BISPECIFIC ANTIBODIES AGAINST HER2 AND CD3
First Claim
1. A bispecific antibody comprising a first antigen-binding region and a second antigen-binding region, which second antigen-binding region binds an epitope on human CD3 and the first antigen-binding region binds an epitope on human epidermal growth factor receptor 2 (HER2) and blocks the binding to HER2, optionally soluble HER2, of a reference antibody selected from the group consisting of:
- a) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
63 and a VL region comprising the sequence of SEQ ID NO;
67,b) an antibody comprising a variable heavy (VH) region comprising the sequence of SEQ ID NO;
1 and a variable light (VL) region comprising the sequence of SEQ ID NO;
5,c) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
165 and a VL region comprising the sequence of SEQ ID NO;
169, andd) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
22 and a VL region comprising the sequence of SEQ ID NO;
26.
1 Assignment
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Accused Products
Abstract
Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.
37 Citations
83 Claims
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1. A bispecific antibody comprising a first antigen-binding region and a second antigen-binding region, which second antigen-binding region binds an epitope on human CD3 and the first antigen-binding region binds an epitope on human epidermal growth factor receptor 2 (HER2) and blocks the binding to HER2, optionally soluble HER2, of a reference antibody selected from the group consisting of:
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a) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
63 and a VL region comprising the sequence of SEQ ID NO;
67,b) an antibody comprising a variable heavy (VH) region comprising the sequence of SEQ ID NO;
1 and a variable light (VL) region comprising the sequence of SEQ ID NO;
5,c) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
165 and a VL region comprising the sequence of SEQ ID NO;
169, andd) an antibody comprising a VH region comprising the sequence of SEQ ID NO;
22 and a VL region comprising the sequence of SEQ ID NO;
26. - View Dependent Claims (2, 3, 6, 9, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 34, 54, 55, 56, 57, 58, 59, 61, 62, 63, 64, 65, 66, 67, 68, 73, 74, 76, 77, 78, 80, 81, 82, 83)
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4-5. -5. (canceled)
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7. A bispecific antibody comprising a first antigen-binding region and a second antigen-binding region, which second antigen-binding region binds an epitope on human CD3 and the first antigen-binding region binds an epitope on HER2, wherein the first antigen-binding region comprises a VH region and a VL region selected from the group consisting of
a) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs: - 2, 3 and 4, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
6, DAS, and SEQ ID NO;
7, respectively;b) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
9, 10 and 11, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
13, AAS, and SEQ ID NO;
14, respectively;c) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
16, 17 and 18, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
20, VAS, and SEQ ID NO;
21, respectively;d) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
23, 24 and 25, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
27, AAS, and SEQ ID NO;
28, respectively;e) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
30, 163 and 31, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
33, AAS, and SEQ ID NO;
34, respectively;f) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
36, 37 and 38, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
40, DAS, and SEQ ID NO;
41, respectively;g) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
43, 44 and 45, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
47, AAS, and SEQ ID NO;
48, respectively;h) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
50, 51 and 52, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
54, AAS, and SEQ ID NO;
55, respectively;i) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
57, 58 and 59, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
60, AAS, and SEQ ID NO;
61, respectively;j) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
64, 65 and 66, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
68, DAS, and SEQ ID NO;
69, respectively;k) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
71, 72 and 73, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
75, DAS, and SEQ ID NO;
76, respectively;l) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
166, 167 and 168, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NO;
170, GAS and SEQ ID NO;
171, respectively;m) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
173, 174 and 175, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
177, DAS, and SEQ ID NO;
178, respectively;n) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
180, 181 and 182, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
184, GAS, and SEQ ID NO;
185, respectively;o) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
187, 188 and 189, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
191, GAS, and SEQ ID NO;
192, respectively;p) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
194, 195 and 196, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
198, GAS, and SEQ ID NO;
199, respectively;q) a VH region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
201, 202 and 203, respectively; and
a VL region comprising the CDR1, CDR2 and CDR3 sequences of SEQ ID NOs;
205, GAS, and SEQ ID NO;
206, respectively.
- 2, 3 and 4, respectively; and
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10-12. -12. (canceled)
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14-16. -16. (canceled)
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31. (canceled)
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35-53. -53. (canceled)
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60. (canceled)
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69. An in vitro method for generating a bispecific antibody, said method comprising the steps of:
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a) providing a first antibody binding to an epitope on HER2 and comprising a first Fc region, said Fc region comprising a first CH3 region, b) providing a second antibody binding to an epitope on human CD3 and comprising a second Fc region, said Fc region comprising a second CH3 region, c) incubating said first antibody together with said second antibody under reducing conditions, and d) obtaining said bispecific antibody, wherein the sequences of said first and second CH3 regions are different and are such that the heterodimeric interaction between said first and second CH3 regions is stronger than each of the homodimeric interactions of said first and second CH3 regions. - View Dependent Claims (70, 71, 72)
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75. (canceled)
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79. (canceled)
Specification