PD-1 ANTIBODY

• US 20130095098A1
• Filed: 03/09/2011
• Published: 04/18/2013
• Est. Priority Date: 03/11/2010
• Status: Active Grant

• Current Assignee: Ucb Biopharma Sprl (UCB SA)
• Original Assignee: UCB Pharma SA (UCB SA)
• Inventors: Tyson, Kerry Louise
• Granted Patent: US 8,993,731 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• 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 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 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 derived from human sub-group sequence VH4 3-1 4-30.4+JH4 (SEQ ID NO;

     33)

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 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.

8. An agonistic antibody molecule according to any one of claim 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 or a fragment thereof, such as a Fab, modified Fab′

, Fab′

, F(ab′

)₂, Fv, VH, VL or scFv fragment.

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

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

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

15. A pharmaceutical composition according to claim 14, additionally comprising other active ingredients.

18. A method for the treatment or prophylaxis of an immune disorder comprising administering the antibody according to any one of claim 1, 4, or 7.

19. The method of claim 18, wherein the immune disorder is selected from the group consisting of allergy, COPD, rheumatoid arthritis, and asthma, or combinations thereof.

20. The method of claim 18, wherein the immune disorder is an autoimmune disease.

21. A method for the treatment or prophylaxis of an inflammatory disease comprising administering the antibody according to any one of claim 1, 4, or 7.

22. A method for the treatment or prophylaxis of pain comprising administering the antibody according to any one of claim 1, 4, or 7.

23. A method for the treatment or prophylaxis of an immune disorder comprising administering the pharmaceutical composition according to claim 14.

24. The method of claim 23, wherein the immune disorder is selected from the group consisting of allergy, COPD, rheumatoid arthritis, and asthma, or combinations thereof.

25. The method of claim 23, wherein the immune disorder is an autoimmune disease.

26. A method for the treatment or prophylaxis of an inflammatory disease comprising administering the pharmaceutical composition according to claim 14.

27. A method for the treatment or prophylaxis of pain comprising administering the pharmaceutical composition according to claim 14.

4. A humanised agonistic antibody which binds human PD-1 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 derived from human sub-group sequence VK2 4-1-1 A18+JK2 (SEQ ID NO;

31)

5. A humanised antibody according to claim 4 wherein the residue at least one of positions 2, 3, 45, 62, and 87 of the variable domain of the light chain 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. A humanised agonistic antibody which binds human PD-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.

9. A humanised agonistic antibody which binds human PD-1, wherein the variable domain of the light chain comprises a sequence having at least 80% identity or similarity to the light chain variable domain of the antibody of claim 7 and wherein the variable domain of the heavy chain comprises a sequence having at least 80% identity or similarity to the heavy chain variable domain of the antibody of claim 7.

16. (canceled)

17. (canceled)