RU2581020C2 - Композиции вакцин - Google Patents
Композиции вакцин Download PDFInfo
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- RU2581020C2 RU2581020C2 RU2012131162/15A RU2012131162A RU2581020C2 RU 2581020 C2 RU2581020 C2 RU 2581020C2 RU 2012131162/15 A RU2012131162/15 A RU 2012131162/15A RU 2012131162 A RU2012131162 A RU 2012131162A RU 2581020 C2 RU2581020 C2 RU 2581020C2
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- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| US61/289,083 | 2009-12-22 | ||
| PCT/IB2010/055674 WO2011077309A2 (en) | 2009-12-22 | 2010-12-08 | Vaccine compositions |
Publications (2)
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| RU2012131162A RU2012131162A (ru) | 2014-01-27 |
| RU2581020C2 true RU2581020C2 (ru) | 2016-04-10 |
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| RU2012131162/15A RU2581020C2 (ru) | 2009-12-22 | 2010-12-08 | Композиции вакцин |
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| EP (2) | EP3257525A3 (enExample) |
| JP (2) | JP6007105B2 (enExample) |
| KR (1) | KR20120120185A (enExample) |
| CN (2) | CN102762224A (enExample) |
| AU (1) | AU2010334428B2 (enExample) |
| CA (1) | CA2785585A1 (enExample) |
| IL (1) | IL220308A0 (enExample) |
| MX (1) | MX337070B (enExample) |
| NZ (2) | NZ600978A (enExample) |
| RU (1) | RU2581020C2 (enExample) |
| SG (2) | SG10201408505SA (enExample) |
| WO (1) | WO2011077309A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112012020855B8 (pt) * | 2010-02-21 | 2021-05-25 | Bayer Healthcare Llc | método para produzir um conjugado de biomolécula |
| KR101502360B1 (ko) * | 2013-03-20 | 2015-03-25 | 주식회사 옵티팜 | 신규한 국내형 돼지생식기호흡기증후군 바이러스 |
| EP3824906A1 (en) | 2016-12-21 | 2021-05-26 | Amgen Inc. | Anti-tnf alpha antibody formulations |
| KR20210027493A (ko) | 2018-07-19 | 2021-03-10 | 주식회사 헬릭스미스 | 네이키드 dna 유전자 요법을 위한 동결 건조된 약제학적 조성물 |
| US20220273755A1 (en) * | 2019-11-21 | 2022-09-01 | Multiple Fortune Holding Limited | Pharmaceutical composition, use and method for applying ganoderma microsporum immunomodulatory protein and keyhole limpet hemocyanin in carcinoma treatment |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999006840A1 (en) * | 1997-07-31 | 1999-02-11 | Metra Biosystems, Inc. | Collagen-peptide assay method |
| CA2530172A1 (en) * | 2003-06-27 | 2005-02-10 | Abgenix, Inc. | Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof |
| WO2007056061A2 (en) * | 2005-11-02 | 2007-05-18 | Duke University | Concurrent chemotherapy and immunotherapy |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH600453A5 (enExample) | 1976-12-30 | 1978-06-15 | Autelca Ag | |
| GB8815795D0 (en) | 1988-07-02 | 1988-08-10 | Bkl Extrusions Ltd | Glazing bead |
| NZ230747A (en) | 1988-09-30 | 1992-05-26 | Bror Morein | Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina |
| HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
| ATE135373T1 (de) | 1989-09-08 | 1996-03-15 | Univ Johns Hopkins | Modifikationen der struktur des egf-rezeptor-gens in menschlichen glioma |
| EP0761231B1 (en) | 1992-06-25 | 2000-01-12 | SMITHKLINE BEECHAM BIOLOGICALS s.a. | Vaccine composition containing adjuvants |
| ES2162139T5 (es) | 1993-03-23 | 2008-05-16 | Smithkline Beecham Biologicals S.A. | Composiciones de vacuna que contienen monofosforil-lipido a 3-o-desacilado. |
| GB9326253D0 (en) | 1993-12-23 | 1994-02-23 | Smithkline Beecham Biolog | Vaccines |
| FR2719479B1 (fr) * | 1994-05-04 | 1996-07-26 | Sanofi Elf | Formulation stable lyophilisée comprenant une protéine: kit de dosage. |
| EP0772619B2 (en) | 1994-07-15 | 2010-12-08 | The University of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| AUPM873294A0 (en) | 1994-10-12 | 1994-11-03 | Csl Limited | Saponin preparations and use thereof in iscoms |
| DE69532767T2 (de) * | 1994-11-28 | 2004-08-12 | Thomas Jefferson University | Peptid umfassend eine Sequenz aus einer Fusionsverbindungsstelle in einem mutierten EGF-Rezeptor vom Typ III |
| GB9513261D0 (en) | 1995-06-29 | 1995-09-06 | Smithkline Beecham Biolog | Vaccines |
| ATE292980T1 (de) | 1996-10-11 | 2005-04-15 | Univ California | Immunostimulierende oligonucleotidekonjugate |
| AUPO517897A0 (en) | 1997-02-19 | 1997-04-11 | Csl Limited | Chelating immunostimulating complexes |
| AU738513B2 (en) | 1997-02-28 | 2001-09-20 | University Of Iowa Research Foundation, The | Use of nucleic acids containing unmethylated CpG dinucleotide in the treatment of LPS-associated disorders |
| EP1005368B1 (en) | 1997-03-10 | 2009-09-02 | Ottawa Hospital Research Institute | Use of nucleic acids containing unmethylated CpG dinucleotide in combination with alum as adjuvants |
| DE69838294T2 (de) | 1997-05-20 | 2009-08-13 | Ottawa Health Research Institute, Ottawa | Verfahren zur Herstellung von Nukleinsäurekonstrukten |
| ATE432348T1 (de) | 1997-06-06 | 2009-06-15 | Univ California | Inhibitoren von immunstimulatorischen dna sequenz aktivität |
| GB9712347D0 (en) | 1997-06-14 | 1997-08-13 | Smithkline Beecham Biolog | Vaccine |
| ATE505478T1 (de) * | 1997-08-27 | 2011-04-15 | Novartis Vaccines & Diagnostic | Molekular-mimetika von meningokokkalen b epitopen |
| DE69838992T2 (de) | 1997-09-05 | 2008-12-24 | Glaxosmithkline Biologicals S.A., Rixensart | Öl-in-Wasser Emulsionen mit Saponinen |
| US6303114B1 (en) | 1998-03-05 | 2001-10-16 | The Medical College Of Ohio | IL-12 enhancement of immune responses to T-independent antigens |
| WO1999052549A1 (en) | 1998-04-09 | 1999-10-21 | Smithkline Beecham Biologicals S.A. | Adjuvant compositions |
| GB9817052D0 (en) | 1998-08-05 | 1998-09-30 | Smithkline Beecham Biolog | Vaccine |
| TW570805B (en) * | 1998-09-01 | 2004-01-11 | Hoffmann La Roche | Water-soluble pharmaceutical composition in an ionic complex |
| CZ301212B6 (cs) | 1998-10-16 | 2009-12-09 | Smithkline Beecham Biologicals S. A. | Vakcinacní prostredek |
| AUPP807399A0 (en) | 1999-01-08 | 1999-02-04 | Csl Limited | Improved immunogenic lhrh composition and methods relating thereto |
| EP1150710B1 (en) | 1999-02-17 | 2010-04-21 | Csl Limited | Immunogenic complexes and methods relating thereto |
| EP1162999B1 (en) | 1999-03-19 | 2006-11-29 | Glaxosmithkline Biologicals S.A. | Vaccine against Streptococcus pneumoniae |
| JP2001163801A (ja) * | 1999-04-02 | 2001-06-19 | Oriental Yeast Co Ltd | 乾燥ｃ反応性タンパク質組成物 |
| TR200103018T2 (tr) | 1999-04-19 | 2002-02-21 | Beecham Biologicals S.A. Smithkline | İmmünostimülatör oligonükleotid ve saponin içeren katkı bileşikleri. |
| JP2003509473A (ja) | 1999-09-24 | 2003-03-11 | スミスクライン ビーチャム バイオロジカルズ ソシエテ アノニム | ワクチン |
| KR20020048942A (ko) | 1999-09-24 | 2002-06-24 | 장 스테판느 | 폴리옥시에틸렌 알킬 에테르 또는 에스테르 및 하나이상의 비이온성 계면활성제를 포함하는 애쥬번트 |
| US6911204B2 (en) * | 2000-08-11 | 2005-06-28 | Favrille, Inc. | Method and composition for altering a B cell mediated pathology |
| WO2003068259A1 (fr) * | 2002-02-14 | 2003-08-21 | Chugai Seiyaku Kabushiki Kaisha | Produits pharmaceutiques en solution contenant des anticorps |
| JP4393382B2 (ja) * | 2002-08-14 | 2010-01-06 | 三菱化学株式会社 | 中枢性タウ蛋白質特異的抗体 |
| JP4504098B2 (ja) * | 2003-05-28 | 2010-07-14 | 武田薬品工業株式会社 | 抗体およびその用途 |
| PL1684719T3 (pl) * | 2003-11-14 | 2012-11-30 | Baxalta Inc | Kompozycje alfa 1-antytrypsyny i sposoby leczenia z zastosowaniem takich kompozycji |
| JP2008506683A (ja) | 2004-07-18 | 2008-03-06 | コーリー ファーマシューティカル グループ， リミテッド | 先天免疫応答を誘導するための方法および組成物 |
| KR20100018029A (ko) | 2004-07-18 | 2010-02-16 | 씨에스엘 리미티드 | 면역자극 복합체 및 향상된 인터페론-감마 반응을 유도하기 위한 올리고뉴클레오티드 제제 |
| CN101222941A (zh) * | 2005-05-24 | 2008-07-16 | 尼奥瓦克斯公司 | 用于制备包含TNFα和载体蛋白质的抗原杂络物的稳定的免疫原产品的方法 |
| BRPI0815416A2 (pt) * | 2007-08-15 | 2014-10-21 | Amunix Inc | Composições e métodos para modificar propriedades de polipeptídeos biologicamente ativos |
| NZ586383A (en) * | 2007-12-28 | 2012-11-30 | Baxter Int | Recombinant vwf formulations |
-
2010
- 2010-12-08 WO PCT/IB2010/055674 patent/WO2011077309A2/en not_active Ceased
- 2010-12-08 SG SG10201408505SA patent/SG10201408505SA/en unknown
- 2010-12-08 NZ NZ600978A patent/NZ600978A/en not_active IP Right Cessation
- 2010-12-08 US US13/517,394 patent/US20130034573A1/en not_active Abandoned
- 2010-12-08 NZ NZ629256A patent/NZ629256A/en not_active IP Right Cessation
- 2010-12-08 JP JP2012545493A patent/JP6007105B2/ja not_active Expired - Fee Related
- 2010-12-08 SG SG2012042784A patent/SG181628A1/en unknown
- 2010-12-08 CA CA2785585A patent/CA2785585A1/en not_active Abandoned
- 2010-12-08 AU AU2010334428A patent/AU2010334428B2/en not_active Ceased
- 2010-12-08 EP EP17170910.8A patent/EP3257525A3/en not_active Withdrawn
- 2010-12-08 CN CN2010800584328A patent/CN102762224A/zh active Pending
- 2010-12-08 RU RU2012131162/15A patent/RU2581020C2/ru not_active IP Right Cessation
- 2010-12-08 EP EP10807742.1A patent/EP2515934B1/en not_active Not-in-force
- 2010-12-08 CN CN201611022843.7A patent/CN107412754A/zh active Pending
- 2010-12-08 MX MX2012007283A patent/MX337070B/es active IP Right Grant
- 2010-12-08 KR KR1020127016787A patent/KR20120120185A/ko not_active Ceased
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2012
- 2012-06-11 IL IL220308A patent/IL220308A0/en unknown
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2014
- 2014-12-04 US US14/560,462 patent/US20150087815A1/en not_active Abandoned
-
2015
- 2015-05-26 JP JP2015105966A patent/JP6146927B2/ja not_active Expired - Fee Related
-
2019
- 2019-01-10 US US16/244,358 patent/US20190365886A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999006840A1 (en) * | 1997-07-31 | 1999-02-11 | Metra Biosystems, Inc. | Collagen-peptide assay method |
| CA2530172A1 (en) * | 2003-06-27 | 2005-02-10 | Abgenix, Inc. | Antibodies directed to the deletion mutants of epidermal growth factor receptor and uses thereof |
| WO2007056061A2 (en) * | 2005-11-02 | 2007-05-18 | Duke University | Concurrent chemotherapy and immunotherapy |
Non-Patent Citations (1)
| Title |
|---|
| R. J. SCHMITTLING et al. Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines. Journal of Immunological Methods, 339, 2008, PP. 74-81. AMY B. HEIMBERGER et al. Epidermal Growth Factor Receptor VIII Peptide Vaccination Is Efficacious against Established Intracerebral Tumors. Clin Cancer Res September 15, 2003, 9, PP. 4247-4254. * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2515934B1 (en) | 2017-05-17 |
| NZ600978A (en) | 2014-08-29 |
| JP6146927B2 (ja) | 2017-06-14 |
| EP2515934A2 (en) | 2012-10-31 |
| CA2785585A1 (en) | 2011-06-30 |
| CN102762224A (zh) | 2012-10-31 |
| MX2012007283A (es) | 2012-07-30 |
| NZ629256A (en) | 2016-02-26 |
| EP3257525A2 (en) | 2017-12-20 |
| JP6007105B2 (ja) | 2016-10-12 |
| IL220308A0 (en) | 2012-07-31 |
| US20130034573A1 (en) | 2013-02-07 |
| AU2010334428B2 (en) | 2015-05-21 |
| CN107412754A (zh) | 2017-12-01 |
| US20150087815A1 (en) | 2015-03-26 |
| JP2015180667A (ja) | 2015-10-15 |
| RU2012131162A (ru) | 2014-01-27 |
| WO2011077309A2 (en) | 2011-06-30 |
| MX337070B (es) | 2016-02-11 |
| SG181628A1 (en) | 2012-07-30 |
| JP2013515049A (ja) | 2013-05-02 |
| EP3257525A3 (en) | 2018-02-28 |
| US20190365886A1 (en) | 2019-12-05 |
| AU2010334428A1 (en) | 2012-07-05 |
| KR20120120185A (ko) | 2012-11-01 |
| WO2011077309A3 (en) | 2011-10-06 |
| SG10201408505SA (en) | 2015-02-27 |
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| MM4A | The patent is invalid due to non-payment of fees |
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