ANTIBODIES AND OTHER MOLECULES THAT BIND B7-H1 AND PD-1

• US 20160130348A1
• Filed: 10/29/2015
• Published: 05/12/2016
• Est. Priority Date: 04/20/2011
• Status: Abandoned Application

• Current Assignee: Medimmune LLC (Astrazeneca PLC)
• Original Assignee: Medimmune LLC (Astrazeneca PLC)
• Inventors: Langermann, Solomon, Liu, Linda, Marshall, Shannon, Yao, Sheng
• Application Number:
  US14/926,732
• Publication Number:
  US 20160130348A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 33/6854 Immunoglobulins

Abstract

The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.

Claims

1. A molecule, comprising an antigen-binding fragment of an antibody that immunospecifically binds to B7-H1 or PD-1.

2. The molecule of claim 1, wherein said immunospecifically bound B7-H1 or PD-1 is expressed on the surface of a live cell at an endogenous or transfected level.

3. The molecule of claim 1, wherein said B7-H1 is human B7-H1 and said PD-1 is human PD-1.

4. The molecule of claim 1, wherein said antigen-binding fragment binds to B7-H1, and wherein said live cell is a tumor cell, a pathogen-infected cell or an Antigen Presenting Cell.

5. The molecule of claim 2, wherein said antigen-binding fragment binds to PD-1, and wherein said live cell is a T cell.

6. The molecule of claim 1, wherein said molecule is a monoclonal antibody, a human antibody, a chimeric antibody or a humanized antibody.

7. The antibody of claim 6, wherein said antibody is a bispecific, trispecific or multispecific antibody.

8. The molecule of claim 3, wherein the molecule or antibody binds to B7-H1, and wherein said antigen-binding fragment thereof comprises six CDRs, wherein said CDRs comprise at least one consensus CDR of the CDRs of anti-B7-H1 antibodies 1E12, 1F4, 2G11, 3B6, and 3D10 with all remaining CDRs selected from:

(A) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 1E12;

(B) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 1F4;

(C) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 2G1;

(D) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 3B6;

or

(E) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 3D10.

9. The molecule of claim 8, wherein said six CDRs are:

(A) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 1E12;

(B) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 1F4;

(C) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 2G1;

(D) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 3B6;

or

(E) the three light chain and the three heavy chain CDRs of anti-B7-H1 antibody 3D10.

10. The antibody of claim 6, wherein said antibody binds to B7-H1 and comprises a variable domain of antibody h3D10 Var 1, h3D10 Var 2, h3D10 Var 3, h3D10 Var 4, h3D10 Var 5, h3D10 Var 6, h3D10 Var 7, h3D10 Var 8, h3D10 Var 9, h3D10 Var 10, h3D10 Var 11, h3D10 Var 12, h3D10 Var 13, ir h3D10 Var 14.

11. The molecule of claim 3, wherein the molecule or antibody binds to B7-H1, and wherein said antigen-binding fragment thereof comprises six CDRs, wherein said CDRs comprise at least one consensus CDR of the CDRs of anti-PD-1 antibodies 1E3, 1E8, and 1H3 with all remaining CDRs selected from:

(A) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1E3;

(B) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1E8;

or

(C) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1H3.

12. The molecule of claim 11, wherein said six CDRs are:

(A) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1E3;

(B) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1E8;

or

(C) the three light chain and the three heavy chain CDRs of anti-PD-1 antibody 1H3.

13. The antibody of claim 6, wherein said antibody binds to PD-1 and comprises a variable domain of antibody h1H3 Var 1, h1H3 Var 2, h1H3 Var 3, h1H3 Var 4, h1H3 Var 5, h1H3 Var 6, h1H3 Var 7, h1H3 Var 8, h1H3 Var 9, h1H3 Var 10, h1H3 Var 11, h1H3 Var 12, h1H3 Var 13, or h1H3 Var 14.

14. The molecule of claim 5, wherein said molecule or antibody is detectably labeled or comprises a conjugated toxin, drug, receptor, enzyme, or receptor ligand.

15. The molecule of claim 1, wherein said molecule or antibody:

(A) modulates signal transduction mediated by B7-H1 or PD-1;

(B) attenuates the ability of B7-H1 to bind to a B7-H1 receptor or attenuates the ability of PD-1 to bind to a PD-1 ligand;

(C) agonizes B7-H1 or PD-1 mediated signal transduction;

(D) mediates T cell proliferation;

or

(E) enhances the production of IFN-γ

.

16. A pharmaceutical composition comprising a therapeutically effective amount of the molecule of claim 15, and a physiologically acceptable carrier or excipient.

17-20. -20. (canceled)