RU2006122037A - Новые анти-il 13 антитела и их использование - Google Patents
Новые анти-il 13 антитела и их использование Download PDFInfo
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- RU2006122037A RU2006122037A RU2006122037/13A RU2006122037A RU2006122037A RU 2006122037 A RU2006122037 A RU 2006122037A RU 2006122037/13 A RU2006122037/13 A RU 2006122037/13A RU 2006122037 A RU2006122037 A RU 2006122037A RU 2006122037 A RU2006122037 A RU 2006122037A
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- 102000003816 Interleukin-13 Human genes 0.000 claims abstract 23
- 108090000176 Interleukin-13 Proteins 0.000 claims abstract 23
- 208000006673 asthma Diseases 0.000 claims abstract 10
- 101100286681 Homo sapiens IL13 gene Proteins 0.000 claims abstract 6
- 208000010668 atopic eczema Diseases 0.000 claims abstract 5
- 230000000694 effects Effects 0.000 claims abstract 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract 4
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract 4
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract 3
- 208000024780 Urticaria Diseases 0.000 claims abstract 3
- 230000001404 mediated effect Effects 0.000 claims abstract 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract 2
- 201000004624 Dermatitis Diseases 0.000 claims abstract 2
- 208000004262 Food Hypersensitivity Diseases 0.000 claims abstract 2
- 208000001132 Osteoporosis Diseases 0.000 claims abstract 2
- 206010039710 Scleroderma Diseases 0.000 claims abstract 2
- 206010046851 Uveitis Diseases 0.000 claims abstract 2
- 201000009961 allergic asthma Diseases 0.000 claims abstract 2
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract 2
- 230000000172 allergic effect Effects 0.000 claims abstract 2
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract 2
- 235000020932 food allergy Nutrition 0.000 claims abstract 2
- 239000012634 fragment Substances 0.000 claims 15
- 239000000427 antigen Substances 0.000 claims 11
- 102000036639 antigens Human genes 0.000 claims 11
- 108091007433 antigens Proteins 0.000 claims 11
- 125000003275 alpha amino acid group Chemical group 0.000 claims 10
- 239000003814 drug Substances 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 5
- 238000002360 preparation method Methods 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 3
- 208000035475 disorder Diseases 0.000 claims 3
- 210000004408 hybridoma Anatomy 0.000 claims 3
- 230000002163 immunogen Effects 0.000 claims 3
- 101000690301 Homo sapiens Aldo-keto reductase family 1 member C4 Proteins 0.000 claims 2
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 claims 2
- 241001529936 Murinae Species 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims 2
- 102000054751 human RUNX1T1 Human genes 0.000 claims 2
- 230000036046 immunoreaction Effects 0.000 claims 2
- 238000001802 infusion Methods 0.000 claims 2
- 229940102223 injectable solution Drugs 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
- 238000001990 intravenous administration Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000002953 phosphate buffered saline Substances 0.000 claims 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims 2
- 102000005962 receptors Human genes 0.000 claims 2
- 108020003175 receptors Proteins 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- 230000009885 systemic effect Effects 0.000 claims 2
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 1
- 206010002198 Anaphylactic reaction Diseases 0.000 claims 1
- 101100227726 Arabidopsis thaliana FRL3 gene Proteins 0.000 claims 1
- 206010066091 Bronchial Hyperreactivity Diseases 0.000 claims 1
- 101100120609 Caenorhabditis elegans frh-1 gene Proteins 0.000 claims 1
- 206010012434 Dermatitis allergic Diseases 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 206010014950 Eosinophilia Diseases 0.000 claims 1
- 101150023991 FMNL1 gene Proteins 0.000 claims 1
- 101150005226 FRL1 gene Proteins 0.000 claims 1
- 101150065691 FRL2 gene Proteins 0.000 claims 1
- 102100028930 Formin-like protein 1 Human genes 0.000 claims 1
- 102100032789 Formin-like protein 3 Human genes 0.000 claims 1
- 102000004559 Interleukin-13 Receptors Human genes 0.000 claims 1
- 108010017511 Interleukin-13 Receptors Proteins 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000036783 anaphylactic response Effects 0.000 claims 1
- 208000003455 anaphylaxis Diseases 0.000 claims 1
- 206010009887 colitis Diseases 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 101150029401 fmnl3 gene Proteins 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 230000003053 immunization Effects 0.000 claims 1
- 230000016784 immunoglobulin production Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 239000007928 intraperitoneal injection Substances 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 201000000050 myeloid neoplasm Diseases 0.000 claims 1
- 238000012261 overproduction Methods 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 210000004989 spleen cell Anatomy 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 231100000397 ulcer Toxicity 0.000 claims 1
- 230000003612 virological effect Effects 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 abstract 1
- 101100286685 Mus musculus Il13 gene Proteins 0.000 abstract 1
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 abstract 1
- 201000006704 Ulcerative Colitis Diseases 0.000 abstract 1
- 208000026935 allergic disease Diseases 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- A—HUMAN NECESSITIES
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
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- A61P35/00—Antineoplastic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07K2317/00—Immunoglobulins specific features
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- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C07K2317/00—Immunoglobulins specific features
- 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
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- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Immunology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
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- Dermatology (AREA)
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- Orthopedic Medicine & Surgery (AREA)
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- Ophthalmology & Optometry (AREA)
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Claims (52)
1. Антитело или его антигенсвязывающий фрагмент, которое (который) связывается специфически и с высокой аффинностью как с гликозилированным, так и с негликозилированным IL13 человека, не связывает мышиный IL13 и нейтрализует активность IL13 человека при примерном молярном соотношении 1:2 (MAb:IL13).
2. Антитело, которое нейтрализует активность IL13 человека, причем антитело представляет собой 228В/С1, 228А-4, 227-26 или 227-43.
3. Антитело, в котором антитело содержит антигенсвязывающие области, полученные из вариабельных областей легкой и тяжелой цепи антитела по п.1.
4. Антитело по п.3, в котором указанное антитело имеет VL последовательность, по меньшей мере, на 95% гомологичную последовательности, изложенной в SEQ ID NO:3, 5 или 7, и VH-последовательность, по меньшей мере, на 95% гомологичную последовательности, изложенной в SEQ ID NO:4, 6 или 8.
5. Антитело по любому из пп.1-4, в котором антитело является моноклональным антителом.
6. Антитело по п.5, в котором указанное антитело является антителом человека, химерным антителом, гуманизированным антителом.
7. Антитело по п.1, в котором антитело является антителом с одним доменом.
8. Антитело по п.1, в котором антитело является антигенсвязывающим фрагментом, таким как Fab, Fab', F(ab')2, Fd, Fv(scFv) с одной цепочкой, антителом с одной цепочкой или Fvs(sdFv), связанным с дисульфидом.
9. Антитело, которое связывается с эпитопом, имеющим аминокислотную последовательность ESLINVSG.
10. Антитело, которое связывается с эпитопом, имеющим аминокислотную последовательность YCAALESLINVS.
11. Гибридомная клеточная линия, которая продуцирует антитело по любому из пп.1-4.
12. Вариабельная область легкой цепи, содержащая аминокислотную последовательность, имеющую формулу FRL1-CDRL1-FRL2-CDRL2-FRL3-CDRL3-FRL4, в которой FRL1 состоит из любой из SEQ ID NOs:20-25, CDRL1 состоит из любой из SEQ ID NOs:99-103, FRL2 состоит из SEQ ID NO:29; CDRL2 состоит из любой из SEQ ID NOs:104-114; FRL3 состоит из любой из SEQ ID Nos:30-56; CDRL3 состоит из любой из SEQ ID NOs:115-116; и FRL4 состоит из SEQ ID NO:57-59.
13. Вариабельная область легкой цепи, содержащая любую из SEQ ID NOs:3, 5, 7, 93, 95, 97, 142, 144 и 150.
14. Вариабельная область легкой цепи по п.12 или 13, дополнительно содержащая константную область.
15. Вариабельная область тяжелой цепи, содержащая аминокислотную последовательность, имеющую формулу FRH1-CDRH1-FRH2-CDRH2-FRH3-CDRH3-FRH4, в которой FRH1 состоит из любой из SEQ ID NOs:60-66; CDRH1 состоит из любой из SEQ ID NOs:117-122; FRH2 состоит из любой из SEQ ID NOs:67-75; CDRH2 состоит из любой из SEQ ID NOs:123-134; FRH3 состоит из любой из SEQ ID NOs:76-90; CDRH3 состоит из любой из SEQ ID NOs:135-141; и FRH4 состоит из SEQ ID NO:91-92.
16. Вариабельная область тяжелой цепи, содержащая любую из SEQ ID NOs:4, 6, 8, 94, 96, 98, 143, 145, 146, 147, 148 и 149.
17. Вариабельная область тяжелой цепи по п.15 или содержащая любую из SEQ ID NOs:4, 6, 8, 94, 96, 98, 143, 145, 146, 147, 148 и 149, кроме того содержащая, по меньшей мере, СН1-домен константной области.
18. Вариабельная область тяжелой цепи по п.17, содержащая СН1-, СН2- и СН3-домены константной области.
19. Вариабельная область тяжелой цепи по п.17, в которой константная область означает из lgG-антитела.
20. Вариабельная область тяжелой цепи по п.19, в которой lgG-антитело означает lgG1-антитело, lgG2-антитело, lgG3-антитело или lgG4-антитело.
21. Антитело или его антигенсвязывающий фрагмент, содержащий вариабельную область легкой цепи по п.12 или 13, в котором антитело связывается специфически с IL13.
22. Антитело или его антигенсвязывающий фрагмент, содержащий вариабельную область тяжелой цепи по любому из пп.15-20, в котором антитело связывается специфически с IL13.
23. Антитело, содержащее вариабельную область легкой цепи по п.12 или 13 и вариабельную тяжелую цепь по любому из пп.15-20, в котором антитело связывается специфически с IL13.
24. Антитело по п.23, содержащее вариабельную область легкой цепи, имеющую аминокислотную последовательность, изложенную в SEQ ID NO:142 и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, изложенную в SEQ ID NO:143.
25. Антитело по п.23, содержащее вариабельную область легкой цепи, имеющую аминокислотную последовательность, изложенную в SEQ ID NO:150, и вариабельную область тяжелой цепи, имеющую аминокислотную последовательность, изложенную в SEQ ID NO:151.
26. Антитело по п.1, в котором антитело означает антитело с одной цепью, имеющее последовательность, изложенную в SEQ ID NO:152.
27. Антитело, которое нейтрализует активность IL-13, содержащее SEQ ID NO:99, SEQ ID NO:104, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:123 и SEQ ID NO:135.
28. Рекомбинантная молекула антитела или ее IL13 связывающий фрагмент, содержащая, по меньшей мере, одну тяжелую цепь антитела, или ее IL-13 связывающий фрагмент, содержащий не относящиеся к человеку CDR в положениях 31-35 (CDR1), 50-65 (CDR2) и 95-102 (CDR3) (нумерация Кэбата) из мышиного анти-IL13 антитела, в котором положения 27-30 имеют аминокислоты Gly 26, Phe 27, Ser 28, Leu 29, Asn 30; и, по меньшей мере, одну легкую цепь антитела или его IL13-связывающий фрагмент, содержащий CDR, не относящиеся к человеку, в положениях 24-34 (CDR1), 50-56 (CDR2) и 89-97 (CDR3) из мышиного анти-IL13 антитела и каркасные области из моноклонального антитела.
29. Последовательность ДНК, кодирующая антитело по любому из пп.1-4, 6-10 или 24-27.
30. Вектор, содержащий последовательность ДНК по п.29.
31. Клетка-хозяин, содержащая вектор по п.30.
32. Способ изготовления антитела по п.1, содержащий этапы а) изготовления иммуногенного соединения, содержащего компонент гликозилированного IL13 и иммуногенный компонент; b) приготовления инъецируемого раствора, содержащего указанное иммуногенное соединение в буферном фосфатном физиологическом растворе (PBS) и адъювант; с) иммунизации мыши посредством указанного инъецируемого раствора сочетанием внутривенных и интраперитональных инъекций, d) изготовления гибридомы слиянием клетки селезенки указанной иммунизированной мыши с миеломной клеткой; е) отбора гибридомы, продуцирующей антитело, имеющего характеристики антитела по п.1; и f) выделения указанного антитела.
33. Антитело или его антигенсвязывающий фрагмент по любому из пп.1-4, 6-10 или 24-27 в качестве лекарственного средства.
34. Использование антитела или его антигенсвязывающего фрагмента по любому из пп.1-4, 6-10 или 24-27 для приготовления лекарственного средства для лечения пациента, страдающего от астматических симптомов.
35. Использование по п.34, в котором лечение предполагает введение количества антитела, достаточного для уменьшения астматических симптомов.
36. Использование по пп.34, в котором антитело отрицательно регулирует активность IL13 у пациента.
37. Использование по п.34, в котором антитело снижает бронхиальную гиперчувствительность у пациента.
38. Использование по п.34, в котором антитело снижает эозинофилию в легких пациента.
39. Использование по п.34, в котором лечение предусматривает введение антитела одним или несколькими путями, выбранными из группы, состоящей из внутривенного, интраперитонеального, ингаляции, внутримышечного, подкожного и перорального.
40. Использование антитела или его антигенсвязывающего фрагмента по любому из пп.1-4, 6-10 или 24-27 для приготовления лекарственного средства для лечения пациента путем ингибирования продукции IgE антитела.
41. Использование по п.40, в котором лечение предусматривает введение пациенту эффективного количества анти-IL13 антитела, достаточного для ингибирования продукции IgE антитела.
42. Использование по п.40, в котором ингибирование продукции IgE антитела предназначено для предупреждения бронхиальной астмы, предупреждения аллергических ринитов, для предупреждения аллергических дерматитов, для лечения бронхиальной астмы, для лечения аллергических ринитов, для лечения крапивницы, для предупреждения анафилаксии или для лечения атопических дерматитов.
43. Использование антитела или его антигенсвязывающего фрагмента по любому из пп.1-4, 6-10 или 24-27 для приготовления лекарственного средства для лечения lgE-опосредованного нарушения у пациента, в котором лечение предусматривает введение пациенту эффективного количества антитела или его антигенсвязывающего фрагмента, достаточного для ингибирования одной или большего числа функций, ассоциированных со связыванием интерлейкина-13 с указанным рецептором.
44. Использование по п.43, в котором нарушение выбирается из группы, состоящей из аллергической астмы, не аллергической (наследственной) астмы, аллергического ринита, атопического дерматита, аллергического конъюнктивита, экземы, крапивницы, пищевых аллергий, хронического обструктивного легочного заболевания, неспецифического язвенного колита, респираторно-синцитиальной вирусной (RVS) инфекции, увеиты, склеродермы и остеопороза.
45. Использование антитела или его антигенсвязывающего фрагмента по любому из пп.1-4, 6-10 или 24-27 для приготовления лекарственного средства для лечения IgE-опосредованного нарушения у пациента, предусматривающее введение пациенту эффективного количества антитела или антигенсвязывающего фрагмента, достаточного для ингибирования одной или большего числа функций, ассоциированных со связыванием интерлейкина-13 с указанным рецептором.
46. Использование антитела или его антигенсвязывающего фрагмента для приготовления лекарственного средства для лечения млекопитающего путем снижения тяжести астмы указанного млекопитающего, в котором лечение предусматривает введение млекопитающему терапевтически эффективного количества анти-IL13 моноклонального антитела, имеющего, по меньшей мере, одну из следующих характеристик: способность связывать человеческий IL13 с Кд между примерно 1Ч109 и примерно 1Ч1012 М; способность ингибировать одну или большее число функций, ассоциированных со связыванием интерлейкина IL13 с рецептором IL13; и неспособность антитела связывать мышиный IL13.
47. Использование по п.40, в котором анти-IL13 антитело вводят ингаляцией, системно, болюсным инъецированием или непрерывной инфузией.
48. Использование по п.43, в котором анти-IL13 антитело вводят ингаляцией, системно, болюсным инъецированием или непрерывной инфузией.
49. Способ обнаружения белка интерлейкина-13 в пробе пациента, включающий в себя этап приведения антитела по любому из пп.1-4, 6-10 или 24-27 в контакт с пробой; и обнаружение интерлейкина-13 через возникновение иммунореакции.
50. Способ диагностики сверхпродукции IL13 у пациента, включающий в себя следующие этапы: (а) получение пробы от пациента; (b) комбинирование пробы с антителом по любому из пп.1-4, 6-10 или 24-27 при условиях, позволяющих иммунореакцию с IL13; и (с) определение того, сверхпродуктивен ли IL13 относительно нормального уровня экспрессии IL13.
51. Пептид, состоящий существенно из аминокислотной последовательности ESLINVSG (SEQ ID NO:18).
52. Пептид, состоящий существенно из аминокислотной последовательности YCAALESLINVS (SEQ ID NO:19).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2671481C2 (ru) * | 2013-09-13 | 2018-10-31 | Дженентек, Инк. | Способы и композиции, включающие очищенные рекомбинантные полипептиды |
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