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公开(公告)号：US20180044399A1
公开(公告)日：2018-02-15
申请号：US15525906
申请日：2015-11-09
发明人： Arvind RAJPAL , Shobha Chowdary POTLURI , Laurent POIROT , Alexandre JUILLERAT , Thomas Charles PERTEL , Donna Marie STONE , Barbra Johnson SASU
IPC分类号： C07K14/705 , C07K14/725 , A61K35/17 , C07K16/28 , C12N5/0783
CPC分类号： C07K14/70503 , A61K35/17 , A61K2039/5156 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K14/70578 , C07K16/2803 , C07K16/3069 , C07K2317/622 , C07K2317/76 , C07K2319/03 , C07K2319/70 , C07K2319/74 , C12N5/0636 , C12N2510/00
摘要： The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising an extracellular domain comprising an antigen binding domain, a transmembrane domain, and, an intracellular domain wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein X1 is an amino acid X2 is an amino acid X3 is an amino acid and X4 is V or
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2.发明申请公开(公告)号：US20170313787A1
公开(公告)日：2017-11-02
申请号：US15593259
申请日：2017-05-11
发明人： Pavel STROP , Magdalena Grazyna DORYWALSKA , Arvind RAJPAL , David SHELTON , Shu-Hui LIU , Jaume PONS , Russell DUSHIN
CPC分类号： C07K17/02 , A61K47/68 , A61K47/6803 , A61K47/6851 , A61K47/6889 , C07K16/30 , C07K2317/31 , C07K2317/73
摘要： The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.
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公开(公告)号：US20160159905A1
公开(公告)日：2016-06-09
申请号：US14958053
申请日：2015-12-03
发明人： Yasmina Noubia ABDICHE , Helen Kim CHO , Weihsien HO , Karen Ute JOOSS , Arvind RAJPAL , Sawsan YOUSSEF
IPC分类号： C07K16/28 , A61K39/39 , A61K39/00 , A61K39/395 , A61K45/06
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/507 , A61K2039/53 , A61K2039/545 , C07K16/2818 , C07K16/2878 , C07K2317/24 , C07K2317/33 , C07K2317/55 , C07K2317/74 , C07K2317/76 , C07K2317/92 , C07K2317/94 , A61K2300/00
摘要： The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.
摘要翻译： 本发明提供了结合程序性细胞死亡蛋白1（PD-1）的拮抗性抗体及其使用方法。 抗PD-1抗体可以治疗性地单独使用或与其它治疗剂组合用于治疗癌症和其它疾病。
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公开(公告)号：US20130122020A1
公开(公告)日：2013-05-16
申请号：US13670730
申请日：2012-11-07
发明人： Shu-Hui LIU , Wei-Hsien HO , Pavel STROP , Magdalena Grazyna DORYWALSKA , Arvind RAJPAL , David Louis SHELTON , Thomas-Toan TRAN
IPC分类号： C07K16/30
CPC分类号： C07K16/28 , A61K38/08 , A61K47/6817 , A61K47/6849 , A61K47/6851 , A61K47/6859 , A61K47/6863 , A61K47/6869 , A61K2039/505 , C07K16/30 , C07K16/3015 , C07K16/3023 , C07K16/303 , C07K16/3046 , C07K16/3069 , C07K16/3076 , C07K2317/24 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/92 , C07K2317/94
摘要： The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.
摘要翻译： 本发明提供特异性结合滋养层细胞表面抗原-2（Trop-2）的抗体。 本发明进一步提供了包含此类抗体的抗体缀合物，编码抗体的核酸，以及获得此类抗体的方法。 本发明还涉及这些抗体和Trop-2抗体缀合物用于治疗与Trop-2表达（例如癌症）如结肠，食管，胃，头颈部，肺， 卵巢癌或胰腺癌。
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公开(公告)号：US20220332850A1
公开(公告)日：2022-10-20
申请号：US17846933
申请日：2022-06-22
发明人： Weihsien HO , Jaume PONS , Arvind RAJPAL , Pavel STROP
摘要： The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.
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公开(公告)号：US20200024366A1
公开(公告)日：2020-01-23
申请号：US16296852
申请日：2019-03-08
发明人： Jaume PONS , Jeffrey Raymond CHABOT , Javier Fernando CHAPARRO RIGGERS , Bruce Charles GOMES , Hong LIANG , KapiI MAYAWALA , Jerome Thomas METTETAL, II , Arvind RAJPAL , David Louis SHELTON
摘要： The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the KD or koff ratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent KDs at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g., GMCSF receptor).
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公开(公告)号：US20190100603A1
公开(公告)日：2019-04-04
申请号：US16157951
申请日：2018-10-11
发明人： Weihsien HO , Jaume PONS , Arvind RAJPAL , Pavel STROP
摘要： The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.
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公开(公告)号：US20170058054A1
公开(公告)日：2017-03-02
申请号：US15351275
申请日：2016-11-14
发明人： Weihsien HO , Jaume PONS , Arvind RAJPAL , Pavel STROP
CPC分类号： C07K16/468 , A61K2039/505 , C07K16/28 , C07K16/2809 , C07K16/283 , C07K16/2887 , C07K16/30 , C07K16/46 , C07K2317/21 , C07K2317/31 , C07K2317/526 , C07K2317/53 , C07K2317/73 , C07K2317/76 , C07K2317/92
摘要： The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.
摘要翻译： 本发明涉及工程化的异源多聚体蛋白质，更具体地，涉及用于产生和纯化异二聚体蛋白质的方法，例如双特异性抗体和包含免疫球蛋白样铰链序列的其它异二聚体蛋白质。 还提供了用于生产和纯化这些工程异二聚体蛋白的方法及其在诊断和治疗中的应用。
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公开(公告)号：US20170043033A1
公开(公告)日：2017-02-16
申请号：US15306481
申请日：2015-04-21
发明人： Pavel STROP , Katherine Anne DELARIA , Magdalena DORYWALSKA , Davide Luciano FOLETTI , Russell George DUSHIN , David Louis SHELTON , Arvind RAJPAL
IPC分类号： A61K47/48 , G01N33/574 , C07K16/30 , A61K31/427
CPC分类号： A61K31/427 , A61K47/65 , A61K47/6803 , A61K47/6849 , A61K47/6851 , A61K47/6889 , A61K2039/505 , C07K16/3076 , G01N33/57492 , G01N2333/705
摘要： The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.
摘要翻译： 本发明提供了具有高抗体药物比例（DAR）的转谷氨酰胺酶介导的抗体 - 药物偶联物，其包含1）含有抗体工程或工程化转谷氨酰胺酶（例如，谷氨酰胺）的反应产生的含谷氨酰胺的标签，内源性谷氨酰胺和/或内源性谷氨酰胺， 改变底物特异性）; 和2）包含胺供体单元，接头和试剂部分的胺供体试剂，其中DAR为至少约5.本发明还提供了制备方法和使用这种高加载药物的抗体 - 药物共轭物的方法。
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公开(公告)号：US20160257746A1
公开(公告)日：2016-09-08
申请号：US15160742
申请日：2016-05-20
发明人： Shu-Hui LIU , Wei-Hsien HO , Pavel STROP , Magdalena Grazyna DORYWALSKA , Arvind RAJPAL , David Louis SHELTON , Thomas-Toan TRAN
CPC分类号： C07K16/28 , A61K38/08 , A61K47/6817 , A61K47/6849 , A61K47/6851 , A61K47/6859 , A61K47/6863 , A61K47/6869 , A61K2039/505 , C07K16/30 , C07K16/3015 , C07K16/3023 , C07K16/303 , C07K16/3046 , C07K16/3069 , C07K16/3076 , C07K2317/24 , C07K2317/565 , C07K2317/73 , C07K2317/732 , C07K2317/92 , C07K2317/94
摘要： The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.
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