Anti-interleukin-33 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2021002361-A1
Application number	US-202016903300-A
Country	US
Kind code	A1
Filing date	Jun 16, 2020
Priority date	Nov 10, 2014
Publication date	Jan 7, 2021
Grant date	—

Abstract

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

First claim

1 - 348 . (canceled)

349 . A method of treating an IL-33 mediated disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of 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).

350 . The method of claim 349 , wherein the IL-33-mediated disorder is an ophthalmologic disorder, an inflammatory condition, an immune disorder, a fibrotic disorder, an eosinophilic disorder, an infection, pain, a central nervous system disorder, or a solid tumor.

351 . The method of claim 350 , wherein:
(i) the ophthalmologic disorder is AMD, or wherein the ophthalmologic disorder is
(a) wet AMD, dry AMD, or geographic atrophy (GA), or
(b) intermediate AMD or advanced AMD;
(ii) the ophthalmologic disorder is retinopathy of the eye, or wherein the ophthalmologic disorder is
(a) diabetic retinopathy (DR) or retinopathy of prematurity (ROP); or
(b) high-altitude DR; or
(iii) the ophthalmologic disorder is conjunctivitis, or wherein the ophthalmologic disorder is
(a) infectious conjunctivitis or non-infectious conjunctivitis; or
(b) allergic conjunctivitis.

352 . The method of claim 350 , wherein:
(i) the inflammatory condition is asthma, sepsis, septic shock, atopic dermatitis, allergic rhinitis, rheumatoid arthritis, or chronic obstructive pulmonary disease (COPD); (ii) the immune disorder is asthma, rheumatoid arthritis, allergy, anaphylaxis, anaphylactic shock, allergic rhinitis, psoriasis, inflammatory bowel disease (IBD), Crohn's disease, diabetes, or liver disease; (iii) the fibrotic disease is idiopathic pulmonary fibrosis (IPF); (iv) the eosinophilic disorder is an eosinophil-associated gastrointestinal disorder (EGID); (v) the infection is a helminth infection, a protozoan infection, or a viral infection; (vi) pain, wherein the pain is inflammatory pain; (vii) the central nervous system disorder is Alzheimer's disease; or (viii) the solid tumor is a breast tumor, colon tumor, prostate tumor, lung tumor, kidney tumor, liver tumor, pancreas tumor, stomach tumor, intestinal tumor, brain tumor, bone tumor, or skin tumor.

353 . The method of claim 349 , further comprising administering to the subject an ST2 binding antagonist, a Factor D binding antagonist, an HtrA1 binding antagonist, a VEGF antagonist, a tryptase-beta binding antagonist, a chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) binding antagonist, an interleukin-13 (IL-13) binding antagonist, an interleukin-17 (IL-17) binding antagonist, a JAK1 antagonist, and/or an interleukin-5 (IL-5) binding antagonist.

354 . The method of claim 349 , wherein the antibody is administered subcutaneously, intravenously, intramuscularly, topically, orally, transdermally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, intranasally, intravitreally, intraocularly, periocularly, conjunctivally, subconjunctivally, subtenonly, intracamerally, subretinally, retrobulbarly, or intracanalicularly.

355 . The method of claim 349 , 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).

356 . The method of claim 349 , wherein the antibody specifically binds human IL-33, cynomolgus monkey (cyno) IL-33, or both human and cyno IL-33.

357 . The method of claim 356 , wherein:
(i) the antibody specifically binds both human and cyno IL-33 with a K D of about 1 nM or lower; and/or (ii) the antibody is capable of inhibiting the binding of IL-33 to an IL-33 receptor.

358 . The method of claim 349 , wherein:
(i) the antibody comprises an aglycosylation site mutation; (ii) the antibody is monoclonal, human, humanized, or chimeric; (iii) the antibody is an antibody fragment that binds IL-33; or (iv) the antibody is a full-length antibody.

359 . The method of claim 358 , wherein the antibody fragment is selected from the group consisting of Fab, Fab′-SH, Fv, scFv, and (Fab′) 2 fragments.

360 . The method of claim 359 , wherein the antibody fragment is an Fab fragment.

361 . The method of claim 358 , wherein the full-length antibody is an IgG antibody.

362 . The method of claim 361 , wherein the IgG antibody is an IgG1 antibody or an IgG4 antibody.

363 . The method of claim 362 , wherein the IgG4 antibody comprises a mutation in the hinge region.

364 . The method of claim 363 , wherein the mutation is a substitution mutation at amino acid residue S228 (EU numbering).

365 . The method of claim 364 , wherein the substitution mutation is an S228P mutation.

366 . The method of claim 349 , wherein the antibody is a monospecific antibody, a multispecific antibody, or a bispecific antibody.

367 . The method of claim 366 , 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.

368 . The method of claim 367 , wherein the second biological molecule is IL-13.

369 . The method of claim 368 , 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).

370 . A method of treating an IL-33 mediated disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody that specifically binds IL-33, wherein the antibody a first binding domain that specifically binds IL-33 comprising 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 comp

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

• C07K2317/92

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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07K2317/41

  Glycosylation, sialylation, or fucosylation · CPC title