Anti-interleukin-33 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2025002575-A1
Application number	US-202418658118-A
Country	US
Kind code	A1
Filing date	May 8, 2024
Priority date	Nov 10, 2021
Publication date	Jan 2, 2025
Grant date	—

Abstract

The invention provides interleukin-33 (IL-33) antibodies and methods of making and using the same, e.g., for detection of IL-33 in biological samples.

First claim

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 SEQ ID NO: 1; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 2; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 3; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 4; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

2 - 5 . (canceled)

6 . An isolated antibody that specifically binds IL-33, or an antigen-binding fragment thereof, wherein the antibody comprises a binding domain comprising the following six CDRs:
(a) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 19; (b) a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 20; (c) a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 21; (d) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 22; (e) a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 23; and (f) a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24.

7 . The antibody of claim 6 , comprising (a) a VH domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 25; (b) a VL domain having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26; or (c) a VH domain as in (a) and a VL domain as in (b).

8 . The antibody of claims 6 , wherein the VH domain comprises the amino acid sequence of SEQ ID NO: 25, and the VL domain comprises the amino acid sequence of SEQ ID NO: 26.

9 . The antibody of claim 6 , wherein the antibody comprises an HC having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27; (b) an LC having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 28; or (c) an HC as in (a) and an LC as in (b).

10 . The antibody of claim 6 , wherein the HC comprises the amino acid sequence of SEQ ID NO: 27, and the LC comprises the amino acid sequence of SEQ ID NO: 28.

11 . The antibody of claim 6 , wherein the antibody binds to oxidized or reduced IL-33, and/or the antibody binds to IL-33 bound to soluble interleukin 1 receptor like 1 (sST2) protein and to IL-33 not bound to sST2 with within two-fold K D .

12 - 14 . (canceled)

15 . An isolated nucleic acid encoding the antibody of claim 6 or a set of isolated nucleic acids together encoding the antibody.

16 . A vector or a set of vectors comprising the isolated nucleic acid or set of isolated nucleic acids of claim 15 .

17 . A host cell comprising the vector or the set of vectors of claim 16 .

18 . A method of producing an antibody that specifically binds to IL-33, the method comprising culturing the host cell claim 17 in a culture medium.

19 . An immunoconjugate comprising the antibody of claim 6 , wherein the antibody is linked to a label.

20 . A method of detecting the presence or level of IL-33 in a biological sample comprising:
contacting the biological sample with the immunoconjugate of claim 19 and detecting the presence of the bound immunoconjugate.

21 . The method of claim 20 , wherein the detecting is by IHC, IF, flow cytometry, ELISA, immunoblotting, or iPCR.

22 . The method of claim 20 , wherein the detecting is by iPCR, and wherein the method comprises contacting the biological sample with the immunoconjugate in the presence of a second anti-IL-33 antibody that specifically binds an epitope on IL-33 that is different from the epitope to which the anti-IL-33 antibody in the immunoconjugate specifically binds, and detecting the presence of the bound immunoconjugate.

23 . The method of claim 20 , wherein the biological sample is a blood sample, an ocular sample, a nasal sample, or a cell culture sample.

24 . The method of claim 20 , wherein biological sample is from a subject having, or at risk of, an IL- 33 -mediated disorder.

25 . (canceled)

26 . The method of claim 20 , wherein the presence or level of IL-33 is the presence or level of total IL-33, reduced IL-33, or IL-33 bound to sST2.

27 - 28 . (canceled)

29 . An assay for identifying a subject having an IL-33 mediated disorder who is a candidate for treatment comprising an IL-33 axis binding antagonist, wherein the assay comprises determining the presence or level of IL-33 in a biological sample obtained from the subject using the immunoconjugate of claim 19 .

30 . A kit comprising:
(a) the antibody of the immunoconjugate of claim 19 ; and (b) a package insert comprising instructions for use of the antibody to detect the presence or level of IL-33 in a biological sample

Assignees

• Genentech Inc

Inventors

• Lowe John Hok Nin
• Loyet Kelly Michele
• Mai Elaine
• Maia Mauricio Silva
• Nakamura Gerald R
• Bevers Iii Jack
• Chan Hiu Nam
• Comps-Agrar Laetitia D
• Corpuz Racquel

Classifications

• G01N2333/54

  Interleukins [IL] · CPC title

• G01N33/6878

  in epitope analysis · CPC title

• G01N33/6869

  Interleukin · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• G01N2333/545

  IL-1 · CPC title