PD-1 agonist and method of using same
Provided is a PD-1-binding agent comprising an immunoglobulin heavy chain polypeptide and immunoglobulin light chain polypeptide, as well as related compositions and methods for making and using same.
1 . A PD-1 binding agent comprising an immunoglobulin heavy chain variable region and an immunoglobulin light chain variable region, wherein
the immunoglobulin heavy chain variable region comprises at least the CDR regions of any one of SEQ ID NOs: 43-47 or 61-63, and the immunoglobulin light chain variable region comprises at least the CDR regions of any one of SEQ ID NOs: 48-50.
2 . The PD-1 binding agent of claim 1 , wherein the PD-1 binding agent comprises the following CDR regions when determined according to Kabat:
CDRH1: SEQ ID NO: 64
CDRH2: SEQ ID NO: 65
CDRH3: SEQ ID NO: 66
CDRL1: SEQ ID NO: 67
CDRL2: SEQ ID NO: 68
CDRL3: SEQ ID NO: 69;
or wherein the PD-1 binding agent comprises the following CDR regions when determined according to IMGT:
CDRH1: SEQ ID NO: 70
CDRH2: SEQ ID NO: 71
CDRH3: SEQ ID NO: 72
CDRL1: SEQ ID NO: 73
CDRL2: SEQ ID NO: 74
CDRL3: SEQ ID NO: 75.
3 . The PD-1 binding agent of claim 1 , wherein the immunoglobulin heavy chain variable region comprises at least 80% sequence identity to any one of SEQ ID NOs: 43-47 or 61-63, and the immunoglobulin light chain variable region comprises at least 80% sequence identity to SEQ ID NOs: 48-50.
4 . The PD-1 binding agent of claim 1 , wherein the immunoglobulin heavy chain variable region comprises any one of SEQ ID NOs: 43-47 or 61-63, and the immunoglobulin light chain variable region comprises any one of SEQ ID NOs: 48-50.
5 . The PD-1 binding agent of claim 1 , wherein the immunoglobulin heavy chain variable region comprises SEQ ID NO: 47, and the immunoglobulin light chain variable region comprises SEQ ID NO: 49.
6 . The PD-1 binding agent of claim 1 , wherein the immunoglobulin heavy chain variable region comprises SEQ ID NO: 46, and the immunoglobulin light chain variable region comprises SEQ ID NO: 50.
7 . The PD-1 binding agent of claim 1 , wherein the immunoglobulin heavy chain comprises SEQ ID NO: 51, and the immunoglobulin light chain comprises SEQ ID NO: 52.
8 . The PD-1 binding agent of claim 1 , wherein the PD-1 binding agent is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
9 . The PD-1 binding agent of claim 1 , wherein the PD-1 binding agent is a F(ab′) 2 , Fab′, Fab, Fv, scFv, dsFv, or a single chain binding polypeptide.
10 . The anti-PD-1 binding agent of claim 1 , wherein the PD-1 binding agent comprises an IgG Fc region that binds an Fc receptor on an antigen presenting cell.
11 . The PD-1 binding agent of claim 1 , wherein the PD-1 binding agent comprises an Fc region of IgG1 or other Fc region that binds an FcγR.
12 . The PD-1 binding agent of claim 1 , wherein the PD-1 binding agent is an IgG1 antibody.
13 . The anti-PD-1 binding agent of claim 2 , wherein the PD-1 binding agent comprises an IgG Fc region that binds an Fc receptor on an antigen presenting cell.
14 . The PD-1 binding agent of claim 2 , wherein the PD-1 binding agent comprises an Fc region of IgG1 or other Fc region that binds an FcγR.
15 . The PD-1 binding agent of claim 2 , wherein the PD-1 binding agent is an IgG1 antibody.
16 . The anti-PD-1 binding agent of claim 5 , wherein the PD-1 binding agent comprises an IgG Fc region that binds an Fc receptor on an antigen presenting cell.
17 . The PD-1 binding agent of claim 5 , wherein the PD-1 binding agent comprises an Fc region of IgG1 or other Fc region that binds an FcγR.
18 . A nucleic acid encoding the immunoglobulin heavy chain and/or immunoglobulin light chain of the anti-PD-1 binding agent of claim 1 .
19 . A nucleic acid encoding the immunoglobulin heavy chain and/or immunoglobulin light chain of the anti-PD-1 binding agent of claim 5 .
20 . A cell that expresses the anti-PD-1 binding agent of claim 5 .
21 . A method of preparing the anti-PD-1 binding agent of claim 5 , the method comprising expressing a nucleic acid encoding the immunoglobulin heavy chain and a nucleic acid encoding the immunoglobulin light chain in a cell, wherein the immunoglobulin heavy and light chains can be expressed from a single nucleic acid or the immunoglobulin heavy and light chains can be expressed from separate nucleic acids.
22 . A pharmaceutical composition comprising (a) anti-PD-1 binding agent of claim 14 , and (b) a pharmaceutically acceptable carrier.
23 . A pharmaceutical composition comprising (a) anti-PD-1 binding agent of claim 17 , and (b) a pharmaceutically acceptable carrier.
24 . A pharmaceutical composition comprising (a) anti-PD-1 binding agent of claim 11 , and (b) a pharmaceutically acceptable carrier.