UA80331C2 - Human serum albumin-free stabilised interferon liquid formulations - Google Patents
Human serum albumin-free stabilised interferon liquid formulations Download PDFInfo
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- UA80331C2 UA80331C2 UAA200509798A UA2005009798A UA80331C2 UA 80331 C2 UA80331 C2 UA 80331C2 UA A200509798 A UAA200509798 A UA A200509798A UA 2005009798 A UA2005009798 A UA 2005009798A UA 80331 C2 UA80331 C2 UA 80331C2
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- composition according
- concentration
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- interferon
- solution
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03101210 | 2003-05-01 | ||
| PCT/EP2004/004806 WO2004096263A2 (en) | 2003-05-01 | 2004-04-29 | Human serum albumin-free stabilized interferon liquid formulations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA80331C2 true UA80331C2 (en) | 2007-09-10 |
Family
ID=36908159
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA200509798A UA80331C2 (en) | 2003-05-01 | 2004-04-29 | Human serum albumin-free stabilised interferon liquid formulations |
| UAA200704143A UA94032C2 (ru) | 2003-05-01 | 2004-04-29 | Жидкая стабализированная композиция интерферона без hsa |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA200704143A UA94032C2 (ru) | 2003-05-01 | 2004-04-29 | Жидкая стабализированная композиция интерферона без hsa |
Country Status (29)
| Country | Link |
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| US (1) | US8309069B2 (xx) |
| EP (1) | EP1617861B1 (xx) |
| JP (2) | JP4870550B2 (xx) |
| KR (1) | KR101116058B1 (xx) |
| CN (1) | CN1816347B (xx) |
| AR (1) | AR044147A1 (xx) |
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| BR (1) | BRPI0410488B8 (xx) |
| CA (1) | CA2521560A1 (xx) |
| DK (1) | DK1617861T3 (xx) |
| EA (2) | EA009995B1 (xx) |
| ES (1) | ES2417061T3 (xx) |
| HK (1) | HK1088847A1 (xx) |
| HR (1) | HRP20130512T1 (xx) |
| IL (1) | IL171709A (xx) |
| ME (1) | ME00404B (xx) |
| MX (1) | MXPA05011718A (xx) |
| MY (1) | MY151121A (xx) |
| NO (1) | NO335674B1 (xx) |
| NZ (2) | NZ566625A (xx) |
| PL (1) | PL1617861T3 (xx) |
| PT (1) | PT1617861E (xx) |
| RS (1) | RS52869B (xx) |
| SG (1) | SG159389A1 (xx) |
| SI (1) | SI1617861T1 (xx) |
| TW (1) | TWI272948B (xx) |
| UA (2) | UA80331C2 (xx) |
| WO (1) | WO2004096263A2 (xx) |
| ZA (2) | ZA200508124B (xx) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2374530T3 (es) * | 2003-12-11 | 2012-02-17 | Ares Trading S.A. | Formulaciones líquidas de interferón estabilizado. |
| CA2566364A1 (en) * | 2004-05-17 | 2005-11-24 | Ares Trading S.A. | Hydrogel interferon formulations |
| WO2005117949A1 (en) * | 2004-06-01 | 2005-12-15 | Ares Trading S.A. | Stabilized interferon liquid formulations |
| ATE543506T1 (de) * | 2004-06-01 | 2012-02-15 | Ares Trading Sa | Methode zur stabilisierung von proteinen |
| ES2378686T3 (es) * | 2005-09-14 | 2012-04-17 | Ares Trading S.A. | Método para la determinación de poloxámeros |
| US9925151B2 (en) | 2006-05-24 | 2018-03-27 | Merck Serono Sa | Cladribine regimen for treating multiple sclerosis |
| WO2008066322A1 (en) * | 2006-11-28 | 2008-06-05 | Daewoong Co., Ltd. | A stable hsa-free and antioxidant-free pharmaceutical composition comprising interferon-beta |
| JPWO2008065752A1 (ja) * | 2006-11-30 | 2010-03-04 | 国立大学法人北海道大学 | ｄｉＲＮＡを有効成分とする免疫治療用薬剤 |
| WO2008119160A1 (en) * | 2007-03-30 | 2008-10-09 | Pharmaderm Laboratories Ltd. | Biphasic lipid-vesicle composition and method for treating cervical dysplasia by intravaginal delivery |
| WO2008145323A1 (en) * | 2007-05-31 | 2008-12-04 | F. Hoffmann-La Roche Ag | Pharmaceutical formulation for interferons |
| JP5563475B2 (ja) | 2007-12-20 | 2014-07-30 | メルク セローノ ソシエテ アノニム | Ｐｅｇインターフェロン−ベータ製剤 |
| KR20150074167A (ko) | 2012-10-26 | 2015-07-01 | 루핀 리미티드 | Ｐｅｇ 인터페론 알파-2ｂ의 안정한 약학 조성물 |
| US10159646B2 (en) | 2013-08-12 | 2018-12-25 | Altum-Avro Pharma Partnership | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| US8986732B2 (en) | 2013-08-12 | 2015-03-24 | Helix Biopharma Corporation | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| EP3200767A1 (en) * | 2014-09-23 | 2017-08-09 | F.Hoffmann-La Roche Ag | Stable, benzyl alcohol-free aqueous solution formulations containing alpha-type interferon |
| US9937223B2 (en) | 2015-01-30 | 2018-04-10 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US9925233B2 (en) | 2015-01-30 | 2018-03-27 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US9744209B2 (en) | 2015-01-30 | 2017-08-29 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US9744239B2 (en) | 2015-01-30 | 2017-08-29 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US9687526B2 (en) | 2015-01-30 | 2017-06-27 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| US9750785B2 (en) | 2015-01-30 | 2017-09-05 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
| KR101943160B1 (ko) | 2016-10-06 | 2019-01-30 | 에이비온 주식회사 | 인터페론 베타 변이체의 안정화 제제 |
| KR20240118230A (ko) * | 2023-01-26 | 2024-08-05 | 에이비온 주식회사 | 인터페론 베타 건조 분말 제제 및 이의 제조방법 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| US4588585A (en) | 1982-10-19 | 1986-05-13 | Cetus Corporation | Human recombinant cysteine depleted interferon-β muteins |
| US4737462A (en) | 1982-10-19 | 1988-04-12 | Cetus Corporation | Structural genes, plasmids and transformed cells for producing cysteine depleted muteins of interferon-β |
| US4959314A (en) | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
| US5116943A (en) | 1985-01-18 | 1992-05-26 | Cetus Corporation | Oxidation-resistant muteins of Il-2 and other protein |
| US5017691A (en) | 1986-07-03 | 1991-05-21 | Schering Corporation | Mammalian interleukin-4 |
| US4879111A (en) | 1986-04-17 | 1989-11-07 | Cetus Corporation | Treatment of infections with lymphokines |
| US4965195A (en) | 1987-10-26 | 1990-10-23 | Immunex Corp. | Interleukin-7 |
| US4904584A (en) | 1987-12-23 | 1990-02-27 | Genetics Institute, Inc. | Site-specific homogeneous modification of polypeptides |
| IT1272252B (it) | 1994-05-16 | 1997-06-16 | Applied Research Systems | Formulazioni liquide di interferone beta |
| JP2758154B2 (ja) * | 1995-04-06 | 1998-05-28 | エフ・ホフマン−ラ ロシユ アーゲー | インターフェロンを含む液体製剤 |
| ZA9610374B (en) * | 1995-12-11 | 1997-06-23 | Elan Med Tech | Cartridge-based drug delivery device |
| WO1998028007A1 (en) * | 1996-12-24 | 1998-07-02 | Biogen, Inc. | Stable liquid interferon formulations |
| US6013253A (en) | 1997-08-15 | 2000-01-11 | Amgen, Inc. | Treatment of multiple sclerosis using consensus interferon and IL-1 receptor antagonist |
| JP4293497B2 (ja) * | 1997-09-23 | 2009-07-08 | レントシュレール ビオテクノロジー ゲー・エム・ベー・ハー | インターフェロン−β液状組成物 |
| CA2311681A1 (en) * | 1997-12-08 | 1999-06-17 | Genentech, Inc. | Human interferon-epsilon: a type i interferon |
| CZ298597B6 (cs) | 1998-04-28 | 2007-11-21 | Applied Research Systems Ars Holding N. V. | Zpusob postupné vazby polyethylenglykolových skupin na polypeptid |
| DE59914392D1 (de) * | 1998-05-11 | 2007-08-09 | Basf Ag | Verfahren zur herstellung von isoxazolin-3-yl-acylbenzolen |
| CN1175901C (zh) * | 1999-12-06 | 2004-11-17 | 天津华立达生物工程有限公司 | 一种稳定的干扰素水溶液 |
| US6465425B1 (en) * | 2000-02-10 | 2002-10-15 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of biologically active acid-stable or free sulfhydryl-containing proteins |
| US6887462B2 (en) | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
| AR034749A1 (es) * | 2001-07-09 | 2004-03-17 | Schering Ag | Formulaciones de interferon beta humano |
| ES2374530T3 (es) | 2003-12-11 | 2012-02-17 | Ares Trading S.A. | Formulaciones líquidas de interferón estabilizado. |
| CA2566364A1 (en) | 2004-05-17 | 2005-11-24 | Ares Trading S.A. | Hydrogel interferon formulations |
| ATE543506T1 (de) | 2004-06-01 | 2012-02-15 | Ares Trading Sa | Methode zur stabilisierung von proteinen |
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2004
- 2004-04-23 TW TW093111368A patent/TWI272948B/zh not_active IP Right Cessation
- 2004-04-29 JP JP2006505383A patent/JP4870550B2/ja not_active Expired - Lifetime
- 2004-04-29 EP EP04730264.1A patent/EP1617861B1/en not_active Expired - Lifetime
- 2004-04-29 CN CN2004800188759A patent/CN1816347B/zh not_active Expired - Lifetime
- 2004-04-29 RS YU20050821A patent/RS52869B/sr unknown
- 2004-04-29 ME MEP-2008-604A patent/ME00404B/me unknown
- 2004-04-29 ZA ZA200508124A patent/ZA200508124B/xx unknown
- 2004-04-29 PT PT47302641T patent/PT1617861E/pt unknown
- 2004-04-29 UA UAA200509798A patent/UA80331C2/uk unknown
- 2004-04-29 SG SG200705206-1A patent/SG159389A1/en unknown
- 2004-04-29 NZ NZ566625A patent/NZ566625A/en not_active IP Right Cessation
- 2004-04-29 DK DK04730264.1T patent/DK1617861T3/da active
- 2004-04-29 CA CA002521560A patent/CA2521560A1/en not_active Withdrawn
- 2004-04-29 BR BRPI0410488A patent/BRPI0410488B8/pt active IP Right Grant
- 2004-04-29 KR KR1020057020444A patent/KR101116058B1/ko active IP Right Grant
- 2004-04-29 SI SI200432066T patent/SI1617861T1/sl unknown
- 2004-04-29 MX MXPA05011718A patent/MXPA05011718A/es active IP Right Grant
- 2004-04-29 NZ NZ542912A patent/NZ542912A/en not_active IP Right Cessation
- 2004-04-29 AU AU2004233603A patent/AU2004233603B2/en not_active Expired
- 2004-04-29 US US10/554,602 patent/US8309069B2/en active Active
- 2004-04-29 WO PCT/EP2004/004806 patent/WO2004096263A2/en active Application Filing
- 2004-04-29 ES ES04730264T patent/ES2417061T3/es not_active Expired - Lifetime
- 2004-04-29 EA EA200501699A patent/EA009995B1/ru not_active IP Right Cessation
- 2004-04-29 PL PL04730264T patent/PL1617861T3/pl unknown
- 2004-04-29 UA UAA200704143A patent/UA94032C2/ru unknown
- 2004-04-29 EA EA200800327A patent/EA200800327A1/ru unknown
- 2004-04-29 MY MYPI20041605 patent/MY151121A/en unknown
- 2004-04-30 AR ARP040101486A patent/AR044147A1/es not_active Application Discontinuation
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2005
- 2005-11-01 IL IL171709A patent/IL171709A/en active IP Right Grant
- 2005-11-30 NO NO20055666A patent/NO335674B1/no unknown
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2006
- 2006-10-03 HK HK06110914.6A patent/HK1088847A1/xx not_active IP Right Cessation
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2007
- 2007-10-04 ZA ZA200708484A patent/ZA200708484B/xx unknown
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2009
- 2009-03-31 AU AU2009201261A patent/AU2009201261A1/en not_active Abandoned
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2011
- 2011-07-15 JP JP2011156524A patent/JP5346065B2/ja not_active Expired - Lifetime
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- 2013-06-11 HR HRP20130512TT patent/HRP20130512T1/hr unknown
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