQQRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-208_LC
NO: 8	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTN
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-209_LC
NO: 9	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DSNEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-210_LC
NO: 10	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DIGEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-211_LC
NO: 11	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTTATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-212_LC
NO: 12	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWESRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-213_LC
NO: 13	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	GTRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-214_LC
NO: 14	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-215_LC
NO: 15	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-216_LC
NO: 16	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-217_LC
NO: 17	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-218_LC
NO: 18	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-219_LC
	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
NO: 19	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-220_LC
NO: 20	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-224_LC
NO: 21	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-200_LC
NO: 22	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-201_LC
NO: 23	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIY
	NNQDRPSGIPERFSGTPDIN
	FGTRATLTISGVEAGDEADY
	YCHMWDSRSGFSWSFGGATR
	LTVLGQPKAAPSVTLFPPSS
	EELQANKATLVCLISDFYPG
	AVTVAWKADSSPVKAGVETT
	TPSKQSNNKYAASSYLSLTP
	EQWKSHRSYSCQVTHEGSTV
	EKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-202_LC
NO: 24	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-225_LC
NO: 25	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-226_LC
NO: 26	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-227_LC
NO: 27	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-228_LC
NO: 28	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-229_LC
NO: 29	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-230_LC
NO: 30	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-231_LC
NO: 31	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-232_LC
NO: 32	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-233_LC
NO: 33	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-234_LC
NO: 34	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-235_LC
NO: 35	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-236_LC
NO: 36	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-237_LC
NO: 37	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-238_LC
NO: 38	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-239_LC
NO: 39	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINEGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-240_LC
NO: 40	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-241_LC
NO: 41	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-242_LC
NO: 42	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-243_LC
NO: 43	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-244_LC
NO: 44	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-245_LC
NO: 45	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-246_LC
NO: 46	YVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS
SEQ ID	MGWSCIILFLVATATGVHSS	MS-247_LC
NO: 47	PVRPLSVALGETARISCGRQ
	ALGSRAVQWYQHRPGQAPIL
	LIYNNQDRPSGIPERFSGTP
	DINFGTRATLTISGVEAGDE
	ADYYCHMWDSRSGFSWSFGG
	ATRLTVLGQPKAAPSVTLFP
	PSSEELQANKATLVCLISDF
	YPGAVTVAWKADSSPVKAGV
	ETTTPSKQSNNKYAASSYLS
	LTPEQWKSHRSYSCQVTHEG
	STVEKTVAPTECS

TABLE 3
Amino acid sequences of heavy chain variable
regions (highlighted in bold) of the 10-1074
antibody variants
	SEQ
	ID		OTHER
	NO.	SEQUENCE	INFORMATION
	SEQ ID	MGWSCIILFLVATAT	MS-193_HC
	NO: 48	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVMHEA
		LHNHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-194_HC
	NO: 49	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-203_HC
	NO: 50	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-204_HC
	NO: 51	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-205_HC
	NO: 52	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-206_HC
	NO: 53	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-207_HC
	NO: 54	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-208_HC
	NO: 55	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-209_HC
	NO: 56	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-210_HC
	NO: 57	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-211_HC
	NO: 58	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-212_HC
	NO: 59	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-213_HC
	NO: 60	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-214_HC
	NO: 61	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		GSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-215_HC
	NO: 62	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQPP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-216_HC
	NO: 63	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-217_HC
	NO: 64	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-218_HC
	NO: 65	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-219_HC
	NO: 66	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-220_HC
	NO: 67	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGQGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-224_HC
	NO: 68	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLQSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-200_HC
	NO: 69	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-201_HC
	NO: 70	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-202_HC
	NO: 71	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-225_HC
	NO: 72	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-226_HC
	NO: 73	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-227_HC
	NO: 74	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-228_HC
	NO: 75	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-229_HC
	NO: 76	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-230_HC
	NO: 77	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-231_HC
	NO: 78	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-232_HC
	NO: 79	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-233_HC
	NO: 80	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-234_HC
	NO: 81	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-235_HC
	NO: 82	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQLSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-236_HC
	NO: 83	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-237_HC
	NO: 84	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISR
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-238_HC
	NO: 85	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-239_HC
	NO: 86	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISR
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-240_HC
	NO: 87	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-241_HC
	NO: 88	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-242_HC
	NO: 89	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-243_HC
	NO: 90	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQFSLKLNSVT
		PADTAVYYCATARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-244_HC
	NO: 91	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQLSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-245_HC
	NO: 92	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVVISV
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-246_HC
	NO: 93	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K
	SEQ ID	MGWSCIILFLVATAT	MS-247_HC
	NO: 94	GVHSQVQLQESGPGL
		VKPSETLSVTCSVSG
		DSMNNYYWTWIRQSP
		GKGLEWIGYISDRES
		ATYNPSLNSRVTISV
		DTSKNQFSLKLNSVT
		PADTAVYYCARARRG
		QRIYGVVSFGEFFYY
		YSMDVWGKGTTVTVS
		SASTKGPSVFPLAPS
		SKSTSGGTAALGCLV
		KDYFPEPVTVSWNSG
		ALTSGVHTFPAVLQS
		SGLYSLSSVVTVPSS
		SLGTQTYICNVNHKP
		SNTKVDKKVEPKSCD
		KTHTCPPCPAPELLG
		GPSVFLFPPKPKDTL
		MISRTPEVTCVVVDV
		SHEDPEVKFNWYVDG
		VEVHNAKTKPREEQY
		NSTYRVVSVLTVLHQ
		DWLNGKEYKCKVSNK
		ALPAPIEKTISKAKG
		QPREPQVYTLPPSRD
		ELTKNQVSLTCLVKG
		FYPSDIAVEWESNGQ
		PENNYKTTPPVLDSD
		GSFFLYSKLTVDKSR
		WQQGNVFSCSVLHEA
		LHSHYTQKSLSLSPG
		K

TABLE 4
Amino acid sequences of CDR regions of
the 10-1074 antibody variants
		OTHER
SEQ ID NO.	SEQUENCE	INFORMATION
SEQ ID NO: 95	GRQALGSRAVQ	MS-193_LC CDR1
SEQ ID NO: 96	NNQDRPS	MS-193_LC CDR2
SEQ ID NO: 97	HMWDSRSGFSWS	MS-193_LC CDR3
SEQ ID NO: 98	NNYYWT	MS-193_HC CDR1
SEQ ID NO: 99	YISDRESATYNPSLNS	MS-193_HC CDR2
SEQ ID NO: 100	ARRGQRIYGVVSFGEF	MS-193_HC CDR3
	FYYYSMDV
SEQ ID NO: 101	GRQALGSRAVQ	MS-194_LC CDR1
SEQ ID NO: 102	NNQDRPS	MS-194_LC CDR2
SEQ ID NO: 103	HMWDSRSGFSWS	MS-194_LC CDR3
SEQ ID NO: 104	NNYYWT	MS-194_HC CDR1
SEQ ID NO: 105	YISDRESATYNPSLNS	MS-194_HC CDR2
SEQ ID NO: 106	ARRGQRIYGVVSFGEF	MS-194_HC CDR3
	FYYYSMDV
SEQ ID NO: 107	GRQALGSRAVQ	MS-203_LC CDR1
SEQ ID NO: 108	NNQDRPS	MS-203_LC CDR2
SEQ ID NO: 109	HMWDSRSGFSWS	MS-203_LC CDR3
SEQ ID NO: 110	NNYYWT	MS-203_HC CDR1
SEQ ID NO: 111	YISDRESATYNPSLNS	MS-203_HC CDR2
SEQ ID NO: 112	ARRGQRIYGVVSFGEF	MS-203_HC CDR3
	FYYYSMDV
SEQ ID NO: 113	GRQALGSRAVQ	MS-204_LC CDR1
SEQ ID NO: 114	NNQDRPS	MS-204_LC CDR2
SEQ ID NO: 115	HMWDSRSGFSWS	MS-204_LC CDR3
SEQ ID NO: 116	NNYYWT	MS-204_HC CDR1
SEQ ID NO: 117	YISDRESATYNPSLNS	MS-204_HC CDR2
SEQ ID NO: 118	ARRGQRIYGVVSFGEF	MS-204_HC CDR3
	FYYYSMDV
SEQ ID NO: 119	GRQALGSRAVQ	MS-205_LC CDR1
SEQ ID NO: 120	NNQDRPS	MS-205_LC CDR2
SEQ ID NO: 121	HMWDSRSGFSWS	MS-205_LC CDR3
SEQ ID NO: 122	NNYYWT	MS-205_HC CDR1
SEQ ID NO: 123	YISDRESATYNPSLNS	MS-205_HC CDR2
SEQ ID NO: 124	ARRGQRIYGVVSFGEF	MS-205_HC CDR3
	FYYYSMDV
SEQ ID NO: 125	GRQALGSRAVQ	MS-206_LC CDR1
SEQ ID NO: 126	NNQDRPS	MS-206_LC CDR2
SEQ ID NO: 127	HMWDSRSGFSWS	MS-206_LC CDR3
SEQ ID NO: 128	NNYYWT	MS-206_HC CDR1
SEQ ID NO: 129	YISDRESATYNPSLNS	MS-206_HC CDR2
SEQ ID NO: 130	ARRGQRIYGVVSFGEF	MS-206_HC CDR3
	FYYYSMDV
SEQ ID NO: 131	GRQALGSRAVQ	MS-207_LC CDR1
SEQ ID NO: 132	NNQDRPS	MS-207_LC CDR2
SEQ ID NO: 133	HMWDSRSGFSWS	MS-207_LC CDR3
SEQ ID NO: 134	NNYYWT	MS-207_HC CDR1
SEQ ID NO: 135	YISDRESATYNPSLNS	MS-207_HC CDR2
SEQ ID NO: 136	ARRGQRIYGVVSFGEF	MS-207_HC CDR3
	FYYYSMDV
SEQ ID NO: 137	GRQALGSRAVQ	MS-208_LC CDR1
SEQ ID NO: 138	NNQDRPS	MS-208_LC CDR2
SEQ ID NO: 139	HMWDSRSGFSWS	MS-208_LC CDR3
SEQ ID NO: 140	NNYYWT	MS-208_HC CDR1
SEQ ID NO: 141	YISDRESATYNPSLNS	MS-208_HC CDR2
SEQ ID NO: 142	ARRGQRIYGVVSFGEF	MS-208_HC CDR3
	FYYYSMDV
SEQ ID NO: 143	GRQALGSRAVQ	MS-209_LC CDR1
SEQ ID NO: 144	NNQDRPS	MS-209_LC CDR2
SEQ ID NO: 145	HMWDSRSGFSWS	MS-209_LC CDR3
SEQ ID NO: 146	NNYYWT	MS-209_HC CDR1
SEQ ID NO: 147	YISDRESATYNPSLNS	MS-209_HC CDR2
SEQ ID NO: 148	ARRGQRIYGVVSFGEF	MS-209_HC CDR3
	FYYYSMDV
SEQ ID NO: 149	GRQALGSRAVQ	MS-210_LC CDR1
SEQ ID NO: 150	NNQDRPS	MS-210_LC CDR2
SEQ ID NO: 151	HMWDSRSGFSWS	MS-210_LC CDR3
SEQ ID NO: 152	NNYYWT	MS-210_HC CDR1
SEQ ID NO: 153	YISDRESATYNPSLNS	MS-210_HC CDR2
SEQ ID NO: 154	ARRGQRIYGVVSFGEF	MS-210_HC CDR3
	FYYYSMDV
SEQ ID NO: 155	GRQALGSRAVQ	MS-211_LC CDR1
SEQ ID NO: 156	NNQDRPS	MS-211_LC CDR2
SEQ ID NO: 157	HMWDSRSGFSWS	MS-211_LC CDR3
SEQ ID NO: 158	NNYYWT	MS-211_HC CDR1
SEQ ID NO: 159	YISDRESATYNPSLNS	MS-211_HC CDR2
SEQ ID NO: 160	ARRGQRIYGVVSFGEF	MS-211_HC CDR3
	FYYYSMDV
SEQ ID NO: 161	GRQALGSRAVQ	MS-212_LC CDR1
SEQ ID NO: 162	NNQDRPS	MS-212_LC CDR2
SEQ ID NO: 163	HMWESRSGFSWS	MS-212_LC CDR3
SEQ ID NO: 164	NNYYWT	MS-212_HC CDR1
SEQ ID NO: 165	YISDRESATYNPSLNS	MS-212_HC CDR2
SEQ ID NO: 166	ARRGQRIYGVVSFGEF	MS-212_HC CDR3
	FYYYSMDV
SEQ ID NO: 167	GRQALGSRAVQ	MS-213_LC CDR1
SEQ ID NO: 168	NNQDRPS	MS-213_LC CDR2
SEQ ID NO: 169	HMWDSRSGFSWS	MS-213_LC CDR3
SEQ ID NO: 170	NNYYWT	MS-213_HC CDR1
SEQ ID NO: 171	YISDRESATYNPSLNS	MS-213_HC CDR2
SEQ ID NO: 172	ARRGQRIYGVVSFGEF	MS-213_HC CDR3
	FYYYSMDV
SEQ ID NO: 173	GRQALGSRAVQ	MS-214_LC CDR1
SEQ ID NO: 174	NNQDRPS	MS-214_LC CDR2
SEQ ID NO: 175	HMWDSRSGFSWS	MS-214_LC CDR3
SEQ ID NO: 176	NNYYWT	MS-214_HC CDR1
SEQ ID NO: 177	YISDRESATYNPSLNS	MS-214_HC CDR2
SEQ ID NO: 178	ARRGQRIYGVVSFGEF	MS-214_HC CDR3
	FYYYSMDV
SEQ ID NO: 179	GRQALGSRAVQ	MS-215_LC CDR1
SEQ ID NO: 180	NNQDRPS	MS-215_LC CDR2
SEQ ID NO: 181	HMWDSRSGFSWS	MS-215_LC CDR3
SEQ ID NO: 182	NNYYWT	MS-215_HC CDR1
SEQ ID NO: 183	YISDRESATYNPSLNS	MS-215_HC CDR2
SEQ ID NO: 184	ARRGQRIYGVVSFGEF	MS-215_HC CDR3
	FYYYSMDV
SEQ ID NO: 185	GRQALGSRAVQ	MS-216_LC CDR1
SEQ ID NO: 186	NNQDRPS	MS-216_LC CDR2
SEQ ID NO: 187	HMWDSRSGFSWS	MS-216_LC CDR3
SEQ ID NO: 188	NNYYWT	MS-216_HC CDR1
SEQ ID NO: 189	YISDRESATYNPSLNS	MS-216_HC CDR2
SEQ ID NO: 190	ARRGQRIYGVVSFGEF	MS-216_HC CDR3
	FYYYSMDV
SEQ ID NO: 191	GRQALGSRAVQ	MS-217_LC CDR1
SEQ ID NO: 192	NNQDRPS	MS-217_LC CDR2
SEQ ID NO: 193	HMWDSRSGFSWS	MS-217_LC CDR3
SEQ ID NO: 194	NNYYWT	MS-217_HC CDR1
SEQ ID NO: 195	YISDRESATYNPSLNS	MS-217_HC CDR2
SEQ ID NO: 196	ARRGQRIYGVVSFGEF	MS-217_HC CDR3
	FYYYSMDV
SEQ ID NO: 197	GRQALGSRAVQ	MS-218_LC CDR1
SEQ ID NO: 198	NNQDRPS	MS-218_LC CDR2
SEQ ID NO: 199	HMWDSRSGFSWS	MS-218_LC CDR3
SEQ ID NO: 200	NNYYWT	MS-218_HC CDR1
SEQ ID NO: 201	YISDRESATYNPSLNS	MS-218_HC CDR2
SEQ ID NO: 202	ARRGQRIYGVVSFGEF	MS-218_HC CDR3
	FYYYSMDV
SEQ ID NO: 203	GRQALGSRAVQ	MS-219_LC CDR1
SEQ ID NO: 204	NNQDRPS	MS-219_LC CDR2
SEQ ID NO: 205	HMWDSRSGFSWS	MS-219_LC CDR3
SEQ ID NO: 206	NNYYWT	MS-219_HC CDR1
SEQ ID NO: 207	YISDRESATYNPSLNS	MS-219_HC CDR2
SEQ ID NO: 208	ARRGQRIYGVVSFGEF	MS-219_HC CDR3
	FYYYSMDV
SEQ ID NO: 209	GRQALGSRAVQ	MS-220_LC CDR1
SEQ ID NO: 210	NNQDRPS	MS-220_LC CDR2
SEQ ID NO: 211	HMWDSRSGFSWS	MS-220_LC CDR3
SEQ ID NO: 212	NNYYWT	MS-220_HC CDR1
SEQ ID NO: 213	YISDRESATYNPSLNS	MS-220_HC CDR2
SEQ ID NO: 214	ARRGQRIYGVVSFGEF	MS-220_HC CDR3
	FYYYSMDV
SEQ ID NO: 215	GRQALGSRAVQ	MS-224_LC CDR1
SEQ ID NO: 216	NNQDRPS	MS-224_LC CDR2
SEQ ID NO: 217	HMWDSRSGFSWS	MS-224_LC CDR3
SEQ ID NO: 218	NNYYWT	MS-224_HC CDR1
SEQ ID NO: 219	YISDRESATYNPSLQS	MS-224_HC CDR2
SEQ ID NO: 220	ARRGQRIYGVVSFGEF	MS-224_HC CDR3
	FYYYSMDV
SEQ ID NO: 221	GRQALGSRAVQ	MS-200_LC CDR1
SEQ ID NO: 222	NNQDRPS	MS-200_LC CDR2
SEQ ID NO: 223	HMWDSRSGFSWS	MS-200_LC CDR3
SEQ ID NO: 224	NNYYWT	MS-200_HC CDR1
SEQ ID NO: 225	YISDRESATYNPSLNS	MS-200_HC CDR2
SEQ ID NO: 226	ARRGQRIYGVVSFGEF	MS-200_HC CDR3
	FYYYSMDV
SEQ ID NO: 227	GRQALGSRAVQ	MS-201_LC CDR1
SEQ ID NO: 228	NNQDRPS	MS-201_LC CDR2
SEQ ID NO: 229	HMWDSRSGFSWS	MS-201_LC CDR3
SEQ ID NO: 230	NNYYWT	MS-201_HC CDR1
SEQ ID NO: 231	YISDRESATYNPSLNS	MS-201_HC CDR2
SEQ ID NO: 232	ARRGQRIYGVVSFGEF	MS-201_HC CDR3
	FYYYSMDV
SEQ ID NO: 233	GRQALGSRAVQ	MS-202_LC CDR1
SEQ ID NO: 234	NNQDRPS	MS-202_LC CDR2
SEQ ID NO: 235	HMWDSRSGFSWS	MS-202_LC CDR3
SEQ ID NO: 236	NNYYWT	MS-202_HC CDR1
SEQ ID NO: 237	YISDRESATYNPSLNS	MS-202_HC CDR2
SEQ ID NO: 238	ARRGQRIYGVVSFGEF	MS-202_HC CDR3
	FYYYSMDV
SEQ ID NO: 239	GRQALGSRAVQ	MS-225_LC CDR1
SEQ ID NO: 240	NNQDRPS	MS-225_LC CDR2
SEQ ID NO: 241	HMWDSRSGFSWS	MS-225_LC CDR3
SEQ ID NO: 242	NNYYWT	MS-225_HC CDR1
SEQ ID NO: 243	YISDRESATYNPSLNS	MS-225_HC CDR2
SEQ ID NO: 244	ARRGQRIYGVVSFGEF	MS-225_HC CDR3
	FYYYSMDV
SEQ ID NO: 245	GRQALGSRAVQ	MS-226_LC CDR1
SEQ ID NO: 246	NNQDRPS	MS-226_LC CDR2
SEQ ID NO: 247	HMWDSRSGFSWS	MS-226_LC CDR3
SEQ ID NO: 248	NNYYWT	MS-226_HC CDR1
SEQ ID NO: 249	YISDRESATYNPSLNS	MS-226_HC CDR2
SEQ ID NO: 250	ARRGQRIYGVVSFGEF	MS-226_HC CDR3
	FYYYSMDV
SEQ ID NO: 251	GRQALGSRAVQ	MS-227_LC CDR1
SEQ ID NO: 252	NNQDRPS	MS-227_LC CDR2
SEQ ID NO: 253	HMWDSRSGFSWS	MS-227_LC CDR3
SEQ ID NO: 254	NNYYWT	MS-227_HC CDR1
SEQ ID NO: 255	YISDRESATYNPSLNS	MS-227_HC CDR2
SEQ ID NO: 256	ARRGQRIYGVVSFGEF	MS-227_HC CDR3
	FYYYSMDV
SEQ ID NO: 257	GRQALGSRAVQ	MS-228_LC CDR1
SEQ ID NO: 258	NNQDRPS	MS-228_LC CDR2
SEQ ID NO: 259	HMWDSRSGFSWS	MS-228_LC CDR3
SEQ ID NO: 260	NNYYWT	MS-228_HC CDR1
SEQ ID NO: 261	YISDRESATYNPSLNS	MS-228_HC CDR2
SEQ ID NO: 262	ARRGQRIYGVVSFGEF	MS-228_HC CDR3
	FYYYSMDV
SEQ ID NO: 263	GRQALGSRAVQ	MS-229_LC CDR1
SEQ ID NO: 264	NNQDRPS	MS-229_LC CDR2
SEQ ID NO: 265	HMWDSRSGFSWS	MS-229_LC CDR3
SEQ ID NO: 266	NNYYWT	MS-229_HC CDR1
SEQ ID NO: 267	YISDRESATYNPSLNS	MS-229_HC CDR2
SEQ ID NO: 268	ARRGQRIYGVVSFGEF	MS-229_HC CDR3
	FYYYSMDV
SEQ ID NO: 269	GRQALGSRAVQ	MS-230_LC CDR1
SEQ ID NO: 270	NNQDRPS	MS-230_LC CDR2
SEQ ID NO: 271	HMWDSRSGFSWS	MS-230_LC CDR3
SEQ ID NO: 272	NNYYWT	MS-230_HC CDR1
SEQ ID NO: 273	YISDRESATYNPSLNS	MS-230_HC CDR2
SEQ ID NO: 274	ARRGQRIYGVVSFGEF	MS-230_HC CDR3
	FYYYSMDV
SEQ ID NO: 275	GRQALGSRAVQ	MS-231_LC CDR1
SEQ ID NO: 276	NNQDRPS	MS-231_LC CDR2
SEQ ID NO: 277	HMWDSRSGFSWS	MS-231_LC CDR3
SEQ ID NO: 278	NNYYWT	MS-231_HC CDR1
SEQ ID NO: 279	YISDRESATYNPSLNS	MS-231_HC CDR2
SEQ ID NO: 280	ARRGQRIYGVVSFGEF	MS-231_HC CDR3
	FYYYSMDV
SEQ ID NO: 281	GRQALGSRAVQ	MS-232_LC CDR1
SEQ ID NO: 282	NNQDRPS	MS-232_LC CDR2
SEQ ID NO: 283	HMWDSRSGFSWS	MS-232_LC CDR3
SEQ ID NO: 284	NNYYWT	MS-232_HC CDR1
SEQ ID NO: 285	YISDRESATYNPSLNS	MS-232_HC CDR2
SEQ ID NO: 286	ARRGQRIYGVVSFGEF	MS-232_HC CDR3
	FYYYSMDV
SEQ ID NO: 287	GRQALGSRAVQ	MS-233_LC CDR1
SEQ ID NO: 288	NNQDRPS	MS-233_LC CDR2
SEQ ID NO: 289	HMWDSRSGFSWS	MS-233_LC CDR3
SEQ ID NO: 290	NNYYWT	MS-233_HC CDR1
SEQ ID NO: 291	YISDRESATYNPSLNS	MS-233_HC CDR2
SEQ ID NO: 292	ARRGQRIYGVVSFGEF	MS-233_HC CDR3
	FYYYSMDV
SEQ ID NO: 293	GRQALGSRAVQ	MS-234_LC CDR1
SEQ ID NO: 294	NNQDRPS	MS-234_LC CDR2
SEQ ID NO: 295	HMWDSRSGFSWS	MS-234_LC CDR3
SEQ ID NO: 296	NNYYWT	MS-234_HC CDR1
SEQ ID NO: 297	YISDRESATYNPSLNS	MS-234_HC CDR2
SEQ ID NO: 298	ARRGQRIYGVVSFGEF	MS-234_HC CDR3
	FYYYSMDV
SEQ ID NO: 299	GRQALGSRAVQ	MS-235_LC CDR1
SEQ ID NO: 300	NNQDRPS	MS-235_LC CDR2
SEQ ID NO: 301	HMWDSRSGFSWS	MS-235_LC CDR3
SEQ ID NO: 302	NNYYWT	MS-235_HC CDR1
SEQ ID NO: 303	YISDRESATYNPSLNS	MS-235_HC CDR2
SEQ ID NO: 304	ARRGQRIYGVVSFGEF	MS-235_HC CDR3
	FYYYSMDV
SEQ ID NO: 305	GRQALGSRAVQ	MS-236_LC CDR1
SEQ ID NO: 306	NNQDRPS	MS-236_LC CDR2
SEQ ID NO: 307	HMWDSRSGFSWS	MS-236_LC CDR3
SEQ ID NO: 308	NNYYWT	MS-236_HC CDR1
SEQ ID NO: 309	YISDRESATYNPSLNS	MS-236_HC CDR2
SEQ ID NO: 310	ARRGQRIYGVVSFGEF	MS-236_HC CDR3
	FYYYSMDV
SEQ ID NO: 311	GRQALGSRAVQ	MS-237_LC CDR1
SEQ ID NO: 312	NNQDRPS	MS-237_LC CDR2
SEQ ID NO: 313	HMWDSRSGFSWS	MS-237_LC CDR3
SEQ ID NO: 314	NNYYWT	MS-237_HC CDR1
SEQ ID NO: 315	YISDRESATYNPSLNS	MS-237_HC CDR2
SEQ ID NO: 316	ARRGQRIYGVVSFGEF	MS-237_HC CDR3
	FYYYSMDV
SEQ ID NO: 317	GRQALGSRAVQ	MS-238_LC CDR1
SEQ ID NO: 318	NNQDRPS	MS-238_LC CDR2
SEQ ID NO: 319	HMWDSRSGFSWS	MS-238_LC CDR3
SEQ ID NO: 320	NNYYWT	MS-238_HC CDR1
SEQ ID NO: 321	YISDRESATYNPSLNS	MS-238_HC CDR2
SEQ ID NO: 322	ARRGQRIYGVVSFGEF	MS-238_HC CDR3
	FYYYSMDV
SEQ ID NO: 323	GRQALGSRAVQ	MS-239_LC CDR1
SEQ ID NO: 324	NNQDRPS	MS-239_LC CDR2
SEQ ID NO: 325	HMWDSRSGFSWS	MS-239_LC CDR3
SEQ ID NO: 326	NNYYWT	MS-239_HC CDR1
SEQ ID NO: 327	YISDRESATYNPSLNS	MS-239_HC CDR2
SEQ ID NO: 328	ARRGQRIYGVVSFGEF	MS-239_HC CDR3
	FYYYSMDV
SEQ ID NO: 329	GRQALGSRAVQ	MS-240_LC CDR1
SEQ ID NO: 330	NNQDRPS	MS-240_LC CDR2
SEQ ID NO: 331	HMWDSRSGFSWS	MS-240_LC CDR3
SEQ ID NO: 332	NNYYWT	MS-240_HC CDR1
SEQ ID NO: 333	YISDRESATYNPSLNS	MS-240_HC CDR2
SEQ ID NO: 334	ARRGQRIYGVVSFGEF	MS-240_HC CDR3
	FYYYSMDV
SEQ ID NO: 335	GRQALGSRAVQ	MS-241_LC CDR1
SEQ ID NO: 336	NNQDRPS	MS-241_LC CDR2
SEQ ID NO: 337	HMWDSRSGFSWS	MS-241_LC CDR3
SEQ ID NO: 338	NNYYWT	MS-241_HC CDR1
SEQ ID NO: 339	YISDRESATYNPSLNS	MS-241_HC CDR2
SEQ ID NO: 340	ARRGQRIYGVVSFGEF	MS-241_HC CDR3
	FYYYSMDV
SEQ ID NO: 341	GRQALGSRAVQ	MS-242_LC CDR1
SEQ ID NO: 342	NNQDRPS	MS-242_LC CDR2
SEQ ID NO: 343	HMWDSRSGFSWS	MS-242_LC CDR3
SEQ ID NO: 344	NNYYWT	MS-242_HC CDR1
SEQ ID NO: 345	YISDRESATYNPSLNS	MS-242_HC CDR2
SEQ ID NO: 346	ARRGQRIYGVVSFGEF	MS-242_HC CDR3
	FYYYSMDV
SEQ ID NO: 347	GRQALGSRAVQ	MS-243_LC CDR1
SEQ ID NO: 348	NNQDRPS	MS-243_LC CDR2
SEQ ID NO: 349	HMWDSRSGFSWS	MS-243_LC CDR3
SEQ ID NO: 350	NNYYWT	MS-243_HC CDR1
SEQ ID NO: 351	YISDRESATYNPSLNS	MS-243_HC CDR2
SEQ ID NO: 352	ARRGQRIYGVVSFGEF	MS-243_HC CDR3
	FYYYSMDV
SEQ ID NO: 353	GRQALGSRAVQ	MS-244_LC CDR1
SEQ ID NO: 354	NNQDRPS	MS-244_LC CDR2
SEQ ID NO: 355	HMWDSRSGFSWS	MS-244_LC CDR3
SEQ ID NO: 356	NNYYWT	MS-244_HC CDR1
SEQ ID NO: 357	YISDRESATYNPSLNS	MS-244_HC CDR2
SEQ ID NO: 358	ARRGQRIYGVVSFGEF	MS-244_HC CDR3
	FYYYSMDV
SEQ ID NO: 359	GRQALGSRAVQ	MS-245_LC CDR1
SEQ ID NO: 360	NNQDRPS	MS-245_LC CDR2
SEQ ID NO: 361	HMWDSRSGFSWS	MS-245_LC CDR3
SEQ ID NO: 362	NNYYWT	MS-245_HC CDR1
SEQ ID NO: 363	YISDRESATYNPSLNS	MS-245_HC CDR2
SEQ ID NO: 364	ARRGQRIYGVVSFGEF	MS-245_HC CDR3
	FYYYSMDV
SEQ ID NO: 365	GRQALGSRAVQ	MS-246_LC CDR1
SEQ ID NO: 366	NNQDRPS	MS-246_LC CDR2
SEQ ID NO: 367	HMWDSRSGFSWS	MS-246_LC CDR3
SEQ ID NO: 368	NNYYWT	MS-246_HC CDR1
SEQ ID NO: 369	YISDRESATYNPSLNS	MS-246_HC CDR2
SEQ ID NO: 370	ARRGQRIYGVVSFGEF	MS-246_HC CDR3
	FYYYSMDV
SEQ ID NO: 371	GRQALGSRAVQ	MS-247_LC CDR1
SEQ ID NO: 372	NNQDRPS	MS-247_LC CDR2
SEQ ID NO: 373	HMWDSRSGFSWS	MS-247_LC CDR3
SEQ ID NO: 374	NNYYWT	MS-247_HC CDR1
SEQ ID NO: 375	YISDRESATYNPSLNS	MS-247_HC CDR2
SEQ ID NO: 376	ARRGQRIYGVVSFGEF	MS-247_HC CDR3
	FYYYSMDV

TABLE 5
Nucleic acid sequences of light chain variable regions of
the 10-1074 antibody variants
SEQ ID		OTHER
NO.	SEQUENCE	INFORMATION
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-193_LC
NO: 377	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-194_LC
NO: 378	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-203_LC
NO: 379	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-204_LC
NO: 380	GTGCCACCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-205_LC
NO: 381	GTGCGCAGCCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-206_LC
NO: 382	GTGCGCCCGCTGTCAGTGGCCCTGGGGCAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-207_LC
NO: 383	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACAGAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-208_LC
NO: 384	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCAATGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-209_LC
NO: 385	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATTCCAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-210_LC
NO: 386	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTGGCTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-211_LC
NO: 387	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCACCGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-212_LC
NO: 388	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGAGAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-213_LC
NO: 389	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGGAACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-214_LC
NO: 390	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-215_LC
NO: 391	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-216_LC
NO: 392	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-217_LC
NO: 393	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-218_LC
NO: 394	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-219_LC
NO: 395	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCC
	CCTACAGAATGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-220_LC
NO: 396	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-224_LC
NO: 397	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCC
	CCTACAGAATGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-200_LC
NO: 398	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCC
	CCTACAGAATGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-201_LC
NO: 399	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-202_LC
NO: 400	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-225_LC
NO: 401	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCC
	CCTACAGAATGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-226_LC
NO: 402	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-227_LC
NO: 403	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-228_LC
NO: 404	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-229_LC
NO: 405	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-230_LC
NO: 406	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-231_LC
NO: 407	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-232_LC
NO: 408	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCC
	CCTACAGAATGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-233_LC
NO: 409	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-234_LC
NO: 410	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-235_LC
NO: 411	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-236_LC
NO: 412	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-237_LC
NO: 413	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-238_LC
NO: 414	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-239_LC
NO: 415	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-240_LC
NO: 416	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-241_LC
NO: 417	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-242_LC
NO: 418	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-243_LC
NO: 419	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-244_LC
NO: 420	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-245_LC
NO: 421	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCTAT	MS-246_LC
NO: 422	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA
SEQ ID	ATGGGATGGAGCTGTATCATCCTGTTCCTCGTGGCCACAGCAACCGGTGTACATTCTTCCCCT	MS-247_LC
NO: 423	GTGCGCCCGCTGTCAGTGGCCCTGGGGGAGACGGCCAGGATTTCCTGTGGACGACAGGCCCTT
	GGAAGTAGAGCTGTTCAGTGGTATCAACATAGGCCAGGCCAGGCCCCTATATTGCTCATTTAT
	AATAATCAAGACCGGCCCTCAGGGATCCCTGAGCGATTCTCTGGCACCCCTGATATTAATTTT
	GGGACCAGGGCCACCCTGACCATCAGCGGGGTCGAAGCCGGGGATGAAGCCGACTATTACTGT
	CACATGTGGGATAGTAGAAGTGGCTTCAGTTGGTCTTTCGGCGGGGCGACCAGGCTGACCGTC
	CTAGGTCAGCCCAAGGCTGCCCCCTCGGTCACTCTGTTCCCGCCCTCCTCTGAGGAGCTTCAA
	GCCAACAAGGCCACACTGGTGTGTCTCATAAGTGACTTCTACCCGGGAGCCGTGACAGTGGCC
	TGGAAGGCAGATAGCAGCCCCGTCAAGGCGGGAGTGGAGACCACCACACCCTCCAAACAAAGC
	AACAACAAGTACGCGGCCAGCAGCTATCTGAGCCTGACGCCTGAGCAGTGGAAGTCCCACAGA
	AGCTACAGCTGCCAGGTCACGCATGAAGGGAGCACCGTGGAGAAGACAGTGGCCCCTACAGAA
	TGTTCA

TABLE 6
Nucleic acid sequences of heavy chain variable regions of the 10-1074 antibody variants
SEQ ID		OTHER
NO.	SEQUENCE	INFORMATION
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-193_HC
NO: 424	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGAT
	GCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-194_HC
NO: 425	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-203_HC
NO: 426	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-204_HC
NO: 427	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-205_HC
NO: 428	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-206_HC
NO: 429	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-207_HC
NO: 430	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-208_HC
NO: 431	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-209_HC
NO: 432	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-210_HC
NO: 433	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-211_HC
NO: 434	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-212_HC
NO: 435	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-213_HC
NO: 436	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-214_HC
NO: 437	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGGTTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-215_HC
NO: 438	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGCCACCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-216_HC
NO: 439	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-217_HC
NO: 440	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-218_HC
NO: 441	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-219_HC
NO: 442	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-220_HC
NO: 443	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCCAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-224_HC
NO: 444	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCCAAAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-200_HC
NO: 445	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-201_HC
NO: 446	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-202_HC
NO: 447	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-225_HC
NO: 448	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-226_HC
NO: 449	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-227_HC
NO: 450	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-228_HC
NO: 451	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-229_HC
NO: 452	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-230_HC
NO: 453	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-231_HC
NO: 454	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-232_HC
NO: 455	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-233_HC
NO: 456	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-234_HC
NO: 457	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-235_HC
NO: 458	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-236_HC
NO: 459	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-237_HC
NO: 460	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCACGAGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-238_HC
NO: 461	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-239_HC
NO: 462	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCACGAGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-240_HC
NO: 463	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-241_HC
NO: 464	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-242_HC
NO: 465	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-243_HC
NO: 466	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGACAGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-244_HC
NO: 467	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTGTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-245_HC
NO: 468	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCGTCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-246_HC
NO: 469	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA
SEQ ID	ATGGGATGGTCATGTATCATCCTTTTTCTAGTAGCAACTGCAACCGGTGTACACTCGCAGGTGC	MS-247_HC
NO: 470	AGCTGCAGGAGTCGGGCCCAGGACTGGTGAAACCTTCGGAGACCCTGTCCGTCACCTGCAGTG
	TCTCTGGAGATTCCATGAATAATTACTACTGGACTTGGATCCGGCAGTCCCCCGGAAAGGGAC
	TGGAGTGGATAGGCTATATCTCTGACAGAGAATCAGCGACTTACAACCCCTCCCTCAATAGTC
	GAGTCACCATATCAGTTGACACGTCGAAAAACCAATTTTCCCTAAAATTAAACTCCGTCACCC
	CTGCGGACACGGCCGTCTATTACTGTGCGCGCGCGCGCCGAGGACAGAGGATTTATGGAGTGG
	TTTCCTTTGGAGAGTTCTTCTACTACTACTCCATGGACGTCTGGGGCAAGGGGACCACGGTCAC
	CGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACC
	TCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAGCCGGTGACGGTG
	TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA
	GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC
	ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATC
	TTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT
	CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGC
	GTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGT
	GGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGG
	TCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT
	CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGA
	GAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTG
	ACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAG
	CCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAC
	AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTG
	CATGAGGCTCTGCACTCCCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAA

TABLE 7
Nucleic acid sequences of CDR regions
of the 10-1074 antibody variants
	SEQ ID		OTHER
	NO.	SEQUENCE	INFORMATION
	SEQ ID	ATGGGATGGAGCTGT	MS-193_LC
	NO: 471	ATCATCCTGTTCCTC
		GTGGCCACAGCAACC
		GGTGTACATTCTTCC
		TATGTGCGCCCGCTG
		TCAGTGGCCCTGGGG
		GAGACGGCCAGGATT
		TCCTGTGGACGACAG
		GCCCTTGGAAGTAGA
		GCTGTTCAGTGGTAT
		CAACATAGGCCAGGC
		CAGGCCCCTATATTG
		CTCATTTATAATAAT
		CAAGACCGGCCCTCA
		GGGATCCCTGAGCGA
		TTCTCTGGCACCCCT
		GATATTAATTTTGGG
		ACCAGGGCCACCCTG
		ACCATCAGCGGGGTC
		GAAGCCGGGGATGAA
		GCCGACTATTACTGT
		CACATGTGGGATAGT
		AGAAGTGGCTTCAGT
		TGGTCTTTCGGCGGG
		GCGACCAGGCTGACC
		GTCCTAGGTCAGCCC
		AAGGCTGCCCCCTCG
		GTCACTCTGTTCCCG
		CCCTCCTCTGAGGAG
		CTTCAAGCCAACAAG
		GCCACACTGGTGTGT
		CTCATAAGTGACTTC
		TACCCGGGAGCCGTG
		ACAGTGGCCTGGAAG
		GCAGATAGCAGCCCC
		GTCAAGGCGGGAGTG
		GAGACCACCACACCC
		TCCAAACAAAGCAAC
		AACAAGTACGCGGCC
		AGCAGCTATCTGAGC
		CTGACGCCTGAGCAG
		TGGAAGTCCCACAGA
		AGCTACAGCTGCCAG
		GTCACGCATGAAGGG
		AGCACCGTGGAGAAG
		ACAGTGGCCCCTACA
		GAATGTTCA
	SEQ ID	GGACGACAGGCCCTT	MS-193_LC CDR1
	NO: 472	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-193_LC CDR2
	NO: 473	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-193_LC CDR3
	NO: 474	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-193_HC CDR1
	NO: 475	ACT
	SEQ ID	TATATCTCTGACAGA	MS-193_HC CDR2
	NO: 476	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-193_HC CDR3
	NO: 477	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-194_LC CDR1
	NO: 478	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-194_LC CDR2
	NO: 479	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-194_LC CDR3
	NO: 480	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-194_HC CDR1
	NO: 481	ACT
	SEQ ID	TATATCTCTGACAGA	MS-194_HC CDR2
	NO: 482	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-194_HC CDR3
	NO: 483	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-203_LC CDR1
	NO: 484	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-203_LC CDR2
	NO: 485	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-203_LC CDR3
	NO: 486	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-203_HC CDR1
	NO: 487	ACT
	SEQ ID	TATATCTCTGACAGA	MS-203_HC CDR2
	NO: 488	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-203_HC CDR3
	NO: 489	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-204_LC CDR1
	NO: 490	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-204_LC CDR2
	NO: 491	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-204_LC CDR3
	NO: 492	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-204_HC CDR1
	NO: 493	ACT
	SEQ ID	TATATCTCTGACAGA	MS-204_HC CDR2
	NO: 494	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-204_HC CDR3
	NO: 495	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-205_LC CDR1
	NO: 496	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-205_LC CDR2
	NO: 497	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-205_LC CDR3
	NO: 498	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-205_HC CDR1
	NO: 499	ACT
	SEQ ID	TATATCTCTGACAGA	MS-205_HC CDR2
	NO: 500	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-205_HC CDR3
	NO: 501	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-206_LC CDR1
	NO: 502	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-206_LC CDR2
	NO: 503	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-206_LC CDR3
	NO: 504	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-206_HC CDR1
	NO: 505	ACT
	SEQ ID	TATATCTCTGACAGA	MS-206_HC CDR2
	NO: 506	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-206_HC CDR3
	NO: 507	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-207_LC CDR1
	NO: 508	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-207_LC CDR2
	NO: 509	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-207_LC CDR3
	NO: 510	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-207_HC CDR1
	NO: 511	ACT
	SEQ ID	TATATCTCTGACAGA	MS-207_HC CDR2
	NO: 512	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-207_HC CDR3
	NO: 513	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-208_LC CDR1
	NO: 514	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-208_LC CDR2
	NO: 515	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-208_LC CDR3
	NO: 516	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-208_HC CDR1
	NO: 517	ACT
	SEQ ID	TATATCTCTGACAGA	MS-208_HC CDR2
	NO: 518	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-208_HC CDR3
	NO: 519	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-209_LC CDR1
	NO: 520	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-209_LC CDR2
	NO: 521	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-209_LC CDR3
	NO: 522	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-209_HC CDR1
	NO: 523	ACT
	SEQ ID	TATATCTCTGACAGA	MS-209_HC CDR2
	NO: 524	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-209_HC CDR3
	NO: 525	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-210_LC CDR1
	NO: 526	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-210_LC CDR2
	NO: 527	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-210_LC CDR3
	NO: 528	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-210_HC CDR1
	NO: 529	ACT
	SEQ ID	TATATCTCTGACAGA	MS-210_HC CDR2
	NO: 530	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-210_HC CDR3
	NO: 531	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-211_LC CDR1
	NO: 532	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-211_LC CDR2
	NO: 533	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-211_LC CDR3
	NO: 534	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-211_HC CDR1
	NO: 535	ACT
	SEQ ID	TATATCTCTGACAGA	MS-211_HC CDR2
	NO: 536	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-211_HC CDR3
	NO: 537	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-212_LC CDR1
	NO: 538	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-212_LC CDR2
	NO: 539	CCCTCA
	SEQ ID	CACATGTGGGAGAGT	MS-212_LC CDR3
	NO: 540	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-212_HC CDR1
	NO: 541	ACT
	SEQ ID	TATATCTCTGACAGA	MS-212_HC CDR2
	NO: 542	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-212_HC CDR3
	NO: 543	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-213_LC CDR1
	NO: 544	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-213_LC CDR2
	NO: 545	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-213_LC CDR3
	NO: 546	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-213_HC CDR1
	NO: 547	ACT
	SEQ ID	TATATCTCTGACAGA	MS-213_HC CDR2
	NO: 548	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-213_HC CDR3
	NO: 549	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-214_LC CDR1
	NO: 550	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-214_LC CDR2
	NO: 551	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-214_LC CDR3
	NO: 552	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-214_HC CDR1
	NO: 553	ACT
	SEQ ID	TATATCTCTGACAGA	MS-214_HC CDR2
	NO: 554	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-214_HC CDR3
	NO: 555	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-215_LC CDR1
	NO: 556	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-215_LC CDR2
	NO: 557	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-215_LC CDR3
	NO: 558	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-215_HC CDR1
	NO: 559	ACT
	SEQ ID	TATATCTCTGACAGA	MS-215_HC CDR2
	NO: 560	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-215_HC CDR3
	NO: 561	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-216_LC CDR1
	NO: 562	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-216_LC CDR2
	NO: 563	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-216_LC CDR3
	NO: 564	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-216_HC CDR1
	NO: 565	ACT
	SEQ ID	TATATCTCTGACAGA	MS-216_HC CDR2
	NO: 566	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-216_HC CDR3
	NO: 567	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-217_LC CDR1
	NO: 568	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-217_LC CDR2
	NO: 569	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-217_LC CDR3
	NO: 570	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-217_HC CDR1
	NO: 571	ACT
	SEQ ID	TATATCTCTGACAGA	MS-217_HC CDR2
	NO: 572	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-217_HC CDR3
	NO: 573	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-218_LC CDR1
	NO: 574	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-218_LC CDR2
	NO: 575	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-218_LC CDR3
	NO: 576	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-218_HC CDR1
	NO: 577	ACT
	SEQ ID	TATATCTCTGACAGA	MS-218_HC CDR2
	NO: 578	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-218_HC CDR3
	NO: 579	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-219_LC CDR1
	NO: 580	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-219_LC CDR2
	NO: 581	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-219_LC CDR3
	NO: 582	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-219_HC CDR1
	NO: 583	ACT
	SEQ ID	TATATCTCTGACAGA	MS-219_HC CDR2
	NO: 584	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-219_HC CDR3
	NO: 585	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-220_LC CDR1
	NO: 586	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-220_LC CDR2
	NO: 587	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-220_LC CDR3
	NO: 588	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-220_HC CDR1
	NO: 589	ACT
	SEQ ID	TATATCTCTGACAGA	MS-220_HC CDR2
	NO: 590	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-220_HC CDR3
	NO: 591	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-224_LC CDR1
	NO: 592	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-224_LC CDR2
	NO: 593	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-224_LC CDR3
	NO: 594	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-224_HC CDR1
	NO: 595	ACT
	SEQ ID	TATATCTCTGACAGA	MS-224_HC CDR2
	NO: 596	GAATCAGCGACTTAC
		AACC
		CCTCCCTCCAAAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-224_HC CDR3
	NO: 597	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-200_LC CDR1
	NO: 598	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-200_LC CDR2
	NO: 599	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-200_LC CDR3
	NO: 600	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-200_HC CDR1
	NO: 601	ACT
	SEQ ID	TATATCTCTGACAGA	MS-200_HC CDR2
	NO: 602	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-200_HC CDR3
	NO: 603	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-201_LC CDR1
	NO: 604	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-201_LC CDR2
	NO: 605	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-201_LC CDR3
	NO: 606	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-201_HC CDR1
	NO: 607	ACT
	SEQ ID	TATATCTCTGACAGA	MS-201_HC CDR2
	NO: 608	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-201_HC CDR3
	NO: 609	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-202_LC CDR1
	NO: 610	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-202_LC CDR2
	NO: 611	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-202_LC CDR3
	NO: 612	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-202_HC CDR1
	NO: 613	ACT
	SEQ ID	TATATCTCTGACAGA	MS-202_HC CDR2
	NO: 614	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-202_HC CDR3
	NO: 615	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-225_LC CDR1
	NO: 616	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-225_LC CDR2
	NO: 617	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-225_LC CDR3
	NO: 618	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-225_HC CDR1
	NO: 619	ACT
	SEQ ID	TATATCTCTGACAGA	MS-225_HC CDR2
	NO: 620	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-225_HC CDR3
	NO: 621	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-226_LC CDR1
	NO: 622	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-226_LC CDR2
	NO: 623	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-226_LC CDR3
	NO: 624	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-226_HC CDR1
	NO: 625	ACT
	SEQ ID	TATATCTCTGACAGA	MS-226_HC CDR2
	NO: 626	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-226_HC CDR3
	NO: 627	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-227_LC CDR1
	NO: 628	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-227_LC CDR2
	NO: 629	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-227_LC CDR3
	NO: 630	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-227_HC CDR1
	NO: 631	ACT
	SEQ ID	TATATCTCTGACAGA	MS-227_HC CDR2
	NO: 632	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-227_HC CDR3
	NO: 633	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-228_LC CDR1
	NO: 634	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-228_LC CDR2
	NO: 635	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-228_LC CDR3
	NO: 636	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-228_HC CDR1
	NO: 637	ACT
	SEQ ID	TATATCTCTGACAGA	MS-228_HC CDR2
	NO: 638	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-228_HC CDR3
	NO: 639	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-229_LC CDR1
	NO: 640	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-229_LC CDR2
	NO: 641	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-229_LC CDR3
	NO: 642	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-229_HC CDR1
	NO: 643	ACT
	SEQ ID	TATATCTCTGACAGA	MS-229_HC CDR2
	NO: 644	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-229_HC CDR3
	NO: 645	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-230_LC CDR1
	NO: 646	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-230_LC CDR2
	NO: 647	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-230_LC CDR3
	NO: 648	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-230_HC CDR1
	NO: 649	ACT
	SEQ ID	TATATCTCTGACAGA	MS-230_HC CDR2
	NO: 650	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-230_HC CDR3
	NO: 651	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-231_LC CDR1
	NO: 652	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-231_LC CDR2
	NO: 653	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-231_LC CDR3
	NO: 654	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-231_HC CDR1
	NO: 655	ACT
	SEQ ID	TATATCTCTGACAGA	MS-231_HC CDR2
	NO: 656	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-231_HC CDR3
	NO: 657	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-232_LC CDR1
	NO: 658	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-232_LC CDR2
	NO: 659	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-232_LC CDR3
	NO: 660	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-232_HC CDR1
	NO: 661	ACT
	SEQ ID	TATATCTCTGACAGA	MS-232_HC CDR2
	NO: 662	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-232_HC CDR3
	NO: 663	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-233_LC CDR1
	NO: 664	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-233_LC CDR2
	NO: 665	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-233_LC CDR3
	NO: 666	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-233_HC CDR1
	NO: 667	ACT
	SEQ ID	TATATCTCTGACAGA	MS-233_HC CDR2
	NO: 668	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-233_HC CDR3
	NO: 669	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-234_LC CDR1
	NO: 670	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-234_LC CDR2
	NO: 671	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-234_LC CDR3
	NO: 672	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-234_HC CDR1
	NO: 673	ACT
	SEQ ID	TATATCTCTGACAGA	MS-234_HC CDR2
	NO: 674	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-234_HC CDR3
	NO: 675	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-235_LC CDR1
	NO: 676	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-235_LC CDR2
	NO: 677	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-235_LC CDR3
	NO: 678	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-235_HC CDR1
	NO: 679	ACT
	SEQ ID	TATATCTCTGACAGA	MS-235_HC CDR2
	NO: 680	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-235_HC CDR3
	NO: 681	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-236_LC CDR1
	NO: 682	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-236_LC CDR2
	NO: 683	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-236_LC CDR3
	NO: 684	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-236_HC CDR1
	NO: 685	ACT
	SEQ ID	TATATCTCTGACAGA	MS-236_HC CDR2
	NO: 686	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-236_HC CDR3
	NO: 687	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-237_LC CDR1
	NO: 688	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-237_LC CDR2
	NO: 689	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-237_LC CDR3
	NO: 690	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-237_HC CDR1
	NO: 691	ACT
	SEQ ID	TATATCTCTGACAGA	MS-237_HC CDR2
	NO: 692	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-237_HC CDR3
		AGGATTTATGGAGTG
		GTTT
	NO: 693	CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-238_LC CDR1
	NO: 694	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-238_LC CDR2
	NO: 695	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-238_LC CDR3
	NO: 696	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-238_HC CDR1
	NO: 697	ACT
	SEQ ID	TATATCTCTGACAGA	MS-238_HC CDR2
	NO: 698	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-238_HC CDR3
	NO: 699	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-239_LC CDR1
	NO: 700	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-239_LC CDR2
	NO: 701	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-239_LC CDR3
	NO: 702	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-239_HC CDR1
	NO: 703	ACT
	SEQ ID	TATATCTCTGACAGA	MS-239_HC CDR2
	NO: 704	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-239_HC CDR3
	NO: 705	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-240_LC CDR1
	NO: 706	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-240_LC CDR2
	NO: 707	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-240_LC CDR3
	NO: 708	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-240_HC CDR1
	NO: 709	ACT
	SEQ ID	TATATCTCTGACAGA	MS-240_HC CDR2
	NO: 710	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-240_HC CDR3
	NO: 711	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-241_LC CDR1
	NO: 712	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-241_LC CDR2
	NO: 713	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-241_LC CDR3
	NO: 714	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-241_HC CDR1
	NO: 715	ACT
	SEQ ID	TATATCTCTGACAGA	MS-241_HC CDR2
	NO: 716	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-241_HC CDR3
	NO: 717	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-242_LC CDR1
	NO: 718	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-242_LC CDR2
	NO: 719	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-242_LC CDR3
	NO: 720	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-242_HC CDR1
	NO: 721	ACT
	SEQ ID	TATATCTCTGACAGA	MS-242_HC CDR2
	NO: 722	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-242_HC CDR3
	NO: 723	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-243_LC CDR1
	NO: 724	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-243_LC CDR2
	NO: 725	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-243_LC CDR3
	NO: 726	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-243_HC CDR1
	NO: 727	ACT
	SEQ ID	TATATCTCTGACAGA	MS-243_HC CDR2
	NO: 728	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-243_HC CDR3
	NO: 729	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-244_LC CDR1
	NO: 730	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-244_LC CDR2
	NO: 731	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-244_LC CDR3
	NO: 732	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-244_HC CDR1
	NO: 733	ACT
	SEQ ID	TATATCTCTGACAGA	MS-244_HC CDR2
	NO: 734	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-244_HC CDR3
	NO: 735	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-245_LC CDR1
	NO: 736	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-245_LC CDR2
	NO: 737	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-245_LC CDR3
	NO: 738	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-245_HC CDR1
	NO: 739	ACT
	SEQ ID	TATATCTCTGACAGA	MS-245_HC CDR2
	NO: 740	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-245_HC CDR3
	NO: 741	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-246_LC CDR1
	NO: 742	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-246_LC CDR2
	NO: 743	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-246_LC CDR3
	NO: 744	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-246_HC CDR1
	NO: 745	ACT
	SEQ ID	TATATCTCTGACAGA	MS-246_HC CDR2
	NO: 746	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-246_HC CDR3
	NO: 747	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC
	SEQ ID	GGACGACAGGCCCTT	MS-247_LC CDR1
	NO: 748	GGAAGTAGAGCTGTT
		CAG
	SEQ ID	AATAATCAAGACCGG	MS-247_LC CDR2
	NO: 749	CCCTCA
	SEQ ID	CACATGTGGGATAGT	MS-247_LC CDR3
	NO: 750	AGAAGTGGCTTCAGT
		TGGT
		CT
	SEQ ID	AATAATTACTACTGG	MS-247_HC CDR1
	NO: 751	ACT
	SEQ ID	TATATCTCTGACAGA	MS-247_HC CDR2
	NO: 752	GAATCAGCGACTTAC
		AACC
		CCTCCCTCAATAGT
	SEQ ID	GCGCGCCGAGGACAG	MS-247_HC CDR3
	NO: 753	AGGATTTATGGAGTG
		GTTT
		CCTTTGGAGAGTTCT
		TCTACTACTACTCCA
		TGGAC
		GTC

TABLE 8
Methods for characterizing anti-HIV antibody 10-1074 variants
Method Name	Discard limits	Priority molecules
Titer (with caveat that	Discard molecules with	Variants with significant
transient titer is not	significant reduction in titer	increase in titer over
correlative with stable titer)		parental
Purification Yield	Discard molecules with a	Variants with yield close
	significant decrease in yield as	to 100% based on the
	compared to the titer	titer
Neutralization	Discard molecules with greater	Variants with no decrease
	than 3-fold reduction in	in potency
	neutralization potency for any
	given virus
Size Exclusion	Dimer and higher order	Molecules with less than
Chromatography (SEC)	aggregates less than 10%.	5% dimer and higher
	Priority for molecules with	order aggregates
	lower values.
Differential Scanning	Discard molecules with loss of	Molecules with increased
Fluorimetry (DSF)	Tm2	or additional Tm
Chemical Unfolding by	Discard molecules with	Molecules with inflection
Guanidine-HCl	inflection point of unfolding	point of unfolding greater
	less than parental molecule	than parental molecule
Relative Solubility Analysis	Discard molecules with	Molecules with increased
(RSA)	decreased solubility	relative solubility given
		priority
Low pH Stability	Discard molecules with greater	No change in aggregation
	than 5% increase in aggregation	level following low pH
	following low pH incubation	incubation

TABLE 9
Molecule sets and biophysical analysis of 10-1074 antibody variants (Round 1)
			Amount			DSF Tm1,	DSF Tm2,	DSF Tm1,	DSF Tm2,
Molecule			Purified	SEC	SEC	° C.	° C.	° C.	° C.
Set	LC	IgG1 HC	(mg)	(% Monomer)	(% HMW)	(rep 1)	(rep 1)	(rep 2)	(rep 2)
MS-194			1.20	91.52	8.48	69.8		70.0
MS-203	LmdV: Y2P		0.60	95.24	4.76	69.3	81.6	69.3	81.1
MS-204	LmdV: R7P		0.87	65.98	34.02	69.9		70.1
MS-205	LmdV: P9S		1.25	71.66	28.34	70.1		70.2
MS-206	LmdV: E17Q		1.25	91.35	8.65	70.0		70.0
MS-207	LmdV: H46Q		0.87	65.30	34.70	69.8	80.8	69.9
MS-208	LmdV: P81.1N		0.24	88.68	11.32	68.8	81.3	69.0
MS-209	LmdV: I81.3S		1.27	60.79	39.21	70.0	81.3	70.1	80.1
MS-210	LmdV: N82G		0.28	88.24	11.76	70.1	81.7	70.3	81.3
MS-211	LmdV: R88T		0.22	83.11	16.89	66.9		67.1
MS-212	LmdV: D110E		0.25	82.78	17.22	68.5		68.6
MS-213	LmdV: A142G		0.44	90.48	9.52	68.1		68.2
MS-214		HV: D29G	2.01	94.00	6.00	69.9		69.9
MS-215		HV: S47P	2.68	92.88	7.12	70.0		70.1
MS-216		HV: V79T	1.48	94.67	5.33	69.8	81.8	69.9	80.1
MS-217		HV: R82V	1.31	94.21	5.79	69.8	80.9	69.9	80.1
MS-218		HV: L89F	0.68	96.33	3.67	70.0	80.9	70.1	81.3
MS-219		HV: T108R	2.24	91.93	8.07	70.3	75.4	70.3	76.0
MS-220		HV: K141Q	2.87	94.56	5.44	69.9		69.9
MS-224		HV: N75Q	0.05			70.2		69.9	80.8

TABLE 10
Molecule sets and neutralization analysis against 10-
1074 sensitive virus panel in TZM.bl cells (Round 1)
Molecule	Du156.12	WITO4160.33	CNE17	CNE30	CAAN5342.A2	Du172.17
Set	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80
Control	0.010	0.030	0.168	1.173	1.201	6.067	0.164	0.605	0.009	0.029	0.110	0.391
MS-203	0.008	0.025	0.205	0.979	1.291	4.519	0.193	0.546	0.009	0.024	0.084	0.295
MS-204	0.014	0.040	0.236	1.664	1.211	5.895	0.270	0.902	0.017	0.048	0.092	0.334
MS-205	0.012	0.035	0.162	0.922	1.237	4.411	0.249	0.824	0.011	0.029	0.098	0.329
MS-206	0.010	0.035	0.161	1.142	0.986	3.484	0.225	0.614	0.009	0.024	0.095	0.272
MS-207	0.010	0.036	0.252	0.840	1.285	5.873	0.240	0.836	0.026	0.115	0.211	0.875
MS-208	0.007	0.036	0.699	5.174	3.569	17.98	0.206	1.018	0.016	0.047	0.231	0.816
MS-209	0.007	0.025	0.276	1.833	1.155	5.751	0.174	0.618	0.009	0.029	0.088	0.303
MS-210	0.005	0.013	0.091	0.594	0.598	2.834	0.097	0.340	0.003	0.013	0.044	0.156
MS-211	0.008	0.028	0.237	1.514	1.151	4.240	0.205	0.744	0.010	0.025	0.092	0.309
MS-212	0.009	0.041	0.304	1.938	1.395	6.928	0.242	1.130	0.007	0.031	0.113	0.399
MS-213	0.007	0.028	0.183	1.271	0.955	5.049	0.141	0.689	0.011	0.033	0.119	0.315
MS-214	0.005	0.018	0.221	1.553	0.987	4.567	0.185	0.630	0.009	0.024	0.090	0.238
MS-215	0.007	0.023	0.157	1.118	1.174	5.438	0.224	0.760	0.011	0.031	0.095	0.305
MS-216	0.007	0.020	0.132	0.887	1.116	4.999	0.194	0.517	0.009	0.032	0.084	0.277
MS-217	0.010	0.037	0.260	1.678	1.159	5.397	0.216	0.743	0.010	0.038	0.075	0.275
MS-218	0.005	0.018	0.142	1.016	0.815	4.195	0.156	0.557	0.010	0.027	0.091	0.312
MS-219	0.006	0.020	0.308	1.349	0.966	3.559	0.176	0.609	0.007	0.022	0.104	0.278
MS-220	0.009	0.027	0.215	1.023	1.242	4.415	0.193	0.528	0.009	0.027	0.099	0.335
MS-224	0.005	0.022	0.269	1.219	1.147	4.026	0.162	0.564	0.009	0.032	0.096	0.329

TABLE 11
Reasons for including or excluding variants based on neutralization
activity and biophysical analysis (Round1)
Molecule Set Reason for inclusion/exclusion in Round 2
MS-203       Include: presence of Tm2 by DSF, HMW <10%
MS-204       Exclude: Lack of Tm2
MS-205       Exclude: Lack of Tm2
MS-206       Exclude: Lack of Tm2
MS-207       Exclude: Lack of Tm2
MS-208       Exclude: Lack of Tm2; Reduced neutralization activity
MS-209       Exclude: SEC shows HMW of 39.2%
MS-210       Exclude: Low production titer
MS-211       Exclude: Lack of Tm2
MS-212       Exclude: Lack of Tm2
MS-213       Exclude: Lack of Tm2
MS-214       Exclude: Lack of Tm2
MS-215       Exclude: Lack of Tm2
MS-216       Include: presence of Tm2 by DSF, HMW <10%
MS-217       Include: presence of Tm2 by DSF, HMW <10%
MS-218       Include: presence of Tm2 by DSF, HMW <10%
MS-219       Include: presence of Tm2 by DSF, HMW <10%
MS-220       Exclude: Lack of Tm2
MS-224       Exclude: Low production titer

TABLE 12
Molecule sets of anti-HIV antibody 10-1074 variants (Round 2)
Molecule
Set	LC	IgG1 HC
MS-194
MS-225	LmdV: Y2P	HV: V79T
MS-226	LmdV: Y2P	HV: R82V
MS-227	LmdV: Y2P	HV: L89F
MS-228	LmdV: Y2P	HV: T108R
MS-229		HV: V79T, HV: R82V
MS-230		HV: V79T, HV: L89F
MS-231		HV: V79T, HV: T108R
MS-232		HV: R82V, HV: L89F
MS-233		HV: R82V, HV: T108R
MS-234		HV: L89F, HV: T108R
MS-235	LmdV: Y2P	HV: V79T, HV: R82V
MS-236	LmdV: Y2P	HV: V79T, HV: L89F
MS-237	LmdV: Y2P	HV: V79T, HV: T108R
MS-238	LmdV: Y2P	HV: R82V, HV: L89F
MS-200	LmdV: Y2P	HV: R82V, HV: T108R
MS-239	LmdV: Y2P	HV: L89F, HV: T108R
MS-240		HV: V79T, HV: R82V, HV: L89F
MS-241		HV: V79T, HV: R82V, HV: T108R
MS-201		HV: V79T, HV: L89F, HV: T108R
MS-242		HV: R82V, HV: L89F, HV: T108R
MS-243	LmdV: Y2P	HV: V79T, HV: R82V, HV: L89F
MS-244	LmdV: Y2P	HV: V79T, HV: R82V, HV: T108R
MS-202	LmdV: Y7P	HV: V79T, HV: L89F, HV: T108R
MS-245	LmdV: Y2P	HV: R82V, HV: L89F, HV: T108R
MS-246		HV: V79T, HV: R82V, HV: L89F, HV: T108R
MS-247	LmdV: Y2P	HV: V79T, HV: R82V, HV: L89F, HV: T108R

TABLE 13
Molecule sets and biophysical analysis of 10-1074 antibody variants (Round 2)
				DSF Tm1		DSF Tm2
Molecule	SEC	SEC	SEC	° C.	DSF Tm1	° C.	DSF Tm2
Set	(% monomer)	(% dimer)	(% Oligomer)	(Avg. n = 2)	(Std Dev)	(Avg. n = 2)	(Std Dev)
MS-194	92.40	3.72	3.89	70.00	0.01
MS-225	89.07	3.12	7.81	69.44	0.05
MS-226	93.49	3.51	3.00	69.52	0.03
MS-227	90.18	3.10	6.72	69.76	0.07
MS-228	95.37	3.59	1.04	70.48	0.02	74.50	0.00
MS-229	93.39	4.03	2.58	70.04	0.05
MS-230	94.00	3.42	2.58	70.25	0.05
MS-231	95.35	3.87	0.79	70.41	0.02	74.50	0.03
MS-232	94.62	3.52	1.86	70.07	0.03
MS-233	95.45	3.94	0.61	70.30	0.00	76.69	0.15
MS-234	96.70	2.94	0.36	70.40	0.06	76.85	0.11
MS-235	92.77	3.46	3.77	69.74	0.05
MS-236	93.06	3.78	3.16	69.92	0.10
MS-237	94.61	4.03	1.36	70.47	0.02	74.50	0.00
MS-238	91.73	3.94	4.33	69.36	0.01
MS-200	94.64	4.56	0.80	70.15	0.01	74.62	0.33
MS-239	95.99	3.35	0.66	70.28	0.01	75.42	0.09
MS-240	94.87	3.61	1.52	69.99	0.01
MS-241	94.36	4.93	0.71	70.11	0.02	76.41	0.04
MS-201	94.58	4.68	0.73	70.28	0.04	76.69	0.01
MS-242	94.82	4.52	0.66	70.25	0.02	77.30	0.03
MS-243	91.81	4.51	3.67	69.57	0.06
MS-244	93.97	5.04	0.99	70.17	0.02	74.70	0.18
MS-202	93.88	5.04	1.08	70.42	0.00	75.43	0.15
MS-245	93.40	5.61	0.99	70.36	0.02	76.15	0.04
MS-246	94.88	4.59	0.53	70.19	0.05	77.13	0.09
MS-247	94.37	4.88	0.75	69.44	0.05

TABLE 14
Additional biophysical characterization for the combination variants (Round 2)
	Shoulder		Inflection Pt		pH 3.3		PEG
Molecule	Score		of Unfolding		HMW %		solubility
Set	(Avg. n = 2)	(Std Dev)	(Avg n = 3)	Std Dev	(Avg n = 2)	Std Dev	(avg. n = 2)	Std Dev
MS-194	7.65	0.17	2.44	0.01	39.76	0.19	0.14	0.02
MS-225	7.22	0.97	2.37	0.03	40.43	14.01	0.18	0.02
MS-226	7.72	0.16	2.49	0.04	14.33	6.02	0.19	0.01
MS-227	8.12	0.61	2.53	0.03	28.13	14.86	0.18	0.02
MS-228	16.25	0.55	2.64	0.02	9.10	6.29	0.17	0.02
MS-229	9.03	0.98	2.60	0.01	9.77	2.43	0.19	0.02
MS-230	10.03	0.39	2.62	0.05	12.14	2.04	0.18	0.02
MS-231	20.80	0.22	2.63	0.02	3.35	0.16	0.14	0.02
MS-232	9.70	0.25	2.65	0.06	8.67	1.77	0.19	0.01
MS-233	20.00	0.23	2.98	0.03	2.48	0.03	0.17	0.02
MS-234	28.36	2.18	2.97	0.19	2.61	0.51	0.15	0.02
MS-235	7.79	0.22	2.60	0.03	13.92	1.48	0.19	0.01
MS-236	8.32	0.07	2.53	0.00	22.13	6.12	0.19	0.02
MS-237	16.01	0.05	2.65	0.05	4.58	0.49	0.15	0.03
MS-238	8.21	0.56	2.57	0.01	31.37	25.30	0.20	0.01
MS-200	16.12	0.42	2.93	0.04	2.93	0.01	0.19	0.02
MS-239	22.28	0.72	2.98	0.04	3.19	0.49	0.18	0.02
MS-240	9.98	0.18	2.71	0.03	9.63	4.33	0.19	0.02
MS-241	21.39	0.09	2.98	0.06	3.12	0.06	0.17	0.03
MS-201	29.39	0.45	3.15	0.03	2.21	0.06	0.17	0.02
MS-242	23.85	0.29	2.89	0.14	2.49	0.06	0.19	0.02
MS-243	7.62	0.22	2.57	0.03	9.86	1.38	0.18	0.01
MS-244	16.12	0.51	2.90	0.08	3.25	0.16	0.18	0.02
MS-202	22.49	1.53	3.08	0.09	3.64	0.09	0.17	0.02
MS-245	18.77	0.55	3.06	0.07	3.29	0.30	0.18	0.02
MS-246	22.39	0.97	3.29	0.03	2.32	0.23	0.17	0.03
MS-247	7.22	0.97	2.91	0.07	3.14	0.24	0.19	0.02

TABLE 15
Neutralization analysis of selected variants in Round 2 in TZM.bl
cells. Loss of potency are values > 3-fold of control value
Molecule	SC422661.8	WITO4160.33	CAAN5342.A2	DU156.12	DU172.17	CNE17
Set	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80
Control	0.045	0.157	0.205	1.439	0.005	0.019	0.008	0.034	0.055	0.156	1.34	4.574
MS-228	0.03	0.114	0.097	0.71	0.002	0.01	0.003	0.017	0.036	0.134	0.928	3.21
MS-231	0.032	0.092	0.092	0.646	0.001	0.012	0.003	0.017	0.034	0.125	0.796	2.719
MS-233	0.037	0.128	0.172	0.789	0.005	0.015	0.004	0.02	0.033	0.124	0.625	3.085
MS-234	0.04	0.136	0.22	0.932	0.003	0.011	0.004	0.017	0.058	0.232	0.734	2.646
MS-237	0.028	0.126	0.113	0.744	0.004	0.016	0.004	0.019	0.037	0.117	0.792	3.673
MS-200	0.036	0.156	0.13	0.794	0.005	0.02	0.007	0.028	0.037	0.152	0.922	3.21
MS-239	0.033	0.114	0.199	0.951	0.003	0.012	0.005	0.017	0.03	0.125	0.63	2.887
MS-241	0.034	0.106	0.229	0.999	0.004	0.014	0.008	0.02	0.038	0.137	0.81	2.939
MS-201	0.027	0.104	0.177	1.153	0.002	0.011	0.005	0.016	0.028	0.102	0.782	2.62
MS-242	0.04	0.116	0.145	0.889	0.003	0.012	0.006	0.021	0.034	0.161	0.762	3.331
MS-244	0.041	0.123	0.172	1.169	0.005	0.017	0.003	0.017	0.045	0.167	0.694	3.637
MS-202	0.028	0.135	0.185	0.708	0.003	0.011	0.004	0.021	0.028	0.104	0.825	2.903
MS-245	0.029	0.102	0.132	0.774	0.002	0.012	0.006	0.022	0.038	0.139	0.991	4.443
MS-246	0.037	0.128	0.145	0.82	0.004	0.017	0.006	0.025	0.039	0.146	0.907	3.175
MS-247	0.034	0.151	0.107	0.611	0.003	0.014	0.009	0.032	0.03	0.149	0.642	3.141
Molecule	CNE30	CNE53	235-47	X1193_c1	X1254_c3	3301.v1.c24
Set	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80	IC50	IC80
Control	0.258	0.709	0.017	0.049	0.029	0.116	0.04	0.139	0.055	0.154	0.008	0.021
MS-228	0.215	0.595	0.007	0.028	0.019	0.086	0.03	0.13	0.039	0.117	0.003	0.013
MS-231	0.184	0.517	0.007	0.025	0.016	0.078	0.028	0.12	0.035	0.116	0.002	0.012
MS-233	0.186	0.649	0.006	0.023	0.03	0.113	0.03	0.133	0.041	0.129	0.003	0.016
MS-234	0.184	0.5	0.008	0.037	0.019	0.077	0.031	0.142	0.03	0.122	0.003	0.014
MS-237	0.17	0.46	0.005	0.027	0.022	0.086	0.042	0.146	0.035	0.101	0.002	0.014
MS-200	0.17	0.583	0.007	0.027	0.022	0.085	0.059	0.177	0.047	0.133	0.005	0.019
MS-239	0.175	0.588	0.004	0.02	0.023	0.088	0.03	0.182	0.036	0.102	0.002	0.011
MS-241	0.181	0.498	0.006	0.023	0.028	0.08	0.042	0.155	0.034	0.119	0.003	0.01
MS-201	0.173	0.471	0.003	0.025	0.011	0.067	0.033	0.154	0.037	0.1	0.003	0.008
MS-242	0.197	0.535	0.004	0.023	0.028	0.092	0.042	0.185	0.031	0.107	0.003	0.009
MS-244	0.18	0.639	0.001	0.014	0.032	0.113	0.041	0.184	0.027	0.108	0.001	0.005
MS-202	0.16	0.568	0.005	0.021	0.022	0.084	0.037	0.139	0.028	0.117	0.005	0.018
MS-245	0.156	0.553	0.004	0.019	0.028	0.1	0.049	0.172	0.04	0.137	0.006	0.019
MS-246	0.204	0.557	0.002	0.021	0.037	0.128	0.046	0.199	0.047	0.164	0.007	0.021
MS-247	0.197	0.554	0.005	0.027	0.036	0.126	0.043	0.203	0.029	0.113	0.008	0.023

TABLE 16
Reasons for excluding combinatorial variants
based on biophysical analysis (Round 2)
Molecule Reasons for exclusion of molecules from
Set      further in-depth analysis
MS-225   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-226   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-227   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-228   Excluded: Lower chemical unfolding stability, aggregation
         at pH 3.3 > 5%
MS-229   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-230   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-231   Excluded: Aggregation at 65° C., Lower chemical
         unfolding stability
MS-232   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-233   Excluded: Aggregation at 65° C.
MS-234   Excluded: Low titer
MS-235   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-236   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-237   Excluded: Lower chemical unfolding stability
MS-238   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-200   Include
MS-239   Excluded: Low Titer
MS-240   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-241   Excluded: Similar to 19, but slightly less stability to
         chemical unfolding
MS-201   Include
MS-242   Exclude: Decreased chemical unfolding stability compared
         to 19
MS-243   Excluded: Lack of Tm2, Aggregation at 65° C., Lower
         chemical unfolding stability, aggregation at pH 3.3 > 5%
MS-244   Excluded: Aggregation at 65° C.
MS-202   Include
MS-245   Exclude: No improvement over variants 15, 19, or 23
MS-246   Excluded: Low titer (less than parental)
MS-247   Excluded: Low titer (less than parental)

The foregoing examples and description of the preferred embodiments should be taken as illustrating, rather than as limiting the present invention as defined by the claims. As will be readily appreciated, numerous variations and combinations of the features set forth above can be utilized without departing from the present invention as set forth in the claims. Such variations are not regarded as a departure from the scope of the invention, and all such variations are intended to be included within the scope of the following claims. All references cited herein are incorporated herein in their entireties.

Claims

1. An isolated anti-HIV antibody, or antigen-binding portion thereof, comprising a light chain variable region having a light chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the light chain variable regions of SEQ ID NOs: 3-13, 22, 24-28, 35-39, 43-45, and 47, wherein the isolated anti-HIV antibody, or antigen-binding portion thereof comprises one or more light chain substitutions at one or more residues selected from the group consisting of LmdV:Y2, LmdV:R7, LmdV:P9, LmdV:E17, LmdV:H46, LmdV:P81.1, LmdV:I81.3, LmdV:N82, LmdV:R88, LmdV:D110, and LmdV:A142.

2. An isolated anti-HIV antibody, or antigen-binding portion thereof, comprising a heavy chain variable region having a heavy chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94, wherein the isolated anti-HIV antibody, or antigen-binding portion thereof comprises one or more heavy chain substitutions at one or more residues selected from the group consisting of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

3. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1, further comprising a heavy chain variable region having an heavy chain amino acid sequence that is at least 75% identical to a polypeptide sequence selected from the group consisting of the heavy chain variable regions of SEQ ID NOs: 61-94, wherein the isolated anti-HIV antibody, or antigen-binding portion thereof comprises one or more heavy chain substitutions at one or more residues selected from the group consisting of HV:D29, HV:S47, HV:N75, HV:V79, HV:R82, HV:L89, HV:T108, and HV:K141.

4. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1, comprising the one or more light chain substitutions selected from the group consisting of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof.

5. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, comprising the one or more heavy chain substitutions selected from the group consisting of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof.

6. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, comprising the one or more light chain substitutions selected from the group consisting of LmdV:Y2P, LmdV:R7P, LmdV:P9S, LmdV:E17Q, LmdV:H46Q, LmdV:P81.1N, LmdV:I81.3S, LmdV:N82G, LmdV:R88T, LmdV:D110E, and LmdV:A142G or conservative substitutions thereof and the one or more heavy chain substitutions selected from the group consisting of HV:D29G, HV:S47P, HV:N75Q, HV:V79T, HV:R82V, HV:L89F, HV:T108R, and HV:K141Q or conservative substitutions thereof.

7. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1, wherein the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 3 and comprises a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2.

8. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 63 and comprises an HV:V79T substitution or a conservative substitution of threonine at HV:V79.

9. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 64 and comprises an HV:R82V substitution or a conservative substitution of valine at HV:R82.

10. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 65 and comprises an HV:L89F substitution or a conservative substitution of phenylalanine of HV:L89.

11. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 66 and comprises an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

12. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, wherein the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 22 and comprises a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 69 and comprises: an HV:R82V substitution or a conservative substitution of valine at HV:R82,and an HV:T108R substitution or a conservative substitution of arginine at HV:T108.

13. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 70 and comprises: an HV:V79T substitution or a conservative substitution of threonine at HV:V79,an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, andan HV:T108R substitution or a conservative substitution of arginine at HV:T108.

14. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, wherein the light chain amino acid sequence is at least 75% identical to the light chain variable region of SEQ ID NO.: 24 and comprises a LmdV:Y2P substitution or a conservative substitution of proline at LmdV:Y2, and wherein the heavy chain amino acid sequence is at least 75% identical to the heavy chain variable region of SEQ ID NO.: 71 and comprises: an HV:V79T substitution or a conservative substitution of threonine at HV:V79,an HV:L89F substitution or a conservative substitution of phenylalanine at HV:L89, andan HV:T108R substitution or a conservative substitution of arginine at HV:T108.

15. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1, comprising SEQ NO.: 3.

16. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 2, comprising SEQ NO.: 63, 64, 65, 66, or 70.

17. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, wherein the light chain variable region comprises the light variable region of SEQ NO.: 22 and the heavy chain variable region comprises the heavy variable region of SEQ No.: 69.

18. The isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 3, wherein the light chain variable region comprises the light variable region of SEQ NO.: 24 and the heavy chain variable region comprises the heavy variable region of SEQ No.: 71.

19. A pharmaceutical composition comprising the isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1, and a pharmaceutically acceptable carrier or excipient.

20. The pharmaceutical composition further comprising a second therapeutic agent.

21. A nucleic acid, or a codon-optimized nucleic acid, encoding the isolated anti-HIV antibody, or antigen-binding portion thereof, of claim 1.

22. A vector or vector system comprising at least one nucleic acid of claim 21.

23. A cell comprising the nucleic acid of claim 21.

24. A method of making recombinant anti-HIV antibody, or antigen-binding portion thereof, comprising: a. obtaining the cell of claim 23;b. culturing the cell in a medium under conditions permitting expression of a polypeptide encoded by the vector and assembling of an antibody or fragment thereof, andc. purifying the antibody or fragment from the cultured cell or the medium of the cell.

25. A method of preventing or treating an HIV infection or an HIV-related disease comprising the steps of: a. identifying a patient in need of such prevention or treatment, andb. administering to said patient a first therapeutic agent comprising a therapeutically effective amount of at least one anti-HIV antibody of claim 1, or antigen-binding portion thereof.

26. The method of claim 25, further comprising administering a second therapeutic agent.

27. The method of claim 26, wherein the second therapeutic agent is administered before, concurrently with or after the administration of the anti-HIV antibody or antigen-binding portion thereof.

28. The method of claim 24 and the pharmaceutical composition of claim 20, wherein the second therapeutic agent is an anti-HIV-1 broadly neutralizing antibody (bNAb).

29. The method of claim 26, wherein the anti-HIV-1 broadly neutralizing antibody is 3BNC117.

30. A kit comprising a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of at least one isolated anti-HIV antibody according to claim 1, or antigen-binding portion thereof.

31. The kit of claim 30 further comprising a pharmaceutically acceptable dose unit of a pharmaceutically effective amount of an anti-HIV agent, wherein the two pharmaceutically acceptable dose units can optionally take the form of a single pharmaceutically acceptable dose unit.

32. The kit of claim 31, wherein the anti-HIV agent is one selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an entry or fusion inhibitor, and an integrase inhibitor.

33. The kit of claim 31, wherein the anti-HIV agent is an anti-HIV broadly neutralizing antibody.

34. The kit of claim 33, wherein the anti-HIV broadly neutralizing antibody is 3BNC117.