Anti-B7-H5 antibodies and their uses
The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H5 ligand of the B7-H5:CD28H pathway, and to the uses of such molecules in the treatment and diagnosis of autoimmune disease, transplant rejection and other inflammatory diseases.
1. An antibody or antigen binding fragment thereof comprising six complementarity determining regions (CDRs), wherein the CDRs comprise
(1) the three light chain CDRs of SEQ ID NO: 11 and the three heavy chain CDRs of SEQ ID NO: 9, or
(2) the three light chain CDRs of SEQ ID NO: 15 and the three heavy chain CDRs of SEQ ID NO: 13, and
wherein the antibody or antigen binding fragment thereof binds to human B7-H5 as set forth in SEQ ID NO: 1.
2. The antibody or antigen binding fragment thereof of claim 1 , wherein the three light chain CDRs comprise a first light chain CDR comprising amino acids 27-38 of SEQ ID NO: 11, a second light chain CDR comprising amino acids 56-58 of SEQ ID NO: 11, and a third light chain CDR comprising amino acids 95-102 of SEQ ID NO: 11;
wherein the three heavy chain CDRs comprise a first heavy chain CDR comprising amino acids 26-33 of SEQ ID NO: 9, a second heavy chain CDR comprising amino acids 51-58 of SEQ ID NO: 9, and a third heavy chain CDR comprising amino acids 97-106 of SEQ ID NO: 9;
wherein the three light chain CDRs comprise a first light chain CDR comprising amino acids 27-38 of SEQ ID NO: 15, a second light chain CDR comprising amino acids 56-58 of SEQ ID NO: 15, and a third light chain CDR comprising amino acids 95-102 of SEQ ID NO: 15; or
wherein the three heavy chain CDRs comprise a first heavy chain CDR comprising amino acids 26-33 of SEQ ID NO: 13, a second heavy chain CDR comprising amino acids 51-58 of SEQ ID NO: 13, and a third heavy chain CDR comprising amino acids 97-106 of SEQ ID NO: 13.
3. The antibody or antigen binding fragment thereof of claim 1 comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 9; or comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 15 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13.
4. The antibody or antigen binding fragment thereof of claim 1 , wherein the bound B7-H5 is arrayed on the surface of a live cell or expressed at an endogenous or transfected concentration.
5. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof
(A) attenuates the ability of B7-H5 to bind to CD28H;
(B) antagonizes signal transduction that occurs as a consequence of B7-H5 binding to CD28H;
(C) inhibits an allogeneic T cell response;
(D) a combination thereof.
6. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is detectably labeled or comprises a conjugated toxin, drug, receptor, enzyme, or receptor ligand.
7. A humanized antibody or antigen binding fragment thereof comprising one or more human IgG4 constant domains and
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 9, or
a light chain variable region comprising the amino acid sequence of SEQ ID NO: 15, a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13.
8. A pharmaceutical composition comprising the antibody or an antigen binding fragment thereof of claim 1 , and a physiologically acceptable carrier or excipient.
9. A method of down-modulating the immune system of a subject who has an autoimmune or inflammatory disease, or has received or will receive a transplant, the method comprising administering the pharmaceutical composition of claim 8 in an effective amount to down-modulate the subject's immune system via binding of the antibody or an antigen binding fragment thereof to human B7-H5.
10. The method of claim 9 , wherein the subject has is an autoimmune disease.
11. The method of claim 9 , wherein the subject has is an inflammatory disease.
12. The method of claim 9 , wherein the subject has received or will receive a transplant.