ES2192585T3 - Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion. - Google Patents

Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion.

Info

Publication number
ES2192585T3
ES2192585T3 ES95940409T ES95940409T ES2192585T3 ES 2192585 T3 ES2192585 T3 ES 2192585T3 ES 95940409 T ES95940409 T ES 95940409T ES 95940409 T ES95940409 T ES 95940409T ES 2192585 T3 ES2192585 T3 ES 2192585T3
Authority
ES
Spain
Prior art keywords
interleucine
superagonists
antagonists
superantagonists
location
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
ES95940409T
Other languages
English (en)
Inventor
Gennaro Ciliberto
Rocco Savino
Armin Lahm
Carlo Toniatti
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sigma Tau Industrie Farmaceutiche Riunite SpA
Original Assignee
Sigma Tau Industrie Farmaceutiche Riunite SpA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sigma Tau Industrie Farmaceutiche Riunite SpA filed Critical Sigma Tau Industrie Farmaceutiche Riunite SpA
Application granted granted Critical
Publication of ES2192585T3 publication Critical patent/ES2192585T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/54Interleukins [IL]
    • C07K14/5412IL-6
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/08Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/02Nutrients, e.g. vitamins, minerals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869Interleukin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S930/00Peptide or protein sequence
    • Y10S930/01Peptide or protein sequence
    • Y10S930/14Lymphokine; related peptides
    • Y10S930/141Interleukin

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Diabetes (AREA)
  • Toxicology (AREA)
  • Analytical Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Pathology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Obesity (AREA)

Abstract

SE SABE QUE LOS LIGANDOS DEL GRUPO DE CITOQUINAS SIMILAR A LA INTERLEUCINA 6(IL-6), QUE ES ONCOSTATINA-M(OSM), EL FACTOR INHIBITORIO DE LA LEUCEMIA (LIF), EL FACTOR NEUROTROFICO CILIAR (CNTF) E LA INTERLEUCINA II (IL-II), INDUCEN LA FORMACION DE UN COMPLEJO RECEPTOR DEL CUAL FORMA PARTE LA MOLECULA DE MEMBRANA GP 130. LA PRESENTE INVENCION SE REFIERE A UNA METODOLOGIA PARA LA SELECCION DE SUPERAGONISTAS, ANTAGONISTAS Y SUPERANTAGONISTAS DE LA INTERLEUCINA-6 HUMANA QUE COMPRENDE LAS SIGUIENTES OPERACIONES: COMPARAR LA SECUENCIA DE AMINOACIDO DE LA COLONIA DE GRANULOCITOS BOVINOS QUE ESTIMULAN EL FACTOR (BG-CSF) CON LA SECUENCIA DE DICHA HORMONA, Y EN BASE A LA COMPARACION ANTERIORMENTE MENCIONADA, FORMULAR UN MODELO TRIDIMENSIONAL DE DICHA HORMONA, EL CUAL PERMITE LA IDENTIFICACION DE LOS RESIDUOS QUE FORMAN EL EMPLAZAMIENTO DE LA INTERACCION CON EL RECEPTOR ESPECIFICO (EMPLAZAMIENTO 1) Y ESOS QUE CONSTITUYEN EL EMPLAZAMIENTO DE LA INTERACCION CON EL GP 130 (EMPLAZAMIENTO 2) RESPECTIVAMENTE.LA INVENCION PERMITE LA IDENTIFICACION DE ESTOS EMPLAZAMIENTOS EN INTERLEUCINA-6 HUMANA Y EL AISLAMIENTO DE LAS VARIANTES QUE TIENEN, CON RESPECTO A LA HORMONA DE TIPO SALVAJE, UNA MAYOR AFINIDAD PARA EL RECEPTOR ESPECIFICO (SUPERAGONISTAS Y SUPERANTAGONISTAS) O AFINIDAD PARA EL GP 130 REDUCIDO O ABOLIDO (ANTAGONISTAS Y ANTAGONISTAS). LA FIGURA DEMUESTRA UN ESQUEMA QUE ILUSTRA LA METODOLOGIA APLICADA PARA IDENTIFICAR EL EMPLAZAMIENTO 1 Y EL EMPLAZAMIENTO 2 EN EL CASO DE LA INTERLEUCINA-6 HUMANA. LA INVENCION TAMBIEN DESCRIBE LA OBTENCION DE SUPERAGONISTAS Y SUPERANTAGONISTAS ESPECIFICAS DE LA INTERLEUCINA-6 Y EL USO DE SUPERANTAGONISTAS COMO INHIBIDORES DE DOSIS BAJA DEL CRECIMIENTO DE CELULAS DE MIELOMAS HUMANOS DEPENDIENTES DE LA INTERLEUCINA-6 DE TIPO SALAVAJE.
ES95940409T 1994-12-14 1995-12-13 Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion. Expired - Lifetime ES2192585T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ITRM940805A IT1274782B (it) 1994-12-14 1994-12-14 Metodo per selezionare superagonisti, antagonisti e superantagonisti di ormoni del cui complesso recettoriale fa parte gp 130

Publications (1)

Publication Number Publication Date
ES2192585T3 true ES2192585T3 (es) 2003-10-16

Family

ID=11402859

Family Applications (1)

Application Number Title Priority Date Filing Date
ES95940409T Expired - Lifetime ES2192585T3 (es) 1994-12-14 1995-12-13 Superagonistas y antagonistas de la h il-6 y metodo de modelado tridimensional para su seleccion.

Country Status (13)

Country Link
US (2) US5849283A (es)
EP (1) EP0745094B1 (es)
JP (2) JP3206919B2 (es)
CN (1) CN1070866C (es)
AT (1) ATE234864T1 (es)
AU (1) AU702783B2 (es)
CA (1) CA2177838A1 (es)
DE (1) DE69529973T2 (es)
DK (1) DK0745094T3 (es)
ES (1) ES2192585T3 (es)
IT (1) IT1274782B (es)
PT (1) PT745094E (es)
WO (1) WO1996018648A1 (es)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016202A1 (en) * 1995-10-27 1997-05-09 Amrad Operations Pty. Ltd. Cytokines and their use in treatment and/or prophylaxis of breast cancer
JP3824173B2 (ja) * 1995-11-07 2006-09-20 株式会社カネカ 自己抗原
IT1285790B1 (it) 1996-09-24 1998-06-24 Angeletti P Ist Richerche Bio Adenovirus difettivi ricombinanti che codificano per mutanti di interleuchina 6 umana (hil-6) con attivita' antagonista o
AUPO439396A0 (en) 1996-12-24 1997-01-23 Walter And Eliza Hall Institute Of Medical Research, The A method of treatment and prophylaxis
GB9702944D0 (en) * 1997-02-13 1997-04-02 Univ Manchester Reducing fibrosis
ES2312184T3 (es) 1997-03-21 2009-02-16 Chugai Seiyaku Kabushiki Kaisha Agentes preventivos terapeuticos para el tratamiento de esclerosis multiple, que contienen anticuerpos anti-receptores de il-6 antagonistas.
CA2237915A1 (en) * 1998-05-19 1999-11-19 Stephen Shaughnessy Osteoporosis treatment
WO2000001404A1 (en) 1998-07-06 2000-01-13 The Government Of The United States Of America As Represented By The Secretary, Department Of Health And Human Services Compositions and methods for $i(in vitro) fertilization
JP4799516B2 (ja) * 1998-08-24 2011-10-26 中外製薬株式会社 Il−6アンタゴニストを有効成分として含有する膵炎の予防又は治療剤
ES2276525T3 (es) 1998-08-24 2007-06-16 Chugai Seiyaku Kabushiki Kaisha Preventivos o remedios para la pancreatitis que contienen anticuerpos anti-receptor il-6 como ingrediente activo.
US6541244B1 (en) * 1999-06-07 2003-04-01 Cedars-Sinai Medical Center Suppressor of cytokine signaling (SOCS)-3 promoter and methods for its use in genetic therapy in humans
WO2001016166A2 (en) * 1999-08-27 2001-03-08 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Polypeptides, comprising il-6 ligand-binding receptor domains, and related nucleic acids, antibodies, compositions, and methods of use
UA80091C2 (en) * 2001-04-02 2007-08-27 Chugai Pharmaceutical Co Ltd Remedies for infant chronic arthritis-relating diseases and still's disease which contain an interleukin-6 (il-6) antagonist
US7247618B2 (en) * 2001-04-30 2007-07-24 Tripathi Rajavashisth Methods for inhibiting macrophage colony stimulating factor and c-FMS-dependent cell signaling
RU2318829C2 (ru) * 2001-11-14 2008-03-10 Сентокор, Инк. Антитела против il-6, композиции, способы и применение
US20060165683A1 (en) 2001-12-05 2006-07-27 Gerard Karsenty Methods and compositions for control of bone formation via modulation of sympathetic tone
CA2516945A1 (en) 2003-02-24 2004-09-02 Chugai Seiyaku Kabushiki Kaisha Therapeutic agent for spinal cord injury comprising interleukin-6 antagonist
GB2401040A (en) 2003-04-28 2004-11-03 Chugai Pharmaceutical Co Ltd Method for treating interleukin-6 related diseases
RU2554942C2 (ru) 2003-10-17 2015-07-10 Тугаи Сейяку Кабусики Кайся Терапевтический агент для мезотелиомы
US20050100550A1 (en) * 2003-11-10 2005-05-12 Mohit Trikha Anti-angiogenic uses of IL-6 antagonists
AR048210A1 (es) 2003-12-19 2006-04-12 Chugai Pharmaceutical Co Ltd Un agente preventivo para la vasculitis.
PA8672101A1 (es) * 2005-04-29 2006-12-07 Centocor Inc Anticuerpos anti-il-6, composiciones, métodos y usos
AU2006300234B2 (en) 2005-10-14 2013-01-10 Chugai Seiyaku Kabushiki Kaisha Agents for suppressing damage to transplanted islets after islet transplantation
US8945558B2 (en) 2005-10-21 2015-02-03 Chugai Seiyaku Kabushiki Kaisha Methods for treating myocardial infarction comprising administering an IL-6 inhibitor
AR057582A1 (es) 2005-11-15 2007-12-05 Nat Hospital Organization Agentes para suprimir la induccion de linfocitos t citotoxicos
WO2007061029A1 (ja) 2005-11-25 2007-05-31 Keio University 前立腺癌治療剤
EP3135298B1 (en) 2006-01-27 2018-06-06 Keio University Therapeutic agents for diseases involving choroidal neovascularization
EP2025346B1 (en) 2006-04-07 2016-08-10 Osaka University Muscle regeneration promoter
KR101508019B1 (ko) 2007-01-23 2015-04-06 고쿠리츠 다이가쿠 호우징 신슈 다이가쿠 만성 거부반응 억제제
TWI528973B (zh) 2008-06-05 2016-04-11 Chugai Pharmaceutical Co Ltd Nerve infiltration inhibitor
US8188235B2 (en) * 2008-06-18 2012-05-29 Pfizer Inc. Antibodies to IL-6 and their uses
EP2578233B1 (en) 2010-05-28 2017-04-26 National Cancer Center Therapeutic agent for pancreatic cancer
SI2578231T1 (sl) 2010-05-28 2023-01-31 Chugai Seiyaku Kabushiki Kaisha Okrepljen protitumorski T celični odzivnik
EP2787007A3 (en) 2010-11-08 2015-03-11 F. Hoffmann-La Roche AG Subcutaneously administered ANTI-IL-6 receptor antibody
WO2014200018A1 (ja) 2013-06-11 2014-12-18 独立行政法人 国立精神・神経医療研究センター 再発寛解型多発性硬化症(rrms)患者の治療予後予測方法、及び新規治療適応判断方法
EP2898896A1 (en) 2014-01-22 2015-07-29 Université Pierre et Marie Curie (Paris 6) Agents for use in the treatment of retinal inflammation
TWI873632B (zh) 2015-02-27 2025-02-21 日商中外製藥股份有限公司 Il-6受體抗體用於製備醫藥組成物的用途
US20190060286A1 (en) 2016-02-29 2019-02-28 University Of Florida Research Foundation, Incorpo Chemotherapeutic Methods
US11851486B2 (en) 2017-05-02 2023-12-26 National Center Of Neurology And Psychiatry Method for predicting and evaluating therapeutic effect in diseases related to IL-6 and neutrophils
WO2019151418A1 (ja) 2018-01-31 2019-08-08 元一 加藤 Il-6阻害剤を含有する喘息の治療剤
WO2020213665A1 (ja) 2019-04-17 2020-10-22 国立大学法人広島大学 Il-6阻害剤及びccr2阻害剤を組み合わせて投与することを特徴とする泌尿器がんの治療剤

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2147466A1 (en) * 1992-10-20 1994-04-28 Just P. J. Brakenhoff Interleukin-6 receptor antagonists
IT1263022B (it) * 1992-11-06 1996-07-23 Angeletti P Ist Richerche Bio Interleuchina-6 mutante con attivita' biologica migliorata rispetto all'interleuchina-6 selvatica.

Also Published As

Publication number Publication date
AU702783B2 (en) 1999-03-04
DK0745094T3 (da) 2003-06-10
EP0745094A1 (en) 1996-12-04
CN1070866C (zh) 2001-09-12
US5849283A (en) 1998-12-15
AU4187196A (en) 1996-07-03
CN1140456A (zh) 1997-01-15
HK1011032A1 (en) 1999-07-02
CA2177838A1 (en) 1996-06-15
JPH09502460A (ja) 1997-03-11
WO1996018648A1 (en) 1996-06-20
DE69529973T2 (de) 2003-12-04
JP3206919B2 (ja) 2001-09-10
JP3286310B2 (ja) 2002-05-27
JP2001354698A (ja) 2001-12-25
PT745094E (pt) 2003-07-31
ITRM940805A1 (it) 1996-06-14
ATE234864T1 (de) 2003-04-15
EP0745094B1 (en) 2003-03-19
IT1274782B (it) 1997-07-24
DE69529973D1 (de) 2003-04-24
ITRM940805A0 (it) 1994-12-14
US5914106A (en) 1999-06-22

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