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 themInfo
- Publication number
- IL101452A IL101452A IL10145292A IL10145292A IL101452A IL 101452 A IL101452 A IL 101452A IL 10145292 A IL10145292 A IL 10145292A IL 10145292 A IL10145292 A IL 10145292A IL 101452 A IL101452 A IL 101452A
- Authority
- IL
- Israel
- Prior art keywords
- seq
- xaa
- ala
- compound
- leu
- Prior art date
Links
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- 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 factors (GH-RF) (Somatoliberin)
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- A—HUMAN NECESSITIES
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| US68283591A | 1991-04-09 | 1991-04-09 |
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| IL101452A0 IL101452A0 (en) | 1992-12-30 |
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| 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 |
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| CA (1) | CA2084061A1 (de) |
| IE (1) | IE921121A1 (de) |
| IL (1) | IL101452A (de) |
| NZ (1) | NZ242209A (de) |
| WO (1) | WO1992018531A1 (de) |
| ZA (1) | ZA922420B (de) |
Families Citing this family (47)
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| 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 (de) * | 1997-12-03 | 1999-06-16 | Applied Research Systems Ars Holding N.V. | Lösungsphase Verfahrung zur ortspezifischer Herstellung von GRF-PEG Konjugaten |
| 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 |
| EP1204321B1 (de) * | 1999-07-26 | 2005-11-09 | Baylor College Of Medicine | Superaktive, wachstumshormone freisetzende hormonanaloge vom schwein |
| US20040192593A1 (en) * | 1999-07-26 | 2004-09-30 | Baylor College Of Medicine | Protease resistant ti-growth hormone releasing hormone |
| 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 Volkmar | Hochwärmedämmendes Fenster oder Tür |
| US20020061838A1 (en) * | 2000-05-17 | 2002-05-23 | Barton Holmquist | Peptide pharmaceutical formulations |
| WO2002048192A2 (en) | 2000-12-13 | 2002-06-20 | Eli Lilly And Company | Amidated glucagon-like peptide-1 |
| US7268113B2 (en) | 2001-02-02 | 2007-09-11 | Conjuchem Biotechnologies Inc. | Long lasting growth hormone releasing factor derivatives |
| WO2003038112A2 (en) | 2001-10-26 | 2003-05-08 | Baylor College Of Medicine | A composition and method to alter lean body mass and bone properties in a subject |
| US7241744B2 (en) * | 2001-12-11 | 2007-07-10 | Baylor College Of Medicine | Treating anemia in subjects by administration of plasmids encoding growth hormone releasing hormone |
| MXPA04007638A (es) * | 2002-02-07 | 2004-12-06 | Baylor College Medicine | Desarrollo modificado de la glandula pituitaria en productos de madres animales prenadas, tratadas con terapia de hormona liberadora de hormona del crecimiento. |
| MXPA05002991A (es) * | 2002-09-18 | 2005-10-05 | Univ Montreal Ct Hospitalier Chum | Analogos de ghrh. |
| US20040204358A1 (en) * | 2003-01-28 | 2004-10-14 | Advisys, Inc. | Reducing culling in herd animals growth hormone releasing hormone (GHRH) |
| TW200424214A (en) * | 2003-04-21 | 2004-11-16 | Advisys Inc | Plasmid mediated GHRH supplementation for renal failures |
| WO2005016964A2 (en) * | 2003-08-04 | 2005-02-24 | Advisys, Inc. | Canine specific growth hormone releasing hormone |
| EP1711187B1 (de) | 2003-12-31 | 2010-05-12 | VGX Pharmaceuticals, LLC | Reduzierung von arthritis und lahmheit bei personen unter supllement von wachstumshormon freisetzendem hormon (ghrh) |
| CA2595619A1 (en) * | 2004-01-20 | 2005-08-11 | Advisys, Inc. | Enhanced secretion/retention of growth hormone releasing hormone (ghrh) from muscle cells by species-specific signal peptide |
| NZ553274A (en) * | 2004-07-23 | 2010-02-26 | VGX Pharmaceuticals LLC | Growth hormone releasing hormone enhances the immune response induced by vaccination |
| US8058253B2 (en) * | 2006-07-06 | 2011-11-15 | Vgx Pharmaceuticals, Inc. | Growth hormone releasing hormone treatment to decrease cholesterol levels |
| US7960506B2 (en) | 2006-12-14 | 2011-06-14 | Aileron Therapeutics, Inc. | Bis-sulfhydryl macrocyclization systems |
| PT2118123E (pt) | 2007-01-31 | 2016-02-10 | Harvard College | Péptidos de p53 estabilizados e suas utilizações |
| WO2008121767A2 (en) | 2007-03-28 | 2008-10-09 | President And Fellows Of Harvard College | Stitched polypeptides |
| WO2009009727A2 (en) * | 2007-07-12 | 2009-01-15 | Akela Pharma Srl | Ghrh analogs and therapeutic uses thereof |
| WO2009150470A2 (en) | 2008-06-12 | 2009-12-17 | Syntaxin Limited | Suppression of cancers |
| US20100267636A1 (en) * | 2009-04-20 | 2010-10-21 | Theratechnologies Inc. | Use of cytochrome p450-metabolized drugs and grf molecules in combination therapy |
| EP2421547A1 (de) * | 2009-04-20 | 2012-02-29 | Theratechnologies Inc. | Verwendung von (hexenoyl-trans-3)hgrf(1-44)nh2 und ritonavir in einer kombinationstherapie |
| US8980249B2 (en) | 2010-06-03 | 2015-03-17 | University Of Miami | Agonists of growth hormone releasing hormone as effectors for survival and proliferation of pancreatic islets |
| RU2582678C2 (ru) | 2010-08-13 | 2016-04-27 | Эйлерон Терапьютикс, Инк. | Пептидомиметические макроциклы |
| WO2012142706A1 (en) | 2011-04-21 | 2012-10-26 | Theratechnologies Inc. | Growth hormone releasing factor (grf) analogs and uses thereof |
| TWI643868B (zh) | 2011-10-18 | 2018-12-11 | 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 |
| JP6450191B2 (ja) | 2012-02-15 | 2019-01-09 | エイルロン セラピューティクス，インコーポレイテッド | ペプチドミメティック大環状化合物 |
| EP2819688A4 (de) | 2012-02-15 | 2015-10-28 | Aileron Therapeutics Inc | Triazol- und thioethervernetzte peptidomimetische makrozyklen |
| WO2013190520A2 (en) | 2012-06-22 | 2013-12-27 | The General Hospital Corporation | Gh-releasing agents in the treatment of vascular stenosis and associated conditions |
| WO2014071241A1 (en) | 2012-11-01 | 2014-05-08 | Aileron Therapeutics, Inc. | Disubstituted amino acids and methods of preparation and use thereof |
| WO2014100816A2 (en) | 2012-12-21 | 2014-06-26 | University Of Miami | Ghrh agonists for islet cell transplantation and function and the treatment of diabetes |
| WO2014100809A2 (en) | 2012-12-21 | 2014-06-26 | University Of Miami | Ghrh agonists for the treatment of ischemic disorders |
| CA2961550A1 (en) * | 2014-09-24 | 2016-03-31 | University Of Oregon | Proteins increasing pancreatic beta cell number and methods of use |
| KR20170058424A (ko) | 2014-09-24 | 2017-05-26 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방 거대고리 및 이의 용도 |
| JP2018516844A (ja) | 2015-03-20 | 2018-06-28 | エルロン・セラピューティクス・インコーポレイテッドＡｉｌｅｒｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． | ペプチド模倣大環状分子およびその使用 |
| WO2017004548A1 (en) | 2015-07-01 | 2017-01-05 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| CN109153712B (zh) | 2016-04-19 | 2022-09-16 | 格里芬制药国际公司 | Peg化生物活性肽及其用途 |
Family Cites Families (33)
| 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 |
| US4563352A (en) * | 1982-10-04 | 1986-01-07 | The Salk Institute For Biological Studies | Human pancreatic GRF |
| US4595676A (en) * | 1983-04-26 | 1986-06-17 | The Salk Institute For Biological Studies | Rat hypothalamic GRF |
| 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 |
| US4529595A (en) * | 1983-01-13 | 1985-07-16 | The Salk Institute For Biological Studies | GRF Analogs |
| 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 |
| ATE53220T1 (de) * | 1983-03-07 | 1990-06-15 | Hoffmann La Roche | Polypeptide. |
| US4732972A (en) * | 1983-03-07 | 1988-03-22 | Hoffmann-La Roche Inc. | Polypeptides having growth hormone releasing activity |
| 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 |
| WO1989007113A1 (en) * | 1988-01-29 | 1989-08-10 | The Upjohn Company | Grf 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 (en) * | 1989-01-27 | 1990-07-28 | Alan R. Friedman | Stabilized, potent grf analogs |
| DK0477217T3 (da) * | 1989-06-16 | 1995-04-03 | Upjohn Co | Stabiliserede, potente GRF-analoge |
-
1992
- 1992-04-01 JP JP92506862A patent/JPH05507939A/ja active Pending
- 1992-04-01 EP EP92907635A patent/EP0542937A1/de not_active Withdrawn
- 1992-04-01 CA CA002084061A patent/CA2084061A1/en not_active Abandoned
- 1992-04-01 EP EP19920200995 patent/EP0525838A3/de active Pending
- 1992-04-01 WO PCT/EP1992/000723 patent/WO1992018531A1/en not_active Application Discontinuation
- 1992-04-01 AU AU14485/92A patent/AU662731B2/en not_active Ceased
- 1992-04-02 ZA ZA922420A patent/ZA922420B/xx unknown
- 1992-04-02 NZ NZ242209A patent/NZ242209A/en 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 |
|---|---|
| WO1992018531A1 (en) | 1992-10-29 |
| IE921121A1 (en) | 1992-10-21 |
| NZ242209A (en) | 1994-04-27 |
| AU662731B2 (en) | 1995-09-14 |
| EP0542937A1 (de) | 1993-05-26 |
| JPH05507939A (ja) | 1993-11-11 |
| IL101452A0 (en) | 1992-12-30 |
| EP0525838A2 (de) | 1993-02-03 |
| AU1448592A (en) | 1992-11-17 |
| EP0525838A3 (de) | 1993-02-10 |
| ZA922420B (en) | 1992-12-30 |
| US5846936A (en) | 1998-12-08 |
| CA2084061A1 (en) | 1992-10-10 |
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| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |