Bi-specific antibodies against TIM-3 and PD-1 for immunotherapy in chronic immune conditions

• US 9,163,087 B2
• Filed: 06/16/2011
• Issued: 10/20/2015
• Est. Priority Date: 06/18/2010
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Kuchroo, Vijay K., Anderson, Ana C.
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US13/805,030
• Publication Number:
  US 20130156774A1
• Time in Patent Office: 1,587 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• 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 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

Described herein are novel compositions comprising bispecific and multispecific polypeptide agents, and methods using these agents for targeting cells, such as functionally exhausted or unresponsive immune cells, that co-express the inhibitory receptors PD-1 and TIM-3. These compositions and methods are useful for the treatment of chronic immune conditions, such as persistent infections or cancer.

Claims

1. A pharmaceutical composition comprising:

a polypeptide agent that specifically binds to a human PD-1 molecule at a PD-1 ligand interaction site that inhibits interaction of PD-1 with PD-L1, PD-L2, or PD-L1 and PD-L2, and a polypeptide agent that specifically binds to a human TIM-3 molecule at a TIM-3 ligand interaction site that inhibits interaction of TIM-3 with galectin-9, phosphatidylserine, or galectin-9 and phosphatidylserine.

2. The composition of claim 1, wherein the polypeptide agent specifically binds a PD-1 molecule having the sequence set forth in SEQ ID NO:

1.

3. The composition of claim 1, wherein the polypeptide agent specifically binds a TIM-3 molecule having the sequence set forth in SEQ ID NO:

2.

4. The composition of claim 1, wherein the ligand interaction site of PD-1 comprises amino acid residues 41-136 of SEQ ID NO:

1.

5. The composition of claim 1, wherein the TIM-3 ligand interaction site comprises amino acid residues 24-131 of SEQ ID NO:

2.