RU2270691C2 - Композиции и способы достижения иммунной супрессии - Google Patents
Композиции и способы достижения иммунной супрессии Download PDFInfo
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2701301C2 (ru) * | 2014-03-03 | 2019-09-25 | Ситюн Фарма | Способ очистки конъюгатов на основе il-15/il-15r-альфа |
| RU2847345C1 (ru) * | 2020-01-24 | 2025-10-03 | Эйприлбио Ко., Лтд. | Мультиспецифичные антитела, содержащие их композиции, векторы и способы их применения |
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| US7235358B2 (en) | 2001-06-08 | 2007-06-26 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| US6905827B2 (en) | 2001-06-08 | 2005-06-14 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing or monitoring auto immune and chronic inflammatory diseases |
| US7026121B1 (en) | 2001-06-08 | 2006-04-11 | Expression Diagnostics, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| WO2004035787A2 (de) * | 2002-10-14 | 2004-04-29 | F. Hoffmann-La Roche Ag | Transplantierbare zelle mit immunmodulator |
| US7892745B2 (en) | 2003-04-24 | 2011-02-22 | Xdx, Inc. | Methods and compositions for diagnosing and monitoring transplant rejection |
| KR20050082389A (ko) * | 2004-02-18 | 2005-08-23 | 메덱스젠 주식회사 | 직렬 연쇄체를 갖는 면역접합체를 포함하는 장기이식합병증 치료용 약제학적 조성물 |
| CN1946739A (zh) * | 2004-04-14 | 2007-04-11 | 豪夫迈－罗氏公司 | 纯化的白细胞介素－15/Fc融合蛋白及其制备 |
| US7645575B2 (en) * | 2004-09-08 | 2010-01-12 | Xdx, Inc. | Genes useful for diagnosing and monitoring inflammation related disorders |
| US20060263343A1 (en) * | 2005-05-13 | 2006-11-23 | Kenyon Norma S | Molecular dissection of cellular responses to alloantigen or autoantigen in graft rejection and autoimmune disease |
| CN105770871A (zh) * | 2005-06-09 | 2016-07-20 | 汉莎医药有限公司 | IdeS蛋白酶(来自于酿脓链球菌)在自身免疫性疾病和移植排斥的治疗中的用途 |
| EP2366787B1 (en) * | 2006-01-13 | 2019-12-11 | The Government Of The U.S.A, As Represented By The Secretary, Dept. Of Health And Human Services | Codon optimized IL-15 and IL-15R-Alpha genes for expression in mammalian cells |
| WO2008021431A2 (en) | 2006-08-14 | 2008-02-21 | Xdx, Inc. | Methods and compositions for diagnosing and monitoring the status of transplant rejection and immune disorders |
| EP2102367A2 (en) | 2006-11-09 | 2009-09-23 | XDX, Inc. | Methods for diagnosing and monitoring the status of systemic lupus erythematosus |
| EP2388266B1 (en) * | 2007-05-11 | 2014-04-23 | Altor BioScience Corporation | Fusion molecules and IL-15 variants |
| WO2011020047A1 (en) | 2009-08-14 | 2011-02-17 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of il-15 to increase thymic output and to treat lymphopenia |
| US11053299B2 (en) | 2010-09-21 | 2021-07-06 | Immunity Bio, Inc. | Superkine |
| JP6251570B2 (ja) | 2010-09-21 | 2017-12-20 | アルター・バイオサイエンス・コーポレーション | 多量体ｉｌ−１５可溶性融合分子並びにその製造及び使用方法 |
| CA2824515C (en) | 2011-01-18 | 2022-09-13 | Bioniz, Llc | Compositions and methods for modulating gamma-c-cytokine activity |
| US9959384B2 (en) | 2013-12-10 | 2018-05-01 | Bioniz, Llc | Methods of developing selective peptide antagonists |
| CA2953816C (en) | 2014-06-30 | 2022-03-15 | Altor Bioscience Corporation | Il-15-based molecules and methods of use thereof |
| MA41459A (fr) | 2015-02-03 | 2017-12-12 | Als Therapy Development Inst | Anticorps anti-cd40l et méthodes pour traiter des maladies ou des troubles liés aux cd40l |
| EP3978512A1 (en) | 2015-10-09 | 2022-04-06 | Bioniz, LLC | Modulating gamma-c-cytokine activity |
| MX2019004681A (es) | 2016-10-21 | 2019-10-07 | Altor Bioscience Corp | Moleculas basadas en il-15 multimericas. |
| US11629340B2 (en) | 2017-03-03 | 2023-04-18 | Obsidian Therapeutics, Inc. | DHFR tunable protein regulation |
| KR102707650B1 (ko) | 2017-04-07 | 2024-09-19 | 바이오니즈 테라퓨틱스, 아이엔씨. | 감마-c-사이토카인 활성의 안정한 조절자 |
| JP2020517259A (ja) | 2017-04-19 | 2020-06-18 | ボード・オブ・リージエンツ，ザ・ユニバーシテイ・オブ・テキサス・システム | 操作された抗原受容体を発現する免疫細胞 |
| EP3630843A2 (en) | 2017-05-24 | 2020-04-08 | ALS Therapy Development Institute | Therapeutic anti-cd40 ligand antibodies |
| CN107474143B (zh) * | 2017-09-13 | 2020-08-11 | 深圳市因诺赛生物科技有限公司 | (Anti-CD40 mAb)-CTLA4融合蛋白及其用途 |
| WO2019165121A1 (en) | 2018-02-21 | 2019-08-29 | Board Of Regents, The University Of Texas System | Methods for activation and expansion of natural killer cells and uses therof |
| BR112021021878A2 (pt) | 2019-05-03 | 2022-01-18 | Bioniz Llc | Modulação dos efeitos de sinalização da gama-c-citocina para tratamento da alopecia e distúrbios associados |
| CN114651003A (zh) | 2019-09-10 | 2022-06-21 | 黑曜石疗法公司 | 用于可调调节的ca2-il15融合蛋白 |
| BR112022020256A2 (pt) | 2020-04-09 | 2023-01-03 | Aprilbio Co Ltd | anticorpo monoclonal ou um fragmento de ligação ao antígeno do mesmo, ácido nucleico, vetor de expressão, célula, composição, uso da composição e uso do anticorpo monoclonal ou fragmento de ligação ao antígeno do mesmo |
| CN121620592A (zh) * | 2023-05-01 | 2026-03-06 | 西雅图儿童医院d/b/a西雅图儿童研究所 | 表达突变体白细胞介素15的免疫细胞 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19823351A1 (de) * | 1997-05-16 | 1998-12-10 | Krause Hans | Mittel zur Verhinderung der Zellapoptose bei Krankheiten |
Family Cites Families (30)
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| JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・２・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| DK0897983T3 (da) | 1991-10-25 | 2003-08-11 | Immunex Corp | Antistoffer mod CD40-L |
| GB9207732D0 (en) | 1992-04-06 | 1992-05-27 | Isis Innovation | Wound repair |
| KR0170037B1 (ko) | 1992-08-20 | 1999-02-01 | 에릭 에스. 딕커 | 인터루킨-4 및/또는 인터루킨-10을 함유하는 약제학적 조성물 |
| WO1994004570A1 (en) | 1992-08-21 | 1994-03-03 | Schering Corporation | Cd40 ligand, anti cd40 antibodies, and soluble cd40 |
| CA2155109A1 (en) | 1993-02-01 | 1994-08-18 | Daniel Abramowicz | Use of a pharmaceutical composition comprising an effective amount of interleukin-10, an analog and/or an agonist of interleukin-10 |
| US5747024A (en) | 1993-03-08 | 1998-05-05 | Immunex Corporation | Vaccine adjuvant comprising interleukin-15 |
| US5552303A (en) | 1993-03-08 | 1996-09-03 | Immunex Corporation | DNA encoding epithelium-derived T-cell factor |
| US5574138A (en) | 1993-03-08 | 1996-11-12 | Immunex Corporation | Epithelium-derived T-cell factor |
| JP2840131B2 (ja) | 1993-09-02 | 1998-12-24 | トラスティーズ・オブ・ダートマス・カレッジ | 液性免疫の持続性抑制方法 |
| CN1127351C (zh) | 1993-09-02 | 2003-11-12 | 达特茅斯学院理事 | 诱导抗原特异性ｔ细胞耐受的方法 |
| WO1995027722A1 (en) | 1994-04-06 | 1995-10-19 | Immunex Corporation | Interleukin-15 |
| US5683693A (en) | 1994-04-25 | 1997-11-04 | Trustees Of Dartmouth College | Method for inducing T cell unresponsiveness to a tissue or organ graft with anti-CD40 ligand antibody or soluble CD40 |
| US6265556B1 (en) | 1994-12-02 | 2001-07-24 | The Burnham Institute | Nucleic acid encoding CD40 associated proteins |
| US5876950A (en) | 1995-01-26 | 1999-03-02 | Bristol-Myers Squibb Company | Monoclonal antibodies specific for different epitopes of human GP39 and methods for their use in diagnosis and therapy |
| US5795966A (en) | 1995-02-22 | 1998-08-18 | Immunex Corp | Antagonists of interleukin-15 |
| US5833987A (en) | 1995-06-07 | 1998-11-10 | Trustees Of Dartmouth College | Treatment of T cell mediated autoimmune disorders |
| US6001358A (en) | 1995-11-07 | 1999-12-14 | Idec Pharmaceuticals Corporation | Humanized antibodies to human gp39, compositions containing thereof |
| US6440418B1 (en) | 1995-11-07 | 2002-08-27 | Idec Pharmaceuticals Corporation | Methods of treating autoimmune diseases with gp39-specific antibodies |
| US6340459B1 (en) | 1995-12-01 | 2002-01-22 | The Trustees Of Columbia University In The City Of New York | Therapeutic applications for the anti-T-BAM (CD40-L) monoclonal antibody 5C8 in the treatment of reperfusion injury in non-transplant recipients |
| US6132978A (en) | 1995-12-19 | 2000-10-17 | National Jewish Medical And Research Center | Method to regulate CD40 signaling |
| AU1748897A (en) | 1996-01-16 | 1997-08-11 | Biogen, Inc. | Therapeutic applications of T-BAM (CD40-L) technology to treat inflammatory kidney diseases |
| ATE219376T1 (de) | 1996-03-20 | 2002-07-15 | Bristol Myers Squibb Co | Verfahren zur inhibierung der immunreaktion durch blockierung der gp39/cd40 und ctla4/cd28/b7 routen und zusammensetzung zu deren verwendung |
| JP2001502521A (ja) * | 1996-04-26 | 2001-02-27 | ベス イスラエル デアコネス メディカル センター | インターロイキン―１５の拮抗剤 |
| EA004401B1 (ru) | 1996-07-08 | 2004-04-29 | Дзе Трастиз Оф Колумбия Юниверсити Ин Дзе Сити Оф Нью Йорк | Терапевтическое применение т-вам(cd40l)-технологии для лечения заболеваний с участием клеток гладкой мускулатуры |
| SK156099A3 (en) | 1997-05-17 | 2000-06-12 | Biogen Inc | Use of a cd40:cd154 binding interruptor to prevent counter adaptive immune responses, particularly graft rejection |
| EP1009432A4 (en) | 1997-06-11 | 2004-07-07 | Us Navy | COMPOSITIONS AND METHODS FOR THE INHIBITION OF TRANSPLANT REPOSITION AND OTHERS AGAINST THE IMMUNE RESPONSE GIVEN BY T-LYMPHOCYTES |
| EP1034001B1 (en) | 1997-06-20 | 2004-08-04 | Biogen Idec MA Inc. | Cd154 blockade therapy for therapeutic protein inhibitor syndrome |
| WO1999000143A1 (en) | 1997-06-27 | 1999-01-07 | Biogen, Inc. | Cd154 blockade therapy for autoimmune diseases |
-
2001
- 2001-05-14 EP EP01935495A patent/EP1284747A2/en not_active Withdrawn
- 2001-05-14 US US09/855,313 patent/US6797263B2/en not_active Expired - Fee Related
- 2001-05-14 JP JP2001583797A patent/JP2003533488A/ja active Pending
- 2001-05-14 AU AU6158501A patent/AU6158501A/xx active Pending
- 2001-05-14 WO PCT/US2001/015578 patent/WO2001087330A2/en not_active Ceased
- 2001-05-14 CA CA002408691A patent/CA2408691A1/en not_active Abandoned
- 2001-05-14 BR BR0110779-8A patent/BR0110779A/pt not_active IP Right Cessation
- 2001-05-14 RU RU2002133447/15A patent/RU2270691C2/ru not_active IP Right Cessation
- 2001-05-14 AU AU2001261585A patent/AU2001261585B2/en not_active Ceased
- 2001-05-14 CN CN01812646A patent/CN1441675A/zh active Pending
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19823351A1 (de) * | 1997-05-16 | 1998-12-10 | Krause Hans | Mittel zur Verhinderung der Zellapoptose bei Krankheiten |
Non-Patent Citations (1)
| Title |
|---|
| C. Agostmi et al. CD8 T-Cell infiltration in extravascular tissues.... Blood. V.93, n.4, p.1277-1286. * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2701301C2 (ru) * | 2014-03-03 | 2019-09-25 | Ситюн Фарма | Способ очистки конъюгатов на основе il-15/il-15r-альфа |
| RU2847345C1 (ru) * | 2020-01-24 | 2025-10-03 | Эйприлбио Ко., Лтд. | Мультиспецифичные антитела, содержащие их композиции, векторы и способы их применения |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2003533488A (ja) | 2003-11-11 |
| US20020128436A1 (en) | 2002-09-12 |
| US20040219148A1 (en) | 2004-11-04 |
| EP1284747A2 (en) | 2003-02-26 |
| BR0110779A (pt) | 2005-01-11 |
| AU2001261585B2 (en) | 2006-08-31 |
| AU2001261585C1 (en) | 2001-11-26 |
| CN1441675A (zh) | 2003-09-10 |
| CA2408691A1 (en) | 2001-11-22 |
| AU6158501A (en) | 2001-11-26 |
| WO2001087330A3 (en) | 2002-05-30 |
| US6797263B2 (en) | 2004-09-28 |
| WO2001087330A2 (en) | 2001-11-22 |
| US7347995B2 (en) | 2008-03-25 |
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