Anti-PD-L1 antibodies and uses therefor

• US 8,552,154 B2
• Filed: 09/25/2009
• Issued: 10/08/2013
• Est. Priority Date: 09/26/2008
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute, Emory University
• Original Assignee: Dana-Farber Cancer Institute, Emory University
• Inventors: Freeman, Gordon J., Ahmed, Rafi, Jones, Timothy D., Carr, Francis J., Gregson, James P.
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US13/120,406
• Publication Number:
  US 20110271358A1
• Time in Patent Office: 1,474 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 33/10 : Anthelmintics
• CPC Class Codes: A61P 33/12 : Schistosomicides
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• 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: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• 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 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/74 : Inducing cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention is based, in part, on the identification of novel human anti-PD-1, PD-L1, and PD-L2 antibodies. Accordingly, the invention relates to compositions and methods for diagnosing, prognosing, and treating conditions that would benefit from modulating PD-1, PD-L1, and/or PD-L2 activity (e.g., persistent infectious diseases, autoimmune diseases, asthma, transplant rejection, inflammatory disorders and tumors) using the novel human anti-PD-1, PD-L1, and PD-L2 antibodies described herein.

Claims

1. An isolated antibody or antigen-binding fragment thereof, comprising:

a) a heavy chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

13-15; and

/or

b) a light chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

16-18,

wherein the isolated antibody, or antigen-binding fragment thereof, binds to a PD-L1 protein having the amino acid sequence of SEQ ID NO;

4, and the isolated antibody, or antigen-binding fragment thereof, is chimeric, humanized, composite, or human.

2. The isolated antibody or antigen-binding fragment of claim 1, comprising:

a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs;

34-38, or a sequence with at least about 95% homology to a heavy chain sequence selected from the group consisting of SEQ ID NOs;

34-38; and

/or

b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs;

39-42, or a sequence with at least about 95% homology to a light chain sequence selected from the group consisting of SEQ ID NOs;

39-42.

3. The isolated antibody or antigen-binding fragment of claim 2, comprising:

a) a heavy chain variable region sequence comprising SEQ ID NO;

35 or 37, or a sequence with at least about 95% homology to a heavy chain sequence comprising SEQ ID NO;

35 or 37; and

b) a light chain variable region sequence comprising SEQ ID NO;

39, 40 or 42, or a sequence with at least about 95% homology to a light chain sequence comprising SEQ ID NO;

39, 40 or 42.

4. The isolated antibody or antigen-binding fragment of claim 1, wherein the isolated antibody or antigen-binding fragment thereof inhibits the binding of an antibody comprising a heavy chain variable region comprising the sequence of SEQ ID NO:

78 and a light chain variable region comprising the sequence of SEQ ID NO;

79 to Fc-PD-L1.

5. The isolated antibody or antigen-binding fragment of claim 1, wherein the isolated antibody or antigen-binding fragment thereof inhibits a PD-L1-mediated signal.

8. The isolated antibody or antigen-binding fragment of claim 1, comprising:

a) a heavy chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

13-15; and

b) a light chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

16-18.

9. The isolated antibody or antigen-binding fragment of claim 8, comprising:

a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs;

34-38, or a sequence with at least about 95% homology to a heavy chain sequence selected from the group consisting of SEQ ID NOs;

34-38; and

b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs;

39-42, or a sequence with at least about 95% homology to a light chain sequence selected from the group consisting of SEQ ID NOs;

39-42.

10. The isolated antibody or antigen-binding fragment of claim 2, comprising:

a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs;

34-38; and

/or

b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs;

39-42.

11. The isolated antibody or antigen-binding fragment of claim 10, comprising:

a) a heavy chain variable region sequence selected from the group consisting of SEQ ID NOs;

34-38; and

b) a light chain variable region sequence selected from the group consisting of SEQ ID NOs;

39-42.

12. The isolated antibody or antigen-binding fragment of claim 11, comprising:

a) a heavy chain variable region sequence comprising SEQ ID NO;

35 or 37; and

b) a light chain variable region sequence comprising SEQ ID NO;

39, 40 or 42.

6. A pharmaceutical composition, comprising an isolated antibody or antigen-binding fragment thereof and a pharmaceutically-acceptable carrier, wherein the antibody or antigen-binding fragment thereof comprises:

a) a heavy chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

13-15; and

/or

b) a light chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

16-18,

wherein the isolated antibody, or antigen-binding fragment thereof, binds to a PD-L1 protein having the amino acid sequence of SEQ ID NO;

4, and the isolated antibody, or antigen-binding fragment thereof, is chimeric, humanized, composite, or human.

7. A method of producing an antibody or antigen-binding fragment thereof, comprising culturing a cell that produces the antibody or antigen-binding fragment, and recovering the antibody or antigen-binding fragment produced by the cell, wherein the antibody or antigen-binding fragment thereof comprises:

a) a heavy chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

13-15; and

/or

b) a light chain variable region sequence comprising the three CDRs with the sequences of SEQ ID NOs;

16-18,

wherein the antibody, or antigen-binding fragment thereof, binds to a PD-L1 protein having the amino acid sequence of SEQ ID NO;

4, and the antibody, or antigen-binding fragment thereof, is chimeric, humanized, composite, or human.