Anti-interleukin-33 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-11760797-B2
Application number	US-202117199810-A
Country	US
Kind code	B2
Filing date	Mar 12, 2021
Priority date	Mar 13, 2020
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

The invention provides interleukin-33 (IL-33) antibodies and methods of making and using the same, e.g., for treatment of IL-33 mediated disorders (e.g., ocular disorders such as AMD (e.g., geographic atrophy (GA)).

First claim

What is claimed is:

1. An isolated antibody that specifically binds IL-33, or an antigen-binding fragment thereof, wherein the antibody comprises a binding domain comprising a heavy chain variable (VH) domain and a light chain variable (VL) domain, the binding domain comprising the following six complementarity-determining regions (CDRs):
(a) a CDR-H1 comprising the amino acid sequence of NYWMT (SEQ ID NO: 1);
(b) a CDR-H2 comprising the amino acid sequence of SITYTGGGTYYPDSVKG (SEQ ID NO: 2);
(c) a CDR-H3 comprising the amino acid sequence of ANYYYNTYGGFPY (SEQ ID NO: 3);
(d) a CDR-L1 comprising the amino acid sequence of LASEGFSNDLA (SEQ ID NO: 4);
(e) a CDR-L2 comprising the amino acid sequence of AASRLQD (SEQ ID NO: 5); and
(f) a CDR-L3 comprising the amino acid sequence of QQGSKYPLT (SEQ ID NO: 6).

2. The antibody of claim 1 , wherein the antibody comprises a binding domain comprising (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 7; (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 8; or (c) a VH domain as in (a) and a VL domain as in (b).

3. The antibody of claim 1 , wherein the VH domain comprises:
(a) an FR-H1 comprising the amino acid sequence of EVQLVX 1 SGX 2 X 3 X 4 X 5 X 6 PGX 7 SX 8 X 9 X 10 SCX 11 ASGFTFN (SEQ ID NO: 9), wherein X 1 is E or Q; X 2 is G or A; X 3 is G or E; X 4 is L or V; X 5 is V or K; X 6 is Q or K; X 7 is G, A, or T; X 8 is L or V; X 9 is R or K; X 10 is L or V; and X 11 is A, K, or L;
(b) an FR-H2 comprising the amino acid sequence of WX 1 RQAPGX 2 GLEWX 3 X 4 (SEQ ID NO: 10), wherein X 1 is I or V; X 2 is K or Q; X 3 is V, M, or I; and X 4 is A or G;
(c) an FR-H3 comprising the amino acid sequence of RX 1 TX 2 X 3 RDX 4 X 5 X 6 X 7 X 8 X 9 YX 10 X 11 X 12 X 13 SLRX 14 EDTAX 15 YYCTR (SEQ ID NO: 11), wherein X 1 is F or V; X 2 is I or M; X 3 is S or T; X 4 is D, N, or T; X 5 is A or S; X 6 is K or T; X 7 is S or N; X 8 is S or T; X 9 is L or V; X 10 is L or M; X 11 is Q or E; X 12 is M or L; X 13 is N or S; X 14 is A or S; and X 15 is V or T; and
(d) an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 12).

4. The antibody of claim 1 , wherein the VH domain comprises:
(a) an FR-H1 comprising the amino acid sequence of EVQLVESGGGLVQPGGSLRLSCAASGFTFN (SEQ ID NO: 17);
(b) an FR-H2 comprising the amino acid sequence of WIRQAPGKGLEWVA (SEQ ID NO: 18);
(c) an FR-H3 comprising the amino acid sequence of RFTISRDDAKSSLYLQMNSLRAEDTAVYYCTR (SEQ ID NO: 19); and
(d) an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 12).

5. The antibody of claim 1 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 7.

6. The antibody of claim 1 , wherein the VL domain comprises:
(a) an FR-L1 comprising the amino acid sequence of X 1 IX 2 X 3 TQSPX 4 X 5 LSX 6 SX 7 GX 8 X 9 X 10 X 11 X 12 X 13 C (SEQ ID NO: 13), wherein X 1 is D or E; X 2 is Q or V; X 3 is M or L; X 4 is S or A; X 5 is S or T; X 6 is A or L; X 7 is V, P, or L; X 8 is D or E; X 9 is R or T; X 10 is V or A; X 11 is T or S; X 12 is I or L; and X 13 is T, S, or E;
(b) an FR-L2 comprising the amino acid sequence of WX 1 QQKX 2 GX 3 X 4 PX 5 X 6 LIY (SEQ ID NO: 14), wherein X 1 is Y or F; X 2 is P or S; X 3 is K or Q; X 4 is S or A; X 5 is K, R, or Q; and X 6 is L or S;
(c) an FR-L3 comprising the amino acid sequence of GX 1 PX 2 RFSGSGSGTX 3 FX 4 LX 5 ISX 6 X 7 X 8 PEDX 9 AX 10 YX 11 C (SEQ ID NO: 15), wherein X 1 is V or I; X 2 is S or A; X 3 is D or R; X 4 is T or S; X 5 is T or K; X 6 is S or G; X 7 is L or M; X 8 is Q or E; X 9 is F, V, or E; X 10 is T, V, or D; and X 11 is F or Y; and
(d) an FR-L4 comprising the amino acid sequence of FGX 1 GTKX 2 EIK (SEQ ID NO: 16), wherein X 1 is G or S and X 2 is V or L.

7. The antibody of claim 1 , wherein the VL domain comprises:
(a) an FR-L1 comprising the amino acid sequence of DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO: 21);
(b) an FR-L2 comprising the amino acid sequence of WYQQKPGKSPKLLIY (SEQ ID NO: 22);
(c) an FR-L3 comprising the amino acid sequence of GVPSRFSGSGSGTDFTLTISSLQPEDFATYFC (SEQ ID NO: 23); and
(d) an FR-L4 comprising the amino acid sequence of FGGGTKVEIK (SEQ ID NO: 24).

8. The antibody of claim 1 , wherein the VL domain comprises the amino acid sequence of SEQ ID NO: 8.

9. The antibody of claim 1 , wherein the antibody comprises:
(i) a binding domain comprising (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 35; (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 36; or (c) a VH domain as in (a) and a VL domain as in (b);
(ii) a binding domain comprising (a) a heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 37 and (b) a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 38; or
(iii) a binding domain comprising (a) a VH domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 65; (b) a VL domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 69; or (c) a VH domain as in (a) and a VL domain as in (b).

10. The antibody of claim 1 , wherein:
(i) the antibody specifically binds both human and cynomolgus monkey (cyno) interleukin-33 (IL-33) with a K D of about 1 nM or lower;
(ii) the antibody inhibits the binding of human IL-33 to an IL-33 receptor with a 50% inhibitory concentration (IC50) of between about 800 fM and about 100 pM; or
(iii) the antibody specifically binds both human and cyno IL-33 with a K D of about 1 nM or lower and inhibits the binding of human IL-33 to an IL-33 receptor with an IC50 of between about 800 fM and about 100 pM.

11. The antibody of claim 1 , wherein:
(i) the antibody has a viscosity of less than about 5 centipoise (cP) at a concentration of about 180 mg/mL in phosphate-buffered saline (PBS) pH 7.4;
(ii) the antibody has an optical density (OD) of about 0.5 or lower at a concentration of about 150 mg/mL or higher in phosphate-buffered saline (PBS) pH 7.4; or
(iii) the antibody has a viscosity of less than about 5 cP at a concentration of about 180 mg/mL and an OD of about 0.5 or lower at a concentration of about 150 mg/mL or higher in PBS pH 7.4.

12. The antibody of claim 1 , wherein the antibody is monoclonal, human, humanized, or chimeric.

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

14. The antibody of claim 13 , wherein the antibody fragment is an Fab, Fab′-SH, Fv, scFv, or (Fab′) 2 fragment.

15. The antibody of claim 1 , wherein the antibody is a monospecific antibody.

16. The antibody of claim 1 , wherein the antibody is a multispecific antibody.

17. The antibody of claim 16 , wherein the antibody is a bispecific antibody.

18. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.

19. The antibody of claim 1 , wherein the antibody is an Fab.

20. The antibody of claim 1 , wherein the antibody is an IgG1 antibody.

21. An isolated antibody that specifically binds IL-33, or an antigen-binding fragment thereof, wherein the antibody comprises a binding domain comprising (a) a VH domain compr

Assignees

• Genentech Inc

Inventors

• Nakamura Gerald R
• Seshasayee Dhaya
• Van Lookeren Campagne Menno
• Wong Tiffany
• Wu Jia
• Xi Hongkang
• Bevers Iii Jack
• Chan Hiu Nam
• Comps-Agrar Laetitia
• Corpuz Racquel

Classifications

• C07K16/244 Primary

  Interleukins [IL] · CPC title

• A61K39/3955 Primary

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

• C07K2317/33

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

• A61P27/02

  Ophthalmic agents · CPC title

• C07K2317/76

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