NZ730105B2 - Anti-il-25 antibodies and uses thereof - Google Patents
Anti-il-25 antibodies and uses thereofInfo
- Publication number
- NZ730105B2 NZ730105B2 NZ730105A NZ73010515A NZ730105B2 NZ 730105 B2 NZ730105 B2 NZ 730105B2 NZ 730105 A NZ730105 A NZ 730105A NZ 73010515 A NZ73010515 A NZ 73010515A NZ 730105 B2 NZ730105 B2 NZ 730105B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- disease
- antigen
- asthma
- antagonist
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 15
- 208000006673 asthma Diseases 0.000 claims abstract 10
- 208000035475 disorder Diseases 0.000 claims abstract 9
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 claims abstract 8
- 102000055377 human IL25 Human genes 0.000 claims abstract 8
- 102000013691 Interleukin-17 Human genes 0.000 claims abstract 7
- 108050003558 Interleukin-17 Proteins 0.000 claims abstract 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract 5
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims abstract 5
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract 5
- 208000026935 allergic disease Diseases 0.000 claims abstract 5
- 230000007815 allergy Effects 0.000 claims abstract 5
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract 3
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims abstract 2
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims abstract 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract 2
- 208000011231 Crohn disease Diseases 0.000 claims abstract 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract 2
- 239000005557 antagonist Substances 0.000 claims 11
- 239000000427 antigen Substances 0.000 claims 11
- 108091007433 antigens Proteins 0.000 claims 11
- 102000036639 antigens Human genes 0.000 claims 11
- 239000012634 fragment Substances 0.000 claims 11
- 239000008194 pharmaceutical composition Substances 0.000 claims 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims 10
- 201000010099 disease Diseases 0.000 claims 6
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 claims 3
- 230000010085 airway hyperresponsiveness Effects 0.000 claims 3
- 150000003431 steroids Chemical class 0.000 claims 3
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- 108090000978 Interleukin-4 Proteins 0.000 claims 2
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- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims 2
- 230000011664 signaling Effects 0.000 claims 2
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- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims 1
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- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims 1
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- 101710186071 Interleukin-17 receptor B Proteins 0.000 claims 1
- 108010002616 Interleukin-5 Proteins 0.000 claims 1
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- 108090001007 Interleukin-8 Proteins 0.000 claims 1
- 108010002335 Interleukin-9 Proteins 0.000 claims 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
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- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 1
- 206010039085 Rhinitis allergic Diseases 0.000 claims 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims 1
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- ANGKOCUUWGHLCE-HKUYNNGSSA-N [(3s)-1,1-dimethylpyrrolidin-1-ium-3-yl] (2r)-2-cyclopentyl-2-hydroxy-2-phenylacetate Chemical compound C1[N+](C)(C)CC[C@@H]1OC(=O)[C@](O)(C=1C=CC=CC=1)C1CCCC1 ANGKOCUUWGHLCE-HKUYNNGSSA-N 0.000 claims 1
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- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims 1
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- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 claims 1
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- 208000030949 chronic idiopathic urticaria Diseases 0.000 claims 1
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- 229960001265 ciclosporin Drugs 0.000 claims 1
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- 229950001653 cilomilast Drugs 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
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- 229960000265 cromoglicic acid Drugs 0.000 claims 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 claims 1
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- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 claims 1
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Classifications
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
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- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Abstract
The present invention provides antibodies that bind to human interleukin-25 (IL-25) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human IL-25 with high affinity. In certain embodiments, the invention includes antibodies that bind human IL-25 and block IL-25-mediated cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies. The antibodies of the invention are useful for the treatment of various disorders associated with IL-25 activity or expression, including asthma, allergy, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, atopic dermatitis (AD), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), also know as Churg-Strauss Syndrome.
Claims (16)
1. An isolated antibody or antigen-binding fragment thereof that specifically binds human interleukin-25 (IL-25), wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) contained within the heavy chain variable region (HCVR) of the amino acid sequence of SEQ ID NO:114, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within the light chain variable region (LCVR) of the amino acid sequence of SEQ ID NO:122, wherein the heavy chain and light chain CDRs are identified by the Kabat definition, the Chothia definition, or the AbM definition.
2. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof exhibits one or more of the following characteristics: (a) is a fully human monoclonal antibody; (b) binds human IL-25 with a KD of less than about 120 pM as measured by surface plasmon resonance at 25ºC; (c) binds human IL-25 with a dissociative half life (t½) of greater than about 105 minutes as measured by surface plasmon resonance at 25ºC; (d) blocks human IL-25 signaling in cells engineered to express an IL-25 receptor (IL17RA/IL-17RB) with an IC50 of less than about 2 nM; (e) blocks human IL-25 signaling in human peripheral blood mononuclear cells (PBMCs) with an IC50 of less than about 16 nM; (f) reduces circulating and/or lung IgE levels in a mammal that overexpresses IL-25; and (g) reduces goblet cell metaplasia in a mammal that overexpresses IL-25.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO:116, an HCDR2 comprising the amino acid sequence of SEQ ID NO:118, an HCDR3 comprising the amino acid sequence of SEQ ID NO:120, an LCDR1 comprising the amino acid sequence of SEQ ID NO:124, an LCDR2 comprising the amino acid sequence of SEQ ID NO:126, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:128.
4. The isolated antibody or antigen-binding fragment thereof of any one of claims 1-3, wherein the antibody or antigen-binding fragment thereof comprises an HCVR having at least 90% sequence identity to SEQ ID NO:114 and an LCVR having at least 90% sequence identity to SEQ ID NO:122.
5. The isolated antibody or antigen-binding fragment thereof of any one of claims 1-4, comprising an HCVR having at least 95% sequence identity to SEQ ID NO:114 and an LCVR having at least 95% sequence identity to SEQ ID NO:122.
6. The isolated antibody or antigen-binding fragment thereof of any one of claims 1-5, comprising an HCVR comprising the amino acid sequence of SEQ ID NO:114 and an LCVR comprising the amino acid sequence of SEQ ID NO:122.
7. A pharmaceutical composition comprising the antibody or antigen-binding fragment of any one of claims 1-6, and a pharmaceutically acceptable carrier or diluent.
8. The pharmaceutical composition of claim 7 for use in treating a disease or disorder selected from the group consisting of asthma, allergy, allergic rhinitis, allergic airway inflammation, chronic obstructive pulmonary disease (COPD), eosinophilic pneumonia, eosinophilic esophagitis, hypereosinophilic syndrome, graft-versus-host disease, atopic dermatitis (AD), psoriasis, inflammatory bowel disease (IBD), arthritis, uveitis, cardiovascular disease, pain, multiple sclerosis, lupus, vasculitis, chronic idiopathic urticaria and Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome).
9. The pharmaceutical composition for use according to claim 8, wherein the disease or disorder is asthma and is selected from the group consisting of allergic asthma, non-allergic asthma, severe refractory asthma, asthma exacerbations, viral-induced asthma or viral-induced asthma exacerbations, steroid resistant asthma, steroid sensitive asthma, eosinophilic asthma, non-eosinophilic asthma, and other related disorders characterized by airway inflammation or airway hyperresponsiveness (AHR).
10. The pharmaceutical composition for use according to claim 8, wherein the disease or disorder is COPD and is associated in part with, or caused by, cigarette smoke, air pollution, occupational chemicals, allergy or airway hyperresponsiveness.
11. The pharmaceutical composition for use according to claim 8, wherein the disease or disorder is AD and is associated in part with, or caused by epidermal barrier dysfunction, allergy, or radiation exposure.
12. The pharmaceutical composition for use according to claim 8, wherein the allergy is to a food, pollen, mold, dust mites, animals, or animal dander.
13. The pharmaceutical composition for use according to claim 8, wherein the disease or disorder is IBD and is selected from the group consisting of ulcerative colitis, Crohn's Disease, collagenous colitis, lymphocytic colitis, ischemic colitis, diversion colitis, Behcet's syndrome, infective colitis, indeterminate colitis, and other disorders characterized by inflammation of the mucosal layer of the large intestine or colon.
14. The pharmaceutical composition for use according to claim 8, wherein the disease or disorder is arthritis and is selected from the group consisting of osteoarthritis, rheumatoid arthritis and psoriatic arthritis.
15. The pharmaceutical composition for use according to claim 8, wherein the pharmaceutical composition is to be administered to the patient in combination with a second therapeutic agent.
16. The pharmaceutical composition for use according to claim 15, wherein the second therapeutic agent is selected from the group consisting of a non-steroidal anti-inflammatory (NSAID), a steroid, a corticosteroid (inhaled or topical), an immunosuppressant (e.g. cyclophosphamide), an anticholinergic agent (e.g. tiotropium), a muscarinic agent (e.g. glycopyrronium), a phosphodiesterase inhibitor (e.g. theophylline, roflumilast, cilomilast), a beta blocker, cyclosporine, tacrolimus, pimecrolimus, azathioprine, methotrexate, cromolyn sodium, a proteinase inhibitor, a bronchial dilator, a betaagonist, an antihistamine, epinephrine, a decongestant, a leukotriene inhibitor, a mast cell inhibitor, a thymic stromal lymphopoietin (TSLP) antagonist, a TNF antagonist, an IgE antagonist, an IL-1 antagonist, an IL-4 or IL-4R antagonist, an IL-13 or IL-13R antagonist, an IL-4/IL-13 dual antagonist, an IL-5 antagonist, an IL-6 or IL-6R antagonist, an antagonist of IL-8, an IL-9 antagonist, an IL-
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462054167P | 2014-09-23 | 2014-09-23 | |
| PCT/US2015/051407 WO2016049000A2 (en) | 2014-09-23 | 2015-09-22 | Anti-il-25 antibodies and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ730105A NZ730105A (en) | 2024-01-26 |
| NZ730105B2 true NZ730105B2 (en) | 2024-04-30 |
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