DK2844667T3 - Målrettede/immunomodulatoriske fusionsproteiner og fremgangsmåder til fremstilling deraf - Google Patents

Målrettede/immunomodulatoriske fusionsproteiner og fremgangsmåder til fremstilling deraf Download PDF

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DK2844667T3
DK2844667T3 DK13734158.2T DK13734158T DK2844667T3 DK 2844667 T3 DK2844667 T3 DK 2844667T3 DK 13734158 T DK13734158 T DK 13734158T DK 2844667 T3 DK2844667 T3 DK 2844667T3
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Nagaraj Govindappa
Kedarnath Sastry
Maria Melina Soares
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Biocon Ltd
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    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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Claims (3)

1. Kimærisk fusionsprotein, som består af en målretningsenhed rettet mod en cancercelle, en immunomodulerende enhed, som modvirker immunologisk tolerance, og en aminosyrespacer, hvor målretningsenheden og den immunomodulerende enhed er forbundne med en aminosyrespacer med tilstrækkelig længde af aminosyrerester, således at begge enheder kan lykkes med at forbindes til deres individuelle mål, hvor den immunomodulerende enhed er TGF-pRIl, som består af aminosyresekvensen SEQ ID NO: 4; hvor aminosyrespaceren er SEQ ID NO: 3 eller SEQ ID NO:11; og hvor målretningsenheden er Anti-EGFR1, som består af en tungkæde SEQ ID NO: 5 og en letkæde SEQ ID NO: 6; hvor SEQ ID NO:4 er bundet via aminosyrespaceren til C-terminus af SEQ ID NO:5 eller SEQ ID NO:6 af Anti-EGFFM.
2. Polynukleotidsekvens, omfattende en nukleinsyresekvens, som koder for et kimærisk fusionsprotein ifølge krav 1.
3. Kimærisk fusionsprotein ifølge krav 1 til anvendelse i behandlingen af en neoplastisk sygdom hos et individ.
DK13734158.2T 2012-04-30 2013-03-13 Målrettede/immunomodulatoriske fusionsproteiner og fremgangsmåder til fremstilling deraf DK2844667T3 (da)

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IN1689CH2012 2012-04-30
IN1690CH2012 2012-04-30
PCT/IB2013/001155 WO2013164694A1 (en) 2012-04-30 2013-03-13 Targeted/immunomodulatory fusion proteins and methods for making same

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US (9) US8815247B2 (da)
EP (4) EP3489254B9 (da)
JP (4) JP6357467B2 (da)
CN (4) CN110563850A (da)
AU (2) AU2013255542C1 (da)
CA (4) CA2947354C (da)
DK (2) DK2844667T3 (da)
ES (2) ES2678696T3 (da)
HK (3) HK1202295A1 (da)
MY (1) MY174248A (da)
NZ (4) NZ729633A (da)
PL (2) PL2844667T3 (da)
PT (2) PT2844667T (da)
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Families Citing this family (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL300733A (en) 2010-03-05 2023-04-01 Univ Johns Hopkins Compositions and methods for antibodies and fusion proteins targeting immune modulation
MY174248A (en) * 2012-04-30 2020-04-01 Biocon Ltd Targeted/immunomodulatory fusion proteins and methods for making same
US9605084B2 (en) 2013-03-15 2017-03-28 Xencor, Inc. Heterodimeric proteins
EP2943511B1 (en) 2013-01-14 2019-08-07 Xencor, Inc. Novel heterodimeric proteins
US11053316B2 (en) 2013-01-14 2021-07-06 Xencor, Inc. Optimized antibody variable regions
US10968276B2 (en) 2013-03-12 2021-04-06 Xencor, Inc. Optimized anti-CD3 variable regions
PT2970512T (pt) * 2013-03-12 2019-01-17 Biocon Ltd Proteínas de fusão imunomoduladoras e métodos para produção das mesmas
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
EP3705498A1 (en) 2013-08-22 2020-09-09 Acceleron Pharma Inc. Tgf-beta receptor type ii variants and uses thereof
CA2925658C (en) * 2013-10-01 2022-12-06 Mie University Long chain antigen containing interepitope sequence that promotes antigen presentation to t cells
EP2891664A1 (en) * 2014-01-07 2015-07-08 Technische Universität München Novel methods for the stabilisation of immunoglobulin constant domains
US10927154B2 (en) 2014-01-13 2021-02-23 Pieris Pharmaceuticals Gmbh Multi-specific polypeptide useful for localized tumor immunomodulation
SG10202108879SA (en) * 2014-02-10 2021-09-29 Merck Patent Gmbh TARGETED TGFβ INHIBITION
JP6775422B2 (ja) 2014-03-28 2020-10-28 ゼンコー・インコーポレイテッドＸｅｎｃｏｒ、 Ｉｎｃ． Ｃｄ３８及びｃｄ３に結合する二重特異性抗体
US10351621B2 (en) 2014-06-24 2019-07-16 Immunomedics, Inc. Anti-histone therapy in acute kidney injury
US9580495B2 (en) * 2014-06-24 2017-02-28 Immunomedics, Inc. Anti-histone therapy for vascular necrosis in severe glomerulonephritis
MX2017006250A (es) 2014-11-14 2017-11-17 Hoffmann La Roche Moleculas de union a antigeno que comprenden un trimero de ligando de la familia de tnf.
MA41019A (fr) 2014-11-26 2021-05-05 Xencor Inc Anticorps hétérodimériques se liant aux antigènes cd3 et cd38
US10259887B2 (en) 2014-11-26 2019-04-16 Xencor, Inc. Heterodimeric antibodies that bind CD3 and tumor antigens
EP3223845B1 (en) 2014-11-26 2021-05-19 Xencor, Inc. Heterodimeric antibodies that bind cd3 and cd20
CN114751989A (zh) 2015-03-31 2022-07-15 豪夫迈·罗氏有限公司 包含三聚体tnf家族配体的抗原结合分子
US10865250B2 (en) * 2015-05-04 2020-12-15 Pieris Pharmaceuticals Gmbh Anti-cancer fusion polypeptide
EP3328427B1 (en) 2015-07-27 2024-05-29 The General Hospital Corporation Antibody derivatives with conditionally enabled effector function
US9884900B2 (en) 2015-08-04 2018-02-06 Acceleron Pharma Inc. Methods for treating Janus kinase-associated disorders by administering soluble transforming growth factor beta type II receptor
JP2018531625A (ja) * 2015-09-11 2018-11-01 ナセント バイオテック インコーポレイテッド 脳への向上した薬物送達の方法
AR106188A1 (es) 2015-10-01 2017-12-20 Hoffmann La Roche Anticuerpos anti-cd19 humano humanizados y métodos de utilización
SG10201913576RA (en) 2015-10-01 2020-02-27 Heat Biologics Inc Compositions and methods for adjoining type i and type ii extracellular domains as heterologous chimeric proteins
CN115746143A (zh) 2015-10-02 2023-03-07 豪夫迈·罗氏有限公司 对共刺激性tnf受体特异性的双特异性抗体
SI3356411T1 (sl) 2015-10-02 2021-09-30 F. Hoffmann-La Roche Ag Bispecifična protitelesa, specifična za PD1 in TIM3
PE20181349A1 (es) * 2015-10-07 2018-08-22 Hoffmann La Roche Anticuerpos biespecificos con tetravalencia para un receptor de fnt coestimulador
CA3007030A1 (en) 2015-12-07 2017-06-15 Xencor, Inc. Heterodimeric antibodies that bind cd3 and psma
WO2017136818A2 (en) * 2016-02-05 2017-08-10 Washington University Compositions and methods for targeted cytokine delivery
US11542332B2 (en) 2016-03-26 2023-01-03 Bioatla, Inc. Anti-CTLA4 antibodies, antibody fragments, their immunoconjugates and uses thereof
WO2017192536A1 (en) * 2016-05-02 2017-11-09 University Of Kansas Eliminating mhc restriction from the t cell receptor as a strategy for immunotherapy
AR108377A1 (es) * 2016-05-06 2018-08-15 Medimmune Llc Proteínas de unión biespecíficas y sus usos
EP3243836A1 (en) * 2016-05-11 2017-11-15 F. Hoffmann-La Roche AG C-terminally fused tnf family ligand trimer-containing antigen binding molecules
EP3243832A1 (en) * 2016-05-13 2017-11-15 F. Hoffmann-La Roche AG Antigen binding molecules comprising a tnf family ligand trimer and pd1 binding moiety
RU2022104399A (ru) 2016-06-14 2022-05-05 Ксенкор, Инк. Биспецифические антитела-ингибиторы контрольных точек
CN116063545A (zh) 2016-06-28 2023-05-05 Xencor股份有限公司 结合生长抑素受体2的异源二聚抗体
IL264730B1 (en) * 2016-08-12 2024-05-01 Merck Patent Gmbh A pharmaceutical preparation containing TGFbetaRII and another anti-cancer preparation
WO2018045110A1 (en) * 2016-08-30 2018-03-08 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
US10793632B2 (en) 2016-08-30 2020-10-06 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
CA3038526A1 (en) * 2016-09-27 2018-04-05 Epicentrx, Inc. Immunomodulatory fusion proteins
US11739163B2 (en) 2016-09-29 2023-08-29 Aebi Ltd. Therapeutic multi-targeting constructs and uses thereof
CN107915777A (zh) * 2016-10-09 2018-04-17 泰州迈博太科药业有限公司 一种重组免疫细胞因子及其应用
CN108250302A (zh) * 2016-12-29 2018-07-06 天津天锐生物科技有限公司 一种多功能蛋白质
AU2018205890B2 (en) 2017-01-05 2021-09-02 Kahr Medical Ltd. A sirpalpha-41BBL fusion protein and methods of use thereof
US11299530B2 (en) 2017-01-05 2022-04-12 Kahr Medical Ltd. SIRP alpha-CD70 fusion protein and methods of use thereof
EP3565579B9 (en) * 2017-01-05 2023-10-04 KAHR Medical Ltd. A pd1-41bbl fusion protein and methods of use thereof
WO2018127916A1 (en) 2017-01-05 2018-07-12 Kahr Medical Ltd. A pd1-cd70 fusion protein and methods of use thereof
CA3048646A1 (en) * 2017-01-07 2018-07-12 Merck Patent Gmbh Dosing regimens and dosage forms for targeted tgf-b inhibition
CN108440668A (zh) * 2017-02-16 2018-08-24 瑞阳(苏州)生物科技有限公司 Fgf21与igf-1的融合蛋白及其应用
EP3585409A4 (en) 2017-02-27 2020-12-02 Shattuck Labs, Inc. CHEMERICAL PROTEINS BASED ON CSF1R
IL268198B1 (en) 2017-02-27 2024-06-01 Shattuck Labs Inc based chimeric proteins - TIGIT and LIGHT
US11192933B2 (en) 2017-02-27 2021-12-07 Shattuck Labs, Inc. VSIG8-based chimeric proteins
AU2018228435A1 (en) 2017-03-02 2019-10-03 National Research Council Of Canada TGF-beta-receptor ectodomain fusion molecules and uses thereof
WO2018162749A1 (en) 2017-03-09 2018-09-13 Genmab A/S Antibodies against pd-l1
CN107082812B (zh) * 2017-03-29 2018-11-13 上海科医联创生物科技有限公司 一种恢复衰竭性免疫细胞功能的融合蛋白及其应用
AU2018247765B2 (en) 2017-04-03 2023-11-23 F. Hoffmann-La Roche Ag Immunoconjugates of an Anti-PD-1 antibody with a mutant IL-2 or with IL-15
IL268527B2 (en) 2017-04-05 2024-03-01 Hoffmann La Roche Bispecific antibodies bind to PD1 and LAG3 specifically
DK3628049T3 (da) 2017-05-04 2023-08-14 Acceleron Pharma Inc Tgf-beta-receptortype-ii-fusionsproteiner og anvendelser deraf
CN110050000B (zh) * 2017-05-12 2022-07-26 苏州盛迪亚生物医药有限公司 含有TGF-β受体的融合蛋白及其医药用途
CA3064869A1 (en) * 2017-05-26 2018-11-29 The Johns Hopkins University Multifunctional antibody-ligand traps to modulate immune tolerance
CR20200099A (es) 2017-08-03 2020-07-24 Amgen Inc Muteínas de interleucina 21 y métodos de tratamiento
AU2018309339A1 (en) 2017-08-04 2020-02-20 BioNTech SE Binding agents binding to PD-L1 and CD137 and use thereof
EA202090838A1 (ru) 2017-09-27 2020-08-28 Эписентарикс, Инк. Иммуномодулирующие слитые белки
AU2018366199A1 (en) 2017-11-08 2020-05-28 Xencor, Inc. Bispecific and monospecific antibodies using novel anti-PD-1 sequences
US10981992B2 (en) 2017-11-08 2021-04-20 Xencor, Inc. Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors
CA3086199A1 (en) 2017-12-19 2019-06-27 Xencor, Inc. Engineered il-2 fc fusion proteins
MX2020007024A (es) 2018-01-03 2020-10-28 Palleon Pharmaceuticals Inc Sialidasas humanas recombinantes, proteinas de fusion de sialidasa y metodos para usar las mismas.
UY38049A (es) 2018-01-12 2019-07-31 Amgen Inc Anti-pd-1 anticuerpos y métodos de tratamiento
CN108285493B (zh) * 2018-02-02 2020-09-15 上海科医联创生物科技有限公司 一种恢复衰竭性免疫细胞功能的融合蛋白及其应用
CA3090552A1 (en) * 2018-02-07 2019-08-15 Imugene Limited A vaccine composition and uses thereof
JP7319992B2 (ja) 2018-03-09 2023-08-02 アジェナス インコーポレイテッド 抗ｃｄ７３抗体およびそれらの使用方法
CA3089333C (en) * 2018-03-26 2023-10-10 Altor Bioscience Llc Anti-pdl1, il-15 and tgf-beta receptor combination molecules
US10982006B2 (en) 2018-04-04 2021-04-20 Xencor, Inc. Heterodimeric antibodies that bind fibroblast activation protein
CA3097741A1 (en) 2018-04-18 2019-10-24 Xencor, Inc. Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains
EP3781599A1 (en) 2018-04-18 2021-02-24 Xencor, Inc. Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof
AU2019288733C1 (en) 2018-06-22 2023-08-03 Kite Pharma, Inc. Chimeric transmembrane proteins and uses thereof
SG11202100208VA (en) 2018-07-09 2021-02-25 Precigen Inc Fusion constructs and methods of using thereof
US10780121B2 (en) 2018-08-29 2020-09-22 Shattuck Labs, Inc. FLT3L-based chimeric proteins
WO2020072821A2 (en) 2018-10-03 2020-04-09 Xencor, Inc. Il-12 heterodimeric fc-fusion proteins
MA54139A (fr) 2018-11-06 2021-09-15 BioNTech SE Formulation d'anticorps
WO2020094122A1 (zh) 2018-11-09 2020-05-14 江苏恒瑞医药股份有限公司 一种TGF-β受体融合蛋白药物组合物及其用途
MX2021010390A (es) 2019-03-01 2021-11-17 Xencor Inc Anticuerpos heterodimericos que se unen a enpp3 y cd3.
CN110117329B (zh) * 2019-04-03 2020-12-08 河北浓孚雨生物科技有限公司 包含趋化因子与结合伴侣的融合多肽及其用途
CA3143271A1 (en) * 2019-06-21 2020-12-24 Kite Pharma, Inc. Tgf-.beta. receptors and methods of use
WO2020263312A1 (en) * 2019-06-28 2020-12-30 Gensun Biopharma, Inc. ANTITUMOR ANTAGONIST CONSISTING OF A MUTATED TGFβ1 - RII EXTRACELLULAR DOMAIN AND AN IMMUNOGLOBULIN SCAFFOLD
CN114302897A (zh) * 2019-07-03 2022-04-08 帕利昂制药有限公司 唾液酸酶-her2抗体融合蛋白及其使用方法
US20210107969A1 (en) * 2019-07-09 2021-04-15 The Johns Hopkins University Molecules, compositions and methods for treatment of cancer
EP3999527A4 (en) * 2019-07-18 2024-04-17 Memorial Sloan Kettering Cancer Center METHODS AND COMPOSITIONS FOR TARGETING TGF-BETA SIGNALIZING IN CD4+ HELPER T CELLS FOR CANCER IMMUNOTHERAPY
CN110540601B (zh) * 2019-07-29 2021-06-29 因之彩生物科技（武汉）有限公司 重组PLB-hEGF融合蛋白及其应用
CN110354260B (zh) * 2019-08-19 2020-06-26 启辰生生物科技(珠海)有限公司 免疫增强剂、药物组合物及其应用
JP2022548085A (ja) * 2019-09-12 2022-11-16 サーナオミクス インコーポレイテッド がんを治療するためのＴＧＦ－β ｓｉＲＮＡ及びＰＤＬ１ ｓｉＲＮＡの共送達
EP4023672A1 (en) * 2019-09-30 2022-07-06 Harbour Biomed (Shanghai) Co., Ltd Anti-pd-l1 antigen binding protein, and application thereof
EP4048704A4 (en) * 2019-10-21 2023-11-22 Nanjing Leads Biolabs Co., Ltd. RECOMBINANT PROTEIN TARGETING PD-1 AND TGFß
CN111018989B (zh) * 2019-12-16 2021-03-23 郑州大学 一种抗pd-l1单克隆抗体以及在制备抗癌药物方面的应用
CN111690070A (zh) * 2020-05-13 2020-09-22 深圳市众循精准医学研究院 一种sPD-1-Fc-sTGFβRII融合蛋白及其应用
US11919956B2 (en) 2020-05-14 2024-03-05 Xencor, Inc. Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3
US11028174B1 (en) 2020-07-28 2021-06-08 Lepu Biopharma Co., Ltd. Bifunctional molecules targeting PD-L1 and TGF-β
AU2021329378A1 (en) 2020-08-19 2023-03-23 Xencor, Inc. Anti-CD28 compositions
CN114539415B (zh) * 2020-11-24 2024-02-02 普米斯生物技术(珠海)有限公司 一种抗PD-L1/VEGF/TGF-β多特异性抗体及其用途
WO2022132202A1 (en) * 2020-12-15 2022-06-23 Bicara Therapeutics Inc. Combination therapy for the treatment of cancer
CN116917334A (zh) * 2021-02-22 2023-10-20 浙江道尔生物科技有限公司 一种具有抗癌活性的多结构域融合蛋白
IL305663A (en) * 2021-03-05 2023-11-01 Shattuck Labs Inc Combined treatments with SIRPa-based chimeric proteins
WO2022187583A1 (en) * 2021-03-05 2022-09-09 Shattuck Labs, Inc. Combination therapies with tim-3-based chimeric proteins
AU2022232375A1 (en) 2021-03-09 2023-09-21 Xencor, Inc. Heterodimeric antibodies that bind cd3 and cldn6
US11859012B2 (en) 2021-03-10 2024-01-02 Xencor, Inc. Heterodimeric antibodies that bind CD3 and GPC3
US11492394B1 (en) 2021-10-29 2022-11-08 Nascent Biotech, Inc. Kits and containers for treating vimentin expressing tumors
WO2023141724A1 (en) 2022-01-28 2023-08-03 35Pharma Inc. Activin receptor type iib variants and uses thereof
WO2023150788A2 (en) * 2022-02-07 2023-08-10 Ubiquitx Beta-catenin protein degradation

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2120475C1 (ru) 1990-05-17 1998-10-20 Макс-Планк-Гезельшафт Цур Фердерунг дер Виссеншафтен е.ф. Способ получения представляющего интерес полипептида, гибридная днк (варианты), слитый белок (варианты)
US20030171551A1 (en) * 1997-01-31 2003-09-11 Joseph D. Rosenblatt Chimeric antibody fusion proteins for the recruitment and stimulation of an antitumor immune response
AU778611B2 (en) * 1999-08-09 2004-12-16 Merck Patent Gmbh Multiple cytokine-antibody complexes
CA2393618A1 (en) 2000-01-31 2001-08-02 Human Genome Sciences, Inc. Nucleic acids, proteins, and antibodies
ATE336514T1 (de) 2000-02-11 2006-09-15 Merck Patent Gmbh Steigerung der zirkulierenden halbwertzeit von auf antikörpern basierenden fusionsproteinen
CN104087591A (zh) * 2006-06-19 2014-10-08 阿斯克肋匹奥生物制药公司 用于基因治疗的修饰的因子viii和因子ix基因和载体
EP2031064A1 (de) * 2007-08-29 2009-03-04 Boehringer Ingelheim Pharma GmbH & Co. KG Verfahren zur Steigerung von Proteintitern
BRPI0817108B8 (pt) * 2007-09-21 2021-05-25 Univ California composição compreendendo uma proteína de fusão, kit compreendendo a referida composição e uso da mesma.
AU2009223784A1 (en) * 2008-03-08 2009-09-17 Immungene, Inc. Engineered fusion molecules immunotherapy in cancer and inflammatory diseases
US8470552B2 (en) * 2009-10-12 2013-06-25 Keck Graduate Institute Strategy to reduce lactic acid production and control PH in animal cell culture
IL300733A (en) * 2010-03-05 2023-04-01 Univ Johns Hopkins Compositions and methods for antibodies and fusion proteins targeting immune modulation
JP6121904B2 (ja) * 2010-09-08 2017-04-26 ハロザイム インコーポレイテッド 条件的活性治療用タンパク質を評価および同定する、または発展させる方法
RU2592680C2 (ru) * 2011-04-29 2016-07-27 Биокон Рисерч Лимитед Способ снижения накопления лактата при культивировании и способ получения антитела
SE536913C2 (sv) 2012-03-08 2014-10-28 Gambro Lundia Ab Komposition för dialys
MY174248A (en) * 2012-04-30 2020-04-01 Biocon Ltd Targeted/immunomodulatory fusion proteins and methods for making same
PT2970512T (pt) * 2013-03-12 2019-01-17 Biocon Ltd Proteínas de fusão imunomoduladoras e métodos para produção das mesmas

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