Antibodies binding AXL
The present invention relates to anti-AXL antibodies, immunoconjugates, compositions and method of treatment of cancer with such anti-AXL antibodies, immunoconjugates, or compositions.
1 . An antibody which binds to AXL and comprises at least one binding region comprising a pair of variable heavy chain (VH) and variable light chain (VL) regions selected from the group consisting of:
a) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 83, 84, and 85, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 86, the sequence GAS, and SEQ ID NO: 87, respectively;
b) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 88, 89, and 90, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 91, the sequence GAS, and SEQ ID NO: 92, respectively;
c) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 96, the sequence GAS, and SEQ ID NO: 97, respectively;
d) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 98, 99, and 100, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 101, the sequence DAS, and SEQ ID NO: 102, respectively;
e) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOS: 103, 104, and 105, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 106, the sequence GAS, and SEQ ID NO: 107, respectively;
f) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 93, 94, and 95, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 128, the sequence XAS, wherein X is D or G, and SEQ ID NO: 129, respectively; and
g) a VH region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 93, 126, and 127, respectively, and a VL region comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NOs: 96, the sequence GAS, and SEQ ID NO: 97.
2 . The antibody of claim 1 , wherein the antibody comprises at least one binding region comprising a pair of VH and VL regions having sequences at least 90% identical to VH and VL regions selected from the group consisting of:
a) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 25 and 26, respectively;
b) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 21 and 22, respectively;
c) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 23 and 24, respectively;
d) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 27 and 28, respectively; and
e) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 29 and 30, respectively.
3 . The antibody of claim 1 , wherein the antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.
4 . The antibody of claim 1 , wherein the antibody is a full length monoclonal antibody.
5 . The antibody of claim 1 , wherein said antibody is a monovalent antibody or a stabilized antibody.
6 . The antibody of claim 1 , wherein the antibody is a single-chain antibody.
7 . The antibody of claim 1 , wherein the antibody has reduced effector function or is devoid of effector function.
8 . An immunoconjugate comprising the antibody of claim 1 , and a therapeutic moiety.
9 . The antibody of claim 1 , wherein the antibody is a bispecific antibody.
10 . A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutical acceptable carrier.
11 . A kit for detecting the presence of AXL antigen, or a cell expressing AXL, in a sample, wherein the kit comprises the antibody of claim 1 .
12 . An antibody which binds to AXL and comprises at least one binding region comprising variable heavy chain (VH) and variable light chain (VL) regions selected from the group consisting of:
a) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 25 and 26, respectively;
b) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 21 and 22, respectively;
c) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 23 and 24, respectively;
d) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 27 and 28, respectively; and
e) VH and VL regions comprising the amino acid sequences of SEQ ID NOs: 29 and 30, respectively.
13 . The antibody of claim 12 , wherein the antibody comprises a heavy chain of an isotype selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.
14 . The antibody of claim 12 , wherein the antibody is a full length monoclonal antibody.
15 . The antibody of claim 12 , wherein said antibody is a monovalent antibody or a stabilized antibody.
16 . The antibody of claim 12 , wherein the antibody is a single-chain antibody.
17 . The antibody of claim 12 , wherein the antibody has reduced effector function or is devoid of effector function.
18 . An immunoconjugate comprising the antibody of claim 12 , and a therapeutic moiety.
19 . The antibody of claim 12 , wherein the antibody is a bispecific antibody.
20 . A pharmaceutical composition comprising the antibody of claim 12 , and a pharmaceutical acceptable carrier.
21 . A kit for detecting the presence of AXL antigen, or a cell expressing AXL, in a sample, wherein the kit comprises the antibody of claim 12 .