SK284848B6 - Použitie leptínu na výrobu liečiva na liečbu rakoviny - Google Patents

Použitie leptínu na výrobu liečiva na liečbu rakoviny Download PDF

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Publication number: SK284848B6
Authority: SK; Slovakia
Prior art keywords: leptin; insulin; receptor; cells; medicament
Prior art date: 1997-04-29

Application number

SK1471-99A

Other languages

English (en)

Slovak (sk)

Other versions

SK147199A3 (en

Inventor

Dalit Barkan

Batya Cohen

Menachem Rubinstein

Original Assignee

Yeda Research And Development Company Limited

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.)

1997-04-29

Filing date

1998-04-26

Publication date

2006-01-05

1998-04-26 Application filed by Yeda Research And Development Company Limited filed Critical Yeda Research And Development Company Limited

2000-06-12 Publication of SK147199A3 publication Critical patent/SK147199A3/sk

2006-01-05 Publication of SK284848B6 publication Critical patent/SK284848B6/sk

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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2264—Obesity-gene products, e.g. leptin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Epidemiology (AREA)
Immunology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Gastroenterology & Hepatology (AREA)
Zoology (AREA)
Endocrinology (AREA)
Obesity (AREA)
Genetics & Genomics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK1471-99A 1997-04-29 1998-04-26 Použitie leptínu na výrobu liečiva na liečbu rakoviny SK284848B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IL12073397A IL120733A0 (en)	1997-04-29	1997-04-29	Leptin as an inhibitor of cell proliferation
PCT/IL1998/000196 WO1998048831A1 (en)	1997-04-29	1998-04-26	Leptin as an inhibitor of tumor cell proliferation

Publications (2)

Publication Number	Publication Date
SK147199A3 SK147199A3 (en)	2000-06-12
SK284848B6 true SK284848B6 (sk)	2006-01-05

Family

ID=11070075

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1471-99A SK284848B6 (sk)	1997-04-29	1998-04-26	Použitie leptínu na výrobu liečiva na liečbu rakoviny

Country Status (25)

Country	Link
US (1)	US7109159B1 (cs)
EP (1)	EP0981365B1 (cs)
JP (1)	JP4330662B2 (cs)
KR (1)	KR100507731B1 (cs)
CN (1)	CN1168497C (cs)
AR (1)	AR012626A1 (cs)
AT (1)	ATE283702T1 (cs)
AU (1)	AU742927B2 (cs)
BG (1)	BG63490B1 (cs)
CA (1)	CA2288238A1 (cs)
CZ (1)	CZ299872B6 (cs)
DE (1)	DE69827942T2 (cs)
EA (1)	EA002353B1 (cs)
EE (1)	EE04801B1 (cs)
ES (1)	ES2232944T3 (cs)
HU (1)	HUP0002427A3 (cs)
IL (2)	IL120733A0 (cs)
NO (1)	NO322304B1 (cs)
NZ (1)	NZ500589A (cs)
PL (1)	PL195275B1 (cs)
PT (1)	PT981365E (cs)
SK (1)	SK284848B6 (cs)
UA (1)	UA66793C2 (cs)
WO (1)	WO1998048831A1 (cs)
ZA (1)	ZA983608B (cs)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7208572B2 (en)	1998-08-21	2007-04-24	Albany Medical College	Leptin-related peptides
US6777388B1 (en)	1998-08-21	2004-08-17	Clf Medical Technology Acceleration Program, Inc.	Leptin-related peptides
US20050272652A1 (en)	1999-03-29	2005-12-08	Gault Victor A	Peptide analogues of GIP for treatment of diabetes, insulin resistance and obesity
IL132312A0 (en) *	1999-09-05	2001-03-19	Yeda Res & Dev	Use of leptin in inhibition of endothelial cell proliferation
KR20140011431A (ko)	2004-02-11	2014-01-28	아밀린 파마슈티칼스, 엘엘씨.	선택가능한 특성을 갖는 하이브리드 폴리펩티드
US8076288B2 (en)	2004-02-11	2011-12-13	Amylin Pharmaceuticals, Inc.	Hybrid polypeptides having glucose lowering activity
US8969291B2 (en)	2004-10-08	2015-03-03	Enzo Therapeutics, Inc.	Methods for decreasing leptin levels or activity for treating inflammation
US7863240B2 (en) *	2004-10-08	2011-01-04	Enzo Therapeutics, Inc.	Methods and uses of leptin in hepatocellular carcinoma
CA2597649A1 (en)	2005-02-11	2006-08-17	Amylin Pharmaceuticals, Inc.	Gip analog and hybrid polypeptides with selectable properties
US8263545B2 (en)	2005-02-11	2012-09-11	Amylin Pharmaceuticals, Inc.	GIP analog and hybrid polypeptides with selectable properties
EP2330125A3 (en)	2005-08-11	2012-12-12	Amylin Pharmaceuticals, Inc.	Hybrid polypeptides with selectable properties
EP1922336B1 (en)	2005-08-11	2012-11-21	Amylin Pharmaceuticals, LLC	Hybrid polypeptides with selectable properties
US8227408B2 (en) *	2005-09-07	2012-07-24	Neurotez, Inc.	Leptin as an anti-amyloidogenic biologic and methods for delaying the onset and reducing Alzheimer's disease-like pathology
US8497240B2 (en)	2006-08-17	2013-07-30	Amylin Pharmaceuticals, Llc	DPP-IV resistant GIP hybrid polypeptides with selectable properties
SG188143A1 (en) *	2008-02-08	2013-03-28	Ambrx Inc	Modified leptin polypeptides and their uses
KR20110028457A (ko) *	2008-05-21	2011-03-18	뉴로테즈 인코포레이티드	신경섬유 매듭과 연관된 신경변성 장애를 치료하는 방법
CA2742600A1 (en) *	2008-11-04	2010-05-14	Nikolaos Tezapsidis	Leptin compositions and methods for treating progressive cognitive function disorders resulting from accumulation of neurofibrillary tangles and amlyoid beta
WO2010146059A2 (en)	2009-06-16	2010-12-23	F. Hoffmann-La Roche Ag	Biomarkers for igf-1r inhibitor therapy
TWI824372B (zh)	2015-10-12	2023-12-01	美商再生元醫藥公司	活化瘦素受體的抗原結合蛋白
MA45801B1 (fr)	2016-11-08	2021-11-30	Regeneron Pharma	Protéines de liaison à l'antigène qui sont des antagonistes du récepteur de leptine
SG11202005146VA (en)	2017-12-18	2020-06-29	Regeneron Pharma	Bispecific antigen binding molecules that bind leptin receptor and/or gp130, and methods of use thereof
SMT202500283T1 (it)	2018-04-06	2025-09-12	Regeneron Pharma	Un anticorpo agonista del recettore della leptina da utilizzare per aumentare la massa ossea in un soggetto affetto da disfunzione metabolica o ipoleptinemia
CN120629571B (zh) *	2025-06-13	2026-03-27	蚌埠医学院第一附属医院（蚌埠医学院附属肿瘤医院）	Lepr基因或蛋白作为靶标在制备胆管细胞癌治疗产品中的用途

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU695934B2 (en) *	1995-06-30	1998-08-27	Eli Lilly And Company	Methods for treating diabetes
AU7072896A (en) *	1995-09-19	1997-04-09	Eli Lilly And Company	Dna encoding medicinal proteins
AU731685C (en) *	1996-01-23	2002-08-22	Indevus Pharmaceuticals, Inc.	Methods for using the obese gene and its gene product to stimulate hematopoietic development

1997
- 1997-04-29 IL IL12073397A patent/IL120733A0/xx unknown
1998
- 1998-04-26 UA UA99116415A patent/UA66793C2/uk unknown
- 1998-04-26 EE EEP199900510A patent/EE04801B1/xx not_active IP Right Cessation
- 1998-04-26 ES ES98917580T patent/ES2232944T3/es not_active Expired - Lifetime
- 1998-04-26 JP JP54678798A patent/JP4330662B2/ja not_active Expired - Fee Related
- 1998-04-26 CA CA002288238A patent/CA2288238A1/en not_active Abandoned
- 1998-04-26 AU AU70762/98A patent/AU742927B2/en not_active Ceased
- 1998-04-26 HU HU0002427A patent/HUP0002427A3/hu unknown
- 1998-04-26 AT AT98917580T patent/ATE283702T1/de active
- 1998-04-26 CN CNB988066920A patent/CN1168497C/zh not_active Expired - Fee Related
- 1998-04-26 DE DE69827942T patent/DE69827942T2/de not_active Expired - Lifetime
- 1998-04-26 EP EP98917580A patent/EP0981365B1/en not_active Expired - Lifetime
- 1998-04-26 NZ NZ500589A patent/NZ500589A/xx not_active IP Right Cessation
- 1998-04-26 PT PT98917580T patent/PT981365E/pt unknown
- 1998-04-26 EA EA199900981A patent/EA002353B1/ru not_active IP Right Cessation
- 1998-04-26 CZ CZ0384899A patent/CZ299872B6/cs not_active IP Right Cessation
- 1998-04-26 SK SK1471-99A patent/SK284848B6/sk not_active IP Right Cessation
- 1998-04-26 US US09/403,897 patent/US7109159B1/en not_active Expired - Fee Related
- 1998-04-26 PL PL98336582A patent/PL195275B1/pl not_active IP Right Cessation
- 1998-04-26 KR KR10-1999-7009705A patent/KR100507731B1/ko not_active Expired - Fee Related
- 1998-04-26 WO PCT/IL1998/000196 patent/WO1998048831A1/en not_active Ceased
- 1998-04-29 ZA ZA983608A patent/ZA983608B/xx unknown
- 1998-04-29 AR ARP980102003A patent/AR012626A1/es unknown
1999
- 1999-10-25 BG BG103832A patent/BG63490B1/bg unknown
- 1999-10-28 NO NO19995267A patent/NO322304B1/no not_active IP Right Cessation
- 1999-10-28 IL IL132633A patent/IL132633A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
CN1168497C (zh)	2004-09-29
IL132633A (en)	2007-07-04
PL336582A1 (en)	2000-07-03
EE9900510A (et)	2000-06-15
ES2232944T3 (es)	2005-06-01
WO1998048831A1 (en)	1998-11-05
CZ299872B6 (cs)	2008-12-17
BG103832A (en)	2000-10-31
AU742927B2 (en)	2002-01-17
PT981365E (pt)	2005-03-31
HUP0002427A3 (en)	2003-02-28
EA199900981A1 (ru)	2000-04-24
HK1028350A1 (en)	2001-02-16
CA2288238A1 (en)	1998-11-05
DE69827942T2 (de)	2005-12-08
HUP0002427A2 (hu)	2000-12-28
EP0981365B1 (en)	2004-12-01
JP2001524968A (ja)	2001-12-04
NO322304B1 (no)	2006-09-11
AR012626A1 (es)	2000-11-08
SK147199A3 (en)	2000-06-12
EA002353B1 (ru)	2002-04-25
KR100507731B1 (ko)	2005-08-10
CN1261802A (zh)	2000-08-02
NO995267D0 (no)	1999-10-28
CZ384899A3 (cs)	2000-06-14
ZA983608B (en)	1998-11-02
KR20010012080A (ko)	2001-02-15
EE04801B1 (et)	2007-04-16
DE69827942D1 (de)	2005-01-05
BG63490B1 (bg)	2002-03-29
EP0981365A1 (en)	2000-03-01
NO995267L (no)	1999-12-28
JP4330662B2 (ja)	2009-09-16
AU7076298A (en)	1998-11-24
ATE283702T1 (de)	2004-12-15
US7109159B1 (en)	2006-09-19
NZ500589A (en)	2001-03-30
UA66793C2 (uk)	2004-06-15
PL195275B1 (pl)	2007-08-31
IL120733A0 (en)	1997-08-14

Legal Events

Date	Code	Title	Description
2014-01-08	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20130426

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