Anti-HER2 antibody variants
First Claim
Patent Images
1. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1, and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein the light chain variable domain of SEQ ID NO;
1 comprises an amino acid substitution selected from the group consisting of N30(VL)S;
T31(VL)S;
Y49(VL)D, and Y49(VL)W numbered according to the Kabat numbering system, and the heavy chain variable domain of SEQ ID NO;
2 comprises an amino acid substitution selected from the group consisting of D98(VH)W, F100(VH)P;
Y102(VH)K; and
Y102(VH)L, numbered according to the Kabat numbering system.
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Abstract
The present invention concerns novel antibody variants, particularly anti-HER2 antibody variants having substitutions at positions within the variable domains of the heavy and light chains
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Citations
30 Claims
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1. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1, and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein the light chain variable domain of SEQ ID NO;
1 comprises an amino acid substitution selected from the group consisting of N30(VL)S;
T31(VL)S;
Y49(VL)D, and Y49(VL)W numbered according to the Kabat numbering system, and the heavy chain variable domain of SEQ ID NO;
2 comprises an amino acid substitution selected from the group consisting of D98(VH)W, F100(VH)P;
Y102(VH)K; and
Y102(VH)L, numbered according to the Kabat numbering system. - View Dependent Claims (2, 3, 5, 6, 7, 8, 9)
- 1, and an antibody heavy chain variable domain of SEQ ID NO;
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4. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1, wherein N30(VL) is substituted with S, H91(VL) is substituted with F, and Y92(VL) is substituted with W, numbered according to the Kabat numbering system, and an antibody heavy chain variable domain of SEQ ID NO;
2, comprising an amino acid substitution selected from the group consisting of substitutions D98(VH)R, F100(VH)P and Y102(VH)K, numbered according to the Kabat numbering.
- 1, wherein N30(VL) is substituted with S, H91(VL) is substituted with F, and Y92(VL) is substituted with W, numbered according to the Kabat numbering system, and an antibody heavy chain variable domain of SEQ ID NO;
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10. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1, and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein said light chain variable domain comprises an amino acid substitution selected from the group consisting of Y49(VL)D, F53(VL)W, and Y55(VL)W, numbered according to the Kabat numbering system. - View Dependent Claims (12, 13)
- 1, and an antibody heavy chain variable domain of SEQ ID NO;
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11. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein in said light chain variable region N30(VL) is substituted with S, H91(VL) is substituted with F, and Y92(VL) is substituted with W.
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
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14. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variabic domain of SEQ ID NO;
2, wherein said heavy chain variable domain comprises amino acid substitutions F100(VH)P and Y102(VH)K, numbered according to the Kabat numbering. - View Dependent Claims (15, 16)
- 1 and an antibody heavy chain variabic domain of SEQ ID NO;
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17. An antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein in the light chain variable domain N30(VL) is substituted with S, H91(VL) is substituted with F, Y92(VL) is substituted with W, T94(VL) is substituted with S, and in the heavy chain variable domain D98(VH) is substituted with W, Y100a(VH) is substituted with F, and Y102(VH) is substituted with V, numbered according to the Kabat numbering system.
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
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18. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises comprising an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2 with the following substitutions;
Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, and Y102(VH)L. - View Dependent Claims (19, 22, 23, 24, 28, 29)
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
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20. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2 with the following substitutions;
Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, and Y102(VH)K. - View Dependent Claims (21)
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
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25. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody ligbt chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2, wherein N30(VL) is substituted with S, H91(VL) is substituted with F, and Y92(VL) is substituted with W, numbered according to the Kabat numbering system.
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
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26. A humanized anti-HER2 antibody 4D5-8, comprising one or more amino acid substitutions selected from the group consisting of N30(VL)S, Y49(VL)W, F53(VL)W, H91(VL)F, Y92(VL)W, and D98(VH)W, numbered according to the Kabat numbering system.
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27. A humanized anti-HER2 antibody 4D5-8, which comprises a combination of amino acid substitutions selected from the group consisting of (i) Y95(VL)W, F53(VL)V, H91(VL)F and D98(VH)R, F100(VH)L;
- (ii) Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, Y102(VH)K;
(iii) Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, Y102(VH)L;
(iv) Y49(VL)V, F53(VL)V, Y55(VL)W, F100(VH)W, Y102(VH)L;
(v) Y49(VL)W, F53(VL)O, Y55(VL)F, Y102(VH)W;
(vi) Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, Y102(VH)K;
(vii) D28(VL)G, N30(VL)S, T31(VL)S, R66(VL)N, Y92(VL)W, F100(VH)P, Y102(VH)K; and
(viii) D28(VL)G, N30(VL)S, T31(VL)S, R66(VL)M, Y92(VL)F, F100(VH)P, Y102(VH)L.
- (ii) Y49(VL)D, F53(VL)W, Y55(VL)W, F100(VH)P, Y102(VH)K;
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30. An isolated antibody that is capable of binding to the extracellular domain of HER2, which comprises an antibody light chain variable domain of SEQ ID NO:
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
2 wherein the heavy chain variable domain comprises an amino acid substitution 98(VH)W.
- 1 and an antibody heavy chain variable domain of SEQ ID NO;
Specification