RU2696566C2 - Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа - Google Patents
Пептидная вакцина для предупреждения и иммунотерапии деменции альцгеймеровского типа Download PDFInfo
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- RU2696566C2 RU2696566C2 RU2015142996A RU2015142996A RU2696566C2 RU 2696566 C2 RU2696566 C2 RU 2696566C2 RU 2015142996 A RU2015142996 A RU 2015142996A RU 2015142996 A RU2015142996 A RU 2015142996A RU 2696566 C2 RU2696566 C2 RU 2696566C2
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| US13/843,883 | 2013-03-15 | ||
| PCT/US2013/037865 WO2014143087A1 (en) | 2013-03-15 | 2013-04-23 | Peptide vaccine for prevention and immunotherapy of dementia of the alzheimer's type |
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|---|---|---|---|---|
| US9102752B2 (en) * | 2013-03-15 | 2015-08-11 | United Biomedical, Inc. | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
| US9315545B2 (en) * | 2014-04-07 | 2016-04-19 | Merganser Biotech, Inc. | Hepcidin mimetic peptides and uses thereof |
| WO2017131468A1 (ko) * | 2016-01-27 | 2017-08-03 | 경상대학교산학협력단 | 아디포넥틴 수용체 활성화 신규 펩티드를 유효성분으로 포함하는 신경질환의 예방, 개선 또는 치료용 조성물 |
| KR20180134373A (ko) * | 2016-04-14 | 2018-12-18 | 타오 헬스 라이프 파마 가부시키가이샤 | 아밀로스페로이드(aspd)형 구조체 및 의약 조성물 |
| CN106565847B (zh) * | 2016-10-26 | 2020-12-01 | 清华大学 | 化合物、多肽及其用途 |
| JP2021508672A (ja) * | 2017-06-16 | 2021-03-11 | ユナイテッド ニューロサイエンスＵｎｉｔｅｄ Ｎｅｕｒｏｓｃｉｅｎｃｅ | シヌクレイノパチーの治療のためのアルファ−シヌクレインタンパク質のｃ末端からのペプチド免疫原及びその製剤 |
| CN119409835A (zh) | 2017-10-27 | 2025-02-11 | 联脑科学公司 | Tau肽免疫原构建体 |
| TWI741241B (zh) * | 2017-12-11 | 2021-10-01 | 美商聯合生物醫學公司 | 用於治療及/或預防異位性皮膚炎之il-31胜肽免疫原及其劑型 |
| RU2769983C2 (ru) * | 2017-12-31 | 2022-04-12 | Юнайтед Байомедикал, Инк. | ПЕПТИДНЫЕ ИММУНОГЕНЫ И СОДЕРЖАЩИЕ ИХ СОСТАВЫ, НАЦЕЛЕННЫЕ НА МЕМБРАНОСВЯЗАННЫЕ IgE ДЛЯ ЛЕЧЕНИЯ ОПОСРЕДОВАННЫХ IgE АЛЛЕРГИЧЕСКИХ ЗАБОЛЕВАНИЙ |
| AU2019222707A1 (en) * | 2018-02-13 | 2020-08-13 | Cedars-Sinai Medical Center | Methods and systems for identification and treatment of pathological neurodegeneration and age-related cognitive decline |
| BR112020020660A2 (pt) | 2018-04-10 | 2021-03-02 | Ac Immune Sa | vacinas terapêuticas anti-abeta |
| BR112020022443A2 (pt) * | 2018-05-04 | 2021-02-09 | Ubi Ip Holdings | epitopos de células t auxiliares promíscuos artificiais que facilitam a produção de anticorpos alvejados com resposta inflamatória de células t limitada |
| TWI676635B (zh) * | 2018-06-15 | 2019-11-11 | 英屬開曼群島商聯腦科學公司 | α－突觸核蛋白Ｃ端胜肽免疫原及其用於治療突觸核蛋白疾病的配方 |
| TWI781347B (zh) * | 2018-10-01 | 2022-10-21 | 美商Ｕｎｓ Ｉｐ控股公司 | 針對源自c9orf72二肽重複蛋白的胜肽免疫原結構 |
| AU2019404226A1 (en) * | 2018-12-19 | 2021-07-15 | United Biomedical, Inc. | Artificial promiscuous T helper cell epitopes as immune stimulators for synthetic peptide immunogens |
| US12350322B2 (en) | 2018-12-28 | 2025-07-08 | United Biomedical, Inc. | Peptide immunogens targeting interleukin 6 (IL-6) and formulations thereof for immunotherapy of diseases impacted by IL-6 dysregulation |
| US20220073582A1 (en) * | 2018-12-31 | 2022-03-10 | United Neuroscience Limited | Peptide immunogens targeting calcitonin gene-related peptide (cgrp) and formulations thereof for prevention and treatment of migraine |
| CN110759987B (zh) * | 2019-10-29 | 2021-06-08 | 中国人民解放军军事科学院军事医学研究院 | 构象特异性的重组Aβ1-42样寡聚体抗原、其制备方法和应用 |
| MX2022009144A (es) * | 2020-01-23 | 2022-08-22 | United Biomedical Inc | Inmunogenos peptidicos dirigidos al peptido activador de adenilato ciclasa hipofisaria (pacap) y formulaciones de los mismos para la prevencion y el tratamiento de migra?a. |
| CA3167073A1 (en) | 2020-03-10 | 2021-09-16 | Preeti BAKRANIA | Cyclic peptides |
| WO2022108950A1 (en) | 2020-11-17 | 2022-05-27 | Iliad Biotechnologies, Llc | Treatment and prevention of neuropathology associated with neurodegenerative diseases |
| US20240159777A1 (en) * | 2021-03-16 | 2024-05-16 | Neurovision Imaging, Inc. | Biofluid-Based Methods for Diagnosing Alzheimer’s Disease-Associated Conditions |
| JP2024534269A (ja) * | 2021-08-30 | 2024-09-18 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッド | 神経変性疾患を治療するための方法および物質 |
| EP4445910A1 (en) | 2021-12-08 | 2024-10-16 | Osaka University | Vaccine composition for inducing anti-il-23 antibody |
| AU2023223603A1 (en) | 2022-02-28 | 2024-08-22 | Tridem Bioscience Gmbh & Co Kg | A CONJUGATE CONSISTING OF OR COMPRISING AT LEAST A ß-GLUCAN OR A MANNAN. |
| KR102530956B1 (ko) * | 2022-09-08 | 2023-05-11 | 주식회사 알츠코리아 | 아밀로이드 베타 유래 에피토프를 유효성분으로 포함하는 알츠하이머성 치매 백신 조성물 및 이의 용도 |
| CN115417915B (zh) * | 2022-11-03 | 2023-02-24 | 北京引正基因科技有限公司 | 多肽载体及其应用 |
| CN117122612B (zh) * | 2023-07-07 | 2024-08-27 | 河络新图生物科技(上海)有限公司 | 外周血单个核细胞在制备治疗/预防阿尔茨海默病的药物中的用途 |
| WO2025109524A1 (en) | 2023-11-22 | 2025-05-30 | Ac Immune Sa | Assays and methods for assessing vaccine preparations |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009897A1 (en) * | 2002-02-14 | 2004-01-15 | Sokoll Kenneth K. | Stabilized synthetic immunogen delivery system |
| US20040247612A1 (en) * | 2001-05-25 | 2004-12-09 | Wang Chang Yi | Immunogenic peptide composition for the prevention and treatment of Alzheimer's Disease |
| WO2008021296A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of alzheimer's disease |
| US20110171243A1 (en) * | 2008-06-12 | 2011-07-14 | Affiris Ag | Compounds for treating amyloidoses |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5753624A (en) | 1990-04-27 | 1998-05-19 | Milkhaus Laboratory, Inc. | Materials and methods for treatment of plaquing disease |
| JP2980677B2 (ja) | 1990-04-27 | 1999-11-22 | マクマイケル，ジョン | 不正常なアミロイドβタンパク質と関連する中枢神経系疾患状態の治療のための方法および組成物 |
| ATE239797T1 (de) | 1993-01-25 | 2003-05-15 | Takeda Chemical Industries Ltd | Antikörper gegen beta-amyloid oder derivative davon und seine verwendung |
| US5955317A (en) | 1993-01-25 | 1999-09-21 | Takeda Chemical Industries, Ltd. | Antibodies to β-amyloids or their derivatives and use thereof |
| US5759551A (en) | 1993-04-27 | 1998-06-02 | United Biomedical, Inc. | Immunogenic LHRH peptide constructs and synthetic universal immune stimulators for vaccines |
| WO1994028412A1 (en) | 1993-05-28 | 1994-12-08 | The Miriam Hospital | Composition and method for in vivo imaging of amyloid deposits |
| AU8091694A (en) | 1993-10-26 | 1995-05-22 | United Biomedical Inc. | Structured synthetic antigen libraries as diagnostics, vaccines and therapeutics |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US6025468A (en) | 1998-06-20 | 2000-02-15 | United Biomedical, Inc. | Artificial T helper cell epitopes as immune stimulators for synthetic peptide immunogens including immunogenic LHRH peptides |
| TWI229679B (en) | 1998-06-20 | 2005-03-21 | United Biomedical Inc | Artificial T helper cell epitopes as immune stimulators for synthetic peptide immunogens |
| CA2349434A1 (en) | 1999-09-03 | 2001-03-15 | Ramot University Authority For Applied Research & Industrial Development Ltd. | Agents and compositions and methods utilizing same useful in diagnosing and/or treating or preventing plaque forming diseases |
| ES2275570T3 (es) | 1999-12-08 | 2007-06-16 | Intellect Neurosciences, Inc. | Peptidos amiloides beta quimericos. |
| US20030165481A1 (en) | 2000-02-24 | 2003-09-04 | Hersh Louis B. | Amyloid peptide inactivating enzyme to treat Alzheimer's disease |
| US20030083277A1 (en) * | 2000-02-24 | 2003-05-01 | Hersh Louis B. | Use of insulin degrading enzyme (IDE) for the treatment of alzheimer's disease in patients |
| AU2003250102B2 (en) * | 2002-07-24 | 2009-09-17 | Innogenetics N.V. | Fragments of beta-amyloid as targets for vaccination against alzheimer disease |
| WO2005072777A2 (en) * | 2004-01-28 | 2005-08-11 | Curix Aps | Conjugates of amyloid proteins as vaccines for amyloid-related diseases |
| CA2638775A1 (en) * | 2006-02-22 | 2007-08-30 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Peptide vaccine for inducing production of anti-amyloid-.beta.-peptide antibody |
| CN101384279B (zh) * | 2006-02-24 | 2012-02-22 | 奇斯药制品公司 | 抗淀粉样蛋白免疫原性组合物、方法和用途 |
| US20110178024A1 (en) * | 2008-09-29 | 2011-07-21 | Ben Gurion University Of The Negev Research And Development Authority | Amyloid beta-peptides and methods of use thereof |
| US9067981B1 (en) * | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| US8916387B2 (en) * | 2010-10-28 | 2014-12-23 | Jonas Nilsson | Diagnosis and treatment of Alzheimer's disease |
| US9102752B2 (en) * | 2013-03-15 | 2015-08-11 | United Biomedical, Inc. | Peptide vaccine for prevention and immunotherapy of dementia of the Alzheimer's type |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040247612A1 (en) * | 2001-05-25 | 2004-12-09 | Wang Chang Yi | Immunogenic peptide composition for the prevention and treatment of Alzheimer's Disease |
| US20040009897A1 (en) * | 2002-02-14 | 2004-01-15 | Sokoll Kenneth K. | Stabilized synthetic immunogen delivery system |
| WO2008021296A2 (en) * | 2006-08-14 | 2008-02-21 | Thymon, L.L.C. | Compositions and methods for the treatment and prophylaxis of alzheimer's disease |
| US20110171243A1 (en) * | 2008-06-12 | 2011-07-14 | Affiris Ag | Compounds for treating amyloidoses |
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