DE3686172D1 - Peptid-derivate. - Google Patents

Peptid-derivate.

Info

Publication number
DE3686172D1
DE3686172D1 DE8686300379T DE3686172T DE3686172D1 DE 3686172 D1 DE3686172 D1 DE 3686172D1 DE 8686300379 T DE8686300379 T DE 8686300379T DE 3686172 T DE3686172 T DE 3686172T DE 3686172 D1 DE3686172 D1 DE 3686172D1
Authority
DE
Germany
Prior art keywords
peptide derivatives
peptide
derivatives
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 - Fee Related
Application number
DE8686300379T
Other languages
English (en)
Other versions
DE3686172T2 (de
Inventor
Scott Haven Bergeson
John Anthony Schwartz
Mark Morris Stein
Richard Alan Wildonger
Philip Duke Edwards
Andrew Shaw
Diane Amy Trainor
Donald John Wolanin
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.)
AstraZeneca Pharmaceuticals LP
Original Assignee
ICI Americas Inc
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
Priority claimed from GB858501524A external-priority patent/GB8501524D0/en
Priority claimed from GB858501523A external-priority patent/GB8501523D0/en
Priority claimed from GB858501522A external-priority patent/GB8501522D0/en
Application filed by ICI Americas Inc filed Critical ICI Americas Inc
Application granted granted Critical
Publication of DE3686172D1 publication Critical patent/DE3686172D1/de
Publication of DE3686172T2 publication Critical patent/DE3686172T2/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
    • C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
    • C07C205/02—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
    • C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0819—Tripeptides with the first amino acid being acidic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
DE8686300379T 1985-01-22 1986-01-20 Peptid-derivate. Expired - Fee Related DE3686172T2 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB858501524A GB8501524D0 (en) 1985-01-22 1985-01-22 Tetrapeptide derivatives
GB858501523A GB8501523D0 (en) 1985-01-22 1985-01-22 Tripeptide derivatives
GB858501522A GB8501522D0 (en) 1985-01-22 1985-01-22 Dipeptide derivatives

Publications (2)

Publication Number Publication Date
DE3686172D1 true DE3686172D1 (de) 1992-09-03
DE3686172T2 DE3686172T2 (de) 1993-01-14

Family

ID=27262565

Family Applications (1)

Application Number Title Priority Date Filing Date
DE8686300379T Expired - Fee Related DE3686172T2 (de) 1985-01-22 1986-01-20 Peptid-derivate.

Country Status (25)

Country Link
US (2) US4910190A (de)
EP (1) EP0189305B1 (de)
JP (2) JPH0759591B2 (de)
KR (1) KR910002689B1 (de)
CN (1) CN1027640C (de)
AU (1) AU594658B2 (de)
CA (1) CA1341023C (de)
CZ (1) CZ278063B6 (de)
DE (1) DE3686172T2 (de)
DK (1) DK172736B1 (de)
ES (3) ES8706169A1 (de)
FI (1) FI84171C (de)
GB (1) GB8600263D0 (de)
GR (1) GR860169B (de)
HK (1) HK18097A (de)
HU (1) HU206370B (de)
IE (1) IE58957B1 (de)
IL (1) IL77680A (de)
NO (1) NO169493C (de)
PH (1) PH26575A (de)
PL (1) PL150268B1 (de)
PT (1) PT81887B (de)
SK (1) SK278095B6 (de)
UA (1) UA39093C2 (de)
ZW (1) ZW1486A1 (de)

Families Citing this family (62)

* Cited by examiner, † Cited by third party
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GB8600263D0 (en) * 1985-01-22 1986-02-12 Ici America Inc Peptide derivatives
US5055450A (en) * 1985-01-22 1991-10-08 Ici Americas Inc. Peptide derivatives
CA1341029C (en) * 1985-02-04 2000-06-20 Michael Kolb Peptidase inhibitors
US5496927A (en) * 1985-02-04 1996-03-05 Merrell Pharmaceuticals Inc. Peptidase inhibitors
DE3683541D1 (de) * 1985-06-07 1992-03-05 Ici America Inc Selektionierte difluorverbindungen.
EP0276101A3 (de) * 1987-01-19 1989-11-23 Ici Americas Inc. Substituierte Peptid-Derivate
GB8809316D0 (en) * 1987-05-11 1988-05-25 Ici America Inc Heterocyclic ketones
US5296608A (en) * 1988-04-25 1994-03-22 Hoffman-La Roche Inc. Intermediates for analogs of tyrosine sulfate or tyrosine phosphate containing peptides
US5182263A (en) * 1988-04-25 1993-01-26 Hoffmann-La Roche Inc. Analogs of tyrosine sulfate or tyrosine phosphate containing peptides
IL90872A0 (en) * 1988-07-08 1990-02-09 Smithkline Beckman Corp Retroviral protease binding peptides
EP0369391A3 (de) * 1988-11-15 1991-09-25 Boehringer Ingelheim Pharmaceuticals Inc. N-substituierte Amide
GB8910547D0 (en) * 1989-05-08 1989-06-21 Ici America Inc Substituted ketones
GB8910550D0 (en) * 1989-05-08 1989-06-21 Ici America Inc Substituted amides
US5221665A (en) * 1989-10-27 1993-06-22 Boehringer Ingelheim Pharmaceuticals, Inc. N-substituted amides
US5162348A (en) * 1990-05-24 1992-11-10 Imperial Chemical Industries Plc Treatment of cystic fibrosis
ES2129401T3 (es) * 1990-05-24 1999-06-16 Zeneca Ltd Uso de un compuesto terapeutico para el tratamiento de bronquitis.
DE69129083T2 (de) * 1990-05-24 1998-07-09 Zeneca Ltd Therapeutisches Mittel zur Vorbeugung und Behandlung des Atemnotsyndroms bei Erwachsenen
GB9014132D0 (en) * 1990-06-25 1990-08-15 Ici Plc Agent for therapy
US5296591A (en) * 1990-12-31 1994-03-22 Fujisawa Pharmaceutical Co., Ltd. Trifluoromethylketone derivatives, processes for preparation thereof and use thereof
US5521179A (en) * 1991-04-18 1996-05-28 Zeneca Limited Heterocyclic amides
GB9207145D0 (en) * 1991-04-18 1992-05-13 Ici Plc Heterocyclic amides
US5340801A (en) * 1991-05-08 1994-08-23 Rhone-Poulenc Rorer Pharmaceuticals Inc. Compounds having cholecystokinin and gastrin antagonistic properties
ATE181925T1 (de) * 1991-05-23 1999-07-15 Merrell Pharma Inc Hemmstoffe für kathepsin-g und elastase zur verhütung von bindegewebsabbau
GB9113164D0 (en) * 1991-06-18 1991-08-07 Ici Plc Pharmaceutical agent
WO1993003011A1 (en) * 1991-08-08 1993-02-18 Yamanouchi Pharmaceutical Co., Ltd. Urea derivative
AU658426B2 (en) * 1991-08-15 1995-04-13 Zeneca Limited Substituted heterocycles
GB9216272D0 (en) * 1991-08-15 1992-09-09 Ici Plc Substituted heterocycles
US5714470A (en) * 1991-08-22 1998-02-03 Merrell Pharmaceuticals, Inc. Orally-active elastase inhibitors
US5478811A (en) * 1991-08-22 1995-12-26 Merrell Dow Pharmaceuticals Inc. Orally-active elastase inhibitors
US5486529A (en) * 1992-04-16 1996-01-23 Zeneca Limited Certain pyridyl ketones for treating diseases involving leukocyte elastase
JPH07505877A (ja) * 1992-04-16 1995-06-29 ゼネカ・リミテッド α−アミノボロン酸ペプチド及びエラスターゼ阻害剤としてのそれらの使用
GB9211783D0 (en) * 1992-06-04 1992-07-15 Ici Plc Amide derivatives
GB9214053D0 (en) * 1992-07-02 1992-08-12 Ici Plc Heterocyclic amides
FR2694295B1 (fr) * 1992-07-28 1994-09-02 Adir Nouveaux peptides dérivés de trifluoromethylcetones, leur procéde de préparation et les compositions pharmaceutiques qui les contiennent.
US5780590A (en) * 1993-10-15 1998-07-14 Rhone-Poulenc Rorer Pharmaceuticals Inc. Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
GB9402680D0 (en) * 1994-02-11 1994-04-06 Zeneca Ltd Pyrrolidine derivatives
FR2719589B1 (fr) * 1994-05-05 1996-06-14 Adir Nouveaux peptides dérivés de trifluorométhylcétones, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
US6693072B2 (en) * 1994-06-02 2004-02-17 Aventis Pharmaceuticals Inc. Elastase inhibitors
SI0804465T1 (en) * 1994-06-02 2003-12-31 Aventis Pharmaceuticals Inc. Novel elastase inhibitors
HU221310B1 (en) * 1994-06-02 2002-09-28 Merrell Pharma Inc Acylated enol di and tripeptide derivatives, their use and pharmaceutical compositions comprising thereof
JP3721538B2 (ja) * 1994-06-02 2005-11-30 メレル ファーマスーティカルズ インコーポレイテッド エラスターゼのパーフルオロアルキルケトン阻害剤およびそれらを製造する方法
GB9502152D0 (en) * 1995-02-03 1995-03-29 Zeneca Ltd Proline derivatives
US5948886A (en) * 1996-11-20 1999-09-07 Hoechst Marion Roussel, Inc. Acylated enol derivatives of α-ketoesters and α-ketoamides
US6172044B1 (en) 1995-12-01 2001-01-09 Aventis Pharmaceuticals Inc. Acylated enol derivative of α-ketoesters and α-ketoamides
US6362341B1 (en) 1997-07-31 2002-03-26 Athena Neurosciences, Inc. Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4
US6492421B1 (en) 1997-07-31 2002-12-10 Athena Neurosciences, Inc. Substituted phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4
US7030114B1 (en) 1997-07-31 2006-04-18 Elan Pharmaceuticals, Inc. Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6583139B1 (en) * 1997-07-31 2003-06-24 Eugene D. Thorsett Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6939855B2 (en) * 1997-07-31 2005-09-06 Elan Pharmaceuticals, Inc. Anti-inflammatory compositions and method
US6423688B1 (en) * 1997-07-31 2002-07-23 Athena Neurosciences, Inc. Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4
US6559127B1 (en) * 1997-07-31 2003-05-06 Athena Neurosciences, Inc. Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6682554B2 (en) * 1998-09-05 2004-01-27 Jomed Gmbh Methods and apparatus for a stent having an expandable web structure
JP2000256396A (ja) 1999-03-03 2000-09-19 Dainippon Pharmaceut Co Ltd 複素環式化合物およびその中間体ならびにエラスターゼ阻害剤
GB9928882D0 (en) * 1999-12-08 2000-02-02 Zeneca Ltd Assay method
US6403612B2 (en) * 2000-01-31 2002-06-11 Merck & Co., Inc. Thrombin receptor antagonists
US20040006093A1 (en) * 2000-10-17 2004-01-08 Thorsett Eugene D. Compounds which inhibit leukocyte adhesion mediated by VLA-4
EP2290098A1 (de) 2002-01-28 2011-03-02 Ambion, Inc. Herstellung biologische Rohderivaten unter Einzetsung Proteasen, geeignet für cDNA Synthese
PL371539A1 (en) 2002-02-05 2005-06-27 Dainippon Pharmaceutical Co, Ltd. Heterocyclic compounds having elastase-inhibiting activity and intermediates thereof
US7964350B1 (en) 2007-05-18 2011-06-21 Applied Biosystems, Llc Sample preparation for in situ nucleic acid analysis
EP2367954B1 (de) 2008-12-19 2015-02-18 Life Technologies Corporation Proteinase k inhibitore, verfahren und zusammensetzungen davon
US10710957B2 (en) 2017-01-09 2020-07-14 University Of Central Florida Research Foundation, Inc. Motuporamine derivatives as antimicrobial agents and antibiotic enhancers against resistant gram-negative bacteria
US11548893B2 (en) 2017-07-15 2023-01-10 Arisan Therapeutics Inc. Enantiomerically pure adamantane carboxamides for the treatment of filovirus infection

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB195212A (en) * 1922-01-30 1923-03-29 Edward Crawshaw Improvements in expansion joints between steam boilers and their settings or flue walls
US4277395A (en) * 1980-06-16 1981-07-07 Richardson-Merrell Inc. Novel enzyme inhibitors
EP0124317B1 (de) * 1983-04-27 1990-04-11 Ici Americas Inc. Prolin-Derivate
US4518528A (en) * 1983-05-19 1985-05-21 Rasnick David W α Amino fluoro ketones
GB8600263D0 (en) * 1985-01-22 1986-02-12 Ici America Inc Peptide derivatives
CA1341029C (en) * 1985-02-04 2000-06-20 Michael Kolb Peptidase inhibitors
CH672792A5 (de) * 1985-02-19 1989-12-29 Sandoz Ag
DE3683541D1 (de) * 1985-06-07 1992-03-05 Ici America Inc Selektionierte difluorverbindungen.
EP0249349B1 (de) * 1986-06-05 1992-10-14 Ici Americas Inc. Difluorketoverbindungen

Also Published As

Publication number Publication date
JPH0680039B2 (ja) 1994-10-12
AU594658B2 (en) 1990-03-15
KR910002689B1 (ko) 1991-05-03
DK30886D0 (da) 1986-01-21
FI84171B (fi) 1991-07-15
SK278095B6 (en) 1995-12-06
HK18097A (en) 1997-02-13
IL77680A (en) 1990-12-23
NO860190L (no) 1986-07-23
DK30886A (da) 1986-07-23
CN1027640C (zh) 1995-02-15
DK172736B1 (da) 1999-06-21
AU5262386A (en) 1986-07-31
JPH0759591B2 (ja) 1995-06-28
PH26575A (en) 1992-08-19
ES557048A0 (es) 1987-08-01
EP0189305A3 (en) 1988-10-05
IE860180L (en) 1986-07-22
GB8600263D0 (en) 1986-02-12
ES8706169A1 (es) 1987-05-16
FI860281A (fi) 1986-07-23
UA39093C2 (uk) 2001-06-15
EP0189305A2 (de) 1986-07-30
KR860005835A (ko) 1986-08-13
JPS61218518A (ja) 1986-09-29
PT81887B (pt) 1988-05-27
HUT39464A (en) 1986-09-29
CN86101066A (zh) 1986-11-05
ES557363A0 (es) 1988-07-01
EP0189305B1 (de) 1992-07-29
FI84171C (fi) 1991-10-25
DE3686172T2 (de) 1993-01-14
NO169493C (no) 1992-07-01
US5726158A (en) 1998-03-10
US4910190A (en) 1990-03-20
PL150268B1 (en) 1990-05-31
CZ278063B6 (en) 1993-08-11
ES8707551A1 (es) 1987-08-01
CS39586A3 (en) 1992-01-15
HU206370B (en) 1992-10-28
FI860281A0 (fi) 1986-01-21
PT81887A (en) 1986-02-01
IE58957B1 (en) 1993-12-01
ES551113A0 (es) 1987-05-16
ES8802526A1 (es) 1988-07-01
CA1341023C (en) 2000-06-13
JPH05246984A (ja) 1993-09-24
NO169493B (no) 1992-03-23
PL257573A1 (en) 1987-03-23
GR860169B (en) 1986-05-15
ZW1486A1 (en) 1987-09-30

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Legal Events

Date Code Title Description
8364 No opposition during term of opposition
8327 Change in the person/name/address of the patent owner

Owner name: ZENECA INC., WILMINGTON, DEL., US

8339 Ceased/non-payment of the annual fee
8327 Change in the person/name/address of the patent owner

Owner name: ASTRAZENECA PHARMACEUTICALS LP,, WILMINGTON, DEL.,