SG154441A1 - Treatment of demyelinating disorders - Google Patents

Treatment of demyelinating disorders

Info

Publication number
SG154441A1
SG154441A1 SG200904473-6A SG2009044736A SG154441A1 SG 154441 A1 SG154441 A1 SG 154441A1 SG 2009044736 A SG2009044736 A SG 2009044736A SG 154441 A1 SG154441 A1 SG 154441A1
Authority
SG
Singapore
Prior art keywords
treatment
demyelinating disorders
demyelinating
disorders
lymphotoxin
Prior art date
Application number
SG200904473-6A
Other languages
English (en)
Inventor
Jeffrey Browning
Jenny P-Y Ting
Original Assignee
Biogen Idec Inc
Univ North Carolina
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 Biogen Idec Inc, Univ North Carolina filed Critical Biogen Idec Inc
Publication of SG154441A1 publication Critical patent/SG154441A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1793Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • 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
    • A61P25/00Drugs for disorders of the nervous system
    • 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
    • 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
    • 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
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70578NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/30Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Rheumatology (AREA)
  • Toxicology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
SG200904473-6A 2006-10-20 2007-10-18 Treatment of demyelinating disorders SG154441A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US86234306P 2006-10-20 2006-10-20

Publications (1)

Publication Number Publication Date
SG154441A1 true SG154441A1 (en) 2009-08-28

Family

ID=39314832

Family Applications (2)

Application Number Title Priority Date Filing Date
SG2012004578A SG178002A1 (en) 2006-10-20 2007-10-18 Treatment of demyelinating disorders
SG200904473-6A SG154441A1 (en) 2006-10-20 2007-10-18 Treatment of demyelinating disorders

Family Applications Before (1)

Application Number Title Priority Date Filing Date
SG2012004578A SG178002A1 (en) 2006-10-20 2007-10-18 Treatment of demyelinating disorders

Country Status (14)

Country Link
US (2) US8067375B2 (de)
EP (2) EP2311481A3 (de)
JP (3) JP2010506955A (de)
KR (2) KR20090071652A (de)
CN (2) CN101600450A (de)
AU (1) AU2007311052B2 (de)
BR (1) BRPI0718283A2 (de)
CA (1) CA2666934A1 (de)
EA (1) EA200900581A1 (de)
IL (1) IL198196A0 (de)
MX (1) MX2009004134A (de)
NZ (1) NZ576424A (de)
SG (2) SG178002A1 (de)
WO (1) WO2008049053A2 (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8338376B2 (en) 2006-10-20 2012-12-25 Biogen Idec Ma Inc. Compositions comprising variant LT-B-R-IG fusion proteins
CA2680792A1 (en) * 2007-03-15 2008-09-18 Biogen Idec Ma Inc. Treatment of autoimmune disorders
MX2012006938A (es) * 2009-12-17 2012-07-10 Sanofi Sa Modelo animal que expresa luciferasa bajo el control del promotor de proteina basica de mielina (mbp-luci) y el uso del modelo para formacion de imagenes bioluminiscentes in vivo.
CA2899961C (en) * 2013-02-14 2022-08-09 Cornell University Methods to protect against and treat multiple sclerosis
WO2014178892A1 (en) * 2013-05-03 2014-11-06 Scanlan Thomas S Use of sobetirome in the treatment of x-linked adrenolenoleukodystrophy
JP6382499B2 (ja) 2013-10-31 2018-08-29 株式会社Nttドコモ 無線基地局、ユーザ端末及び無線通信方法
CN104922670A (zh) * 2015-05-06 2015-09-23 武汉奥斯梅得生物医药有限公司 融合免疫蛋白在制备治疗多发性硬化症药物中的应用
CN107213456B (zh) * 2017-05-25 2020-08-21 苏州华测生物技术有限公司 淋巴毒素衍生物的新用途
US11827596B2 (en) 2018-12-12 2023-11-28 Autobahn Therapeutics, Inc. Thyromimetics
EP3931180A1 (de) 2019-03-01 2022-01-05 Autobahn Therapeutics, Inc. Neuartige thyromimetika
CN112305226A (zh) * 2019-07-31 2021-02-02 首都医科大学附属北京天坛医院 抗人gfap自身抗体检测试剂盒及制备方法

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) * 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US4338397A (en) * 1980-04-11 1982-07-06 President And Fellows Of Harvard College Mature protein synthesis
IE52535B1 (en) 1981-02-16 1987-12-09 Ici Plc Continuous release pharmaceutical compositions
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4485045A (en) * 1981-07-06 1984-11-27 Research Corporation Synthetic phosphatidyl cholines useful in forming liposomes
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
DE3218121A1 (de) 1982-05-14 1983-11-17 Leskovar, Peter, Dr.-Ing., 8000 München Arzneimittel zur tumorbehandlung
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4816567A (en) * 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
US4544545A (en) * 1983-06-20 1985-10-01 Trustees University Of Massachusetts Liposomes containing modified cholesterol for organ targeting
US4758549A (en) * 1983-12-13 1988-07-19 Kabushiki Kaisha Mayashibara Seibutsu Kagaku Kenkyujo Lymphokine, monoclonal antibody specific to the lymphokine and their production and uses
US4959457A (en) * 1984-05-31 1990-09-25 Genentech, Inc. Anti-lymphotoxin
NZ212207A (en) 1984-05-31 1991-07-26 Genentech Inc Recombinant lymphotoxin
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
GB8529014D0 (en) * 1985-11-25 1986-01-02 Biogen Nv Enhanced secretion of heterologous proteins
US4822605A (en) * 1986-02-18 1989-04-18 Exovir, Inc. Compositions and methods employing the same for the treatment of viral and cancerous skin lesions and the like
US4849509A (en) * 1987-02-20 1989-07-18 The Wistar Institute Monoclonal antibodies against melanoma-associated antigens and hybrid cell lines producing these antibodies
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
CA2001756A1 (en) 1988-10-31 1991-04-30 Seiichi Uesugi New human lymphotoxin n-end deletion mutant
US5225538A (en) * 1989-02-23 1993-07-06 Genentech, Inc. Lymphocyte homing receptor/immunoglobulin fusion proteins
EP0480923B1 (de) 1989-07-04 1993-09-29 Novo Nordisk A/S Verfahren zur herstellung von proteinen mit fviii aktivität und/oder fviii derivate
US5605690A (en) * 1989-09-05 1997-02-25 Immunex Corporation Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5795964A (en) * 1990-06-27 1998-08-18 Biogen, Inc. Lymphotoxin-beta and lymphotoxin-beta complexes
US7030080B2 (en) * 1990-06-27 2006-04-18 Biogen, Inc. Lymphotoxin-β, lymphotoxin-β complexes, pharmaceutical preparations and therapeutic uses thereof
CA2086264C (en) 1990-06-27 2002-12-24 Jeffrey L. Browning Surface complexed lymphotoxin
NZ240718A (en) 1990-11-30 1996-10-28 Bio Technology General Corp Somatotropin analogues carrying mutations in the alpha-helix-1 region
WO1994004679A1 (en) 1991-06-14 1994-03-03 Genentech, Inc. Method for making humanized antibodies
US5447851B1 (en) * 1992-04-02 1999-07-06 Univ Texas System Board Of Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
AU670125B2 (en) 1992-09-15 1996-07-04 Immunex Corporation Method of treating tnf-dependent inflammation using tumor necrosis factor antagonists
EP0672143B1 (de) 1992-12-04 2008-06-04 Biogen Idec MA Inc. Lymphotoxin-beta, lymphotoxin-beta komplexe, pharmazeutische zubereitungen und therapeutische verwendungen davon
US5691196A (en) 1992-12-31 1997-11-25 American Cyanamid Company Recombinant nucleic acid containing a response element
US5856179A (en) * 1994-03-10 1999-01-05 Genentech, Inc. Polypeptide production in animal cell culture
US5747023A (en) 1994-07-01 1998-05-05 Genentech, Inc. Cancer therapy using lymphotoxin
US5726039A (en) * 1994-07-21 1998-03-10 Yissum Research Development Co. Of The Hebrew University Of Jerusalem Vectors and transformed host cells for recombinant protein production at reduced temperatures
US5541087A (en) * 1994-09-14 1996-07-30 Fuji Immunopharmaceuticals Corporation Expression and export technology of proteins as immunofusins
US5876950A (en) 1995-01-26 1999-03-02 Bristol-Myers Squibb Company Monoclonal antibodies specific for different epitopes of human GP39 and methods for their use in diagnosis and therapy
PT809510E (pt) 1995-01-26 2004-09-30 Biogen Inc Complexos de linfotoxina-alfa/beta e anticorpos receptores de anti-linfotoxina-beta como agentes anti-tumor
US6312691B1 (en) * 1996-01-26 2001-11-06 Jeffrey L. Browning Lymphotoxin-α/β complexes and anti-lympotoxin-β receptor antibodies as anti-tumor agents
US5721121A (en) * 1995-06-06 1998-02-24 Genentech, Inc. Mammalian cell culture process for producing a tumor necrosis factor receptor immunoglobulin chimeric protein
GB9514518D0 (en) 1995-07-15 1995-09-13 Sod Conseils Rech Applic Guanidine salt inhibitors of NO synthase and cyclooxygenase
US5925351A (en) * 1995-07-21 1999-07-20 Biogen, Inc. Soluble lymphotoxin-β receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological disease
US6291207B1 (en) 1995-07-28 2001-09-18 Northwestern University Herpes virus entry receptor protein
JP4306813B2 (ja) * 1995-09-19 2009-08-05 アスビオファーマ株式会社 動物細胞の新規培養方法
JP2000510113A (ja) 1996-05-08 2000-08-08 エフ・ホフマン―ラ ロシュ アーゲー TNFR―Igによる喘息の治療
US7255854B1 (en) * 1996-10-25 2007-08-14 Biogen, Inc. Use of lymphotoxin-β receptor blocking agents for the treatment of antibody mediated immunological diseases
AU726357B2 (en) 1996-10-25 2000-11-02 Biogen Idec Ma Inc. Soluble lymphotoxin-beta receptors, anti-lymphotoxin receptor antibodies, and anti-lymphotoxin ligand antibodies as therapeutic agents for the treatment of immunological diseases
GB9622660D0 (en) 1996-10-31 1997-01-08 Biocine Spa Immunogenic detoxified mutant toxin
EP0948543A1 (de) 1996-12-12 1999-10-13 Genentech, Inc. Hemv-polyptide und ihre verwendung
CA2229449A1 (en) 1997-04-25 1998-10-25 Takeda Chemical Industries, Ltd. Novel receptor protein and its use
US7060667B1 (en) * 1998-01-30 2006-06-13 Biogen Idec Ma, Inc. Treatment of follicular lymphomas using inhibitors of the LT pathway
BR9908214A (pt) 1998-01-30 2000-11-28 Biogen Inc Tratamento para linfomas foliculares utilizando inibidores da via da linfotoxina (lt)
EP1071769A1 (de) 1998-04-16 2001-01-31 Genentech, Inc. Ausscheidung von von glykosylierten proteinen mit hilfe einergewebe plasminogen aktivator pro-sequenz
BR9915025A (pt) 1998-10-09 2001-08-14 Biogen Inc Reversão de choque sistêmico induzido por vìrus e insuficiência respiratória por bloqueio da via linfotoxina-beta
TR200504220T2 (tr) * 1998-12-17 2007-04-24 Biogen Idec Ma Inc. Aktif limfotoksin-beta reseptör imunoglobülin şimeAktif limfotoksin-beta reseptör imunoglobülin şimerik proteinlerinin yüksek düzey ifadesi ve saflaştrik proteinlerinin yüksek düzey ifadesi ve saflaştırılması için bir yöntem.ırılması için bir yöntem.
US7294481B1 (en) * 1999-01-05 2007-11-13 Immunex Corporation Method for producing recombinant proteins
JP2004532608A (ja) * 2000-10-13 2004-10-28 バイオジェン・アイデック・エムエイ・インコーポレイテッド ヒト化抗LT−β−R抗体
AU2003248782A1 (en) * 2002-07-01 2004-01-19 Biogen Idec Ma Inc. Humanized anti-lymphotoxin beta receptor antibodies
JP2006515750A (ja) * 2002-12-20 2006-06-08 バイオジェン・アイデック・エムエイ・インコーポレイテッド 多価リンホトキシンβレセプターアゴニストおよびそれを使用する治療
KR20050094819A (ko) * 2002-12-20 2005-09-28 바이오겐 아이덱 엠에이 인코포레이티드 화학요법제와 조합된 림프독소 베타 수용체 약제
AU2005227322A1 (en) * 2004-03-23 2005-10-06 Biogen Idec Ma Inc. Receptor coupling agents and therapeutic uses thereof
EP2040751A2 (de) 2006-06-15 2009-04-01 Biogen Idec MA Inc. Kombinationstherapie mit lymphotoxin beta rezeptor-bindungsmolekülen in kombination mit sekundären mitteln
CA2680792A1 (en) * 2007-03-15 2008-09-18 Biogen Idec Ma Inc. Treatment of autoimmune disorders

Also Published As

Publication number Publication date
KR20090083958A (ko) 2009-08-04
US20120244153A1 (en) 2012-09-27
AU2007311052B2 (en) 2014-01-16
EA200900581A1 (ru) 2009-08-28
CN101653599A (zh) 2010-02-24
NZ576424A (en) 2012-09-28
SG178002A1 (en) 2012-02-28
AU2007311052A1 (en) 2008-04-24
CA2666934A1 (en) 2008-04-24
WO2008049053A3 (en) 2008-10-23
JP2009242419A (ja) 2009-10-22
BRPI0718283A2 (pt) 2013-11-12
EP2311481A3 (de) 2013-10-16
JP2013227340A (ja) 2013-11-07
US20100099608A1 (en) 2010-04-22
WO2008049053A2 (en) 2008-04-24
IL198196A0 (en) 2011-08-01
JP2010506955A (ja) 2010-03-04
EP2311481A2 (de) 2011-04-20
KR20090071652A (ko) 2009-07-01
MX2009004134A (es) 2009-08-12
US8067375B2 (en) 2011-11-29
EP2073833A2 (de) 2009-07-01
CN101600450A (zh) 2009-12-09

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