NO341986B1 - Pegylert PTH som PTH reseptor modulatorer, sammensetninger inneholdende slike og anvendelser derav - Google Patents
Pegylert PTH som PTH reseptor modulatorer, sammensetninger inneholdende slike og anvendelser derav Download PDFInfo
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- NO341986B1 NO341986B1 NO20091691A NO20091691A NO341986B1 NO 341986 B1 NO341986 B1 NO 341986B1 NO 20091691 A NO20091691 A NO 20091691A NO 20091691 A NO20091691 A NO 20091691A NO 341986 B1 NO341986 B1 NO 341986B1
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- Prior art keywords
- bone
- compound according
- pharmaceutically acceptable
- acceptable salt
- mpeg
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Classifications
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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
- C07K14/635—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
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- A—HUMAN NECESSITIES
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- 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
- A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
Landscapes
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- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Radar Systems Or Details Thereof (AREA)
- Input Circuits Of Receivers And Coupling Of Receivers And Audio Equipment (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82938306P | 2006-10-13 | 2006-10-13 | |
| PCT/US2007/080367 WO2008048784A1 (en) | 2006-10-13 | 2007-10-04 | Pegylated pth as pth receptor modulators and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20091691L NO20091691L (no) | 2009-05-11 |
| NO341986B1 true NO341986B1 (no) | 2018-03-12 |
Family
ID=42828673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20091691A NO341986B1 (no) | 2006-10-13 | 2009-04-28 | Pegylert PTH som PTH reseptor modulatorer, sammensetninger inneholdende slike og anvendelser derav |
Country Status (16)
| Country | Link |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2964463C (en) | 2014-10-22 | 2024-02-13 | Extend Biosciences, Inc. | Therapeutic vitamin d conjugates |
| MA45277A (fr) * | 2016-03-01 | 2019-01-09 | Ascendis Pharma Bone Diseases As | Promédicaments de pth |
| SMT202500059T1 (it) | 2016-09-29 | 2025-03-12 | Ascendis Pharma Bone Diseases As | Composti pth a rilascio controllato |
| CA3037447A1 (en) * | 2016-09-29 | 2018-04-05 | Ascendis Pharma Bone Diseases A/S | Pth compounds with low peak-to-trough ratios |
| PL3518960T3 (pl) | 2016-09-29 | 2023-12-27 | Ascendis Pharma Bone Diseases A/S | Schemat dawkowania związku pth o kontrolowanym uwalnianiu |
| WO2019232283A1 (en) * | 2018-05-30 | 2019-12-05 | Purdue Research Foundation | Targeting anabolic drugs for accelerated fracture repair |
| CN113423383A (zh) | 2019-02-11 | 2021-09-21 | 阿森迪斯药物骨疾病股份有限公司 | Pth缀合物的液体药物制剂 |
| AU2023353057A1 (en) | 2022-09-30 | 2025-05-01 | Extend Biosciences, Inc. | Long-acting parathyroid hormone |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004084918A1 (ja) * | 2003-03-25 | 2004-10-07 | Sekisui Chemical Co., Ltd. | 皮膚止痒外用組成物 |
| EP1477496A1 (en) * | 2002-02-01 | 2004-11-17 | Chugai Seiyaku Kabushiki Kaisha | Peg-conjugated pth or peg-conjugated pth derivate |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| FR2550204B1 (fr) * | 1983-08-05 | 1987-11-13 | Toyo Jozo Kk | Derives peptidiques de (nle8,nle1b, tyr34)-h-pth |
| JPS6360940A (ja) | 1986-09-01 | 1988-03-17 | Toyo Jozo Co Ltd | 白内障の予防または治療剤 |
| US4771124A (en) * | 1987-05-26 | 1988-09-13 | Merck & Co., Inc. | Parathyroid hormone antagonists with simplified synthetic methodology |
| EP0293158A3 (en) | 1987-05-26 | 1990-05-09 | Merck & Co. Inc. | Parathyroid hormone antagonists |
| JPH0532696A (ja) | 1990-09-28 | 1993-02-09 | Takeda Chem Ind Ltd | 副甲状腺ホルモン誘導体 |
| JPH05271279A (ja) * | 1991-08-07 | 1993-10-19 | Takeda Chem Ind Ltd | ヒト副甲状腺ホルモンムテインおよびその製造法 |
| US5814603A (en) | 1992-06-12 | 1998-09-29 | Affymax Technologies N.V. | Compounds with PTH activity |
| US5589452A (en) * | 1992-07-14 | 1996-12-31 | Syntex (U.S.A.) Inc. | Analogs of parathyroid hormone and parathyroid hormone related peptide: synthesis and use for the treatment of osteoporosis |
| AU672790B2 (en) * | 1992-07-15 | 1996-10-17 | Novartis Ag | Variants of parathyroid hormone and its fragments |
| US5556940A (en) * | 1994-06-20 | 1996-09-17 | National Research Council Of Canada | Parathyroid hormone analogues for the treatment of osteoporosis |
| US6110892A (en) * | 1994-06-20 | 2000-08-29 | National Research Council Of Canada | Parathyroid hormone analogues for the treatment of osteoporosis |
| US5747456A (en) | 1994-12-19 | 1998-05-05 | Beth Israel Deaconess Medical Center | Continuous low-dose administration of parathyroid hormone or its agonist |
| US5717062A (en) * | 1995-06-07 | 1998-02-10 | Beth Israel Hospital Association | Cyclic analogs of PTH and PTHrP |
| CA2178894A1 (en) | 1995-06-15 | 1996-12-16 | Tsunehiko Fukuda | Parathyroid hormone derivatives and their use |
| US5955574A (en) * | 1995-07-13 | 1999-09-21 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A. | Analogs of parathyroid hormone |
| US6544949B1 (en) * | 1995-07-13 | 2003-04-08 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Analogs of parathyroid hormone |
| US5723577A (en) | 1995-07-13 | 1998-03-03 | Biomeasure Inc. | Analogs of parathyroid hormone |
| SI9720057A (sl) | 1996-08-02 | 1999-12-31 | National Research Council Of Canada | Paratiroidni hormonski analogi za zdravljenje osteoporoze |
| HUP0003349A3 (en) * | 1997-05-14 | 2001-12-28 | Aventis Pharmaceuticals Inc Co | Peptide parathyroid hormone analogs, pharmaceutical compositions comprising thereof and their use |
| EP1030658A1 (en) * | 1997-10-14 | 2000-08-30 | Eli Lilly And Company | Method of building and maintaining bone |
| CA2321026A1 (en) | 1998-03-09 | 1999-09-16 | Zealand Pharmaceuticals A/S | Pharmacologically active peptide conjugates having a reduced tendency towards enzymatic hydrolysis |
| EA200001071A1 (ru) | 1998-04-15 | 2001-08-27 | Авентис Фармасьютикалз Продактс Инк. | Способ получения полимер-связанных циклических пептидов |
| HUP0300891A2 (hu) | 1998-05-05 | 2003-07-28 | Beth Israel Deaconess Medical Center, Inc. | PTH2 receptor szelektív vegyületek és alkalmazásuk gyógyszerkészítmények előállÍtására |
| US6316410B1 (en) * | 1999-09-22 | 2001-11-13 | National Research Council Of Canada | Parathyroid hormone analogues for the treatment of osteoporosis |
| US7022815B1 (en) * | 1999-09-29 | 2006-04-04 | The General Hospital Corporation | Polypeptide derivatives of parathyroid hormone (PTH) |
| WO2001023521A2 (en) | 1999-09-29 | 2001-04-05 | The General Hospital Corporation | Polypeptide derivatives of parathyroid hormone (pth) |
| US6756480B2 (en) | 2000-04-27 | 2004-06-29 | Amgen Inc. | Modulators of receptors for parathyroid hormone and parathyroid hormone-related protein |
| US20050124537A1 (en) * | 2000-04-27 | 2005-06-09 | Amgen Inc. | Modulators of receptors for parathyroid hormone and parathyroid hormone-related protein |
| EP1439854B1 (en) * | 2001-07-23 | 2016-12-14 | The General Hospital Corporation | Conformationally constrained parathyroid hormone (pth) analogs |
| US7799757B2 (en) * | 2002-06-13 | 2010-09-21 | Michael Chorev | Analogs of parathyroid hormone and PTH-related protein as bone anabolic agents |
| TW533925U (en) * | 2002-09-26 | 2003-05-21 | Lee Yeong Ind Co Ltd | Improvement of speed-changing transmission mechanism for cutting tools of drill sharpening machine |
| WO2004060386A1 (en) | 2002-11-01 | 2004-07-22 | Amgen, Inc. | Modulators of receptors for parathyrois hormone and parathyroid hormone-related protein |
| MXPA05007151A (es) | 2002-12-31 | 2005-09-21 | Nektar Therapeutics Al Corp | Polimeros terminados en maleimida hidroliticamente estables. |
| US20040220094A1 (en) * | 2003-05-01 | 2004-11-04 | Skinner Keith K. | Inverse agonist and agonist peptides that stimulate/inhibit hair growth |
| EP1758927A4 (en) | 2004-01-21 | 2008-09-17 | Unigene Lab Inc | PARATHYROID HORMONE AMIDE FRAGMENTS AND USES THEREOF |
-
2007
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- 2007-10-04 KR KR1020097007424A patent/KR101108354B1/ko not_active Expired - Fee Related
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1477496A1 (en) * | 2002-02-01 | 2004-11-17 | Chugai Seiyaku Kabushiki Kaisha | Peg-conjugated pth or peg-conjugated pth derivate |
| WO2004084918A1 (ja) * | 2003-03-25 | 2004-10-07 | Sekisui Chemical Co., Ltd. | 皮膚止痒外用組成物 |
Non-Patent Citations (1)
| Title |
|---|
| NA DONG HEE et al., Capillary electrophoretic characterization of PEGylated human parathyroid hormone with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Analytical Biochemistry, 2004, vol. 331 (2), side 322-328, Dated: 01.01.0001 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101522709A (zh) | 2009-09-02 |
| BRPI0719885A2 (pt) | 2014-04-29 |
| KR20090067168A (ko) | 2009-06-24 |
| AU2007313001A1 (en) | 2008-04-24 |
| US7820179B2 (en) | 2010-10-26 |
| ATE469173T1 (de) | 2010-06-15 |
| NO20091691L (no) | 2009-05-11 |
| JP2010506844A (ja) | 2010-03-04 |
| AU2007313001B2 (en) | 2012-03-22 |
| MX2009003740A (es) | 2009-04-22 |
| BRPI0719885B1 (pt) | 2018-12-11 |
| EA200970376A1 (ru) | 2009-10-30 |
| DK2084183T3 (da) | 2010-08-16 |
| WO2008048784A1 (en) | 2008-04-24 |
| BRPI0719885B8 (pt) | 2021-05-25 |
| EP2084183A1 (en) | 2009-08-05 |
| EA014696B1 (ru) | 2010-12-30 |
| CN101522709B (zh) | 2013-03-20 |
| KR101108354B1 (ko) | 2012-01-25 |
| JP5200027B2 (ja) | 2013-05-15 |
| EP2084183B1 (en) | 2010-05-26 |
| US20090253630A1 (en) | 2009-10-08 |
| CA2672907A1 (en) | 2008-04-24 |
| SI2084183T1 (sl) | 2010-09-30 |
| PL2084183T3 (pl) | 2010-10-29 |
| CA2672907C (en) | 2013-08-06 |
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