Method of treating pruritus with IL-31 monoclonal antibody formulations

• US 9,982,044 B2
• Filed: 07/12/2017
• Issued: 05/29/2018
• Est. Priority Date: 12/07/2007
• Status: Active Grant

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company), Merck Serono SA (Merck & Co., Inc.)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company), Merck Serono SA (Merck & Co., Inc.)
• Inventors: Bondensgaard, Kent, Beckmann, Roland
• Primary Examiner(s): Kemmerer, Elizabeth C.
• Application Number:
  US15/648,252
• Publication Number:
  US 20170313768A1
• Time in Patent Office: 321 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/00114 Interleukins [IL]
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/244 Interleukins [IL]
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• 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: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.

Claims

1. A method of treating pruritus in a mammal comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds to human IL-31 and a pharmaceutically acceptable carrier, wherein the monoclonal antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

44, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

26, and wherein the composition is suitable for intravenous, intraarterial, intraperitoneal, intramuscular or subcutaneous injection.

2. The method according to claim 1, wherein the monoclonal antibody is in a lyophilized form and reconstituted in the pharmaceutically acceptable carrier prior to injection.

3. The method according to claim 1, wherein the monoclonal antibody comprises a human Fc domain.

4. The method according to claim 3, wherein the isotype of the human Fc domain is IgG1, IgG2, IgG3 or IgG4.

5. The method according to claim 3, wherein the isotype of the human Fc domain is IgG4.

6. The method according to claim 5, wherein the IgG4 human Fc domain has a serine to proline mutation at position 241 as determined by Kabat.

7. The method according to claim 1, wherein the heavy chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

47.

8. The method according to claim 1, wherein the light chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

46.

9. A method of treating a pruritic disease in a mammal comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds to human IL-31 and a pharmaceutically acceptable carrier, wherein the monoclonal antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

44, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

26, wherein the composition is suitable for intravenous, intraarterial, intraperitoneal, intramuscular or subcutaneous injection, and wherein the pruritic disease is selected from the group consisting of atopic dermatitis, contact dermatitis, dermatitis, prurigo nodularis, eczema, vitiligo, alopecia aerata, acne rosacea, acne vulgaris and bullous pemphigoid.

10. The method according to claim 9, wherein the monoclonal antibody is in a lyophilized form and reconstituted in the pharmaceutically acceptable carrier prior to injection.

11. The method according to claim 9, wherein the monoclonal antibody comprises a human Fc domain.

12. The method according to claim 11, wherein the isotype of the human Fc domain is IgG1, IgG2, IgG3 or IgG4.

13. The method according to claim 11, wherein the isotype of the human Fc domain is IgG4.

14. The method according to claim 13, wherein the IgG4 human Fc domain has a serine to proline mutation at position 241 as determined by Kabat.

15. The method according to claim 9, wherein the heavy chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

47.

16. The method according to claim 9, wherein the light chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

46.

17. A method of treating atopic dermatitis in a mammal comprising administering to the mammal with atopic dermatitis a therapeutically effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds to human IL-31 and a pharmaceutically acceptable carrier, wherein the monoclonal antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

44, and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

26, and wherein the composition is suitable for intravenous, intraarterial, intraperitoneal, intramuscular or subcutaneous injection.

18. The method according to claim 17, wherein the monoclonal antibody is in a lyophilized form and reconstituted in the pharmaceutically acceptable carrier prior to injection.

19. The method according to claim 17, wherein the monoclonal antibody comprises a human Fc domain.

20. The method according to claim 19, wherein the isotype of the human Fc domain is IgG1, IgG2, IgG3 or IgG4.

21. The method according to claim 19, wherein the isotype of the human Fc domain is IgG4.

22. The method according to claim 21, wherein the IgG4 human Fc domain has a serine to proline mutation at position 241 as determined by Kabat.

23. The method according to claim 17, wherein the heavy chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

47.

24. The method according to claim 17, wherein the light chain domain of the monoclonal antibody comprises the amino acid sequence of SEQ ID NO:

46.