Anti-MET antibodies and methods of use thereof
Provided herein are compositions, methods and uses involving antibodies that specifically bind to MET, a receptor tyrosine kinase, and modulate the expression and/or activity of MET. Also provided are uses and methods for managing, treating, or preventing disorders, such as cancer. In one aspect, provided herein is a monoclonal antibody or antigen-binding fragment thereof that binds to the Sema/PSI domain of human MET. Also provided herein is a kit comprising an antibody or antigen-binding fragment provided herein. Also provided herein is a method of managing, protecting against, or treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment provided herein.
1. A monoclonal antibody or antigen-binding fragment thereof that binds to human MET, wherein the antibody or antigen-binding fragment thereof comprises:
a. a light chain variable region (“VL”) comprising:
i. a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 13;
ii. a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 14; and
iii. a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and
b. a heavy chain variable region (“VH”) comprising:
i. a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 16;
ii. a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 17; and
iii. a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 18.
2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
a. a VL comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identical to SEQ ID NO: 56; and
b. a VH comprising an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or 100% identical to SEQ ID NO: 63.
3. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody comprises a human IgG constant region.
4. The antibody or antigen-binding fragment thereof of claim 3 , wherein the antibody comprises a human IgG2 constant region.
5. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody comprises a human kappa light chain constant region or a human lambda light chain constant region.
6. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a chimeric antibody or a humanized antibody.
7. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody is a bispecific antibody or antigen-binding fragment thereof.
8. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is fused to a heterologous polypeptide.
9. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or the antigen-binding fragment thereof is conjugated to an agent.
10. A composition comprising a therapeutically effective amount of the antibody or antigen-binding fragment of claim 1 .
11. An isolated cell producing the antibody or antigen-binding fragment of claim 1 .
12. A kit comprising the antibody or antigen-binding fragment of claim 1 .
13. The antibody or antigen-binding fragment of claim 1 , wherein:
a. the VL comprises an amino acid sequence that is identical to SEQ ID NO: 56; and
b. the VH comprises an amino acid sequence that is identical to SEQ ID NO: 63.
14. A monoclonal antibody or antigen-binding fragment thereof that binds to human MET, wherein the antibody or antigen-binding fragment thereof comprises:
a. a VL comprising the same VL CDR1, VL CDR2 and VL CDR3 present in the VL as shown in SEQ ID NO: 56; and
b. a VH comprising the same VH CDR1, VH CDR2 and VH CDR3 present in the VH as shown in SEQ ID NO: 63.
15. The antibody or antigen-binding fragment of claim 14 , wherein:
a. the VL comprises:
i. a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 145;
ii. a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 146; and
iii. a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 264; and
b. the VH comprises:
i. a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 142;
ii. a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 143; and
iii. a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 144.
16. The antibody or antigen-binding fragment of claim 14 , wherein:
a. the VL comprises:
i. a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 175;
ii. a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 176; and
iii. a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 177; and
b. the VH comprises:
i. a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 172;
ii. a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 173; and
iii. a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 174.