Anti-mertk agonistic antibodies and uses thereof
AssigneeThe Rockefeller University
InventorsSohail Tavazoie, Nils Halberg, Masoud Tavazoie
Life of this patent
Estimating the term…
Abstract
The present disclosure provides antibodies that specifically bind to Mer Tyrosine Kinase (MERTK) (e.g., human MERTK, or both human and mouse MERTK) and compositions comprising such antibodies, wherein said antibody agonizes MERTK signaling on endothelial cells. The present disclosure also provides methods for treating cancer, by administering an antibody that specifically binds to MERTK and agonizes MERTK signaling on endothelial cells.
Claims26
1-94. (canceled)
A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically effective amount of an antibody or an antigen-binding fragment thereof that specifically binds to human Mer Tyrosine Kinase (“MERTK”), and (b) a pharmaceutically acceptable carrier;
- wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein:
- (i) the VH comprises a complementarity determining region (CDR) 1 of SEQ ID NO:
- 1, a VH CDR2 of SEQ ID NO:
- 6, and a VH CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22;
- (ii) the VH comprises a CDR1 of SEQ ID NO:
- 2, a CDR2 of SEQ ID NO:
- 7, and a CDR3 of SEQ ID NO:
- 12, and the VL comprises a CDR1 of SEQ ID NO:
- 16, a CDR2 of SEQ ID NO:
- 20, and a CDR3 of SEQ ID NO:
- 23;
- (iii) the VH comprises a CDR1 of SEQ ID NO:
- 3, a CDR2 of SEQ ID NO:
- 8, and a CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22;
- (iv) the VH comprises a CDR1 of SEQ ID NO:
- 4, a CDR2 of SEQ ID NO:
- 9, and a CDR3 of SEQ ID NO:
- 13, and the VL comprises a CDR1 of SEQ ID NO:
- 17, a CDR2 of SEQ ID NO:
- 21, and a CDR3 of SEQ ID NO:
- 24;
- (v) the VH comprises a CDR1 of SEQ ID NO:
- 5, a CDR2 of SEQ ID NO:
- 10, and a CDR3 of SEQ ID NO:
- 14, and the VL comprises CDR1 of SEQ ID NO:
- 18, a CDR2 of SEQ ID NO:
- 20, and a CDR3 of SEQ ID NO:
- 22;
- or
- (vi) the VH comprises CDR1 of SEQ ID NO:
- 3, a CDR2 of SEQ ID NO:
- 6, and a CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22.
A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically amount of an antibody or an antigen-binding fragment thereof that specifically binds to human Mer Tyrosine Kinase (“MERTK”), and (b) a pharmaceutically acceptable carrier;
- wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein:
- (i) the VH comprises a CDR1 of SEQ ID NO:
- 25, a CDR2 of SEQ ID NO:
- 30, and a CDR3 of SEQ ID NO:
- 35, and the VL comprises a CDR1 of SEQ ID NO:
- 39, a CDR2 of SEQ ID NO:
- 43, and a CDR3 of SEQ ID NO:
- 46;
- (ii) the VH comprises a CDR1 of SEQ ID NO:
- 26, a CDR2 of SEQ ID NO:
- 31, and a CDR3 of SEQ ID NO:
- 36, and the VL comprises a CDR1 of SEQ ID NO:
- 40, a CDR2 of SEQ ID NO:
- 44, and a CDR3 of SEQ ID NO:
- 47;
- (iii) the VH comprises a CDR1 of SEQ ID NO:
- 27, a CDR2 of SEQ ID NO:
- 32, and a CDR3 of SEQ ID NO:
- 35, and the VL comprises a CDR1 of SEQ ID NO:
- 39, a CDR2 of SEQ ID NO:
- 43, and a CDR3 of SEQ ID NO:
- 46;
- (iv) the VH comprises a CDR1 of SEQ ID NO:
- 28, a CDR2 of SEQ ID NO:
- 33, and a CDR3 of SEQ ID NO:
- 37, and the VL comprises a CDR1 of SEQ ID NO:
- 41, a CDR2 of SEQ ID NO:
- 45, and a CDR3 of SEQ ID NO:
- 48;
- (v) the VH comprises a CDR1 of SEQ ID NO:
- 29, a CDR2 of SEQ ID NO:
- 34, and a CDR3 of SEQ ID NO:
- 38, and the VL comprises a CDR1 of SEQ ID NO:
- 42, a CDR2 of SEQ ID NO:
- 44, and a CDR3 of SEQ ID NO:
- 46;
- or
- (vi) the VH comprises a CDR1 of SEQ ID NO:
- 27, a CDR2 of SEQ ID NO:
- 30, and a CDR3 of SEQ ID NO:
- 35, and the VL comprises a CDR1 of SEQ ID NO:
- 39, a CDR2 of SEQ ID NO:
- 43, and a CDR3 of SEQ ID NO:
- 46.
A method of treating cancer in a human subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically amount of a humanized antibody or an antigen-binding fragment thereof that specifically binds to human Mer Tyrosine Kinase (“MERTK”), and (b) a pharmaceutically acceptable carrier;
- wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein:
- (i) the VH comprises a complementarity determining region (CDR) 1 of SEQ ID NO:
- 1, a VH CDR2 of SEQ ID NO:
- 6, and a VH CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22;
- (ii) the VH comprises a CDR1 of SEQ ID NO:
- 2, a CDR2 of SEQ ID NO:
- 7, and a CDR3 of SEQ ID NO:
- 12, and the VL comprises a CDR1 of SEQ ID NO:
- 16, a CDR2 of SEQ ID NO:
- 20, and a CDR3 of SEQ ID NO:
- 23;
- (iii) the VH comprises a CDR1 of SEQ ID NO:
- 3, a CDR2 of SEQ ID NO:
- 8, and a CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22;
- (iv) the VH comprises a CDR1 of SEQ ID NO:
- 5, a CDR2 of SEQ ID NO:
- 10, and a CDR3 of SEQ ID NO:
- 14, and the VL comprises CDR1 of SEQ ID NO:
- 18, a CDR2 of SEQ ID NO:
- 20, and a CDR3 of SEQ ID NO:
- 22;
- or
- (v) the VH comprises CDR1 of SEQ ID NO:
- 3, a CDR2 of SEQ ID NO:
- 6, and a CDR3 of SEQ ID NO:
- 11, and the VL comprises a CDR1 of SEQ ID NO:
- 15, a CDR2 of SEQ ID NO:
- 19, and a CDR3 of SEQ ID NO:
- 22.
Dependencies are inferred from the claim text.