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NO2015027I2 - Mepolizumab - Google Patents

Mepolizumab

Info

Publication number
NO2015027I2
NO2015027I2 NO2015027C NO2015027C NO2015027I2 NO 2015027 I2 NO2015027 I2 NO 2015027I2 NO 2015027 C NO2015027 C NO 2015027C NO 2015027 C NO2015027 C NO 2015027C NO 2015027 I2 NO2015027 I2 NO 2015027I2
Authority
NO
Norway
Prior art keywords
pct
sec
date
mabs
pub
Prior art date
Application number
NO2015027C
Other languages
English (en)
Other versions
NO2015027I1 (no
Original Assignee
Glaxosmithkline Llc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27408594&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO2015027(I2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from US08/470,110 external-priority patent/US5693323A/en
Application filed by Glaxosmithkline Llc filed Critical Glaxosmithkline Llc
Publication of NO2015027I1 publication Critical patent/NO2015027I1/no
Publication of NO2015027I2 publication Critical patent/NO2015027I2/no

Links

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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5409—IL-5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, 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
    • G01N33/6869—Interleukin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
    • C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Pulmonology (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Otolaryngology (AREA)
  • Cardiology (AREA)
  • Dermatology (AREA)
NO2015027C 1994-12-23 2015-12-18 Mepolizumab NO2015027I2 (no)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US36313194A 1994-12-23 1994-12-23
US08/470,110 US5693323A (en) 1994-12-23 1995-06-06 Recombinant IL-5 antagonists useful in treatment of IL-5 mediated disorders
US08/467,420 US5683892A (en) 1994-12-23 1995-06-06 DNA encoding recombinant IL-5 antagonists useful in treatment of IL-5 mediated disorders
PCT/US1995/017082 WO1996021000A2 (en) 1994-12-23 1995-12-22 Recombinant il-5 antagonists useful in treatment of il-5 mediated disorders

Publications (2)

Publication Number Publication Date
NO2015027I1 NO2015027I1 (no) 2015-12-18
NO2015027I2 true NO2015027I2 (no) 2016-01-04

Family

ID=27408594

Family Applications (2)

Application Number Title Priority Date Filing Date
NO19972913A NO324181B1 (no) 1994-12-23 1997-06-20 Monoklonalt antistoff spesifikt for human IL-5 og fragmenter derav, hybridoma cellelinjer, endret antistoff, immunolglobulin-tungkjede-komplementaritetsbestemmende region, nukleinsyremolekyl, kimaert antistoff, farmasoytisk preparat omfattende endret antistoff, anvendelse av antistoff, isolert nukleinsyresekvens, rekombinant plasmid, vertcelle, fremgangsmate for a fremstille et endret antistoff og metoder for a bestemme human IL-50.
NO2015027C NO2015027I2 (no) 1994-12-23 2015-12-18 Mepolizumab

Family Applications Before (1)

Application Number Title Priority Date Filing Date
NO19972913A NO324181B1 (no) 1994-12-23 1997-06-20 Monoklonalt antistoff spesifikt for human IL-5 og fragmenter derav, hybridoma cellelinjer, endret antistoff, immunolglobulin-tungkjede-komplementaritetsbestemmende region, nukleinsyremolekyl, kimaert antistoff, farmasoytisk preparat omfattende endret antistoff, anvendelse av antistoff, isolert nukleinsyresekvens, rekombinant plasmid, vertcelle, fremgangsmate for a fremstille et endret antistoff og metoder for a bestemme human IL-50.

Country Status (21)

Country Link
US (1) US6129913A (no)
EP (1) EP0800536B1 (no)
JP (2) JP2001523083A (no)
CN (1) CN100391977C (no)
AT (1) ATE346867T1 (no)
AU (1) AU708951B2 (no)
BR (1) BR9510499B1 (no)
CA (1) CA2208503C (no)
CZ (1) CZ297045B6 (no)
DE (1) DE69535319T2 (no)
DK (1) DK0800536T3 (no)
ES (1) ES2277336T3 (no)
FI (1) FI119374B (no)
HU (1) HU222992B1 (no)
LU (1) LU92912I2 (no)
MX (1) MX9704779A (no)
NL (1) NL300787I1 (no)
NO (2) NO324181B1 (no)
NZ (1) NZ301916A (no)
PL (1) PL194312B1 (no)
WO (1) WO1996021000A2 (no)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5683892A (en) * 1994-12-23 1997-11-04 Smithkline Beecham Corporation DNA encoding recombinant IL-5 antagonists useful in treatment of IL-5 mediated disorders
US5783184A (en) * 1994-12-23 1998-07-21 Smithkline Beecham Corporation Method for treatment and diagnosis of IL-5 mediated disorders
EP2275541B1 (en) * 1999-04-09 2016-03-23 Kyowa Hakko Kirin Co., Ltd. Method for controlling the activity of immunologically functional molecule
US6946292B2 (en) * 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
JP2005530490A (ja) * 2002-03-29 2005-10-13 シェーリング　コーポレイション インターロイキン−５に対するヒトモノクローナル抗体および方法およびこれを含む組成物
AU2003236017B2 (en) 2002-04-09 2009-03-26 Kyowa Kirin Co., Ltd. Drug containing antibody composition
EP1682571A4 (en) * 2003-10-27 2006-12-06 Medvet Science Pty Ltd BICOORDIN PATTERN AND METHODS OF USE
US8192736B2 (en) 2004-10-28 2012-06-05 Kyowa Hakko Kirin Co., Ltd Remedy for endometriosis
EP2777710A1 (en) 2007-04-30 2014-09-17 Glaxosmithkline LLC Methods for administering anti-IL-5 antibodies
JP4335286B2 (ja) 2008-02-08 2009-09-30 ファナック株式会社 部品保護機能を備えたロボット制御装置及びロボット制御方法
EA201071137A1 (ru) 2008-03-28 2011-04-29 ГЛЭКСОСМИТКЛАЙН ЭлЭлСи Способы лечения
UA104663C2 (xx) * 2010-01-28 2014-02-25 Глаксо Груп Лимитед Антитіло, що зв'язує cd127$антитело, связывающее cd127
KR101941514B1 (ko) 2010-12-22 2019-01-23 테바 파마슈티컬즈 오스트레일리아 피티와이 엘티디 개선된 반감기를 가지는 변형된 항체
CN116474091A (zh) 2015-08-24 2023-07-25 葛兰素史密斯克莱知识产权（第2 号）有限公司 生物医药组合物
CN109195990A (zh) * 2016-03-30 2019-01-11 Musc研究发展基金会 通过靶向糖蛋白a重复优势蛋白(garp)治疗和诊断癌症以及单独或联合提供有效免疫疗法的方法
KR102651290B1 (ko) * 2016-12-23 2024-03-25 세파론 엘엘씨 항-il-5 항체
MX2019014105A (es) 2017-05-26 2020-02-07 Glaxosmithkline Ip Dev Ltd Composiciones biofarmaceuticas y metodos relacionados.
BR112020005766A2 (pt) 2017-09-29 2020-10-13 Jiangsu Hengrui Medicine Co., Ltd. anticorpo il-5, fragmento de ligação ao antígeno do mesmo, e aplicação médica do mesmo
CN109942706A (zh) * 2017-12-21 2019-06-28 三生国健药业（上海）股份有限公司 结合人il-5的单克隆抗体、其制备方法和用途
EP3896085A4 (en) * 2018-12-12 2022-11-30 Shanghai Pharmaexplorer Co., Ltd. MONOCLONAL ANTIBODY TO HUMAN INTERLEUKIN 5 (IL-5) AND ITS USE
EP3939611A4 (en) * 2019-03-29 2022-12-21 Jiangsu Hengrui Pharmaceuticals Co., Ltd. PHARMACEUTICAL COMPOSITION CONTAINING ANTI-IL-5 ANTIBODY AND USE THEREOF
US20250230251A1 (en) 2023-12-20 2025-07-17 Bristol-Myers Squibb Company Antibodies targeting il-18 receptor beta (il-18rb) and related methods

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8800397D0 (en) * 1988-01-08 1988-02-10 Sandoz Ltd Improvements in/relating to organic compounds
US5096704A (en) * 1988-11-03 1992-03-17 Schering Corporation Method of treating eosinophilia
IL92180A (en) * 1988-11-03 1997-04-15 Schering Corp Pharmaceutical composition for preventing or reducing eosinophilia
US5530101A (en) * 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
ZA929328B (en) * 1991-12-02 1993-07-20 Fluor Corp Apparatus and method for economic use of excess compressed air when firing low caloric-value gas in a combustion gas turbine.
CZ291039B6 (cs) * 1992-02-06 2002-12-11 Schering Corporation Monoklonální protilátka, hybridom, polypeptid a způsob jeho přípravy, izolovaná DNA, rekombinantní vektor, hostitelská buňka, humanizovaná protilátka a farmaceutický prostředek
JPH06141885A (ja) * 1992-11-05 1994-05-24 Chemo Sero Therapeut Res Inst モノクローナル抗体
WO1995014040A1 (en) * 1993-11-19 1995-05-26 Baylor College Of Medicine Monoclonal antibodies specific for human interleukin-5
GB9412230D0 (en) * 1994-06-17 1994-08-10 Celltech Ltd Interleukin-5 specific recombiant antibodies
US5683892A (en) * 1994-12-23 1997-11-04 Smithkline Beecham Corporation DNA encoding recombinant IL-5 antagonists useful in treatment of IL-5 mediated disorders
US5783184A (en) * 1994-12-23 1998-07-21 Smithkline Beecham Corporation Method for treatment and diagnosis of IL-5 mediated disorders
WO2001012646A1 (en) * 1999-08-19 2001-02-22 Smithkline Beecham Corporation Sialoadhesin factor-1 agonist and antagonist antibodies

Also Published As

Publication number Publication date
FI119374B (fi) 2008-10-31
HU222992B1 (hu) 2004-01-28
NO972913D0 (no) 1997-06-20
WO1996021000A3 (en) 1996-09-06
FI972703L (fi) 1997-08-22
CZ297045B6 (cs) 2006-08-16
CN100391977C (zh) 2008-06-04
CA2208503C (en) 2009-12-01
EP0800536B1 (en) 2006-11-29
PL194312B1 (pl) 2007-05-31
CA2208503A1 (en) 1996-07-11
JP2008029355A (ja) 2008-02-14
DK0800536T3 (da) 2007-04-02
FI972703A0 (fi) 1997-06-23
JP2001523083A (ja) 2001-11-20
US6129913A (en) 2000-10-10
HUT78055A (hu) 1999-07-28
NO972913L (no) 1997-08-19
BR9510499B1 (pt) 2009-05-05
AU4745096A (en) 1996-07-24
DE69535319D1 (de) 2007-01-11
AU708951B2 (en) 1999-08-19
NO324181B1 (no) 2007-09-03
EP0800536A2 (en) 1997-10-15
PL321088A1 (en) 1997-11-24
EP0800536A4 (en) 2004-12-01
NO2015027I1 (no) 2015-12-18
LU92912I2 (fr) 2016-02-16
DE69535319T2 (de) 2007-07-19
BR9510499A (pt) 1999-03-30
WO1996021000A2 (en) 1996-07-11
ATE346867T1 (de) 2006-12-15
ES2277336T3 (es) 2007-07-01
NL300787I2 (no) 2016-04-05
NZ301916A (en) 1999-05-28
HK1003651A1 (en) 1998-11-06
CZ196397A3 (en) 1997-10-15
CN1175263A (zh) 1998-03-04
MX9704779A (es) 1997-09-30
NL300787I1 (no) 2016-04-05

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Legal Events

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CHAD Change of the owner's name or address (par. 44 patent law, par. patentforskriften)

Owner name: GLAXOSMITHKLINE LLC, US

CHAD Change of the owner's name or address (par. 44 patent law, par. patentforskriften)

Owner name: GLAXOSMITHKLINE LLC, US