ZA200500053B - Method for isolating an intestinal cholesterol binding protein - Google Patents

Method for isolating an intestinal cholesterol binding protein Download PDF

Info

Publication number: ZA200500053B
Authority: ZA; South Africa
Prior art keywords: protein; cholesterol; compound; biological material; intestinal
Prior art date: 2002-08-06

Application number

ZA200500053A

Other languages

English (en)

Inventor

Werner Kramer

Wendelin Frick

Original Assignee

Sanofi Aventis Deutschland

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.)

2002-08-06

Filing date

2005-01-04

Publication date

2006-07-26

2005-01-04 Application filed by Sanofi Aventis Deutschland filed Critical Sanofi Aventis Deutschland

2006-07-26 Publication of ZA200500053B publication Critical patent/ZA200500053B/en

Links

230000000968 intestinal effect Effects 0.000 title claims abstract description 41
238000000034 method Methods 0.000 title claims abstract description 37
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108090000623 proteins and genes Proteins 0.000 claims abstract description 101
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 97
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- 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
- A61P3/06—Antihyperlipidemics
- 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
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Organic Chemistry (AREA)
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General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
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Biochemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Gastroenterology & Hepatology (AREA)
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ZA200500053A 2002-08-06 2005-01-04 Method for isolating an intestinal cholesterol binding protein ZA200500053B (en)

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EP02017504		2002-08-06

Publications (1)

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ZA200500053B true ZA200500053B (en)	2006-07-26

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ZA200500053A ZA200500053B (en)	2002-08-06	2005-01-04	Method for isolating an intestinal cholesterol binding protein

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US (2)	US7435727B2 (de)
EP (1)	EP1529061B1 (de)
JP (1)	JP4575772B2 (de)
KR (1)	KR101095288B1 (de)
CN (1)	CN1330667C (de)
AT (1)	ATE386053T1 (de)
AU (1)	AU2003253341C1 (de)
BR (1)	BR0313217A (de)
CA (1)	CA2493487C (de)
DE (1)	DE60319093T2 (de)
IL (2)	IL166492A (de)
MX (1)	MXPA05001264A (de)
NO (2)	NO333437B1 (de)
RU (1)	RU2345089C2 (de)
WO (1)	WO2004014947A1 (de)
ZA (1)	ZA200500053B (de)

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0215579D0 (en)	2002-07-05	2002-08-14	Astrazeneca Ab	Chemical compounds
US7135556B2 (en)	2002-07-19	2006-11-14	Schering Corporation	NPC1L1 (NPC3) and methods of use thereof
EP1699759B1 (de)	2003-12-23	2010-10-20	AstraZeneca AB	Diphenylazetidinonderivate mit die cholesterinabsorption hemmender wirkung
WO2005069900A2 (en)	2004-01-16	2005-08-04	Merck & Co., Inc.	Npc1l1 (npc3) and methods of identifying ligands thereof
DE602006010870D1 (de)	2005-06-20	2010-01-14	Schering Corp	Als antagonisten von histamin h3 geeignete piperidinderivate
SA06270191B1 (ar)	2005-06-22	2010-03-29	استرازينيكا ايه بي	مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم
EP1986489A2 (de)	2006-02-24	2008-11-05	Schering Corporation	Npc1l1-orthologe
TW200811098A (en)	2006-04-27	2008-03-01	Astrazeneca Ab	Chemical compounds
CN1869704B (zh) *	2006-06-14	2010-06-30	厦门大学	快速鉴定与病原菌互作的宿主蛋白的方法

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4710469A (en)	1986-05-02	1987-12-01	Merck & Co., Inc.	Novel phosphotyrosyl protein phosphatase
CA2441636A1 (en) *	1988-11-10	1990-05-10	The Wistar Institute Of Anatomy And Biology	Natural killer stimulatory factor
JPH06500991A (ja) *	1990-05-16	1994-01-27	ジェネティックス・インスティテュート・インコーポレイテッド	骨および軟骨誘導蛋白質
US5264372A (en) *	1991-03-15	1993-11-23	Amylin Pharmaceuticals, Inc.	Receptor-based screening methods for amylin agonists and antagonists
RU2052960C1 (ru) *	1992-05-22	1996-01-27	Институт терапии СО РАМН	Способ получения холестеринснижающих веществ
US5518911A (en) *	1995-01-06	1996-05-21	Onyx Pharmaceuticals, Inc.	Human PAK65
JP3088681B2 (ja) *	1997-05-22	2000-09-18	宮城県	形質膜局在シアリダーゼ及びそれをコードするｄｎａ
US6383734B1 (en) *	1998-09-30	2002-05-07	Advanced Research And Technology Institute, Inc.	Method to determine inhibition of PAK3 activation of Raf-1
JP2000166545A (ja) *	1998-12-07	2000-06-20	Snow Brand Milk Prod Co Ltd	胆汁酸活性化リパーゼ
WO2000060062A2 (en)	1999-04-01	2000-10-12	Astrazeneca Uk Limited	Human signal transduction serine/threonine protein kinase
WO2000063703A1 (en) *	1999-04-16	2000-10-26	Schering Corporation	Use of azetidinone compounds
DE10042447A1 (de) *	2000-08-29	2002-03-28	Aventis Pharma Gmbh	Protein aus dem Darm von Wirbeltieren, welches Cholesterin absorbiert, sowie Verwendung dieses Proteins zur Identifizierung von Inhibitoren des intestinalen Cholesterintransports

2003
- 2003-07-28 RU RU2005106238/13A patent/RU2345089C2/ru not_active IP Right Cessation
- 2003-07-28 BR BR0313217-0A patent/BR0313217A/pt not_active IP Right Cessation
- 2003-07-28 KR KR1020057002084A patent/KR101095288B1/ko not_active Expired - Fee Related
- 2003-07-28 CA CA2493487A patent/CA2493487C/en not_active Expired - Fee Related
- 2003-07-28 CN CNB038173328A patent/CN1330667C/zh not_active Expired - Fee Related
- 2003-07-28 MX MXPA05001264A patent/MXPA05001264A/es active IP Right Grant
- 2003-07-28 AT AT03784089T patent/ATE386053T1/de not_active IP Right Cessation
- 2003-07-28 JP JP2004526798A patent/JP4575772B2/ja not_active Expired - Fee Related
- 2003-07-28 DE DE60319093T patent/DE60319093T2/de not_active Expired - Lifetime
- 2003-07-28 EP EP03784089A patent/EP1529061B1/de not_active Expired - Lifetime
- 2003-07-28 WO PCT/EP2003/008290 patent/WO2004014947A1/en not_active Ceased
- 2003-07-28 AU AU2003253341A patent/AU2003253341C1/en not_active Ceased
- 2003-08-06 US US10/635,008 patent/US7435727B2/en not_active Expired - Fee Related
2005
- 2005-01-04 ZA ZA200500053A patent/ZA200500053B/en unknown
- 2005-01-25 IL IL166492A patent/IL166492A/en not_active IP Right Cessation
- 2005-03-04 NO NO20051169A patent/NO333437B1/no not_active IP Right Cessation
2007
- 2007-10-16 US US11/872,855 patent/US7786103B2/en not_active Expired - Fee Related
2009
- 2009-06-17 IL IL199409A patent/IL199409A/en not_active IP Right Cessation
2013
- 2013-01-18 NO NO20130115A patent/NO20130115L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
US20080167451A1 (en)	2008-07-10
NO20130115L (no)	2005-05-02
RU2005106238A (ru)	2005-08-27
CA2493487C (en)	2013-01-22
WO2004014947A1 (en)	2004-02-19
AU2003253341C1 (en)	2009-09-24
NO333437B1 (no)	2013-06-03
US7786103B2 (en)	2010-08-31
ATE386053T1 (de)	2008-03-15
CN1668642A (zh)	2005-09-14
JP2006512054A (ja)	2006-04-13
IL199409A (en)	2010-12-30
CN1330667C (zh)	2007-08-08
DE60319093D1 (de)	2008-03-27
NO20051169L (no)	2005-05-02
EP1529061A1 (de)	2005-05-11
MXPA05001264A (es)	2005-04-28
US7435727B2 (en)	2008-10-14
KR20060015443A (ko)	2006-02-17
IL166492A0 (en)	2006-01-15
HK1082509A1 (en)	2006-06-09
IL166492A (en)	2010-12-30
EP1529061B1 (de)	2008-02-13
AU2003253341B2 (en)	2009-04-23
BR0313217A (pt)	2005-06-14
JP4575772B2 (ja)	2010-11-04
DE60319093T2 (de)	2009-02-05
RU2345089C2 (ru)	2009-01-27
KR101095288B1 (ko)	2011-12-16
US20040126812A1 (en)	2004-07-01
CA2493487A1 (en)	2004-02-19
AU2003253341A1 (en)	2004-02-25

Publication	Publication Date	Title
US7786103B2 (en)	2010-08-31	Method for isolating an intestinal cholesterol binding protein
US20230364183A1 (en)	2023-11-16	Cartilage-homing peptides
US6794359B2 (en)	2004-09-21	Vertebrate intestinal protein which absorbs cholesterol, its inhibitors and mehtod of identifying the same
US5045462A (en)	1991-09-03	Basic protein called phospholipase A2 isolated from the venom of a snake of the family elapidae and its amino acid sequence
US7094575B2 (en)	2006-08-22	Therapeutic and prophylactic agents and methods of using same
Hofsteenge	1997	Ribonuclease inhibitor
McGowan et al.	1993	Effects of heparin and other glycosaminoglycans on elastin production by cultured neonatal rat lung fibroblasts
JP3728494B2 (ja)	2005-12-21	新規な血清コレステロール低下ペプチド
HK1082509B (en)	2007-10-26	Method for isolating an intestinal cholesterol binding protein
DE69513788T2 (de)	2000-06-21	Peptid Derivate mit bindendes Aktivität zu modifiziertem Lipoprotein mit niedriger Dichte (LDL)
JPH07503120A (ja)	1995-04-06	細菌からの組換えアポリポタンパク質ｅの精製
US5164315A (en)	1992-11-17	Basic protein phospholiphase A2
JP2016516752A (ja)	2016-06-09	アテローム性動脈硬化症の治療および予防のための環状ペプチドの使用
EP0760376A1 (de)	1997-03-05	Die phospholipase c inhibierende peptide
Trifonov et al.	1994	Biological effects of a novel intestinal peptide—inhibiting enterocytogenin on cultured 3T3 mouse fibroblasts and L5178Y mouse lymphoma cells
JPH0291100A (ja)	1990-03-30	ヒトホスホリパーゼａ↓２阻害蛋白
JPH07147976A (ja)	1995-06-13	Ｃ末端アミド化に関与する酵素並びにその製造方法及びその使用
JPH0740935B2 (ja)	1995-05-10	Ｃ末端アミド化に関与する酵素ならびにその製造方法および使用