NO327718B1 - Anvendelse av et antistoff mot IL-6 reseptoren for dannelse av et middel for inflammatorisk mavesykdom. - Google Patents

Anvendelse av et antistoff mot IL-6 reseptoren for dannelse av et middel for inflammatorisk mavesykdom. Download PDF

Info

Publication number: NO327718B1
Authority: NO; Norway
Prior art keywords: antibody; receptor; cells; cell; human
Prior art date: 1998-03-17

Application number

NO20004581A

Other languages

English (en)

Norwegian (no)

Other versions

NO20004581D0 (no

NO20004581L (no

Inventor

Tadamitsu Kishimoto

Hiroaki Ito

Mitsunari Yamamoto

Original Assignee

Tadamitsu Kishimoto

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.)

1998-03-17

Filing date

2000-09-14

Publication date

2009-09-14

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=13339502&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO327718(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2000-09-14 Application filed by Tadamitsu Kishimoto filed Critical Tadamitsu Kishimoto

2000-09-14 Publication of NO20004581D0 publication Critical patent/NO20004581D0/no

2000-11-10 Publication of NO20004581L publication Critical patent/NO20004581L/no

2009-09-14 Publication of NO327718B1 publication Critical patent/NO327718B1/no

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- 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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Epidemiology (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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NO20004581A 1998-03-17 2000-09-14 Anvendelse av et antistoff mot IL-6 reseptoren for dannelse av et middel for inflammatorisk mavesykdom. NO327718B1 (no)

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JP6725098		1998-03-17
PCT/JP1999/001298 WO1999047170A1 (fr)	1998-03-17	1999-03-16	Agents prophylactiques ou therapeutiques pour affections intestinales inflammatoires renfermant, comme ingredient actif, des antagonistes de il-6

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NO20004581D0 NO20004581D0 (no)	2000-09-14
NO20004581L NO20004581L (no)	2000-11-10
NO327718B1 true NO327718B1 (no)	2009-09-14

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EP (1)	EP1074268B1 (zh)
JP (1)	JP4124573B2 (zh)
KR (1)	KR100407811B1 (zh)
CN (2)	CN101239185A (zh)
AT (1)	ATE383875T1 (zh)
AU (1)	AU754006B2 (zh)
CA (1)	CA2324115C (zh)
CZ (1)	CZ297083B6 (zh)
DE (1)	DE69937994T2 (zh)
DK (1)	DK1074268T3 (zh)
ES (1)	ES2299241T3 (zh)
HK (2)	HK1033911A1 (zh)
HU (1)	HU225539B1 (zh)
NO (1)	NO327718B1 (zh)
PL (1)	PL201461B1 (zh)
PT (1)	PT1074268E (zh)
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Families Citing this family (109)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US8017121B2 (en) *	1994-06-30	2011-09-13	Chugai Seiyaku Kabushika Kaisha	Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component
CZ298325B6 (cs) *	1994-10-21	2007-08-29	Kishimoto@Tadamitsu	Farmaceutický prípravek pro prevenci nebo lécení plasmocytosy
ATE547119T1 (de)	1997-03-21	2012-03-15	Chugai Pharmaceutical Co Ltd	Präventives oder therapeutisches mittel mit einem il-6-antagonisten als wirkstoff für durch sensibilisierte t-zellen vermittelte erkrankungen
US20020187150A1 (en) *	1997-08-15	2002-12-12	Chugai Seiyaku Kabushiki Kaisha	Preventive and/or therapeutic agent for systemic lupus erythematosus comprising anti-IL-6 receptor antibody as an active ingredient
DK1074268T3 (da) *	1998-03-17	2008-04-28	Chugai Pharmaceutical Co Ltd	IL-6-receptorantagonistantistofholdige forebyggende eller terapeutiske midler mod inflammatoriske tarmsygdomme
EP1085906B1 (en) *	1998-06-10	2008-08-13	Ophidian Pharmaceuticals, Inc.	Anti il6 antibodies in the prevention and treatment of inflammatory bowel disease
WO2002036165A1 (fr) *	2000-10-27	2002-05-10	Chugai Seiyaku Kabushiki Kaisha	Agent à base d'antagoniste d'il-6, faisant baisser le niveau des mmp-3 dans le sang
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
AU2003211990A1 (en)	2002-02-14	2003-09-04	Chugai Seiyaku Kabushiki Kaisha	Antibody-containing solution pharmaceuticals
JP4463104B2 (ja) *	2002-08-30	2010-05-12	財団法人化学及血清療法研究所	ヒト抗ヒトインターロイキン−６抗体及び該抗体フラグメント
GB2401040A (en) *	2003-04-28	2004-11-03	Chugai Pharmaceutical Co Ltd	Method for treating interleukin-6 related diseases
WO2005028514A1 (en) *	2003-09-22	2005-03-31	Biovation Gmbh & Co. Kg.	Use of a compound for reducing the biological effectiveness of il-6
DK1690550T3 (da)	2003-10-17	2012-11-05	Chugai Pharmaceutical Co Ltd	Terapeutisk middel til mesothelioma
US8617550B2 (en) *	2003-12-19	2013-12-31	Chugai Seiyaku Kabushiki Kaisha	Treatment of vasculitis with IL-6 antagonist
EP3269738A1 (en)	2004-03-24	2018-01-17	Chugai Seiyaku Kabushiki Kaisha	Subtypes of humanized antibody against interleukin-6 receptor
AR048335A1 (es)	2004-03-24	2006-04-19	Chugai Pharmaceutical Co Ltd	Agentes terapeuticos para trastornos del oido interno que contienen un antagonista de il- 6 como un ingrediente activo
WO2006106905A1 (ja)	2005-03-31	2006-10-12	Chugai Seiyaku Kabushiki Kaisha	会合制御によるポリペプチド製造方法
RU2446826C2 (ru)	2005-10-14	2012-04-10	Фукуока Юниверсити	Агенты для подавления повреждения трансплантированных островков после трансплантации островков
AR058135A1 (es)	2005-10-21	2008-01-23	Chugai Pharmaceutical Co Ltd	Agentes para el tratamiento de cardiopatias
AR057582A1 (es)	2005-11-15	2007-12-05	Nat Hospital Organization	Agentes para suprimir la induccion de linfocitos t citotoxicos
AR057941A1 (es) *	2005-11-25	2007-12-26	Univ Keio	Agentes terapeuticos para el cancer de prostata
JP5033643B2 (ja) *	2006-01-27	2012-09-26	学校法人慶應義塾	脈絡膜血管新生を伴う疾患の治療剤
US11046784B2 (en) *	2006-03-31	2021-06-29	Chugai Seiyaku Kabushiki Kaisha	Methods for controlling blood pharmacokinetics of antibodies
DK2009101T3 (en)	2006-03-31	2018-01-15	Chugai Pharmaceutical Co Ltd	Antibody modification method for purification of a bispecific antibody
CA2648644C (en) *	2006-04-07	2016-01-05	Osaka University	Muscle regeneration promoter
US8080248B2 (en)	2006-06-02	2011-12-20	Regeneron Pharmaceuticals, Inc.	Method of treating rheumatoid arthritis with an IL-6R antibody
ES2398076T3 (es)	2006-06-02	2013-03-13	Regeneron Pharmaceuticals, Inc.	Anticuerpos de alta afinidad contra el receptor de IL-6 humano
EP2064241B1 (en)	2006-08-03	2015-10-07	Vaccinex, Inc.	Anti-il-6 monoclonal antibodies and uses thereof
CN101528778A (zh) *	2006-08-18	2009-09-09	埃博灵克斯股份有限公司	用于治疗与il-6-介导的信号传导相关的疾病和病症的针对il-6r的氨基酸序列以及包括其的多肽
AU2007327096A1 (en) *	2006-11-30	2008-06-05	Astrazeneca Ab	Antibodies specific for the complex of Interleukin-6 and the Interleukin-6 receptor
JP2010095445A (ja) *	2006-12-27	2010-04-30	Tokyo Medical & Dental Univ	Ｉｌ−６アンタゴニストを有効成分とする炎症性筋疾患治療剤
RU2450829C2 (ru)	2007-01-23	2012-05-20	Синсу Юниверсити	Ингибитор хронического отторжения
WO2008092231A1 (en)	2007-02-01	2008-08-07	Resverlogix Corp.	Compounds for the prevention and treatment of cardiovascular diseases
US7906117B2 (en) *	2007-05-21	2011-03-15	Alderbio Holdings Llc	Antagonists of IL-6 to prevent or treat cachexia, weakness, fatigue, and/or fever
US8252286B2 (en)	2007-05-21	2012-08-28	Alderbio Holdings Llc	Antagonists of IL-6 to prevent or treat thrombosis
US8062864B2 (en)	2007-05-21	2011-11-22	Alderbio Holdings Llc	Nucleic acids encoding antibodies to IL-6, and recombinant production of anti-IL-6 antibodies
US20090238825A1 (en) *	2007-05-21	2009-09-24	Kovacevich Brian R	Novel rabbit antibody humanization methods and humanized rabbit antibodies
US8178101B2 (en) *	2007-05-21	2012-05-15	Alderbio Holdings Inc.	Use of anti-IL-6 antibodies having specific binding properties to treat cachexia
CA2688829A1 (en) *	2007-05-21	2008-11-27	Alder Biopharmaceuticals, Inc.	Novel rabbit antibody humanization methods and humanized rabbit antibodies
SI2164514T1 (sl) *	2007-05-21	2017-04-26	Alderbio Holdings Llc	Protitelesa proti IL-6 in njihova uporaba
US9701747B2 (en)	2007-05-21	2017-07-11	Alderbio Holdings Llc	Method of improving patient survivability and quality of life by anti-IL-6 antibody administration
US8404235B2 (en)	2007-05-21	2013-03-26	Alderbio Holdings Llc	Antagonists of IL-6 to raise albumin and/or lower CRP
SI2202245T1 (sl)	2007-09-26	2016-10-28	Chugai Seiyaku Kabushiki Kaisha	Postopek modificiranja izoelektrične točke protitelesa preko aminokislinske substitucije v CDR
MY163473A (en) *	2007-09-26	2017-09-15	Chugai Pharmaceutical Co Ltd	Modified antibody constant region
EP2206775B1 (en) *	2007-09-26	2016-06-29	Chugai Seiyaku Kabushiki Kaisha	Anti-il-6 receptor antibody
DK2236604T3 (en) *	2007-12-05	2016-10-03	Chugai Pharmaceutical Co Ltd	The anti-NR10 antibody and use thereof
PE20091174A1 (es)	2007-12-27	2009-08-03	Chugai Pharmaceutical Co Ltd	Formulacion liquida con contenido de alta concentracion de anticuerpo
CN107488228A (zh)	2008-04-11	2017-12-19	中外制药株式会社	与多个分子的抗原反复结合的抗原结合分子
CA2724279C (en)	2008-05-13	2017-03-07	Novimmune S.A.	Anti-il-6/il-6r antibodies and methods of use thereof
CN102256623A (zh) *	2008-06-05	2011-11-23	独立行政法人国立癌症研究中心	神经浸润抑制剂
US8188235B2 (en)	2008-06-18	2012-05-29	Pfizer Inc.	Antibodies to IL-6 and their uses
TWI440469B (zh)	2008-09-26	2014-06-11	Chugai Pharmaceutical Co Ltd	Improved antibody molecules
US9452227B2 (en) *	2008-11-25	2016-09-27	Alderbio Holdings Llc	Methods of treating or diagnosing conditions associated with elevated IL-6 using anti-IL-6 antibodies or fragments
US8420089B2 (en)	2008-11-25	2013-04-16	Alderbio Holdings Llc	Antagonists of IL-6 to raise albumin and/or lower CRP
US8992920B2 (en)	2008-11-25	2015-03-31	Alderbio Holdings Llc	Anti-IL-6 antibodies for the treatment of arthritis
US8337847B2 (en)	2008-11-25	2012-12-25	Alderbio Holdings Llc	Methods of treating anemia using anti-IL-6 antibodies
US8323649B2 (en)	2008-11-25	2012-12-04	Alderbio Holdings Llc	Antibodies to IL-6 and use thereof
US9212223B2 (en)	2008-11-25	2015-12-15	Alderbio Holdings Llc	Antagonists of IL-6 to prevent or treat thrombosis
SG2014007637A (en) *	2009-01-29	2014-03-28	Medimmune Llc	Human anti-il-6 antibodies with extended in vivo half-life and their use in treatment of oncology, autoimmune diseases and inflammatory diseases
JP5795304B2 (ja)	2009-03-18	2015-10-14	レスバーロジックスコーポレイション	新規抗炎症剤
WO2010107110A1 (ja)	2009-03-19	2010-09-23	中外製薬株式会社	抗体定常領域改変体
JP5787446B2 (ja)	2009-03-19	2015-09-30	中外製薬株式会社	抗体定常領域改変体
KR102215167B1 (ko)	2009-04-22	2021-02-16	리스버로직스 코퍼레이션	신규한 소염제
CN102459344A (zh)	2009-05-15	2012-05-16	中外制药株式会社	抗axl抗体
US10150808B2 (en)	2009-09-24	2018-12-11	Chugai Seiyaku Kabushiki Kaisha	Modified antibody constant regions
BR122022001178B1 (pt)	2009-10-26	2022-10-04	F. Hoffmann-La Roche Ag	Método para a produção de uma imunoglobulina glicosilada e seu uso
JO3244B1 (ar) *	2009-10-26	2018-03-08	Amgen Inc	بروتينات ربط مستضادات il – 23 البشرية
US9775921B2 (en)	2009-11-24	2017-10-03	Alderbio Holdings Llc	Subcutaneously administrable composition containing anti-IL-6 antibody
WO2011066378A2 (en)	2009-11-24	2011-06-03	Alder Biopharmaceuticals, Inc.	Antagonists of il-6 to prevent or treat thrombosis
JO3417B1 (ar)	2010-01-08	2019-10-20	Regeneron Pharma	الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r
EP2543730B1 (en)	2010-03-04	2018-10-31	Chugai Seiyaku Kabushiki Kaisha	Antibody constant region variant
PL2578231T3 (pl)	2010-05-28	2023-01-16	Chugai Seiyaku Kabushiki Kaisha	Środek wzmacniający przeciwnowotworową odpowiedź limfocytów t
US20130149302A1 (en)	2010-05-28	2013-06-13	Chugai Seiyaku Kabushiki Kaisha	Therapeutic agents for pancreatic cancer
WO2012064627A2 (en)	2010-11-08	2012-05-18	Genentech, Inc.	Subcutaneously administered anti-il-6 receptor antibody
CA2818813C (en) *	2010-11-23	2020-10-06	Alder Biopharmaceuticals, Inc.	Anti-il-6 antibodies for the treatment of oral mucositis
RU2658504C9 (ru)	2010-11-30	2018-08-21	Чугаи Сейяку Кабусики Кайся	Антигенсвязывающая молекула, способная многократно связываться с множеством антигенных молекул
EP2520292A1 (en)	2011-05-06	2012-11-07	Helmholtz-Zentrum für Infektionsforschung GmbH	Use of spirangiens for the treatment or prevention of IL-8 or IL-6 mediated disorders
MD480Z5 (ro) *	2011-07-07	2012-09-30	Эльвира АНДОН	Metodă de tratament al colitei ulceroase nespecifice acute
AR087305A1 (es)	2011-07-28	2014-03-12	Regeneron Pharma	Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit
TWI589299B (zh)	2011-10-11	2017-07-01	再生元醫藥公司	用於治療類風濕性關節炎之組成物及其使用方法
EP2807190B1 (en)	2012-01-23	2018-12-26	Regeneron Pharmaceuticals, Inc.	Stabilized formulations containing anti-ang2 antibodies
KR101487935B1 (ko)	2012-05-21	2015-02-02	한국생명공학연구원	곰보배추의 추출물 또는 이의 분획물을 유효성분으로 포함하는, stat3 매개 질환의 예방 또는 치료용 약학적 조성물
JP6282591B2 (ja) *	2012-09-13	2018-02-21	中外製薬株式会社	遺伝子ノックイン非ヒト動物
JP6442404B2 (ja)	2013-06-11	2018-12-19	国立研究開発法人国立精神・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
MX363403B (es)	2013-07-04	2019-03-22	Hoffmann La Roche	Inmumoensayo con interferencia suprimida para la deteccion de anticuerpos anti-farmacos en muestras de suero.
BR112016006197B1 (pt)	2013-09-27	2023-04-11	Chugai Seiyaku Kabushiki Kaisha	Método para produzir um anticorpo biespecífico de polipeptídeos
DE202014010499U1 (de)	2013-12-17	2015-10-20	Kymab Limited	Targeting von humaner PCSK9 zur Cholesterinbehandlung
US9017678B1 (en)	2014-07-15	2015-04-28	Kymab Limited	Method of treating rheumatoid arthritis using antibody to IL6R
WO2015116852A1 (en)	2014-01-29	2015-08-06	Regeneron Pharmaceuticals, Inc.	Methods for treating rheumatoid arthritis by administering an il-6r antibody
KR20180095740A (ko)	2015-02-27	2018-08-27	추가이 세이야쿠 가부시키가이샤	Il-6 관련 질환 치료용 조성물
EP3268007B1 (en)	2015-03-13	2022-11-09	Resverlogix Corp.	Compositions and therapeutic methods for the treatment of complement-associated diseases
WO2016159213A1 (ja)	2015-04-01	2016-10-06	中外製薬株式会社	ポリペプチド異種多量体の製造方法
JP6875683B2 (ja)	2015-05-19	2021-05-26	国立研究開発法人国立精神・神経医療研究センター	多発性硬化症（ｍｓ）患者の新規治療適用判断方法
US11174317B2 (en)	2015-06-04	2021-11-16	National Center Of Neurology And Psychiatry	Therapeutic agent for mental illness comprising IL-6 inhibitor as active ingredient
JP2018523684A (ja)	2015-08-18	2018-08-23	リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎＰｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ．	リポタンパク質アフェレーシスを受けている高脂血症の患者を治療するための抗ｐｃｓｋ９阻害抗体
EP3398965A4 (en)	2015-12-28	2019-09-18	Chugai Seiyaku Kabushiki Kaisha	METHOD FOR PROMOTING THE EFFICACY OF PURIFYING A POLYPEPTIDE CONTAINING AN FC REGION
US11484591B2 (en)	2016-02-22	2022-11-01	Ohio State Innovation Foundation	Chemoprevention using controlled-release formulations of anti-interleukin 6 agents, synthetic vitamin A analogues or metabolites, and estradiol metabolites
SG10201607778XA (en)	2016-09-16	2018-04-27	Chugai Pharmaceutical Co Ltd	Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use
JP7182162B2 (ja)	2017-01-27	2022-12-02	株式会社ステムリム	心筋症、陳旧性心筋梗塞および慢性心不全の治療薬
EP3576790A4 (en)	2017-02-01	2020-12-23	Yale University	TREATMENT OF DIURETIC RESISTANCE
CN110603057A (zh)	2017-03-17	2019-12-20	俄亥俄州创新基金会	用于递送化学预防剂的纳米颗粒
JP7185884B2 (ja)	2017-05-02	2022-12-08	国立研究開発法人国立精神・神経医療研究センター	Ｉｌ－６及び好中球の関連する疾患の治療効果の予測及び判定方法
US11692037B2 (en)	2017-10-20	2023-07-04	Hyogo College Of Medicine	Anti-IL-6 receptor antibody-containing medicinal composition for preventing post-surgical adhesion
CN111787950A (zh)	2018-01-05	2020-10-16	科威迪亚治疗公司	用于无免疫抑制地治疗il-6介导的炎症的方法
WO2019177543A1 (en)	2018-03-15	2019-09-19	Chugai Seiyaku Kabushiki Kaisha	Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use
CA3128212A1 (en)	2019-01-31	2020-08-06	Sanofi Biotechnology	Anti-il-6 receptor antibody for treating juvenile idiopathic arthritis
EP3947737A2 (en)	2019-04-02	2022-02-09	INSERM (Institut National de la Santé et de la Recherche Médicale)	Methods of predicting and preventing cancer in patients having premalignant lesions
AU2020418554A1 (en) *	2019-12-31	2022-08-25	Peptinov	Pharmaceutical composition for the prevention or treatment of post-surgical pain
WO2022047730A1 (en) *	2020-09-04	2022-03-10	Shanghai Pharmaceuticals Holding Co., Ltd.	Methods to treat inflammatory bowel disease

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1341152C (en)	1988-01-22	2000-12-12	Tadamitsu Kishimoto	Receptor protein for human b cell stimulatory factor-2
US6428979B1 (en)	1988-01-22	2002-08-06	Tadamitsu Kishimoto	Receptor protein for human B cell stimulatory factor-2
US5670373A (en)	1988-01-22	1997-09-23	Kishimoto; Tadamitsu	Antibody to human interleukin-6 receptor
US5530101A (en) *	1988-12-28	1996-06-25	Protein Design Labs, Inc.	Humanized immunoglobulins
JP2914672B2 (ja)	1989-01-17	1999-07-05	中外製薬株式会社	Ｂｓｆ▲下２▼アンタゴニスト
US5210075A (en)	1990-02-16	1993-05-11	Tanabe Seiyaku Co., Ltd.	Interleukin 6 antagonist peptides
PT97124A (pt)	1990-03-23	1991-12-31	Gist Brocades Nv	Processo para a prparacao de composicoes inibidoras de interleucina - 6 (il-6)
RU2139351C1 (ru)	1991-04-25	1999-10-10	Чугаи Сейяку Кабусики Кайся	Н- и l-цепи моноклонального антитела рм1 (монат) к рецептору il-6r человека и их v-области, модифицированная монат, его н- и l-цепи и их v-области, cdr- последовательности, днк-последовательности
US5888511A (en)	1993-02-26	1999-03-30	Advanced Biotherapy Concepts, Inc.	Treatment of autoimmune diseases, including AIDS
US5888510A (en) *	1993-07-21	1999-03-30	Chugai Seiyaku Kabushiki Kaisha	Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component
WO1995009873A1 (en)	1993-10-06	1995-04-13	Board Of Regents, The University Of Texas System	A monoclonal anti-human il-6 receptor antibody
US5420109A (en)	1993-11-12	1995-05-30	Houghten Pharmaceuticals, Inc.	Cytokine restraining agents
JPH07324097A (ja) *	1994-05-30	1995-12-12	Daicel Chem Ind Ltd	インターロイキン６拮抗剤、及びペプチド類または医薬として許容されるその塩類
WO1995034320A2 (en)	1994-06-07	1995-12-21	Regents Of The University Of Minnesota	Methods for inhibiting antigen specific t cell responses
JPH10503179A (ja)	1994-06-24	1998-03-24	イミュネックス・コーポレーション	放出制御性ポリペプチド組成物および炎症性腸疾患の治療方法
JPH0850829A (ja)	1994-08-05	1996-02-20	Tokai Rika Co Ltd	レバースイッチ
EP0785276A4 (en)	1994-09-29	2002-01-09	Ajinomoto Kk	MODIFICATION OF A PEPTIDE AND A PROTEIN
ATE552012T1 (de)	1994-10-07	2012-04-15	Chugai Pharmaceutical Co Ltd	Hemmung des abnormalen wachstums von synovialzellen durch il-6-antagonisten als wirkstoff
CZ298325B6 (cs)	1994-10-21	2007-08-29	Kishimoto@Tadamitsu	Farmaceutický prípravek pro prevenci nebo lécení plasmocytosy
JPH08245414A (ja) *	1995-01-27	1996-09-24	Private Biolog Corp	Ｉｌ−６関連疾患の治療用組成物および方法
US5569680A (en) *	1995-02-13	1996-10-29	Trustees Of The Univ. Of Penna	Method of treating inflammatory bowel disease with tributyrin
WO1996025174A1 (fr) *	1995-02-13	1996-08-22	Chugai Seiyaku Kabushiki Kaisha	Inhibiteur de decomposition des proteines musculaires contenant un anticorps du recepteur de l'interleukine-6
ATE390933T1 (de)	1995-04-27	2008-04-15	Amgen Fremont Inc	Aus immunisierten xenomäusen stammende menschliche antikörper gegen il-8
JPH08311098A (ja)	1995-05-22	1996-11-26	Daicel Chem Ind Ltd	新規ペプチド類およびそれを含有するインターロイキン６拮抗剤
US5571513A (en) *	1995-05-31	1996-11-05	The Board Of Regents Of The University Of Oklahoma	Anti-gp130 monoclonal antibodies
WO1996040966A1 (en) *	1995-06-07	1996-12-19	Private Biologicals Corporation	Compositions and methods of treating il-6 associated diseases
JPH09235276A (ja) *	1995-12-27	1997-09-09	Takeda Chem Ind Ltd	オキサゾール誘導体、その製造法および用途
WO1997024340A1 (en)	1995-12-27	1997-07-10	Takeda Chemical Industries, Ltd.	Oxazole derivatives, their production and use
CA2251355C (en) *	1996-04-09	2009-06-09	Applied Research Systems Ars Holding N.V.	Il-6 mutein
GB9625640D0 (en)	1996-12-10	1997-01-29	Celltech Therapeutics Ltd	Biological products
US20020187150A1 (en)	1997-08-15	2002-12-12	Chugai Seiyaku Kabushiki Kaisha	Preventive and/or therapeutic agent for systemic lupus erythematosus comprising anti-IL-6 receptor antibody as an active ingredient
DK1074268T3 (da) *	1998-03-17	2008-04-28	Chugai Pharmaceutical Co Ltd	IL-6-receptorantagonistantistofholdige forebyggende eller terapeutiske midler mod inflammatoriske tarmsygdomme
EP1085906B1 (en) *	1998-06-10	2008-08-13	Ophidian Pharmaceuticals, Inc.	Anti il6 antibodies in the prevention and treatment of inflammatory bowel disease
WO2002036165A1 (fr)	2000-10-27	2002-05-10	Chugai Seiyaku Kabushiki Kaisha	Agent à base d'antagoniste d'il-6, faisant baisser le niveau des mmp-3 dans le sang
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
EP1499305A2 (en)	2002-04-12	2005-01-26	Pfizer Japan Inc.	Use of ep4 receptor ligands in the treatment of il-6 involved diseases
GB2401040A (en)	2003-04-28	2004-11-03	Chugai Pharmaceutical Co Ltd	Method for treating interleukin-6 related diseases

1999
- 1999-03-16 DK DK99907951T patent/DK1074268T3/da active
- 1999-03-16 US US09/646,188 patent/US6723319B1/en not_active Expired - Lifetime
- 1999-03-16 KR KR10-2000-7010242A patent/KR100407811B1/ko not_active IP Right Cessation
- 1999-03-16 PL PL342938A patent/PL201461B1/pl unknown
- 1999-03-16 AT AT99907951T patent/ATE383875T1/de active
- 1999-03-16 JP JP2000536409A patent/JP4124573B2/ja not_active Expired - Fee Related
- 1999-03-16 CN CNA2008100813567A patent/CN101239185A/zh active Pending
- 1999-03-16 EP EP99907951A patent/EP1074268B1/en not_active Expired - Lifetime
- 1999-03-16 CN CNB998052094A patent/CN100374159C/zh not_active Expired - Fee Related
- 1999-03-16 HU HU0101694A patent/HU225539B1/hu not_active IP Right Cessation
- 1999-03-16 WO PCT/JP1999/001298 patent/WO1999047170A1/ja active IP Right Grant
- 1999-03-16 RU RU2000126295/14A patent/RU2195960C2/ru not_active IP Right Cessation
- 1999-03-16 ES ES99907951T patent/ES2299241T3/es not_active Expired - Lifetime
- 1999-03-16 CA CA002324115A patent/CA2324115C/en not_active Expired - Fee Related
- 1999-03-16 PT PT99907951T patent/PT1074268E/pt unknown
- 1999-03-16 AU AU27481/99A patent/AU754006B2/en not_active Ceased
- 1999-03-16 CZ CZ20003297A patent/CZ297083B6/cs not_active IP Right Cessation
- 1999-03-16 DE DE69937994T patent/DE69937994T2/de not_active Expired - Lifetime
2000
- 2000-09-14 NO NO20004581A patent/NO327718B1/no not_active IP Right Cessation
2001
- 2001-07-05 HK HK01104649A patent/HK1033911A1/xx not_active IP Right Cessation
- 2001-10-08 HK HK01107040A patent/HK1036018A1/xx not_active IP Right Cessation
2003
- 2003-10-03 US US10/677,227 patent/US7824674B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EP1074268B1 (en)	2008-01-16
CN100374159C (zh)	2008-03-12
HU225539B1 (en)	2007-02-28
ES2299241T3 (es)	2008-05-16
PL201461B1 (pl)	2009-04-30
ATE383875T1 (de)	2008-02-15
CA2324115A1 (en)	1999-09-23
KR20010041933A (ko)	2001-05-25
JP4124573B2 (ja)	2008-07-23
HK1036018A1 (en)	2001-12-21
CN1297357A (zh)	2001-05-30
HUP0101694A3 (en)	2003-08-28
PT1074268E (pt)	2008-02-28
WO1999047170A1 (fr)	1999-09-23
KR100407811B1 (ko)	2003-12-01
US6723319B1 (en)	2004-04-20
HK1033911A1 (en)	2001-10-05
AU2748199A (en)	1999-10-11
US7824674B2 (en)	2010-11-02
CZ20003297A3 (cs)	2001-02-14
AU754006B2 (en)	2002-10-31
EP1074268A1 (en)	2001-02-07
CA2324115C (en)	2008-12-23
NO20004581D0 (no)	2000-09-14
DK1074268T3 (da)	2008-04-28
NO20004581L (no)	2000-11-10
PL342938A1 (en)	2001-07-16
HUP0101694A1 (hu)	2002-12-28
DE69937994D1 (de)	2008-03-06
CN101239185A (zh)	2008-08-13
RU2195960C2 (ru)	2003-01-10
CZ297083B6 (cs)	2006-09-13
US20040071706A1 (en)	2004-04-15
EP1074268A4 (en)	2002-11-20
DE69937994T2 (de)	2008-12-24

Legal Events

Date	Code	Title	Description
2014-11-03	MM1K	Lapsed by not paying the annual fees

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