公开(公告)号：US10030063B2

公开(公告)日：2018-07-24

申请号：US14651694

申请日：2013-12-16

申请人： Mara Fornaro ,  David Jonathan Glass ,  Thomas Jostock ,  Holger Laux ,  Sandrine Romand

发明人： Mara Fornaro ,  David Jonathan Glass ,  Thomas Jostock ,  Holger Laux ,  Sandrine Romand

IPC分类号： C07K14/65 ,  C12N15/113 ,  C12P21/02 ,  C12N15/11

摘要： The invention relates to methods for the production of therapeutic proteins in mammalian cells. In one embodiment, the method comprises producing a therapeutic protein such as IGF-1 in a mammalian cell endogenously expressing a cognate receptor of said recombinant therapeutic protein and wherein binding of said therapeutic protein to said cognate receptor results in a low titer of the therapeutic protein, the method comprising with a mammalian cell being deficient in the expression of the cognate receptor of said therapeutic protein and being transformed with an expression vector comprising a nucleic acid molecule encoding the therapeutic protein: a. Cultivating said cell under conditions allowing the expression of the therapeutic protein; and b. Harvesting the therapeutic protein from the mammalian cell cultivated in step a, wherein said mammalian cell produces at least 1.5 fold more therapeutic protein than a cell in which the expression of the cognate receptor has not been so modified.

公开(公告)号：US20100234290A1

公开(公告)日：2010-09-16

申请号：US12304068

申请日：2007-06-06

申请人： David Jonathan Glass ,  Mara Fornaro

发明人： David Jonathan Glass ,  Mara Fornaro

IPC分类号： A61K38/16 ,  C07K14/00 ,  C07H21/00 ,  C12N15/74 ,  C12N5/10 ,  A61P3/10 ,  A61P7/06

CPC分类号： C07K14/475 ,  A61K38/30 ,  C07K14/65

摘要： The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

摘要翻译： 本发明涉及具有IGF-1或IGF-2序列和E肽序列的稳定的多肽，其中预防了来自IGF的E-肽的天然生理切割。

公开(公告)号：US08343918B2

公开(公告)日：2013-01-01

申请号：US12304068

申请日：2007-06-06

申请人： David Jonathan Glass ,  Mara Fornaro

发明人： David Jonathan Glass ,  Mara Fornaro

IPC分类号： A61K38/30 ,  C07K14/65 ,  C07H21/04

CPC分类号： C07K14/475 ,  A61K38/30 ,  C07K14/65

摘要： The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

摘要翻译： 本发明涉及具有IGF-1或IGF-2序列和E肽序列的稳定的多肽，其中预防了来自IGF的E-肽的天然生理切割。

公开(公告)号：US20100173839A1

公开(公告)日：2010-07-08

申请号：US12303623

申请日：2007-06-06

申请人： David Jonathan Glass

发明人： David Jonathan Glass

IPC分类号： A61K38/16 ,  C07K14/00 ,  A61P43/00

CPC分类号： C07K14/475 ,  A61K38/30 ,  C07K14/65

摘要： The invention relates to stabilized polypeptides having an IGF-1 or IGF-2 sequence and an E-peptide sequence, where the natural physiological cleavage of the E-peptide from the IGF is prevented.

摘要翻译： 本发明涉及具有IGF-1或IGF-2序列和E肽序列的稳定的多肽，其中预防了来自IGF的E-肽的天然生理切割。

公开(公告)号：US20160311907A1

公开(公告)日：2016-10-27

申请号：US15105074

申请日：2014-12-19

申请人： Jennifer Brogdon ,  Boris Engels ,  David Jonathan Glass ,  Brian Granda ,  John Hastewell ,  Andreas Loew ,  Joan Mannick ,  Michael Milone ,  Leon Murphy ,  William Raj Sellers ,  Huijuan Song ,  Brian Edward Vash ,  Jan Weiler ,  Qilong Wu ,  Li Zhou

发明人： Jennifer Brogdon ,  Boris Engels ,  David Jonathan Glass ,  Brian Granda ,  John Hastewell ,  Andreas Loew ,  Joan Mannick ,  Michael Milone ,  Leon Murphy ,  William Raj Sellers ,  Huijuan Song ,  Brian Edward Vash ,  Jan Weiler ,  Qilong Wu ,  Li Zhou

IPC分类号： C07K16/28 ,  A61K35/17 ,  C12N9/90 ,  C07K14/705 ,  C07K14/71 ,  C07K14/725 ,  A61K31/436

CPC分类号： C07K16/2863 ,  A61K31/436 ,  A61K35/17 ,  C07K14/7051 ,  C07K14/70521 ,  C07K14/70578 ,  C07K14/71 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C07K2319/41 ,  C07K2319/43 ,  C07K2319/70 ,  C12N9/1205 ,  C12N9/90 ,  C12Y502/00

摘要： Compositions and methods relating to regulatable chimeric antigen receptors (RCARs), where the intracellular signaling or proliferation of the RCAR can be controlled to optimize the use of an RCAR-expressing cell to provide an immune response, are provided. For example, a RCAR can comprise a dimerization switch that, upon the presence of a dimerization molecule, can couple an intracellular signaling domain to an extracellular recognition element, e.g., an antigen binding domain, an inhibitory counter ligand binding domain, or costimulatory ECD domain. An RCAR can be engineered to include an appropriate antigen binding domain that is specific to a desired antigen target and used in the treatment of a disease.

摘要翻译： 提供了与可调节嵌合抗原受体（RCAR）相关的组合物和方法，其中可以控制RCAR的细胞内信号传导或增殖以优化使用表达RCAR的细胞以提供免疫应答。 例如，RCAR可以包含二聚转换开关，其在二聚化分子的存在下可以将细胞内信号结构域偶联到细胞外识别元件，例如抗原结合结构域，抑制性反配体结合结构域或共刺激ECD结构域 。 RCAR可以被设计成包括对所需抗原靶特异性并用于治疗疾病的合适的抗原结合结构域。