Anti-mertk agonistic antibodies and uses thereof
AssigneeThe Rockefeller University
InventorsSohail Tavazoie, Nils Halberg, Masoud Tavazoie
Life of this patent
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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.
Claims93
An antibody or an antigen-binding fragment thereof that specifically binds to human Mer Tyrosine Kinase (MERTK), wherein said antibody agonizes human MERTK signaling of endothelial cells.
An antibody or antigen-binding fragment thereof that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein the VH comprises CDR1 of SEQ ID NO:
- 3, a CDR2 of SEQ ID NO:
- 6, and a CDR3 of SEQ ID NO:
- 11.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An antibody or antigen-binding fragment thereof of that specifically binds to human MERTK, comprising a heavy chain variable region (VH), wherein 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.
An immunoglobulin that specifically binds to human MERTK, comprising:
- (A) (i) a heavy chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 51, and (ii) a light chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 52;
- or
- (B) (i) a heavy chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 49, and (ii) a light chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 50.
An antibody which competes for binding to MERTK with a reference antibody selected from the group consisting of:
- (a) a first immunoglobulin comprising (i) a heavy chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 51, and (ii) a light chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 52;
- and
- (b) a second immunoglobulin comprising (i) a heavy chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 49, and (ii) a light chain variable region that comprises the amino acid sequence of SEQ ID NO:
- 50.
An antibody heavy chain wherein the heavy chain comprises:
- (A) a VH CDR1 of SEQ ID NO:
- 1, a VH CDR2 of SEQ ID NO:
- 6, and a VH CDR3 of SEQ ID NO:
- 11;
- (B) a VH CDR1 of SEQ ID NO:
- 2, a VH CDR2 of SEQ ID NO:
- 7, and a VH CDR3 of SEQ ID NO:
- 12;
- (C) a VH CDR1 of SEQ ID NO:
- 3, a VH CDR2 of SEQ ID NO:
- 8, and a VH CDR3 of SEQ ID NO:
- 11;
- (D) a VH CDR1 of SEQ ID NO:
- 4, a VH CDR2 of SEQ ID NO:
- 9, and a VH CDR3 of SEQ ID NO:
- 13;
- (E) a VH CDR1 of SEQ ID NO:
- 5, a VH CDR2 of SEQ ID NO:
- 10, and a VH CDR3 of SEQ ID NO:
- 14;
- (F) a VH CDR1 of SEQ ID NO:
- 3, a VH CDR2 of SEQ ID NO:
- 6, and a VH CDR3 of SEQ ID NO:
- 11;
- (G) a VH CDR1 of SEQ ID NO:
- 25, a VH CDR2 of SEQ ID NO:
- 30, and a VH CDR3 of SEQ ID NO:
- 35;
- (H) a VH CDR1 of SEQ ID NO:
- 26, a VH CDR2 of SEQ ID NO:
- 31, and a VH CDR3 of SEQ ID NO:
- 36;
- (I) a VH CDR1 of SEQ ID NO:
- 27, a VH CDR2 of SEQ ID NO:
- 32, and a VH CDR3 of SEQ ID NO:
- 35;
- (J) a VH CDR1 of SEQ ID NO:
- 28, a VH CDR2 of SEQ ID NO:
- 33, and a VH CDR3 of SEQ ID NO:
- 37;
- (K) a VH CDR1 of SEQ ID NO:
- 29, a VH CDR2 of SEQ ID NO:
- 34, and a VH CDR3 of SEQ ID NO:
- 38;
- or
- (L) a VH CDR1 of SEQ ID NO:
- 27, a VH CDR2 of SEQ ID NO:
- 30, and a VH CDR3 of SEQ ID NO:
- 35.
An antibody light chain wherein the light chain comprises:
- (A) a light chain variable region (VL) CDR1 of SEQ ID NO:
- 15, a VL CDR2 of SEQ ID NO:
- 19, and a VL CDR3 of SEQ ID NO:
- 22;
- (B) a VL CDR1 of SEQ ID NO:
- 16, a VL CDR2 of SEQ ID NO:
- 20, and a VL CDR3 of SEQ ID NO:
- 23;
- (C) a VL CDR1 of SEQ ID NO:
- 17, a VL CDR2 of SEQ ID NO:
- 21, and a VL CDR3 of SEQ ID NO:
- 24;
- (D) a VL CDR1 of SEQ ID NO:
- 18, a VL CDR2 of SEQ ID NO:
- 20, and a VL CDR3 of SEQ ID NO:
- 22;
- (E) a VL CDR1 of SEQ ID NO:
- 39, a VL CDR2 of SEQ ID NO:
- 43, and a VL CDR3 of SEQ ID NO:
- 46;
- (F) a VL CDR1 of SEQ ID NO:
- 40, a VL CDR2 of SEQ ID NO:
- 44, and a VL CDR3 of SEQ ID NO:
- 47;
- (G) a VL CDR1 of SEQ ID NO:
- 41, a VL CDR2 of SEQ ID NO:
- 45, and a VL CDR3 of SEQ ID NO:
- 48;
- or
- (H) a VL CDR1 of SEQ ID NO:
- 42, a VL CDR2 of SEQ ID NO:
- 44, and a VL CDR3 of SEQ ID NO:
- 46.
Dependencies are inferred from the claim text.