CA2487585A1 - Formulations for amylin agonist peptides - Google Patents
Formulations for amylin agonist peptides Download PDFInfo
- Publication number
- CA2487585A1 CA2487585A1 CA002487585A CA2487585A CA2487585A1 CA 2487585 A1 CA2487585 A1 CA 2487585A1 CA 002487585 A CA002487585 A CA 002487585A CA 2487585 A CA2487585 A CA 2487585A CA 2487585 A1 CA2487585 A1 CA 2487585A1
- Authority
- CA
- Canada
- Prior art keywords
- formulation
- insulin
- amylin
- amylin agonist
- delivery
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 262
- 238000009472 formulation Methods 0.000 title claims abstract description 235
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 title claims abstract description 128
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 title claims abstract description 125
- 239000000556 agonist Substances 0.000 title claims abstract description 73
- 108090000765 processed proteins & peptides Proteins 0.000 title description 110
- 102000004196 processed proteins & peptides Human genes 0.000 title description 18
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/159,779 US7312196B2 (en) | 1997-01-08 | 2002-05-31 | Formulations for amylin agonist peptides |
| US10/159,779 | 2002-05-31 | ||
| PCT/US2003/017226 WO2003101395A2 (en) | 2002-05-31 | 2003-05-30 | Formulations for amylin agonist peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2487585A1 true CA2487585A1 (en) | 2003-12-11 |
Family
ID=29709686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002487585A Abandoned CA2487585A1 (en) | 2002-05-31 | 2003-05-30 | Formulations for amylin agonist peptides |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7312196B2 (https=) |
| EP (1) | EP1551436A4 (https=) |
| JP (1) | JP2005537232A (https=) |
| AU (1) | AU2003238862B9 (https=) |
| CA (1) | CA2487585A1 (https=) |
| NZ (1) | NZ536813A (https=) |
| WO (1) | WO2003101395A2 (https=) |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US7312196B2 (en) * | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| WO2004037168A2 (en) * | 2002-10-18 | 2004-05-06 | Amylin Pharmaceuticals, Inc. | Treatment of pancreatitis with amylin |
| EP1663289A2 (en) * | 2003-08-29 | 2006-06-07 | Amylin Pharmaceuticals, Inc. | Methods for treating or ameliorating ghrelin-associated diseases and disorders |
| US20080318837A1 (en) * | 2003-12-26 | 2008-12-25 | Nastech Pharmaceutical Company Inc. | Pharmaceutical Formation For Increased Epithelial Permeability of Glucose-Regulating Peptide |
| WO2007065156A2 (en) * | 2005-12-02 | 2007-06-07 | Nastech Pharmaceutical Company Inc. | Pharmaceutical formulation for increased epithelial permeability of glucose-regulating peptide |
| US20050143303A1 (en) * | 2003-12-26 | 2005-06-30 | Nastech Pharmaceutical Company Inc. | Intranasal administration of glucose-regulating peptides |
| US20060210614A1 (en) * | 2003-12-26 | 2006-09-21 | Nastech Pharmaceutical Company Inc. | Method of treatment of a metabolic disease using intranasal administration of exendin peptide |
| US20060074025A1 (en) * | 2003-12-26 | 2006-04-06 | Nastech Pharmaceutical Company Inc. | Therapeutic formulations for transmucosal administration that increase glucagon-like peptide-1 bioavailability |
| ATE471340T1 (de) * | 2004-02-11 | 2010-07-15 | Amylin Pharmaceuticals Inc | Peptide der amylin familie, verfahren zu deren herstellung und verwendung |
| US7399744B2 (en) * | 2004-03-04 | 2008-07-15 | Amylin Pharmaceuticals, Inc. | Methods for affecting body composition |
| ES2633574T3 (es) | 2005-03-25 | 2017-09-22 | Regeneron Pharmaceuticals, Inc. | Formulaciones de antagonistas de VEGF |
| CN102343084A (zh) | 2005-03-31 | 2012-02-08 | 安米林药品公司 | 用于治疗精神病和精神障碍的胰淀素和胰淀素激动剂 |
| US20080318861A1 (en) * | 2005-12-08 | 2008-12-25 | Nastech Pharmaceutical Company Inc. | Mucosal Delivery of Stabilized Formulations of Exendin |
| EP1996224B1 (en) * | 2006-03-15 | 2012-11-07 | Novo Nordisk A/S | Mixtures of amylin and insulin |
| US7834050B2 (en) | 2006-03-29 | 2010-11-16 | Duke University | Small molecule insulin mimetics absent quinones |
| CA2654510C (en) | 2006-06-16 | 2015-03-17 | Regeneron Pharmaceuticals, Inc. | Vegf antagonist formulations suitable for intravitreal administration |
| WO2008124522A2 (en) * | 2007-04-04 | 2008-10-16 | Biodel, Inc. | Amylin formulations |
| US20100222251A1 (en) * | 2007-09-11 | 2010-09-02 | Novo Nordisk A/S | Mixture comprising an amylin peptide and a protracted insulin |
| EP2036539A1 (en) | 2007-09-11 | 2009-03-18 | Novo Nordisk A/S | Stable formulations of amylin and its analogues |
| EP2060268A1 (en) * | 2007-11-15 | 2009-05-20 | Novo Nordisk A/S | Pharmaceutical compositions for pulmonary or nasal delivery of peptides |
| EP2220115A2 (en) * | 2007-12-13 | 2010-08-25 | Glaxo Group Limited | Polypeptides, antibody variable domains & antagonists |
| MY152979A (en) | 2008-01-09 | 2014-12-15 | Sanofi Aventis Deutschland | Novel insulin derivatives having an extremely delayed time-action profile |
| EP2113253B1 (en) * | 2008-04-30 | 2010-03-31 | Immatics Biotechnologies GmbH | Novel formulations of tumour-associated peptides binding to human leukocyte antigen (HLA) class I or II molecules for vaccines |
| CA2724475C (en) * | 2008-05-16 | 2019-05-07 | The Children's Hospital Of Philadelphia | Genetic alterations on chromosomes 21q, 6q and 15q and methods of use thereof for the diagnosis and treatment of type i diabetes |
| RS59913B1 (sr) | 2008-10-17 | 2020-03-31 | Sanofi Aventis Deutschland | Kombinacija insulina i glp-1-agonista |
| US20130064834A1 (en) | 2008-12-15 | 2013-03-14 | Regeneron Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia using antibodies to pcsk9 |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| US9060927B2 (en) | 2009-03-03 | 2015-06-23 | Biodel Inc. | Insulin formulations for rapid uptake |
| CN101822822A (zh) * | 2009-03-04 | 2010-09-08 | 北京德众万全药物技术开发有限公司 | 一种普兰林肽的药物组合物及其制备方法 |
| CA2755068C (en) | 2009-03-12 | 2018-11-06 | Keybioscience Ag | Treatment of diabetes and metabolic syndrome |
| CN102596175A (zh) | 2009-07-06 | 2012-07-18 | 赛诺菲-安万特德国有限公司 | 含有甲硫氨酸的水性胰岛素制备物 |
| MY180661A (en) | 2009-11-13 | 2020-12-04 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a glp-1 agonist, an insulin and methionine |
| PT3345593T (pt) | 2009-11-13 | 2023-11-27 | Sanofi Aventis Deutschland | Composição farmacêutica compreendendo despro36exendina- 4(1-39)-lys6-nh2 e metionina |
| JO3417B1 (ar) | 2010-01-08 | 2019-10-20 | Regeneron Pharma | الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r |
| PL2611458T3 (pl) | 2010-08-30 | 2017-02-28 | Sanofi-Aventis Deutschland Gmbh | Zastosowanie AVE0010 do produkcji leku do leczenia cukrzycy typu 2 |
| CN102145164B (zh) * | 2010-12-16 | 2013-02-27 | 深圳市健元医药科技有限公司 | 一种更加稳定的iapp类似物注射剂 |
| SG192117A1 (en) | 2011-01-28 | 2013-08-30 | Sanofi Sa | Human antibodies to pcsk9 for use in methods of treating particular groups of subjects |
| JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| WO2012170796A1 (en) * | 2011-06-09 | 2012-12-13 | Amylin Pharmaceuticals, Inc. | Gel compositions |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| AR087693A1 (es) | 2011-08-29 | 2014-04-09 | Sanofi Aventis Deutschland | Combinacion farmaceutica para uso en el control glucemico en pacientes con diabetes de tipo 2 |
| TWI559929B (en) | 2011-09-01 | 2016-12-01 | Sanofi Aventis Deutschland | Pharmaceutical composition for use in the treatment of a neurodegenerative disease |
| HUE069234T2 (hu) | 2011-09-16 | 2025-02-28 | Regeneron Pharma | Eljárások lipoprotein(a)-szint csökkentésére proprotein-konvertáz szubtilizin/kexin 9 (PCSK9) inhibitorának beadásával |
| TWI589299B (zh) | 2011-10-11 | 2017-07-01 | 再生元醫藥公司 | 用於治療類風濕性關節炎之組成物及其使用方法 |
| KR102063028B1 (ko) | 2012-01-23 | 2020-01-07 | 리제너론 파아마슈티컬스, 인크. | 항-ａｎｇ2 항체를 함유하는 안정화된 제형 |
| WO2013177565A1 (en) | 2012-05-25 | 2013-11-28 | Amylin Pharmaceuticals, Llc | Insulin-pramlintide compositions and methods for making and using them |
| AR092325A1 (es) | 2012-05-31 | 2015-04-15 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-dll4 y kit |
| UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
| AU2013366692B2 (en) | 2012-12-21 | 2017-11-23 | Sanofi | Dual GLP1/GIP or trigonal GLP1/GIP/Glucagon agonists |
| US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
| US10313682B2 (en) * | 2013-08-26 | 2019-06-04 | Qualcomm Incorporated | Determining regions when performing intra block copying |
| CN118105480A (zh) | 2013-11-12 | 2024-05-31 | 赛诺菲生物技术公司 | 用于与pcsk9抑制剂一起使用的给药方案 |
| EP3080154B1 (en) | 2013-12-13 | 2018-02-07 | Sanofi | Dual glp-1/gip receptor agonists |
| WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
| EP3080152A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Non-acylated exendin-4 peptide analogues |
| WO2015086733A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Dual glp-1/glucagon receptor agonists |
| TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽－４（Ｅｘｅｎｄｉｎ－４）之肽類雙重ＧＬＰ－１／升糖素受體促效劑 |
| TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重ｇｌｐ－１／昇糖素受體激動劑之艾塞那肽－４衍生物 |
| TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自ｅｘｅｎｄｉｎ－４之雙重ｇｌｐ－１／升糖素受體促效劑 |
| US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
| US9656017B2 (en) | 2014-06-20 | 2017-05-23 | Howard E. Greene | Infusion delivery devices and methods |
| KR20230074283A (ko) | 2014-07-16 | 2023-05-26 | 사노피 바이오테크놀로지 | 이형접합성 가족성 고콜레스테롤혈증(heFH) 환자의 치료방법 |
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| MX2020005916A (es) | 2017-12-07 | 2020-10-19 | Adocia | Composiciones en forma de una solución acuosa inyectable que comprende amilina, un receptor agonista de amilina o un análogo de amilina y un copoliaminoácido. |
| WO2019110797A1 (fr) | 2017-12-07 | 2019-06-13 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un co-polyaminoacide |
| BR112020011479A2 (pt) | 2017-12-07 | 2020-11-17 | Adocia | composições na forma de uma solução aquosa injetável caracterizada pelo fato de que compreende amilina, um agonista do receptor de amilina ou um análogo de amilina e um co-poliaminoácido |
| FR3083085B1 (fr) * | 2018-06-29 | 2020-10-02 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un co-polyaminoacide |
| MA54861A (fr) | 2019-01-31 | 2021-12-08 | Regeneron Pharma | Anticorps anti-récepteur de l'il6 pour traiter l'arthrite idiopathique juvénile |
| SG11202111742QA (en) | 2019-04-24 | 2021-11-29 | Sanofi Biotechnology | Methods of diagnosis and treatment of rheumatoid arthritis |
| CA3142710A1 (en) | 2019-06-04 | 2020-12-10 | Sanofi Biotechnology | Compositions and methods for treating pain in subjects with rheumatoid arthritis |
| JP7761567B2 (ja) * | 2020-02-18 | 2025-10-28 | ノヴォ ノルディスク アー／エス | 医薬製剤 |
| JP7731153B2 (ja) * | 2021-01-19 | 2025-08-29 | 江▲蘇▼普莱医▲藥▼生物技▲術▼有限公司 | 抗菌ペプチド液体組成物およびその製剤 |
| TWI880227B (zh) * | 2022-05-30 | 2025-04-11 | 丹麥商西蘭製藥公司 | 澱粉素類似物之液體調配物 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4654324A (en) | 1981-08-27 | 1987-03-31 | Eli Lilly And Company | Human proinsulin pharmaceutical formulations |
| US5367052A (en) | 1987-04-27 | 1994-11-22 | Amylin Pharmaceuticals, Inc. | Amylin peptides |
| GB8720115D0 (en) | 1987-08-26 | 1987-09-30 | Cooper G J S | Treatment of diabetes mellitus |
| US5280014A (en) | 1988-01-11 | 1994-01-18 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and essential hypertension and related disorders |
| US5364841A (en) | 1988-01-11 | 1994-11-15 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and essential hypertension and related disorders |
| US5266561A (en) | 1988-01-11 | 1993-11-30 | Amylin Pharmaceuticals, Inc. | Treatment of type 2 diabetes mellitus |
| US5175145A (en) | 1988-08-26 | 1992-12-29 | Amylin Pharmaceuticals, Inc. | Treatment of diabetes mellitus with amylin agonists |
| US5321008A (en) | 1991-01-10 | 1994-06-14 | Amylin Pharmaceuticals, Inc. | Methods and compositions for treatment of diabetes mellitus, hypoglycemia, and other conditions |
| US5234906A (en) * | 1991-01-10 | 1993-08-10 | Amylin Pharmaceuticals, Inc. | Hyperglycemic compositions |
| HU222249B1 (hu) | 1991-03-08 | 2003-05-28 | Amylin Pharmaceuticals Inc. | Eljárás amilin agonista peptidszármazékok és ezeket tartalmazó gyógyszerkészítmények előállítására |
| CA2072165C (en) * | 1991-06-24 | 2000-09-19 | Carlton E. Ash | Process for preparing poly(arylene sulfide) polymers using waste material |
| DE4126983A1 (de) | 1991-08-15 | 1993-02-18 | Boehringer Mannheim Gmbh | Verfahren zur herstellung von humanprotein-enthaltenden, konservierten arzneimitteln fuer infusions- oder injektionszwecke |
| CA2100745C (en) | 1991-11-19 | 2007-07-31 | Laura S. L. Gaeta | Amylin agonist peptides and uses therefor |
| US5739106A (en) * | 1995-06-07 | 1998-04-14 | Rink; Timothy J. | Appetite regulating compositions |
| US6143718A (en) | 1995-06-07 | 2000-11-07 | Amylin Pharmaceuticals, Inc. | Treatment of Type II diabetes mellutis with amylin agonists |
| WO1997009025A1 (en) | 1995-09-07 | 1997-03-13 | Elan Medical Technologies Limited | Medicament conversion system |
| US5783556A (en) | 1996-08-13 | 1998-07-21 | Genentech, Inc. | Formulated insulin-containing composition |
| DE19649350A1 (de) * | 1996-11-28 | 1998-06-04 | Hoechst Ag | Inositolglykane mit insulinartiger Wirkung |
| US6136784A (en) * | 1997-01-08 | 2000-10-24 | Amylin Pharmaceuticals, Inc. | Amylin agonist pharmaceutical compositions containing insulin |
| US7312196B2 (en) * | 1997-01-08 | 2007-12-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US6410511B2 (en) * | 1997-01-08 | 2002-06-25 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides |
| US7910548B2 (en) | 1997-06-06 | 2011-03-22 | Amylin Pharmaceuticals, Inc. | Methods for treating obesity |
| EP1044015B1 (en) * | 1998-01-09 | 2008-10-08 | Amylin Pharmaceuticals, Inc. | Formulations for amylin agonist peptides with insulin |
-
2002
- 2002-05-31 US US10/159,779 patent/US7312196B2/en not_active Expired - Fee Related
-
2003
- 2003-05-30 AU AU2003238862A patent/AU2003238862B9/en not_active Ceased
- 2003-05-30 WO PCT/US2003/017226 patent/WO2003101395A2/en not_active Ceased
- 2003-05-30 JP JP2004508753A patent/JP2005537232A/ja active Pending
- 2003-05-30 NZ NZ536813A patent/NZ536813A/en not_active IP Right Cessation
- 2003-05-30 EP EP03734319A patent/EP1551436A4/en not_active Withdrawn
- 2003-05-30 CA CA002487585A patent/CA2487585A1/en not_active Abandoned
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2007
- 2007-12-20 US US11/962,034 patent/US20090018053A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US7312196B2 (en) | 2007-12-25 |
| AU2003238862B2 (en) | 2008-07-31 |
| WO2003101395A2 (en) | 2003-12-11 |
| AU2003238862B9 (en) | 2008-08-21 |
| NZ536813A (en) | 2007-05-31 |
| EP1551436A2 (en) | 2005-07-13 |
| EP1551436A4 (en) | 2008-10-15 |
| WO2003101395A3 (en) | 2004-10-14 |
| US20090018053A1 (en) | 2009-01-15 |
| US20030092606A1 (en) | 2003-05-15 |
| AU2003238862A1 (en) | 2003-12-19 |
| JP2005537232A (ja) | 2005-12-08 |
| AU2003238862A2 (en) | 2003-12-19 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |