ES2653887T3 - Procedimiento para aumentar el efecto inmunológico - Google Patents
Procedimiento para aumentar el efecto inmunológico Download PDFInfo
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- ES2653887T3 ES2653887T3 ES08854580.1T ES08854580T ES2653887T3 ES 2653887 T3 ES2653887 T3 ES 2653887T3 ES 08854580 T ES08854580 T ES 08854580T ES 2653887 T3 ES2653887 T3 ES 2653887T3
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Landscapes
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| US20070154399A1 (en) * | 2000-10-27 | 2007-07-05 | Hadden John W | Immunotherapy for immune suppressed patients |
| US20070031372A1 (en) * | 2004-08-05 | 2007-02-08 | Hadden John W | Vaccine immunotherapy for immune suppressed patients |
| CA2950109C (en) | 2000-10-27 | 2019-02-19 | John W. Hadden | Vaccine immunotherapy for immune suppressed patients |
| US20070025958A1 (en) * | 2000-10-27 | 2007-02-01 | Hadden John W | Vaccine immunotherapy |
| ES2736726T3 (es) * | 2006-03-09 | 2020-01-07 | Aethlon Medical Inc | Eliminación extracorpórea de partículas microvesiculares |
| AU2008329741B2 (en) | 2007-11-28 | 2013-09-12 | Irx Therapeutics, Inc. | Method of increasing immunological effect |
| AU2009251277A1 (en) * | 2008-05-29 | 2009-12-03 | Irx Therapeutics, Inc. | Mechanism of action of primary cell derived biologic |
| CA3017298C (en) | 2009-05-15 | 2021-09-28 | Irx Therapeutics, Inc. | Compositions comprising primary cell-derived biologics for enhancing immune responses in patients |
| CN103097543A (zh) | 2009-12-08 | 2013-05-08 | 伊尔克斯治疗有限公司 | 逆转朗格汉斯细胞免疫抑制的方法 |
| MX2016001304A (es) | 2013-07-30 | 2016-04-07 | Gilead Connecticut Inc | Polimorfo de inhibidores de syk. |
| TWI735853B (zh) | 2013-12-23 | 2021-08-11 | 美商克洛諾斯生技有限公司 | 脾酪胺酸激酶抑制劑 |
| CN115028640A (zh) | 2017-08-25 | 2022-09-09 | 吉利德科学公司 | Syk抑制剂的多晶型物 |
| KR20210131372A (ko) | 2019-02-22 | 2021-11-02 | 크로노스 바이오, 인코포레이티드 | Syk 억제제로서의 축합된 피라진의 고체 형태 |
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| US4079127A (en) | 1976-10-28 | 1978-03-14 | Board Of Regents Of The University Of Texas | Thymosin alpha 1 |
| US4116951A (en) | 1977-04-22 | 1978-09-26 | Hoffmann-La Roche Inc. | [Asn2 ]-thymosin α1 and analogs thereof |
| US4148788A (en) | 1978-01-23 | 1979-04-10 | Hoffmann-La Roche Inc. | Synthesis of thymosin α1 |
| DE2919592A1 (de) | 1979-05-15 | 1981-01-15 | Max Planck Gesellschaft | Verfahren zur herstellung von thymosin- alpha 1 und derivaten davon |
| DE3100974A1 (de) | 1980-01-18 | 1982-01-21 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., 3400 Göttingen | Thymosin(alpha)(pfeil abwaerts)1(pfeil abwaerts)-fragmente enthaltende arzneimittel mit immunregulierender wirkung, und thymosin(alpha)(pfeil abwaerts)1(pfeil abwaerts)-fragmente |
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| US4612365A (en) | 1980-03-25 | 1986-09-16 | Max-Planck-Gesellschaft Zur Foederung Der Wissenschaften | Medicaments containing alpha 1-thymosin and having an immuno regulatory action and alpha 1-thymosin fragments |
| US4293455A (en) | 1980-04-07 | 1981-10-06 | Rockefeller University | N.sup.α -Desacetylthymosinα1 and process |
| IL62903A0 (en) | 1980-05-22 | 1981-07-31 | Deutsches Krebsforsch | Method for the production of interferon ii and stimulated clones for the carrying out of the method |
| US4390623A (en) | 1980-10-02 | 1983-06-28 | Hooper Trading Company | Serum-free and mitogen-free T-cell growth factor and process for making same |
| US4464355A (en) | 1981-03-26 | 1984-08-07 | Hooper Trading Co. | Serum-free and mitogen-free T-cell growth factor and process for making same |
| US4448879A (en) | 1981-03-26 | 1984-05-15 | Hooper Trading Company | High yield process for in vitro production of serum-free and mitogen-free interleukin-2 |
| US4406830A (en) | 1981-04-17 | 1983-09-27 | Shanksville Corporation, N.V. | Regulatory glycoprotein for immune response and the use thereof in the production of T-cell growth factor |
| US4504415A (en) | 1983-04-04 | 1985-03-12 | Hoffman-La Roche Inc. | Synthesis of thymosin α1 and desacetyl thymosin α1 |
| US4614731A (en) | 1983-09-15 | 1986-09-30 | Hoffmann-La Roche Inc. | Peptide having immunopotentiating activity similar to thymosin alpha1 |
| US4659694A (en) | 1983-10-27 | 1987-04-21 | Hoffmann-La Roche Inc. | Prothymosin alpha |
| US4716148A (en) | 1984-08-13 | 1987-12-29 | Hoffman-La Roche Inc. | Prothymosin alpha |
| US5503841A (en) | 1985-09-20 | 1996-04-02 | Cetus Oncology Corporation | Human IL-2 as a vaccine adjuvant |
| US5643565A (en) | 1985-09-20 | 1997-07-01 | Chiron Corporation | Human IL-2 as a vaccine adjuvant |
| US5100664A (en) | 1985-09-20 | 1992-03-31 | Cetus Corporation | Human IL-2 as a vaccine adjuvant |
| US5098702A (en) | 1986-04-09 | 1992-03-24 | Cetus Corporation | Combination therapy using interleukin-2 and tumor necrosis factor |
| JPS63503308A (ja) | 1986-05-09 | 1988-12-02 | スローン‐ケツテリング・インステイテユート・フオー・キヤンサー・リサーチ | 抗腫瘍療法のためのリポ多糖体及び天然因子の組成物及び治療方法 |
| SE8801426D0 (sv) | 1988-04-15 | 1988-04-15 | Ulf Rothman | Forfarande och medel for blodbehandling |
| IL92382A (en) | 1988-11-23 | 1994-12-29 | Univ Michigan | Use of a ligand specific for CD28 in the manufacture of medicament |
| US6534055B1 (en) | 1988-11-23 | 2003-03-18 | Genetics Institute, Inc. | Methods for selectively stimulating proliferation of T cells |
| IT1238231B (it) | 1989-12-18 | 1993-07-12 | Consiglio Nazionale Ricerche | Impiego di immunomodulanti come agenti sinergici di chemioterapici nella terapia dei tumori |
| KR100223255B1 (ko) | 1992-02-10 | 1999-10-15 | 더글라스 테스타 | 개량된 알파 인터페론 조성물 및 인간 말초혈 백혈구로 부터의 제조 방법 |
| CA2139756A1 (en) | 1992-07-08 | 1994-01-20 | Eric M. Bonnem | Use of gm-csf as a vaccine adjuvant |
| US5828784A (en) * | 1992-07-13 | 1998-10-27 | Hitachi Denshi Kabushiki Kaisha | Data coding method and apparatus using a plurality of blocks of different length |
| US6161122A (en) * | 1992-12-10 | 2000-12-12 | Hawkes; Calvert T. | Method and apparatus for interactively providing information at multiple sites |
| CN1094310A (zh) | 1992-12-15 | 1994-11-02 | 托马斯·C·梅里根 | 人体免疫缺陷性病毒感染用组合式化学疗法 |
| US5747024A (en) | 1993-03-08 | 1998-05-05 | Immunex Corporation | Vaccine adjuvant comprising interleukin-15 |
| DK0700430T3 (da) * | 1993-06-04 | 2005-08-15 | Us Navy | Fremgangsmåder til selektivt af stimulere proliferation af T-celler |
| CN1044781C (zh) | 1994-02-05 | 1999-08-25 | 丹东市生物制品免疫技术应用研究中心 | 复方免疫抗生素 |
| DE4412794A1 (de) | 1994-04-14 | 1995-12-14 | Univ Ludwigs Albert | Verfahren zur Herstellung von dendritischen Zellen, so erhaltene Zellen und Behälter zur Durchführung dieses Verfahrens |
| EP0789588B1 (en) | 1994-11-17 | 2005-01-19 | University Of South Florida | Method for making a medicament for treating secondary immunodeficiency |
| US5632983A (en) | 1994-11-17 | 1997-05-27 | University Of South Florida | Method for treating secondary immunodeficiency |
| DE69628921T2 (de) | 1995-05-04 | 2004-04-22 | The Government Of The United States Of America As Represented By The Secretary Of The Navy | Verfahren zur modulation der t-zell-überlebensrate durch von bcl-xl protein-spiegels |
| US5788963A (en) | 1995-07-31 | 1998-08-04 | Pacific Northwest Cancer Foundation | Isolation and/or preservation of dendritic cells for prostate cancer immunotherapy |
| NZ331369A (en) | 1996-02-21 | 2001-04-27 | Franco Lori | Use of a genetic construct that directs virus expression in a lymphoid organ or a transduced cell thereof for genetic immunization |
| US5849589A (en) | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
| US6017527A (en) | 1996-07-10 | 2000-01-25 | Immunex Corporation | Activated dendritic cells and methods for their activation |
| US5849307A (en) | 1997-03-26 | 1998-12-15 | The Picower Institute For Medical Research | Vaccine adjuvant |
| AU748467B2 (en) | 1997-10-17 | 2002-06-06 | University Of South Florida | Method to diagnose and monitor cellular immune deficiencies |
| ATE428769T1 (de) | 1997-10-27 | 2009-05-15 | Univ Rockefeller | Methode und zusammensetzung zur herstellung von reifen dendritischen zellen |
| US20050124645A1 (en) * | 1998-04-20 | 2005-06-09 | Finkel Terri H. | Methods and compositions for increasing CD4lymphocyte immune responsiveness |
| EP0974357A1 (en) | 1998-07-16 | 2000-01-26 | Schering-Plough | Chemokines as adjuvants of immune response |
| US6350589B1 (en) | 1998-12-31 | 2002-02-26 | Viragen, Inc. | Compositions of highly-purified natural mixtures of type I interferon derived from leukocytes and methods |
| US7056503B2 (en) | 1999-08-19 | 2006-06-06 | Regents Of The University Of Michigan | Enclosures housing cell-coated supports for treating tumors |
| US6406699B1 (en) | 1999-10-05 | 2002-06-18 | Gary W. Wood | Composition and method of cancer antigen immunotherapy |
| DK1257632T3 (da) | 2000-02-24 | 2008-01-28 | Xcyte Therapies Inc | Samtidig stimulering og opkoncentrering af celler |
| US7266501B2 (en) * | 2000-03-02 | 2007-09-04 | Akiba Electronics Institute Llc | Method and apparatus for accommodating primary content audio and secondary content remaining audio capability in the digital audio production process |
| US7182942B2 (en) | 2000-10-27 | 2007-02-27 | Irx Therapeutics, Inc. | Vaccine immunotherapy for immune suppressed patients |
| US20070025958A1 (en) | 2000-10-27 | 2007-02-01 | Hadden John W | Vaccine immunotherapy |
| US20060194242A1 (en) | 2000-10-27 | 2006-08-31 | Hadden John W | Immunotherapy for immune suppressed patients |
| CA2950109C (en) * | 2000-10-27 | 2019-02-19 | John W. Hadden | Vaccine immunotherapy for immune suppressed patients |
| US20070031372A1 (en) | 2004-08-05 | 2007-02-08 | Hadden John W | Vaccine immunotherapy for immune suppressed patients |
| US20070154399A1 (en) | 2000-10-27 | 2007-07-05 | Hadden John W | Immunotherapy for immune suppressed patients |
| JP2005510491A (ja) | 2001-10-26 | 2005-04-21 | イミュノ−アールエックス, インコーポレイテッド | 免疫抑制を逆転させるための免疫治療 |
| DE10154579A1 (de) | 2001-11-07 | 2003-05-28 | Medigene Ag | Topikale Verwendung von Cytokinen und Chemokinen zur Behandlung von viralen oder mykotischen Hauterkrankungen oder Tumorerkrankungen |
| WO2003061566A2 (en) | 2002-01-24 | 2003-07-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Anti-cancer combination and use thereof |
| CA2511815A1 (en) | 2002-12-26 | 2004-07-22 | Mountain View Pharmaceuticals, Inc. | Polymer conjugates of cytokines, chemokines, growth factors, polypeptide hormones and antagonists thereof with preserved receptor-binding activity |
| US6896879B2 (en) | 2003-07-03 | 2005-05-24 | Cel-Sci Corporation | Method of pre-sensitizing cancer prior to treatment with radiation and/or chemotherapy and a novel cytokine mixture |
| WO2005077048A2 (en) * | 2004-02-09 | 2005-08-25 | The Johns Hopkins University | Immune modulation by regulating expression of the “minor” gene in immune dendritic cells |
| GB0409799D0 (en) | 2004-04-30 | 2004-06-09 | Isis Innovation | Method of generating improved immune response |
| ES2553133T3 (es) | 2004-06-04 | 2015-12-04 | Cel-Sci Corporation | Método de modificación de la proporción de CD4/CD8 y del infiltrado celular mononuclear en un tumor |
| KR100773539B1 (ko) * | 2004-07-14 | 2007-11-05 | 삼성전자주식회사 | 멀티채널 오디오 데이터 부호화/복호화 방법 및 장치 |
| US20070065415A1 (en) * | 2005-09-16 | 2007-03-22 | Kleinsek Donald A | Compositions and methods for the augmentation and repair of defects in tissue |
| US20090181078A1 (en) | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
| CA2691539C (en) | 2007-06-21 | 2014-08-26 | Angelica Therapeutics, Inc. | Modified toxins |
| AU2008329741B2 (en) | 2007-11-28 | 2013-09-12 | Irx Therapeutics, Inc. | Method of increasing immunological effect |
| WO2009137238A2 (en) | 2008-04-14 | 2009-11-12 | Irx Therapeutics, Inc. | Irx-2 modified manufacturing process |
| AU2009251277A1 (en) | 2008-05-29 | 2009-12-03 | Irx Therapeutics, Inc. | Mechanism of action of primary cell derived biologic |
| CA3017298C (en) | 2009-05-15 | 2021-09-28 | Irx Therapeutics, Inc. | Compositions comprising primary cell-derived biologics for enhancing immune responses in patients |
| CN103097543A (zh) | 2009-12-08 | 2013-05-08 | 伊尔克斯治疗有限公司 | 逆转朗格汉斯细胞免疫抑制的方法 |
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| CA2706445A1 (en) | 2009-06-04 |
| US20090155291A1 (en) | 2009-06-18 |
| WO2009070639A1 (en) | 2009-06-04 |
| EP2234642B1 (en) | 2017-09-27 |
| JP5563472B2 (ja) | 2014-07-30 |
| US8591956B2 (en) | 2013-11-26 |
| AU2008329741A1 (en) | 2009-06-04 |
| US20120141512A1 (en) | 2012-06-07 |
| AU2008329741B2 (en) | 2013-09-12 |
| EP2234642B8 (en) | 2017-11-01 |
| US7993660B2 (en) | 2011-08-09 |
| CA2706445C (en) | 2019-07-23 |
| EP2234642A1 (en) | 2010-10-06 |
| JP2011504932A (ja) | 2011-02-17 |
| MX2010005718A (es) | 2010-08-10 |
| EP2234642A4 (en) | 2012-04-25 |
| DK2234642T3 (en) | 2018-01-08 |
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