Anti-interleukin-33 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-10723795-B2
Application number	US-201816119667-A
Country	US
Kind code	B2
Filing date	Aug 31, 2018
Priority date	Nov 10, 2014
Publication date	Jul 28, 2020
Grant date	Jul 28, 2020

Abstract

The invention provides interleukin-33 (IL-33) antibodies and methods of using the same.

First claim

What is claimed is:

1. An isolated nucleic acid encoding an antibody that specifically binds IL-33, wherein the antibody comprises a binding domain comprising the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SFSX 1 S (SEQ ID NO: 62), wherein X 1 is Met, Leu, or Val;
(b) an HVR-H2 comprising the amino acid sequence of TISGGKTFTDYVDX 1 VKG (SEQ ID NO: 63), wherein X 1 is Ser or Ala;
(c) an HVR-H3 comprising the amino acid sequence of ANYGX 1 X 2 FFEV (SEQ ID NO: 64), wherein X 1 is Asn or Asp, and X 2 is Trp or Phe;
(d) an HVR-L1 comprising the amino acid sequence of RASESVAKYGLSLLN (SEQ ID NO: 4);
(e) an HVR-L2 comprising the amino acid sequence of AASNRGS (SEQ ID NO: 5); and
(f) an HVR-L3 comprising the amino acid sequence of QQSKEVPFT (SEQ ID NO: 6).

2. The nucleic acid of claim 1 , wherein the binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of SFSMS (SEQ ID NO: 1);
(b) an HVR-H2 comprising the amino acid sequence of TISGGKTFTDYVDSVKG (SEQ ID NO: 2);
(c) an HVR-H3 comprising the amino acid sequence of ANYGNWFFEV (SEQ ID NO: 3);
(d) an HVR-L1 comprising the amino acid sequence of RASESVAKYGLSLLN (SEQ ID NO: 4);
(e) an HVR-L2 comprising the amino acid sequence of AASNRGS (SEQ ID NO: 5); and
(f) an HVR-L3 comprising the amino acid sequence of QQSKEVPFT (SEQ ID NO: 6).

3. The nucleic acid of claim 2 , wherein the antibody is monoclonal, human, humanized, or chimeric.

4. The nucleic acid of claim 2 , wherein the antibody is an antibody fragment that binds IL-33.

5. The nucleic acid of claim 4 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.

6. The nucleic acid of claim 5 , wherein the antibody fragment is an Fab fragment.

7. The nucleic acid of claim 2 , wherein the antibody is a full-length antibody.

8. The nucleic acid of claim 1 , wherein the antibody specifically binds human or cynomolgus monkey (cyno) IL-33.

9. The nucleic acid of claim 8 , wherein the antibody specifically binds both human and cyno IL-33.

10. The nucleic acid of claim 9 , wherein the antibody specifically binds both human and cyno IL-33 with a K D of about 1 nM or lower.

11. The nucleic acid of claim 10 , wherein the antibody specifically binds human IL-33 with a K D between about 1 pM and about 500 pM.

12. The nucleic acid of claim 11 , wherein the antibody specifically binds human IL-33 with a K D between about 15 pM and about 140 pM.

13. The nucleic acid of claim 10 , wherein the antibody specifically binds cyno IL-33 with a K D between about 1 pM and about 500 pM.

14. The nucleic acid of claim 13 , wherein the antibody specifically binds cyno IL-33 with a K D between about 125 pM and about 500 pM.

15. The nucleic acid of claim 10 , wherein the antibody specifically binds both human and cyno IL-33 with a K D of between about 1 pM and about 500 pM.

16. The nucleic acid of claim 15 , wherein the antibody specifically binds human IL-33 with a K D of between about 1 pM and about 200 pM.

17. The nucleic acid of claim 1 , wherein the antibody is capable of inhibiting the binding of IL-33 to an IL-33 receptor.

18. The nucleic acid of claim 17 , wherein the inhibiting is measured using a cell-based blocking assay.

19. The nucleic acid of claim 18 , wherein the antibody inhibits the binding of human IL-33 to an IL-33 receptor with a 90% inhibitory concentration (1090) of between about 0.001 μg/ml and about 0.5 μg/ml.

20. The nucleic acid of claim 19 , wherein the 1090 is between about 0.002 μg/ml and about 0.25 μg/ml.

21. The nucleic acid of claim 20 , wherein the 1090 is about 0.004 μg/ml.

22. The nucleic acid of claim 1 , wherein the antibody inhibits binding of human IL-33 to an IL-33 receptor with an 1050 of between about 800 fM and about 10 pM.

23. The nucleic acid of claim 22 , wherein the 1050 is between about 1 pM and about 5 pM.

24. The nucleic acid of claim 23 , wherein the 1050 is about 2.5 pM.

25. The nucleic acid of claim 1 , wherein the antibody inhibits binding of cyno IL-33 to an IL-33 receptor with an 1050 of between about 1 nM and about 5 nM.

26. The nucleic acid of claim 25 , wherein the 1050 is about 4 nM.

27. The nucleic acid of claim 1 , wherein the antibody comprises an aglycosylation site mutation.

28. The nucleic acid of claim 1 , wherein the antibody is monoclonal, human, humanized, or chimeric.

29. The nucleic acid of claim 1 , wherein the antibody is an antibody fragment that binds IL-33.

30. The nucleic acid of claim 29 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.

31. The nucleic acid of claim 30 , wherein the antibody fragment is an Fab fragment.

32. The nucleic acid of claim 1 , wherein the antibody is a full-length antibody.

33. The nucleic acid of claim 32 , wherein the antibody is an IgG antibody.

34. The nucleic acid of claim 33 , wherein the IgG antibody is an IgG1 antibody.

35. The nucleic acid of claim 33 , wherein the IgG antibody is an IgG4 antibody.

36. The nucleic acid of claim 35 , wherein the IgG4 antibody comprises a mutation in the hinge region.

37. The nucleic acid of claim 36 , wherein the mutation is a substitution mutation.

38. The nucleic acid of claim 37 , wherein the substitution mutation is at amino acid residue S228 (EU numbering).

39. The nucleic acid of claim 38 , wherein the substitution mutation is an S228P mutation.

40. The nucleic acid of claim 1 , wherein the antibody is a monospecific antibody.

41. The nucleic acid of claim 1 , wherein the antibody is a multispecific antibody.

42. The nucleic acid of claim 41 , wherein the antibody is a bispecific antibody.

43. The nucleic acid of claim 42 , wherein the bispecific antibody comprises a second binding domain that binds to a second biological molecule, wherein the second biological molecule is selected from the group consisting of interleukin-13 (IL-13), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-17 (IL-17), Factor D, HtrA1, VEGF, and a VEGF receptor.

44. The nucleic acid of claim 43 , wherein the second biological molecule is IL-13.

45. The nucleic acid of claim 44 , wherein the second binding domain comprises the following six HVRs:
(a) an HVR-H1 comprising the amino acid sequence of AYSVN (SEQ ID NO: 296);
(b) an HVR-H2 comprising the amino acid sequence of MIWGDGKIVYNSALKS (SEQ ID NO: 297);
(c) an HVR-H3 comprising the amino acid sequence of DGYYPYAMDN (SEQ ID NO: 298);
(d) an HVR-L1 comprising the amino acid sequence of RASKSVDSYGNSFMH (SEQ ID NO: 299);
(e) an HVR-L2 comprising the amino acid sequence of LASNLES (SEQ ID NO: 300); and
(f) an HVR-L3 comprising the amino acid sequence of QQNNEDPRT (SEQ ID NO: 301).

46. An isolated nucleic acid encoding an antibody that specifically binds both IL-33 and IL-13, wherein the antibody comprises a first binding domain that specifically binds IL-33 comprising the following six HVRs:
(a) an HVR-H1 comprising

Assignees

• Genentech Inc

Inventors

• Hass Philip E
• Hazen Meredith
• Hsiao Yi-Chun
• Khosla Rajita
• Nakamura Gerald R
• Seshasayee Dhaya
• Van Lookeren Campagne Menno
• Xi Hongkang
• Zhai Wenwu
• Bevers Iii Jack
• Chiang Nancy

Classifications

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title