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公开(公告)号：US09469856B2
公开(公告)日：2016-10-18
申请号：US14182863
申请日：2014-02-18
Applicant: REGENERON PHARMACEUTICALS, INC.
Inventor： Changlin Dou , Gang Chen , James P. Fandl
CPC classification number: C12N15/635 , A01K2217/05 , C07K16/00 , C07K2317/14 , C07K2317/21 , C07K2319/00 , C12N15/63 , C12N15/85 , C12N2830/00 , C12N2830/15 , C12N2830/42 , C12N2840/20 , C12P21/00
Abstract: Compositions and methods for the inducible expression of genes in eukaryotic cells are provided. Expression of a nucleotide sequence of interest encoding a protein of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a ligand-binding domain. When a cognate ligand for the ligand-binding domain is present, transcription of the nucleotide sequence of interest is blocked. Upon removal of the cognate ligand, the nucleotide sequence of interest is transcribed. The method is useful for large scale bioreactor production of a desired protein of interest in eukaryotic cells.
Abstract translation: 提供了在真核细胞中可诱导表达基因的组合物和方法。 通过由转录阻断结构域和配体结合结构域组成的调节融合蛋白来控制编码目的蛋白质的目标核苷酸序列的表达。 当存在配体结合结构域的同源配体时，感兴趣的核苷酸序列的转录被阻断。 去除同源配体后，转录目的核苷酸序列。 该方法可用于在真核细胞中大规模生物反应器生产期望的蛋白质。
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公开(公告)号：US20160090410A1
公开(公告)日：2016-03-31
申请号：US14963178
申请日：2015-12-08
Applicant: Regeneron Pharmaceuticals, Inc.
Inventor： Gang Chen , Darya Burakov , James P. Fandl
IPC: C07K16/00
CPC classification number: C12P21/005 , C07K16/00 , C07K16/2863 , C07K16/2866 , C07K2317/14 , C07K2317/41 , C12N9/0006 , C12N15/00 , C12Y101/01271 , Y02P20/52
Abstract: An isolated nucleic acid encoding an FX protein having a serine at position 79, a lysine at position 90, a leucine at position 136, an arginine at position 211, a serine at position 289, and a combination thereof is provided. Cells having a gene encoding a modified FX protein are provided, wherein the cells exhibit a reduced ability to fucosylate a glycoprotein at a first temperature, but exhibit the ability to fucosylate the glycoprotein at a second temperature. Methods and compositions for making glycoproteins with reduced fucosylation are provided.
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公开(公告)号：US09228012B2
公开(公告)日：2016-01-05
申请号：US14754146
申请日：2015-06-29
Applicant: REGENERON PHARMACEUTICALS, INC.
Inventor： Gang Chen , Darya Burakov , Dipali Deshpande
CPC classification number: C07K16/22 , C07K14/47 , C07K14/4705 , C07K16/00 , C07K2317/14 , C07K2317/51 , C07K2317/515 , C12N9/2488 , C12N15/09 , C12N15/63 , C12N15/79 , C12N15/85 , C12N2015/8518 , C12Y302/01
Abstract: The present invention relates to discovery of the ectopic expression of EDEM2 in a production cell to improve the yield of a useful multi-subunit protein. Thus, the present invention provides for production cell lines, such as the canonical mammalian biopharmaceutical production cell—the CHO cell, containing recombinant polynucleotides encoding EDEM2. Also disclosed is a production cell containing both an EDEM2-encoding polynucleotide as well an XBP1-encoding polynucleotide. Improved titers of antibodies produced by these cell lines are disclosed, as well as the improved cell densities attained by these cells in culture.
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公开(公告)号：US09079954B2
公开(公告)日：2015-07-14
申请号：US13904587
申请日：2013-05-29
Applicant: REGENERON PHARMACEUTICALS, INC.
Inventor： Gang Chen , Darya Burakov , Dipali Deshpande
CPC classification number: C07K16/22 , C07K14/47 , C07K14/4705 , C07K16/00 , C07K2317/14 , C07K2317/51 , C07K2317/515 , C12N9/2488 , C12N15/09 , C12N15/63 , C12N15/79 , C12N15/85 , C12N2015/8518 , C12Y302/01
Abstract: The present invention relates to discovery of the ectopic expression of EDEM2 in a production cell to improve the yield of a useful multi-subunit protein. Thus, the present invention provides for production cell lines, such as the canonical mammalian biopharmaceutical production cell—the CHO cell, containing recombinant polynucleotides encoding EDEM2. Also disclosed is a production cell containing both an EDEM2-encoding polynucleotide as well an XBP1-encoding polynucleotide. Improved titers of antibodies produced by these cell lines are disclosed, as well as the improved cell densities attained by these cells in culture.
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公开(公告)号：US20150175676A1
公开(公告)日：2015-06-25
申请号：US14511786
申请日：2014-10-10
Applicant: Regeneron Pharmaceuticals, Inc.
Inventor： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
IPC: C07K14/71
CPC classification number: C07K14/71 , C07H21/04 , C07K16/2863 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/75 , C07K2319/30 , C12P21/02
Abstract: A fusion polypeptide comprising (A)x-M-(A′)y, wherein A and A′ are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A′ may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
Abstract translation: 包含（A）x-M-（A'）y的融合多肽，其中A和A'是能够结合靶受体的多肽。 本发明的融合多肽形成激活靶受体的多聚体蛋白。 A和A'可以各自为来自对靶受体特异的抗体的抗体或片段，例如相同或不同的scFv片段，和/或能够结合靶蛋白的配体或配体片段或衍生物，M是 多聚化组分，X和Y独立地为1-10之间的数。
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公开(公告)号：US08927233B2
公开(公告)日：2015-01-06
申请号：US13857551
申请日：2013-04-05
Applicant: Regeneron Pharmaceuticals, Inc.
Inventor： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
CPC classification number: C07K14/71 , C07H21/04 , C07K16/2863 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/75 , C07K2319/30 , C12P21/02
Abstract: A fusion polypeptide comprising (A)x-M-(A′)y, wherein A and A′ are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A′ may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
Abstract translation: 包含（A）x-M-（A'）y的融合多肽，其中A和A'是能够结合靶受体的多肽。 本发明的融合多肽形成激活靶受体的多聚体蛋白。 A和A'可以各自为来自对靶受体特异的抗体的抗体或片段，例如相同或不同的scFv片段，和/或能够结合靶蛋白的配体或配体片段或衍生物，M是 多聚化组分，X和Y独立地为1-10之间的数。
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公开(公告)号：US08865430B2
公开(公告)日：2014-10-21
申请号：US13892630
申请日：2013-05-13
Applicant: Regeneron Pharmaceuticals, Inc.
Inventor： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
CPC classification number: C07K14/71 , C07H21/04 , C07K16/2863 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/75 , C07K2319/30 , C12P21/02
Abstract: A fusion polypeptide comprising (A)x-M-(A′)y, wherein A and A′ are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A′ may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
Abstract translation: 包含（A）x-M-（A'）y的融合多肽，其中A和A'是能够结合靶受体的多肽。 本发明的融合多肽形成激活靶受体的多聚体蛋白。 A和A'可以各自为来自对靶受体特异的抗体的抗体或片段，例如相同或不同的scFv片段，和/或能够结合靶蛋白的配体或配体片段或衍生物，M是 多聚化组分，X和Y独立地为1-10之间的数。
