IL101452A - Analogs of the factor that releases the growth hormone, their preparation and the pharmaceutical preparations that contain them - Google Patents

Analogs of the factor that releases the growth hormone, their preparation and the pharmaceutical preparations that contain them

Info

Publication number: IL101452A
Authority: IL; Israel
Prior art keywords: seq; xaa; ala; compound; leu
Prior art date: 1991-04-09

Application number

IL10145292A

Other languages

English (en)

Hebrew (he)

Other versions

IL101452A0 (en

Original Assignee

Hoffmann La Roche

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.)

1991-04-09

Filing date

1992-04-02

Publication date

1996-11-14

1992-04-02 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1992-12-30 Publication of IL101452A0 publication Critical patent/IL101452A0/xx

1996-11-14 Publication of IL101452A publication Critical patent/IL101452A/en

Links

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Classifications

- 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
- C07K14/575—Hormones
- C07K14/60—Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Endocrinology (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Biophysics (AREA)
Gastroenterology & Hepatology (AREA)
Biochemistry (AREA)
Zoology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Toxicology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)

IL10145292A 1991-04-09 1992-04-02 Analogs of the factor that releases the growth hormone, their preparation and the pharmaceutical preparations that contain them IL101452A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US68283591A	1991-04-09	1991-04-09

Publications (2)

Publication Number	Publication Date
IL101452A0 IL101452A0 (en)	1992-12-30
IL101452A true IL101452A (en)	1996-11-14

Family

ID=24741366

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10145292A IL101452A (en)	1991-04-09	1992-04-02	Analogs of the factor that releases the growth hormone, their preparation and the pharmaceutical preparations that contain them

Country Status (10)

Country	Link
US (1)	US5846936A (fr)
EP (2)	EP0525838A3 (fr)
JP (1)	JPH05507939A (fr)
AU (1)	AU662731B2 (fr)
CA (1)	CA2084061A1 (fr)
IE (1)	IE921121A1 (fr)
IL (1)	IL101452A (fr)
NZ (1)	NZ242209A (fr)
WO (1)	WO1992018531A1 (fr)
ZA (1)	ZA922420B (fr)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5705483A (en)	1993-12-09	1998-01-06	Eli Lilly And Company	Glucagon-like insulinotropic peptides, compositions and methods
US5512549A (en) *	1994-10-18	1996-04-30	Eli Lilly And Company	Glucagon-like insulinotropic peptide analogs, compositions, and methods of use
JP2000510453A (ja) *	1996-04-19	2000-08-15	ノボノルディスクアクティーゼルスカブ	成長ホルモン遊離特性を有する化合物
US5981488A (en) *	1997-03-31	1999-11-09	Eli Lillly And Company	Glucagon-like peptide-1 analogs
EP0922446A1 (fr) *	1997-12-03	1999-06-16	Applied Research Systems Ars Holding N.V.	Préparation des conjugués du GRF-PEG par un méthode en solution spécifique à un site
US6696063B1 (en) *	1998-12-30	2004-02-24	Applied Research Systems Ars Holding N.V.	Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy
US20040192593A1 (en) *	1999-07-26	2004-09-30	Baylor College Of Medicine	Protease resistant ti-growth hormone releasing hormone
AU772752B2 (en)	1999-07-26	2004-05-06	Baylor College Of Medicine	Super-active porcine growth hormone releasing hormone analog
US6486134B2 (en) *	1999-09-17	2002-11-26	Leadergene Limited	Gene treatment to enhance feed efficiency and growth rate of livestock
DE20004154U1 (de)	2000-03-08	2001-07-19	Heuser, Ralf, 56357 Miehlen	Hochwärmedämmendes Fenster oder Tür
US20020061838A1 (en) *	2000-05-17	2002-05-23	Barton Holmquist	Peptide pharmaceutical formulations
AU2002228608A1 (en)	2000-12-13	2002-06-24	Eli Lilly And Company	Amidated glucagon-like peptide-1
BR0206919A (pt) *	2001-02-02	2004-07-06	Conjuchem Inc	Derivados de fator de liberação de hormÈnio de crescimento de longa duração
AR037038A1 (es)	2001-10-26	2004-10-20	Baylor College Medicine	Una composicion y metodo para alterar la masa corporal magra y las propiedades oseas en un sujeto
AU2002357143B2 (en)	2001-12-11	2009-07-30	Advisys, Inc.	Growth hormone releasing hormone supplementation for treating chronically ill subjects
US7250405B2 (en) *	2002-02-07	2007-07-31	Baylor College Of Medicine	Modified pituitary gland development in offspring from expectant mother animals treated with growth hormone releasing hormone therapy
KR20050071498A (ko) *	2002-09-18	2005-07-07	상트르 오스피딸리에 드 루니버시떼 드 몬트리알	성장 호르몬 방출 호르몬 유사체
CA2513743C (fr) *	2003-01-28	2013-06-25	Advisys, Inc.	Reduction de reforme dans l'hormone de croissance (ghrh) d'animaux de troupeau
TW200424214A (en) *	2003-04-21	2004-11-16	Advisys Inc	Plasmid mediated GHRH supplementation for renal failures
CA2575926C (fr) *	2003-08-04	2014-02-25	Advisys, Inc.	Hormone liberant une hormone de croissance specifique du chien
ATE467417T1 (de) *	2003-12-31	2010-05-15	VGX Pharmaceuticals LLC	Reduzierung von arthritis und lahmheit bei personen unter supllement von wachstumshormon freisetzendem hormon (ghrh)
WO2005073371A2 (fr) *	2004-01-20	2005-08-11	Advisys, Inc.	Secretion/retention ameliorees de somatostatine par des cellules musculaires au moyen de peptides signal specifiques de l'espece
US20060025368A1 (en) *	2004-07-23	2006-02-02	Advisys, Inc.	Growth hormone releasing hormone enhances vaccination response
WO2008006019A2 (fr) *	2006-07-06	2008-01-10	Advisys Inc.	Traitement hormonal libérant une hormone de croissance pour faire baisser le taux de cholestérol
BRPI0720306A2 (pt)	2006-12-14	2014-02-04	Aileron Therapeutics Inc	Sistemas de macrociclização da bis-sufidrila
DK2118123T3 (en)	2007-01-31	2016-01-25	Dana Farber Cancer Inst Inc	Stabilized p53 peptides and uses thereof
US8592377B2 (en)	2007-03-28	2013-11-26	President And Fellows Of Harvard College	Stitched polypeptides
US20090088380A1 (en) *	2007-07-12	2009-04-02	Pierrette Gaudreau	Ghrh analogs and therapeutic uses thereof
CN102083451A (zh)	2008-06-12	2011-06-01	赛恩泰新公司	癌症的抑制
US20100267635A1 (en) *	2009-04-20	2010-10-21	Theratechonolgies Inc.	Use of protease inhibitors and grf molecules in combination therapy
US20100267636A1 (en) *	2009-04-20	2010-10-21	Theratechnologies Inc.	Use of cytochrome p450-metabolized drugs and grf molecules in combination therapy
WO2011153491A2 (fr)	2010-06-03	2011-12-08	University Of Miami	Agonistes de l'hormone de libération de l'hormone de croissance en tant qu'effecteurs de la survie et de la prolifération d'îlots pancréatiques
ES2711526T3 (es)	2010-08-13	2019-05-06	Aileron Therapeutics Inc	Macrociclos peptidomiméticos
KR20140027284A (ko)	2011-04-21	2014-03-06	쎄러테크놀로지스 인코포레이티드	성장 호르몬 방출 인자(grf) 유사체 및 이의 용도
TW201806968A (zh)	2011-10-18	2018-03-01	艾利倫治療公司	擬肽巨環化合物
US9079974B2 (en) *	2011-12-21	2015-07-14	The University Of Miami	GH-RH analogs with potent agonistic effects
EP2819688A4 (fr)	2012-02-15	2015-10-28	Aileron Therapeutics Inc	Macrocycles peptidomimétiques réticulés par triazole et par thioéther
BR112014020103A2 (pt)	2012-02-15	2018-10-09	Aileron Therapeutics, Inc.	macrociclos peptidomiméticos
WO2013190520A2 (fr)	2012-06-22	2013-12-27	The General Hospital Corporation	Agents de libération de gh dans le traitement d'une sténose vasculaire et d'états associés
WO2014071241A1 (fr)	2012-11-01	2014-05-08	Aileron Therapeutics, Inc.	Acides aminés disubstitués et procédés de préparation et d'utilisation de ceux-ci
WO2014100816A2 (fr)	2012-12-21	2014-06-26	University Of Miami	Agonistes de ghrh pour la greffe et fonction de cellules d'îlot et le traitement du diabète
US9855312B2 (en)	2012-12-21	2018-01-02	University Of Miami	GHRH agonists for the treatment of ischemic disorders
EP3197478A4 (fr)	2014-09-24	2018-05-30	Aileron Therapeutics, Inc.	Macrocycles peptidomimétiques et leurs utilisations
WO2016049200A1 (fr)	2014-09-24	2016-03-31	University Of Oregon	Protéines augmentant le nombre de cellules bêta pancréatiques et procédés d'utilisation
WO2016154058A1 (fr)	2015-03-20	2016-09-29	Aileron Therapeutics, Inc.	Macrocycles peptidomimétiques et leurs utilisations
US10059741B2 (en)	2015-07-01	2018-08-28	Aileron Therapeutics, Inc.	Peptidomimetic macrocycles
WO2017181277A1 (fr)	2016-04-19	2017-10-26	Griffon Pharmaceuticals Inc.	Peptides pégylés bioactifs et utilisations correspondantes

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4618598A (en) *	1982-04-12	1986-10-21	Duke University	Method of regulating hormone function or release
US4517181A (en) *	1982-09-15	1985-05-14	The Salk Institute For Biological Studies	Mammalian PGRF
US4595676A (en) *	1983-04-26	1986-06-17	The Salk Institute For Biological Studies	Rat hypothalamic GRF
US4563352A (en) *	1982-10-04	1986-01-07	The Salk Institute For Biological Studies	Human pancreatic GRF
US4529595A (en) *	1983-01-13	1985-07-16	The Salk Institute For Biological Studies	GRF Analogs
US4703035A (en) *	1982-10-04	1987-10-27	The Salk Institute For Biological Studies	Human pancreatic GRF amidated fragments
US4728726A (en) *	1982-10-04	1988-03-01	The Salk Institute For Biological Studies	GRF analogs IIIb
IL70530A (en) *	1983-01-13	1986-09-30	Salk Inst For Biological Studi	Synthetic peptides having growth hormone releasing factor activity and compositions containing them
US4518586A (en) *	1983-01-13	1985-05-21	The Salk Institute For Biological Studies	GRF Analogs III
US4732972A (en) *	1983-03-07	1988-03-22	Hoffmann-La Roche Inc.	Polypeptides having growth hormone releasing activity
AU574064B2 (en) *	1983-03-07	1988-06-30	F. Hoffmann-La Roche Ag	Growth hormone releasing factor analogues
US4628043A (en) *	1983-04-26	1986-12-09	The Salk Institute For Biological Studies	Hypothalamic GRF agonists
US4585756A (en) *	1983-10-12	1986-04-29	The Salk Institute For Biological Studies	Bovine GRF
US4605643A (en) *	1984-03-02	1986-08-12	The Salk Institute For Biological Studies	Ovine GRF
US4610976A (en) *	1983-08-29	1986-09-09	The Salk Institute For Biological Studies	Porcine GRF
US4626523A (en) *	1983-09-13	1986-12-02	The Salk Institute For Biological Studies	GRF analogs II
US4617149A (en) *	1983-09-21	1986-10-14	Eli Lilly And Company	Growth hormone release factor analogs
US4528190A (en) *	1983-10-25	1985-07-09	The Salk Institute For Biological Studies	GRF Analogs IV
US4562175A (en) *	1984-02-03	1985-12-31	Ding Chang	Synthetic peptides
US4649039A (en) *	1984-07-03	1987-03-10	E. I. Du Pont De Nemours And Company	Radiolabeling of methionine-containing proteins and peptides
US4649131A (en) *	1984-09-24	1987-03-10	Hoffmann-La Roche Inc.	Growth hormone releasing factor analogs
US4622312A (en) *	1984-09-24	1986-11-11	Hoffmann-La Roche Inc.	Growth hormone releasing factor analogs
US4734399A (en) *	1985-08-06	1988-03-29	Hoffmann-La Roche Inc.	Growth hormone releasing factor analogs
US4689318A (en) *	1985-08-29	1987-08-25	The Salk Institute For Biological Studies	GRF analogs
US4783524A (en) *	1985-09-17	1988-11-08	Monsanto Company	Growth factors
US4784987A (en) *	1987-01-13	1988-11-15	The Salk Institute For Biological Studies	GRF analogs VI
US4914189A (en) *	1987-02-05	1990-04-03	The Adminstrators Of The Tulane Educational Fund	Synthetic GHRH analogs
US5002931A (en) *	1987-05-22	1991-03-26	The Salk Institute For Biological Studies	GRF analogs VII
AU617426B2 (en) *	1988-01-29	1991-11-28	Upjohn Company, The	Growth hormone releasing factor analogs
US5043322A (en) *	1988-07-22	1991-08-27	The Salk Institute For Biological Studies	Cyclic GRF analogs
US5084442A (en) *	1988-09-06	1992-01-28	Hoffmann-La Roche Inc.	Cyclic growth hormone releasing factor analogs and method for the manufacture thereof
CA2026776A1 (fr) *	1989-01-27	1990-07-28	Alan R. Friedman	Puissants analogues de la somatostatine stabilises
ATE113965T1 (de) *	1989-06-16	1994-11-15	Upjohn Co	Stabilisierte, starke grf-analoga.

1992
- 1992-04-01 CA CA002084061A patent/CA2084061A1/fr not_active Abandoned
- 1992-04-01 AU AU14485/92A patent/AU662731B2/en not_active Ceased
- 1992-04-01 EP EP19920200995 patent/EP0525838A3/fr active Pending
- 1992-04-01 EP EP92907635A patent/EP0542937A1/fr not_active Withdrawn
- 1992-04-01 JP JP92506862A patent/JPH05507939A/ja active Pending
- 1992-04-01 WO PCT/EP1992/000723 patent/WO1992018531A1/fr not_active Ceased
- 1992-04-02 NZ NZ242209A patent/NZ242209A/en unknown
- 1992-04-02 ZA ZA922420A patent/ZA922420B/xx unknown
- 1992-04-02 IL IL10145292A patent/IL101452A/en not_active IP Right Cessation
- 1992-04-08 IE IE112192A patent/IE921121A1/en unknown
1995
- 1995-06-22 US US08/493,594 patent/US5846936A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JPH05507939A (ja)	1993-11-11
CA2084061A1 (fr)	1992-10-10
AU1448592A (en)	1992-11-17
EP0525838A3 (fr)	1993-02-10
NZ242209A (en)	1994-04-27
AU662731B2 (en)	1995-09-14
IL101452A0 (en)	1992-12-30
ZA922420B (en)	1992-12-30
EP0542937A1 (fr)	1993-05-26
WO1992018531A1 (fr)	1992-10-29
US5846936A (en)	1998-12-08
EP0525838A2 (fr)	1993-02-03
IE921121A1 (en)	1992-10-21

Legal Events

Date	Code	Title
1997-04-15	FF	Patent granted
1997-07-13	KB	Patent renewed
1998-10-30	KB	Patent renewed
2003-01-12	MM9K	Patent not in force due to non-payment of renewal fees