PD-1 antibody

• US 8,993,731 B2
• Filed: 03/09/2011
• Issued: 03/31/2015
• Est. Priority Date: 03/11/2010
• Status: Active Grant

• Current Assignee: Ucb Biopharma Sprl (UCB SA)
• Original Assignee: Ucb Biopharma Sprl (UCB SA)
• Inventors: Tyson, Kerry Louise
• Primary Examiner(s): OUSPENSKI, ILIA I
• Application Number:
  US13/583,999
• Publication Number:
  US 20130095098A1
• Time in Patent Office: 1,483 Days
• US Class Current: 530/388.75
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• 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

A humanized agonistic antibody which binds human PD-1 comprising a heavy chain wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:1 for CDR-H1, the sequence given in SEQ ID NO: 2 for CDR-H2 and the sequence given in SEQ ID NO: 3 for CDR-H3 and the heavy chain framework region is derived from human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO: 33). The disclosure also extends to therapeutic uses of the antibody molecules, compositions and methods for producing said antibody molecules.

Claims

1. A humanised agonistic antibody which binds human PD-1 comprising a heavy chain wherein the variable domain of the heavy chain comprises the sequence given in SEQ ID NO:

1 for CDR-H1, the sequence given in SEQ ID NO;

2 for CDR-H2 and the sequence given in SEQ ID NO;

3 for CDR-H3 and the heavy chain framework region is human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO;

     33) or a derivative thereof wherein up to four residues are changed.

2. A humanised antibody according to claim 1 wherein the residue at at least one of positions 25, 44, 48 and 71 of the variable domain of the heavy chain, as numbered according to Kabat, is a donor residue.

3. A humanised antibody according to claim 2 having the heavy chain variable domain sequence given in SEQ ID NO:

23.

4. The antibody of claim 1 further comprising a light chain wherein the variable domain of the light chain comprises the sequence given in SEQ ID NO:

4 for CDR-L1, the sequence given in SEQ ID NO;

5 for CDR-L2 and the sequence given in SEQ ID NO;

6 for CDR-L3 and the light chain framework region is human sub-group sequence VK2 4-1-1 A18+JK2 (SEQ ID NO;

31) or a derivative thereof wherein up to five residues are changed.

5. A humanised antibody according to claim 4 wherein the residue at at least one of positions 2, 3, 45, 62, and 87 of the variable domain of the light chain, as numbered according to Kabat, is a donor residue.

6. A humanised antibody according to claim 5 having the light chain variable domain sequence given in SEQ ID NO:

15.

7. The antibody of claim 1 having a heavy chain comprising a sequence given in SEQ ID NO:

23 and a light chain comprising a sequence given in SEQ ID NO;

15.

8. An agonistic antibody molecule according to any one of claims 1, 4, or 7, wherein the antibody molecule is selected from the group consisting of:

a complete antibody molecule having full length heavy and light chains, an Fab, Fab′

, F(ab′

)₂, Fv, VH, VL and scFv fragment.

10. An isolated DNA sequence encoding the heavy and/or light chain(s) of an antibody according to any one of claims 1, 4, or 7.

11. A cloning or expression vector comprising one or more DNA sequences according to claim 10.

12. A cultured host cell comprising one or more cloning or expression vectors according to claim 11.

13. A process for the production of the antibody comprising culturing the host cell of claim 12 and isolating the antibody.

14. The antibody according to claim 8, wherein the antibody is conjugated to one or more effector molecules.

15. A pharmaceutical composition comprising an antibody according to any one of claims 1, 4, 7, or 14 in combination with one or more of a pharmaceutically acceptable excipient, diluent or carrier.

16. A pharmaceutical composition according to claim 15, additionally comprising other active ingredients.

17. The pharmaceutical composition according to claim 16, wherein the active ingredients are selected from the group consisting of:

an antibody, anti-TNF, anti-IL-1β

, anti-T cell, anti-IFNγ

, anti-LPS, a xanthine, a corticosteroid, fluticasone propionate, a beta-2-agonist, salbutamol, salmeterol, formoterol, an inhibitor of cell growth and proliferation, rapamycin, cyclophosphamide, methotrexate, a CD28 inhibitor and a CD40 inhibitor.

9. A humanised agonistic antibody which binds human PD-1, wherein the variable domain of the light chain comprises a sequence having at least 95% identity to a light chain variable domain comprising a sequence given in SEQ ID NO:

15 and wherein the variable domain of the heavy chain comprises a sequence having at least 95% identity to a heavy chain variable domain comprising a sequence given in SEQ ID NO;

23.