PD-1 specific antibodies and uses thereof

• US 9,181,342 B2
• Filed: 09/14/2009
• Issued: 11/10/2015
• Est. Priority Date: 09/12/2008
• Status: Active Grant

• Current Assignee: Oxford University Innovation Limited (University of Oxford)
• Original Assignee: Isis Innovation Limited
• Inventors: Davis, Simon
• Primary Examiner(s): DUFFY, BRADLEY
• Application Number:
  US13/062,552
• Publication Number:
  US 20110171220A1
• Time in Patent Office: 2,248 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

One aspect of the present disclosure provides antibodies that can act as agonists of PD-1, thereby modulating immune responses regulated by PD-1. Another aspect of the disclosure provides compositions comprising PD-1 specific antibodies and their use in methods of down regulating the immune response. These methods can be practiced on any subject, including humans or animals. Anti-PD-1 antibodies disclosed herein may be used, in another aspect of the invention, to detect PD-1 or its fragments in a biological sample. The amount of PD-1 detected may be correlated with the expression level of PD-1, and associated with the activation status of immune cells (e.g., activated T cells, B cells, and/or monocytes) in the subject.

Claims

1. An isolated antibody selected from the group consisting of:

a) a monoclonal antibody that specifically binds to PD-1 produced by the hybridoma clone 19 or antigen binding fragment thereof, said hybridoma clone being deposited with the European Collection of Cell Cultures (ECACC) under accession number 08090901;

b) an isolated antibody or antigen binding fragment that binds to PD-1 and comprising;

i) a light chain comprising SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising SEQ ID NO;

30 (heavy chain CDR1), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3);

or ii) a light chain comprising SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising amino acids 6-10 of SEQ ID NO;

30 (heavy chain CDR1;

Kabat numbering system), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3); and

c) an isolated antibody or antigen binding fragment that binds to PD-1, said isolated antibody or antigen binding fragment comprising SEQ ID NO;

12 and SEQ ID NO;

14.

2. A pharmaceutical composition comprising an antibody according to claim 1.

3. The isolated antibody according to claim 1, wherein said antibody is the monoclonal antibody that specifically binds to PD-1 produced by the hybridoma clone 19 or antigen binding fragment thereof, said hybridoma clone being deposited with the European Collection of Cell Cultures (ECACC) under accession number 08090901.

4. The isolated antibody according to claim 1, wherein said antibody binds PD-1 and is a humanized, chimeric or single chain antibody comprising:

i) a light chain comprising SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising SEQ ID NO;

30 (heavy chain CDR1), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3);

or ii) a light chain comprising SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising amino acids 6-10 of SEQ ID NO;

30 (heavy chain CDR1;

Kabat numbering system), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3).

5. The isolated antibody according to claim 1, wherein said antibody binds PD-1 and comprises SEQ ID NO:

12 and SEQ ID NO;

14.

6. The isolated antibody according to claim 5, wherein SEQ ID NO:

12 and SEQ ID NO;

14 are fused to human constant regions.

7. The isolated antibody according to claim 1, wherein said antibody is tagged with a detectable label.

8. The isolated antibody according to claim 7, wherein said detectable label is a radiolabel or an enzyme.

9. The pharmaceutical composition according to claim 2, wherein said antibody is the monoclonal antibody that specifically binds to PD-1 produced by the hybridoma clone 19 or antigen binding fragment thereof, said hybridoma clone being deposited with the European Collection of Cell Cultures (ECACC) under accession number 08090901.

10. The pharmaceutical composition according to claim 2, wherein said antibody binds PD-1 and is a humanized, chimeric or single chain antibody comprising a light chain comprising:

i) SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising SEQ ID NO;

30 (heavy chain CDR1), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3);

or ii) a light chain comprising SEQ ID NO;

27 (light chain CDR1), SEQ ID NO;

28 (light chain CDR2), SEQ ID NO;

29 (light chain CDR3) and a heavy chain comprising amino acids 6-10 of SEQ ID NO;

30 (heavy chain CDR1;

Kabat numbering system), SEQ ID NO;

31 (heavy chain CDR2) and SEQ ID NO;

32 (heavy chain CDR3).

11. The pharmaceutical composition according to claim 2, wherein said antibody binds PD-1 and comprises SEQ ID NO:

12 and SEQ ID NO;

14.

12. The pharmaceutical composition according to claim 11, wherein SEQ ID NO:

12 and SEQ ID NO;

14 are fused to human constant regions.

13. The pharmaceutical composition according to claim 2, wherein said antibody is tagged with a detectable label.

14. The pharmaceutical composition according to claim 13, wherein said detectable label is a radiolabel or an enzyme.