RU2570730C2 - Стабильные иммуногенные композиции антигенов staphylococcus aureus - Google Patents
Стабильные иммуногенные композиции антигенов staphylococcus aureus Download PDFInfo
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- RU2570730C2 RU2570730C2 RU2013128277/15A RU2013128277A RU2570730C2 RU 2570730 C2 RU2570730 C2 RU 2570730C2 RU 2013128277/15 A RU2013128277/15 A RU 2013128277/15A RU 2013128277 A RU2013128277 A RU 2013128277A RU 2570730 C2 RU2570730 C2 RU 2570730C2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
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- General Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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| PCT/IB2011/055883 WO2012085872A2 (en) | 2010-12-22 | 2011-12-21 | Stable immunogenic compositions of staphylococcus aureus antigens |
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| RU2013128277A RU2013128277A (ru) | 2015-01-27 |
| RU2570730C2 true RU2570730C2 (ru) | 2015-12-10 |
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| PT (2) | PT2654784T (https=) |
| RU (1) | RU2570730C2 (https=) |
| SI (2) | SI2654784T1 (https=) |
| WO (1) | WO2012085872A2 (https=) |
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| KR20070058631A (ko) | 2004-09-22 | 2007-06-08 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 면역원성 조성물 |
| BRPI1011753B8 (pt) | 2009-06-22 | 2021-05-25 | Wyeth Llc | conjugados imunogênicos de polissacarídeo capsular de staphylococcus aureus de sorotipos 5 e 8, seu uso e composições que os compreendem |
| HUE036372T2 (hu) | 2009-06-22 | 2018-07-30 | Wyeth Llc | Staphylococcus aureus antigének immunogén készítményei |
| PT2575870T (pt) * | 2010-06-04 | 2017-02-10 | Wyeth Llc | Formulações de vacinas |
| US9789176B2 (en) * | 2011-03-16 | 2017-10-17 | Regents Of The University Of Minnesota | Compositions and methods for inducing immune responses against bacteria in the genus staphylococcus |
| GB201310008D0 (en) * | 2013-06-05 | 2013-07-17 | Glaxosmithkline Biolog Sa | Immunogenic composition for use in therapy |
| AU2014359277B2 (en) * | 2013-12-04 | 2017-10-26 | Glaxosmithkline Biologicals S.A. | Prevention of Staphylococcus aureus infections by glycoprotein vaccines synthesized in Escherichia coli |
| IL310015B2 (en) | 2013-12-31 | 2026-02-01 | Access To Advanced Health Inst | Single vial formulation |
| PL3129001T3 (pl) * | 2014-04-10 | 2020-06-29 | Asit Biotech S.A. | Preparat alergenów wolny od hsp |
| CN110996992A (zh) * | 2017-08-16 | 2020-04-10 | 默沙东公司 | 肺炎球菌缀合物疫苗制剂 |
| GB201802339D0 (en) | 2018-02-13 | 2018-03-28 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
| KR102649069B1 (ko) | 2018-05-31 | 2024-03-19 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 안면 홍조 개선용 조성물 |
| JP7079984B2 (ja) * | 2018-07-28 | 2022-06-03 | エクソコバイオ インコーポレイテッド | エキソソームの凍結乾燥方法 |
| KR102163806B1 (ko) | 2018-07-30 | 2020-10-07 | 주식회사 엑소코바이오 | 줄기세포 유래의 엑소좀을 유효성분으로 포함하는 피지분비 감소용 조성물 |
| JP2023512446A (ja) * | 2020-01-13 | 2023-03-27 | アプティーボ リサーチ アンド デベロップメント エルエルシー | 治療的タンパク質の薬物送達システム構成要素への吸着を防ぐ方法および組成物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006032472A2 (en) * | 2004-09-22 | 2006-03-30 | Glaxosmithkline Biologicals S.A. | Immunogenic composition for use in vaccination against staphylococcei |
| WO2007113223A2 (en) * | 2006-03-30 | 2007-10-11 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
| WO2007113222A2 (en) * | 2006-03-30 | 2007-10-11 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
| WO2008057550A2 (en) * | 2006-11-07 | 2008-05-15 | Sanofi Pasteur Biologics Co. | Stabilization of vaccines by lyophilization |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902506A (en) | 1983-07-05 | 1990-02-20 | The University Of Rochester | Immunogenic conjugates |
| US4673574A (en) | 1981-08-31 | 1987-06-16 | Anderson Porter W | Immunogenic conjugates |
| US4708871A (en) | 1983-03-08 | 1987-11-24 | Commonwealth Serum Laboratories Commission | Antigenically active amino acid sequences |
| SE8405493D0 (sv) | 1984-11-01 | 1984-11-01 | Bror Morein | Immunogent komplex samt sett for framstellning derav och anvendning derav som immunstimulerande medel |
| US5078996A (en) | 1985-08-16 | 1992-01-07 | Immunex Corporation | Activation of macrophage tumoricidal activity by granulocyte-macrophage colony stimulating factor |
| US5057540A (en) | 1987-05-29 | 1991-10-15 | Cambridge Biotech Corporation | Saponin adjuvant |
| US4912094B1 (en) | 1988-06-29 | 1994-02-15 | Ribi Immunochem Research Inc. | Modified lipopolysaccharides and process of preparation |
| HU212924B (en) | 1989-05-25 | 1996-12-30 | Chiron Corp | Adjuvant formulation comprising a submicron oil droplet emulsion |
| IT1253009B (it) | 1991-12-31 | 1995-07-10 | Sclavo Ricerca S R L | Mutanti immunogenici detossificati della tossina colerica e della tossina lt, loro preparazione ed uso per la preparazione di vaccini |
| US5571515A (en) | 1994-04-18 | 1996-11-05 | The Wistar Institute Of Anatomy & Biology | Compositions and methods for use of IL-12 as an adjuvant |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6008341A (en) | 1994-08-22 | 1999-12-28 | The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | S. aureus fibrinogen binding protein gene |
| BE1008978A5 (fr) | 1994-12-27 | 1996-10-01 | Solvay | Adjuvants pour vaccins. |
| JPH11514870A (ja) | 1995-10-16 | 1999-12-21 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 新規な唾液結合タンパク質 |
| GB9622159D0 (en) | 1996-10-24 | 1996-12-18 | Solvay Sociutu Anonyme | Polyanionic polymers as adjuvants for mucosal immunization |
| GB9622660D0 (en) | 1996-10-31 | 1997-01-08 | Biocine Spa | Immunogenic detoxified mutant toxin |
| US6113918A (en) | 1997-05-08 | 2000-09-05 | Ribi Immunochem Research, Inc. | Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors |
| AU1537699A (en) | 1997-11-26 | 1999-06-15 | Bioresearch Ireland a division of Eolas - The Irish Science and Technology Agency | Extracellular matrix-binding proteins from (staphylococcus aureus) |
| US6680195B1 (en) | 1997-11-26 | 2004-01-20 | Inhibitex, Inc. | Extracellular matrix-binding proteins from staphylococcus aureus |
| KR100644953B1 (ko) * | 1998-08-31 | 2006-11-10 | 인히비텍스, 인코포레이티드 | 다성분 백신 |
| US6936258B1 (en) | 1999-03-19 | 2005-08-30 | Nabi Biopharmaceuticals | Staphylococcus antigen and vaccine |
| US7115730B1 (en) | 1999-04-27 | 2006-10-03 | Chiron Srl | Immunogenic detoxified mutant E. coli LT-A-toxin |
| US7384640B1 (en) | 1999-09-30 | 2008-06-10 | Wyeth Holdings Corporation | Mutant cholera holotoxin as an adjuvant |
| AU2001281812B2 (en) | 2000-06-08 | 2005-04-07 | Valneva Austria Gmbh | Immunostimulatory oligodeoxynucleotides |
| AT410635B (de) | 2000-10-18 | 2003-06-25 | Cistem Biotechnologies Gmbh | Vakzin-zusammensetzung |
| CA2449670A1 (en) | 2001-06-07 | 2002-12-12 | Wyeth Holdings Corporation | Mutant forms of cholera holotoxin as an adjuvant |
| KR100898648B1 (ko) | 2001-06-07 | 2009-05-22 | 와이어쓰 홀딩스 코포레이션 | 보조제로서 콜레라 홀로톡신의 돌연변이체 형태 |
| JP4424984B2 (ja) | 2001-06-15 | 2010-03-03 | インヒビテックス インコーポレーテッド | コアグラーゼ陰性ブドウ球菌および黄色ブドウ球菌由来の表面蛋白質を認識する、交差反応性モノクローナルおよびポリクローナル抗体 |
| GB0118249D0 (en) * | 2001-07-26 | 2001-09-19 | Chiron Spa | Histidine vaccines |
| BRPI0408167B1 (pt) | 2003-03-07 | 2014-10-21 | Wyeth Corp | Conjugados de polissacarídeo-proteína veículo adesina da superfície estafilocócica para imunização contra infecções nosocomiais |
| US20060251675A1 (en) | 2003-03-17 | 2006-11-09 | Michael Hagen | Mutant cholera holotoxin as an adjuvant and an antigen carrier protein |
| GB0323103D0 (en) | 2003-10-02 | 2003-11-05 | Chiron Srl | De-acetylated saccharides |
| GB0606416D0 (en) * | 2006-03-30 | 2006-05-10 | Glaxosmithkline Biolog Sa | Immunogenic composition |
| WO2007127668A2 (en) | 2006-04-26 | 2007-11-08 | Wyeth | Novel processes for coating container means which inhibit precipitation of polysaccharide-protein conjugate formulations |
| ES2615390T3 (es) | 2008-03-05 | 2017-06-06 | Sanofi Pasteur | Proceso para estabilizar una composición de vacuna que contiene adyuvante |
| HUE036372T2 (hu) * | 2009-06-22 | 2018-07-30 | Wyeth Llc | Staphylococcus aureus antigének immunogén készítményei |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006032472A2 (en) * | 2004-09-22 | 2006-03-30 | Glaxosmithkline Biologicals S.A. | Immunogenic composition for use in vaccination against staphylococcei |
| WO2007113223A2 (en) * | 2006-03-30 | 2007-10-11 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
| WO2007113222A2 (en) * | 2006-03-30 | 2007-10-11 | Glaxosmithkline Biologicals S.A. | Immunogenic composition |
| WO2008057550A2 (en) * | 2006-11-07 | 2008-05-15 | Sanofi Pasteur Biologics Co. | Stabilization of vaccines by lyophilization |
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