BE1003752A4 - Nouveaux derives peptidiques, leur preparation et leur utilisation comme medicaments. - Google Patents
Nouveaux derives peptidiques, leur preparation et leur utilisation comme medicaments. Download PDFInfo
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- BE1003752A4 BE1003752A4 BE8701187A BE8701187A BE1003752A4 BE 1003752 A4 BE1003752 A4 BE 1003752A4 BE 8701187 A BE8701187 A BE 8701187A BE 8701187 A BE8701187 A BE 8701187A BE 1003752 A4 BE1003752 A4 BE 1003752A4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
-
- 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
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
-
- Y—GENERAL 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Analytical Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3634797 | 1986-10-13 | ||
| DE3634826 | 1986-10-13 | ||
| DE3634825 | 1986-10-13 | ||
| DE3712626 | 1987-04-14 | ||
| CH315387 | 1987-08-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BE1003752A4 true BE1003752A4 (fr) | 1992-06-09 |
Family
ID=27509117
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BE8701187A BE1003752A4 (fr) | 1986-10-13 | 1987-10-09 | Nouveaux derives peptidiques, leur preparation et leur utilisation comme medicaments. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US5656721A (esLanguage) |
| JP (2) | JPH0645639B2 (esLanguage) |
| KR (1) | KR960016861B1 (esLanguage) |
| AU (2) | AU617986B2 (esLanguage) |
| BE (1) | BE1003752A4 (esLanguage) |
| CA (1) | CA1340985C (esLanguage) |
| CH (2) | CH682632A5 (esLanguage) |
| DE (1) | DE3790635T1 (esLanguage) |
| DK (1) | DK174337B1 (esLanguage) |
| ES (1) | ES2007418A6 (esLanguage) |
| FI (1) | FI874495L (esLanguage) |
| FR (1) | FR2609991A1 (esLanguage) |
| GB (2) | GB2199829B (esLanguage) |
| GR (1) | GR871567B (esLanguage) |
| HU (3) | HU206890B (esLanguage) |
| IE (1) | IE912442A1 (esLanguage) |
| LU (1) | LU87014A1 (esLanguage) |
| NL (1) | NL194729C (esLanguage) |
| NZ (1) | NZ222133A (esLanguage) |
| PL (1) | PL157156B1 (esLanguage) |
| PT (1) | PT85904B (esLanguage) |
| SE (2) | SE8703938L (esLanguage) |
| WO (1) | WO1988002756A2 (esLanguage) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU206890B (en) * | 1986-10-13 | 1993-01-28 | Sandoz Ag | Process for producing sugar-modified somatostatin peptide derivatives and pharmaceutical compositions containing them as active components |
| DE3822557C2 (de) * | 1987-07-10 | 1998-07-02 | Ciba Geigy Ag | Arzneimittel, enthaltend Somatostatine |
| EP0329295A1 (en) * | 1988-02-01 | 1989-08-23 | The Upjohn Company | Renin inhibiting peptides with polar end groups |
| GB2218102B (en) * | 1988-04-08 | 1992-09-16 | Sandoz Ltd | Calcitonin peptide derivatives |
| DE3910667A1 (de) * | 1988-04-11 | 1989-10-19 | Sandoz Ag | Peptidderivate |
| GB8813339D0 (en) * | 1988-06-06 | 1988-07-13 | Sandoz Ltd | Improvements in/relating to organic compounds |
| FR2638968B1 (fr) * | 1988-11-11 | 1994-10-07 | Sandoz Sa | Nouvelle utilisation therapeutique de la somatostatine et de ses analogues et derives |
| US5776894A (en) * | 1988-12-05 | 1998-07-07 | Novartis Ag | Chelated somatostatin peptides and complexes thereof, pharmaceutical compositions containing them and their use in treating tumors |
| US5753627A (en) * | 1988-12-05 | 1998-05-19 | Novartis Ag | Use of certain complexed somatostatin peptides for the invivo imaging of somatostatin receptor-positive tumors and metastasis |
| MY106120A (en) * | 1988-12-05 | 1995-03-31 | Novartis Ag | Peptide derivatives. |
| IT1229514B (it) * | 1989-01-30 | 1991-09-03 | Farmhispania S A A Montme | Glicoconiugati anfifilici sintetici per impiego neurologico. |
| DK111489D0 (da) * | 1989-03-08 | 1989-03-08 | Novo Nordisk As | Peptider |
| DE4206858A1 (de) * | 1992-03-05 | 1993-09-09 | Behringwerke Ag | Glycopeptid-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende pharmazeutische mittel |
| IT1260156B (it) * | 1992-08-03 | 1996-03-28 | Fidia Spa | Derivati dell'acido neuraminico |
| TW263437B (esLanguage) * | 1992-09-24 | 1995-11-21 | Takeda Pharm Industry Co Ltd | |
| US5710244A (en) * | 1992-12-31 | 1998-01-20 | Labroo; Virender M. | Derivatized calcitonins |
| US5508387A (en) * | 1993-08-04 | 1996-04-16 | Glycomed Incorporated | Selectin binding glycopeptides |
| SI0788509T1 (en) * | 1993-08-09 | 2003-10-31 | Societe De Conseils De Recherches | Therapeutic peptide derivatives |
| US5556939A (en) * | 1994-10-13 | 1996-09-17 | Merck Frosst Canada, Inc. | TC or RE radionuclide labelled chelate, hexapeptide complexes useful for diagnostic or therapeutic applications |
| US5632969A (en) * | 1994-10-13 | 1997-05-27 | Merck & Co., Inc. | N3 S2 chelating ligands optionally radiolabelled with Tc or Re, useful for diagnostic or therapeutic applications |
| JP3896430B2 (ja) * | 1996-07-15 | 2007-03-22 | アークレイ株式会社 | 糖化アミノ化合物の製造方法 |
| IL119029A0 (en) * | 1996-08-07 | 1996-11-14 | Yeda Res & Dev | Long-acting drugs and pharamaceutical compositions comprising them |
| EP0981364B1 (en) | 1997-05-13 | 2006-03-01 | Societe De Conseils De Recherches Et D'applications Scientifiques S.A.S. | Method and compositions for treating hyperlipidemia |
| EP0981363B1 (en) | 1997-05-13 | 2003-07-30 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Somatostatin agonists for decreasing body weight |
| US6004928A (en) * | 1997-05-13 | 1999-12-21 | Biomeasure, Incorporated | Method of treating hyperlipidemia |
| DE69943039D1 (de) * | 1998-02-13 | 2011-01-27 | Amylin Pharmaceuticals Inc | Neue verbindungen mit gemischter amylin aktivität |
| US5968903A (en) * | 1998-05-07 | 1999-10-19 | Biomeasure, Incorporated | Inhibition of H. pylori proliferation |
| US20050037490A1 (en) * | 1999-10-29 | 2005-02-17 | Lawrence Rosenberg | Medium for preparing dedifferentiated cells |
| AU2002254691B8 (en) * | 2001-04-23 | 2008-02-14 | Mallinckrodt Inc. | Tc and Re labeler radioactive glycosylated octreotide derivatives |
| DK2062914T3 (da) | 2001-06-08 | 2014-07-14 | Ipsen Pharma | Somatostatin-dopamin-chimære analoger |
| PT1480998E (pt) * | 2002-02-27 | 2007-02-28 | Ferring Bv | Intermediários e métodos para fazer heptapeptídeos análogos de oxitocina. |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| ATE458491T1 (de) | 2005-08-26 | 2010-03-15 | Univ Leland Stanford Junior | Verfahren zur behandlung von kopfschmerzen durch verabreichung von oxytocin |
| ATE549011T1 (de) | 2005-11-10 | 2012-03-15 | Chemi Spa | Formulierungen mit verzögerter freisetzung, die somatostatin-analoge wachstumshormoninhibitoren enthalten |
| WO2008011168A2 (en) * | 2006-07-21 | 2008-01-24 | Amgen Inc. | Glycosylated peptide antagonists of the bradykinin b1 receptor |
| WO2008095063A1 (en) | 2007-01-31 | 2008-08-07 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| EP2508531B1 (en) | 2007-03-28 | 2016-10-19 | President and Fellows of Harvard College | Stitched polypeptides |
| US8785594B2 (en) | 2007-09-25 | 2014-07-22 | Glycom A/S | Glycoproteins and glycosylated cells and a method for the preparation of the same |
| JP5660898B2 (ja) * | 2007-11-09 | 2015-01-28 | ユニバーシティ オブ テネシー リサーチ ファウンデーション | 経口投与用の抗炎症性キナ酸誘導体 |
| BRPI0915888E2 (pt) | 2008-06-12 | 2020-09-01 | Syntaxin Ltd | polipetídeo, seu método de ativação, sequência de ácido nucléico codificando o mesmo e seu uso |
| ES2732205T3 (es) | 2008-06-12 | 2019-11-21 | Ipsen Bioinnovation Ltd | Proteínas de fusión para uso en el tratamiento del cáncer |
| WO2010089757A2 (en) * | 2008-11-07 | 2010-08-12 | Usv Limited | An improved process for synthesis of cyclic octapeptide |
| GB0820970D0 (en) | 2008-11-17 | 2008-12-24 | Syntaxin Ltd | Suppression of cancer |
| CN103282510A (zh) | 2010-08-13 | 2013-09-04 | 爱勒让治疗公司 | 拟肽大环化合物 |
| RU2627184C2 (ru) | 2011-09-04 | 2017-08-03 | Глитек, Инк. | Гликозилированные полипептиды и лекарственные композиции, содержащие данные полипептиды |
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| KR20140100937A (ko) | 2011-10-18 | 2014-08-18 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
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| EP3956343A1 (en) | 2019-04-16 | 2022-02-23 | Bachem Holding AG | Manufacture of disulfide bonded peptides |
| CA3180317A1 (en) | 2020-04-17 | 2021-10-21 | The Trustees Of Indiana University | Small molecule antiviral drug treatment for human papillomavirus infections |
| US20230399373A1 (en) * | 2020-10-22 | 2023-12-14 | The Trustees Of Indiana University | Molecular designs of glucose-responsive and glucose-cleavable insulin analogues |
| WO2025229200A1 (en) | 2024-05-03 | 2025-11-06 | Bachem Holding Ag | Manufacture of disulfide bonded peptides |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089290A1 (fr) * | 1982-03-15 | 1983-09-21 | ANVAR Agence Nationale de Valorisation de la Recherche | Conjugués d'haptènes et de muramyl-peptides, doués d'activité immunogène et compositions les contenant |
| EP0157753A1 (en) * | 1984-03-26 | 1985-10-09 | TECHLAND, Société Anonyme | New somatostatin compounds, process for their synthesis, preparation for veterinary use containing said compound and process for the treatment of animals |
| DE3439610A1 (de) * | 1984-10-30 | 1986-04-30 | Boehringer Mannheim Gmbh, 6800 Mannheim | Immunogene, verfahren zu deren herstellung sowie damit gewonnene antikoerper gegen glykosiliertes haemoglobin |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4254023A (en) * | 1979-10-16 | 1981-03-03 | Pennwalt Corporation | Synthesis of peptide alcohols by the solid phase method |
| US4280953A (en) * | 1979-11-08 | 1981-07-28 | The Salk Institute For Biological Studies | Glycosylated analogs of somatostatin |
| ATE2512T1 (de) * | 1979-11-27 | 1983-03-15 | Sandoz Ag | Polypeptide, verfahren zu ihrer herstellung, pharmazeutische zusammensetzungen, die diese polypeptide enthalten, und ihre verwendung. |
| US4483792A (en) * | 1982-11-17 | 1984-11-20 | Kim Wan S | Glycosylated insulin derivatives |
| US4444683A (en) * | 1982-11-17 | 1984-04-24 | University Of Utah | Glycosylated insulin derivatives |
| FR2546163B1 (fr) * | 1983-05-16 | 1987-10-09 | Centre Nat Rech Scient | Nouveaux derives acyles hydrosolubles de peptides ou d'amino-acides, leur preparation et leur application |
| FR2548673B1 (fr) * | 1983-07-05 | 1985-10-04 | Essilor Int | Polymeres supports de produits actifs relargables et leur procede de preparation |
| US4564998A (en) * | 1984-10-19 | 1986-01-21 | Westinghouse Electric Corp. | Coil winding methods and apparatus |
| EP0192611A3 (de) * | 1985-02-20 | 1988-05-11 | Ciba-Geigy Ag | Acylierte Hexosederivate und Verfahren zu ihrer Herstellung |
| JPS61264260A (ja) * | 1985-05-17 | 1986-11-22 | Rikagaku Kenkyusho | アルデヒド化多孔性高分子材料によるタンパク質の除去方法 |
| CA1337041C (en) * | 1985-10-09 | 1995-09-19 | Brett Alan Evans | Granular detergent compositions having improved solubility |
| SE8506094D0 (sv) * | 1985-12-20 | 1985-12-20 | Astra Laekemedel Ab | New antibacterial agents and intermediates therefor |
| JPS63165411A (ja) * | 1986-09-11 | 1988-07-08 | Tokyo Organ Chem Ind Ltd | アルデヒド基を有する架橋共重合体の製法 |
| JPS63165410A (ja) * | 1986-09-11 | 1988-07-08 | Tokyo Organ Chem Ind Ltd | アルデヒド基を有する架橋共重合体の製造方法 |
| HU206890B (en) * | 1986-10-13 | 1993-01-28 | Sandoz Ag | Process for producing sugar-modified somatostatin peptide derivatives and pharmaceutical compositions containing them as active components |
| US4859736A (en) * | 1987-03-30 | 1989-08-22 | Ciba-Geigy Corporation | Synthetic polystyrene resin and its use in solid phase peptide synthesis |
| CH679045A5 (esLanguage) * | 1987-06-29 | 1991-12-13 | Sandoz Ag |
-
1987
- 1987-10-01 HU HU874432A patent/HU206890B/hu not_active IP Right Cessation
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-
1988
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1990
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1991
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- 1991-07-12 IE IE244291A patent/IE912442A1/en unknown
-
1993
- 1993-04-07 SE SE9301172A patent/SE518630C2/sv unknown
-
1994
- 1994-07-07 US US08/272,704 patent/US5656721A/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089290A1 (fr) * | 1982-03-15 | 1983-09-21 | ANVAR Agence Nationale de Valorisation de la Recherche | Conjugués d'haptènes et de muramyl-peptides, doués d'activité immunogène et compositions les contenant |
| EP0157753A1 (en) * | 1984-03-26 | 1985-10-09 | TECHLAND, Société Anonyme | New somatostatin compounds, process for their synthesis, preparation for veterinary use containing said compound and process for the treatment of animals |
| DE3439610A1 (de) * | 1984-10-30 | 1986-04-30 | Boehringer Mannheim Gmbh, 6800 Mannheim | Immunogene, verfahren zu deren herstellung sowie damit gewonnene antikoerper gegen glykosiliertes haemoglobin |
Non-Patent Citations (5)
| Title |
|---|
| CARBOHYDRATE RESEARCH, vol. 86, 1980, pages 59-68, Elsevier Scientific Publishing Co., Amsterdam, NL; H.G. GARG et al.: "Synthesis of glycopeptides containing the amino acid sequence 17-23 of bovine pancreatic deoxyribonuclease" * |
| CHEMICAL ABSTRACTS, vol. 80, no. 1, 7 janvier 1974, page 331, résumé no. 3741e, Columbus, Ohio, US; K. HEYNS et al.: "Aldosylamine and ketosylamine rearrangement of weakly basic N-glycosides", & CHEM. BER. 1973, 106(8), 2693-709 * |
| CHEMICAL ABSTRACTS, vol. 80, no. 1, 7 janvier 1974, page 331, résumé no. 3742f, Columbus, Ohio, US; K. HEYNS et al.: "Rearrangement of ketosylamines from ketones and aromatic amines", & CHEM. BER. 1973, 106(8), 2680-92 * |
| CHEMICAL ABSTRACTS, vol. 85, no. 23, 6 décembre 1976, page 576, résumé no. 177955w, Columbus, Ohio, US; H.G. GARG et al.: "Amine sugars. IC. Synthesis of serine-containing glycotripeptides", & PEPT.: CHEM., STRUCT. BIOL., PROC. AM. PEPT. SYMP., 4TH 1975, 379-84 * |
| COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, vol. 45, no. 4, 1980, pages 1424-1446; M. ZAORAL et al.: "Synthesis of peptides, glyco derivatives and glycopeptides from bacterial cell walls" * |
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| Date | Code | Title | Description |
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| RE20 | Patent expired |
Owner name: *NOVARTIS A.G. Effective date: 20071009 |