RU2758139C2 - Иммуноконъюгаты il2 и мутантного tnf - Google Patents
Иммуноконъюгаты il2 и мутантного tnf Download PDFInfo
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- RU2758139C2 RU2758139C2 RU2019117750A RU2019117750A RU2758139C2 RU 2758139 C2 RU2758139 C2 RU 2758139C2 RU 2019117750 A RU2019117750 A RU 2019117750A RU 2019117750 A RU2019117750 A RU 2019117750A RU 2758139 C2 RU2758139 C2 RU 2758139C2
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| EP3584258A1 (en) * | 2018-06-19 | 2019-12-25 | IEO - Istituto Europeo di Oncologia Srl | Antibodies anti tumor associated antigens and method for obtaining them |
| CA3104185A1 (en) | 2018-07-02 | 2020-01-09 | The General Hospital Corporation | Antibody tumor-targeting assembly complexes |
| WO2020070150A1 (en) * | 2018-10-02 | 2020-04-09 | Philogen S.P.A | Il2 immunoconjugates |
| EP3660039A1 (en) * | 2018-11-30 | 2020-06-03 | Philogen S.p.A. | Il2 immunoconjugates |
| AU2019402097A1 (en) | 2018-12-17 | 2021-06-10 | Revitope Limited | Twin immune cell engager |
| CA3138854A1 (en) | 2019-05-02 | 2020-11-05 | The General Hospital Corporation | Teac and attac immunooncology compositions and methods |
| WO2020249757A1 (en) | 2019-06-14 | 2020-12-17 | Philogen S.P.A | Immunoconjugates comprising a single chain diabody and interleukin-15 or interleukin-15 and a sushi domain of interleukin-15 receptor alpha |
| WO2022018126A1 (en) | 2020-07-22 | 2022-01-27 | Philogen S.P.A. | Treatment of pulmonary hypertension |
| KR102614063B1 (ko) * | 2020-12-24 | 2023-12-19 | 대화제약 주식회사 | 엑스트라도메인 b 피브로넥틴에 특이적으로 결합하는 신규한 항체 |
| WO2023050826A1 (en) * | 2021-09-28 | 2023-04-06 | Suzhou Fuse Biosciences Limited | Immunoconjugates containing tnf-alpha and related methods and compositions thereof |
| US20250197485A1 (en) | 2022-03-17 | 2025-06-19 | Universitätsklinikum Jena | Anti-ED-A Antibodies for the Treatment of Pulmonary Hypertension |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005087797A1 (en) * | 2004-03-09 | 2005-09-22 | Microbia, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| RU2363707C2 (ru) * | 2001-02-19 | 2009-08-10 | Мерк Патент Гмбх | Искусственные белки с пониженной иммуногенностью |
| WO2013045125A1 (en) * | 2011-09-26 | 2013-04-04 | Philogen S.P.A. | Immunocytokine combination therapy |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4879226A (en) | 1984-04-06 | 1989-11-07 | Asahi Kasei Kogyo Kabushiki Kaisha | Novel human physiologically active polypeptide |
| JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| AU1346488A (en) | 1987-02-26 | 1988-09-26 | Cetus Corporation | Arginine-depleted human tumor necrosis factor |
| US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| GB9206318D0 (en) | 1992-03-24 | 1992-05-06 | Cambridge Antibody Tech | Binding substances |
| CA2055168A1 (en) | 1990-11-21 | 1992-05-22 | Walter Fiers | Tnf-muteins |
| US5858657A (en) | 1992-05-15 | 1999-01-12 | Medical Research Council | Methods for producing members of specific binding pairs |
| US5962255A (en) | 1992-03-24 | 1999-10-05 | Cambridge Antibody Technology Limited | Methods for producing recombinant vectors |
| US6492160B1 (en) | 1991-05-15 | 2002-12-10 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| US6225447B1 (en) | 1991-05-15 | 2001-05-01 | Cambridge Antibody Technology Ltd. | Methods for producing members of specific binding pairs |
| DE69230142T2 (de) | 1991-05-15 | 2000-03-09 | Cambridge Antibody Technology Ltd. | Verfahren zur herstellung von spezifischen bindungspaargliedern |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| ATE408012T1 (de) | 1991-12-02 | 2008-09-15 | Medical Res Council | Herstellung von autoantikörpern auf phagenoberflächen ausgehend von antikörpersegmentbibliotheken |
| US5872215A (en) | 1991-12-02 | 1999-02-16 | Medical Research Council | Specific binding members, materials and methods |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| EP0672142B1 (en) | 1992-12-04 | 2001-02-28 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
| CA2399866C (en) | 2000-02-24 | 2011-05-10 | Philogen S.R.L. | Compositions and methods for treatment of angiogenesis in pathological lesions |
| US7101974B2 (en) | 2000-03-02 | 2006-09-05 | Xencor | TNF-αvariants |
| IT1317108B1 (it) | 2000-12-06 | 2003-05-26 | Philogen Srl | Processo per la selezione di frammenti anticorporali anti-angiogenesi,frammenti anticorpali anti-angiogenesi cosi' ottenuti e loro uso. |
| SI1817345T1 (sl) | 2004-11-09 | 2009-10-31 | Philogen Spa | Protitelesa proti tenascinu-C |
| BR112016001114B1 (pt) * | 2013-07-19 | 2023-02-14 | Vib Vzw | Composição compreendendo uma proteína de fusão e uso da referida composição |
| US9209965B2 (en) | 2014-01-14 | 2015-12-08 | Microsemi Semiconductor Ulc | Network interface with clock recovery module on line card |
| GB201507908D0 (en) | 2015-05-08 | 2015-06-24 | Philogen Spa | IL2 and TNF immunoconjugates |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2363707C2 (ru) * | 2001-02-19 | 2009-08-10 | Мерк Патент Гмбх | Искусственные белки с пониженной иммуногенностью |
| WO2005087797A1 (en) * | 2004-03-09 | 2005-09-22 | Microbia, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2013045125A1 (en) * | 2011-09-26 | 2013-04-04 | Philogen S.P.A. | Immunocytokine combination therapy |
Non-Patent Citations (14)
| Title |
|---|
| ARNAU J. et al., Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins, Protein expression and purification, 2006, V. 48, N. 1, p.1-13; * |
| CHEN X. et al., Fusion protein linkers: property, design and functionality, Advanced drug delivery reviews, 2013, v. 65, n. 10, p.1357-1369; * |
| FRANKEL A.E. et al., Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor, Protein Eng., 2000, v.13, n.8, p.575-581; * |
| HALIN C. ET AL., Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to interleukin 12 and to tumor necrosis factor alpha, CANCER RESEARCH, 2003, v. 63, n. 12, p.3202 - 3210 * |
| HALIN C. ET AL., Synergistic therapeutic effects of a tumor targeting antibody fragment, fused to interleukin 12 and to tumor necrosis factor alpha, CANCER RESEARCH, 2003, v. 63, n. 12, p.3202 - 3210; * |
| KONTERMANN R. E. et al., Bispecific antibodies, Drug Discovery Today, 2015, V. 7, N. 20, p.838-847; * |
| MAEDA Y. et al., Engineering of functional chimeric protein G-Vargula Luciferase, Analytical biochemistry, 1997, v. 249, n. 2, p.147-152. * |
| OSTADE X VAN ET AL., Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis, EMBO JOURNAL, 1991, v. 10, n. 4, p.827 - 836; * |
| OSTADE X VAN ET AL., Localization of the active site of human tumour necrosis factor (hTNF) by mutational analysis, EMBO JOURNAL, 1991, v. 10, n. 4, p.827 - 836; ШИНГАРОВА Л.Н. и др., МУТАНТЫ ФАКТОРА НЕКРОЗА ОПУХОЛЕЙ ЧЕЛОВЕКА: ПОЛУЧЕНИЕ И НЕКОТОРЫЕ СВОЙСТВА, БИООРГАНИЧЕСКАЯ ХИМИЯ, 1996, Т. 22, Н. 4, с.243-251; KONTERMANN R. E. et al., Bispecific antibodies, Drug Discovery Today, 2015, V. 7, N. 20, p.838-847; * |
| PRETTO F. ET AL., Preclinical evaluation of IL2-based immunocytokines supports their use in combination with dacarbazine, paclitaxel and TNF-based immunotherapy, CANCER IMMUNOLOGY, IMMUNOTHERAPY, 2014, v. 63, n. 9, p. 901 - 910; * |
| RUDIKOFF S. et al., Single amino acid substitution altering antigen-binding specificity, Proc Natl Acad Sci USA, 1982, v.79, n.6, p. 1979-1983; * |
| TOKURIKI N. ET AL., Stability effects of mutations and protein evolvability, Curr. Opin. Struct. Biol., 2009, v.19, n.5, p.596-604; * |
| TOKURIKI N. ET AL., Stability effects of mutations and protein evolvability, Curr. Opin. Struct. Biol., 2009, v.19, n.5, p.596-604; RUDIKOFF S. et al., Single amino acid substitution altering antigen-binding specificity, Proc Natl Acad Sci USA, 1982, v.79, n.6, p. 1979-1983; FRANKEL A.E. et al., Characterization of diphtheria fusion proteins targeted to the human interleukin-3 receptor, Protein Eng., 2000, v.13, n.8, p.575-581; ARNAU J. et al., Current strategies for the use of affinity tags and tag removal for the purification of recombinant proteins, Protein expression and purification, 2006, V. 48, N. 1, p.1-13; CHEN X. et al., Fusion protein linkers: property, design and functionality, Advanced drug delivery reviews, 2013, v. 65, n. 10, p.1357-1369; MAEDA Y. et al., Engineering of functional chimeric protein G-Vargula Luciferase, Analytical biochemistry, 1997, v. 249, n. 2, p.147-152. * |
| ШИНГАРОВА Л.Н. и др., МУТАНТЫ ФАКТОРА НЕКРОЗА ОПУХОЛЕЙ ЧЕЛОВЕКА: ПОЛУЧЕНИЕ И НЕКОТОРЫЕ СВОЙСТВА, БИООРГАНИЧЕСКАЯ ХИМИЯ, 1996, Т. 22, Н. 4, с.243-251; * |
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| CA3043146C (en) | 2021-11-23 |
| AU2017358578A1 (en) | 2019-06-27 |
| ZA201903387B (en) | 2020-09-30 |
| CA3043146A1 (en) | 2018-05-17 |
| EP3538547B1 (en) | 2021-07-07 |
| RU2019117750A (ru) | 2020-12-10 |
| US20200061203A1 (en) | 2020-02-27 |
| AU2017358578B2 (en) | 2022-12-08 |
| AU2017358578A8 (en) | 2019-07-04 |
| EP3896084A1 (en) | 2021-10-20 |
| MX2019005242A (es) | 2019-09-10 |
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