IL-8 antibodies

• US 9,969,800 B2
• Filed: 02/04/2016
• Issued: 05/15/2018
• Est. Priority Date: 02/05/2015
• Status: Active Grant

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Igawa, Tomoyuki, Maeda, Atsuhiko, Nakamura, Genki, Muraoka, Masaru
• Primary Examiner(s): MERTZ, PREMA MARIA
• Application Number:
  US15/015,287
• Publication Number:
  US 20160229908A1
• Time in Patent Office: 831 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• 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 27/02 Ophthalmic agents
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/2866 : against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/36 : against blood coagulation factors
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C07K 16/4291 : against IgE
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• 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 2317/55 : Fab or Fab'
• 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 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/90 : characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/6854 : Immunoglobulins

Abstract

One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.

Claims

1. An isolated anti-IL-8 antibody which comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:

67, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO;

73, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO;

74, (d) HVR-LI comprising the amino acid sequence of SEQ ID NO;

70, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO;

75, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO;

76.

2. The anti-IL-8 antibody of claim 1, which is an IgG antibody.

3. The anti-IL-8 antibody of claim 2, wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

4. The anti-IL-8 antibody of claim 3, wherein the IgG antibody is IgG1.

5. The anti-IL-8 antibody of claim 1, which comprises one or more amino acid substitutions selected from the group consisting of:

L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

6. The anti-IL-8 antibody of claim 5, which comprises amino acid substitution N434A according to EU numbering.

7. The anti-IL-8 antibody of claim 6, which comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

8. The anti-IL-8 antibody of claim 6, which comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

9. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 1 and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 5 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 6 and a pharmaceutically acceptable carrier.

12. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 7 and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 8 and a pharmaceutically acceptable carrier.

14. An isolated anti-IL-8 antibody which comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

78 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

79.

15. The anti-IL-8 antibody of claim 14, which is an IgG antibody.

16. The anti-IL-8 antibody of claim 15, wherein the IgG antibody is IgG1, IgG2, IgG3 or IgG4.

17. The anti-IL-8 antibody of claim 16, wherein the IgG antibody is IgG1.

18. The anti-IL-8 antibody of claim 14, which comprises one or more amino acid substitutions selected from the group consisting of:

L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

19. The anti-IL-8 antibody of claim 18, which comprises amino acid substitution N434A according to EU numbering.

20. The anti-IL-8 antibody of claim 19, which comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

21. The anti-IL-8 antibody of claim 19, which comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

22. The anti-IL-8 antibody of claim 14, which comprises a heavy chain comprising an amino acid sequence selected from the group consisting of:

(a) SEQ ID NO;

80;

(b) SEQ ID NO;

81;

(c) SEQ ID NO;

92; and

(d) SEQ ID NO;

93.

23. The anti-IL-8 antibody of claim 14, which comprises a light chain comprising the amino acid sequence of SEQ ID NO:

82.

24. The anti-IL-8 antibody of claim 14, which comprises a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising an amino acid sequence selected from the group consisting of;

(a) SEQ ID NO;

80;

(b) SEQ ID NO;

81;

(c) SEQ ID NO;

92; and

(d) SEQ ID NO;

93.

25. The anti-IL-8 antibody of claim 24, which comprises a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising the amino acid sequence of SEQ ID NO;

80.

26. The anti-IL-8 antibody of claim 24, which comprises a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising the amino acid sequence of SEQ ID NO;

81.

27. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 14 and a pharmaceutically acceptable carrier.

28. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 18 and a pharmaceutically acceptable carrier.

29. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 19 and a pharmaceutically acceptable carrier.

30. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 20 and a pharmaceutically acceptable carrier.

31. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 21 and a pharmaceutically acceptable carrier.

32. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 22 and a pharmaceutically acceptable carrier.

33. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 23 and a pharmaceutically acceptable carrier.

34. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 24 and a pharmaceutically acceptable carrier.

35. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 25 and a pharmaceutically acceptable carrier.

36. A pharmaceutical composition comprising the anti-IL-8 antibody of claim 26 and a pharmaceutically acceptable carrier.