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1. 发明申请

WO2005000895A2 VEGF TRAPS AND THERAPEUTIC USES THEREOF 审中-公开
标题翻译： VEGF TRAPS及其治疗用途
公开(公告)号：WO2005000895A2
公开(公告)日：2005-01-06
申请号：PCT/US2004/021059
申请日：2004-06-29
申请人： REGENERON PHARMACEUTICALS, INC. , DALY, Thomas, J. , FANDL, James, P. , PAPADOPOULOS, Nicholas, J.
发明人： DALY, Thomas, J. , FANDL, James, P. , PAPADOPOULOS, Nicholas, J.
IPC分类号： C07K14/71
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/00
摘要： Nucleic acid molecules and multimeric proteins capable of binding vascular endothelial growth factor (VEGF). VEGF traps are disclosed which are therapeutically useful for treating VEGF-associated conditions and diseases, and are specifically designed for local administration to specific organs, tissues, and/or cells.
摘要翻译：核酸分子和能够结合血管内皮生长因子（VEGF）的多聚体蛋白质。公开了VEGF治疗用于治疗VEGF相关病症和疾病的捕获剂，并且特别设计用于局部施用于特定器官，组织和/或细胞。

2. 发明申请

WO2007143168A2 HIGH AFFINITY ANTIBODIES TO HUMAN IL-6 RECEPTOR 审中-公开
标题翻译：人类IL-6受体的高亲和力抗体
公开(公告)号：WO2007143168A2
公开(公告)日：2007-12-13
申请号：PCT/US2007/013062
申请日：2007-06-01
申请人： REGENERON PHARMACEUTICALS, INC. , STEVENS, Sean , HUANG, Tammy, T. , MARTIN, Joel, H. , FAIRHURST, Jeanette, L. , RAFIQUE, Ashique , SMITH, Eric , POBURSKY, Kevin, J. , PAPADOPOULOS, Nicholas, J. , FANDL, James, P. , CHEN, Gang , KAROW, Margaret
发明人： STEVENS, Sean , HUANG, Tammy, T. , MARTIN, Joel, H. , FAIRHURST, Jeanette, L. , RAFIQUE, Ashique , SMITH, Eric , POBURSKY, Kevin, J. , PAPADOPOULOS, Nicholas, J. , FANDL, James, P. , CHEN, Gang , KAROW, Margaret
IPC分类号： C07K16/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/14 , C07K2317/21 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92
摘要： A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hlL-6R) with a K D of about 500 pM or less and blocks IL-6 activity with an IC 50 of 200 pM or less. The antibody or antibody fragment binds hlL-6R with an affinity at least 2-fold higher relative to its binding to monkey IL-6R.
摘要翻译：结合人IL-6受体（hIL-6R）的人抗体或抗原结合片段，其具有约500pM以下的K D D以及用IC < 50微米或更小。所述抗体或抗体片段以相对于其与IL-6R的结合至少高2倍的亲和力结合hIL-6R。

3. 发明申请

WO2010141478A1 FUCOSYLATION-DEFICIENT CELLS 审中-公开
标题翻译： FUCOSYLATION缺陷细胞
公开(公告)号：WO2010141478A1
公开(公告)日：2010-12-09
申请号：PCT/US2010/036914
申请日：2010-06-01
申请人： REGENERON PHARMACEUTICALS, INC. , CHEN, Gang , BURAKOV, Darya , FANDL, James, P.
发明人： CHEN, Gang , BURAKOV, Darya , FANDL, James, P.
IPC分类号： C12N15/53 , C12N9/04 , C12N5/10 , C12P21/00 , C07K16/00
CPC分类号： C12P21/005 , C07K16/00 , C07K16/2863 , C07K16/2866 , C07K2317/14 , C07K2317/41 , C12N9/0006 , C12N15/00 , C12Y101/01271 , Y02P20/52
摘要： 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 21 1, 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.
摘要翻译：提供了编码FX蛋白的分离核酸，其在79位具有丝氨酸，在90位具有赖氨酸，136位的亮氨酸，21 1位的精氨酸，289位的丝氨酸及其组合。提供具有编码经修饰的FX蛋白的基因的细胞，其中细胞在第一温度下表现出降低糖蛋白岩藻糖化能力，但在第二温度下表现出对糖蛋白的岩藻糖化能力。提供了用于制备具有降低的岩藻糖基化的糖蛋白的方法和组合物。

4. 发明申请

WO2008151219A1 ENHANCED EXPRESSION AND STABILITY REGIONS 审中-公开
标题翻译：增强表达和稳定性领域
公开(公告)号：WO2008151219A1
公开(公告)日：2008-12-11
申请号：PCT/US2008/065733
申请日：2008-06-04
申请人： REGENERON PHARMACEUTICALS, INC. , CHEN, Gang , BABB, Robert , FANDL, James, P.
发明人： CHEN, Gang , BABB, Robert , FANDL, James, P.
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , C07K16/00 , C07K2319/30 , C12N15/86 , C12N2740/10043 , C12N2800/30 , C12N2840/203 , C12P21/02
摘要： Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.
摘要翻译：提供了用于在真核系统中表达的表达增强核苷酸序列，其允许重组蛋白在真核细胞中增强和稳定表达。提供增强的表达和稳定区（EESYR）用于在真核细胞中表达感兴趣的基因。提供染色体基因座，序列和载体用于真核细胞中基因的增强和稳定表达。

5. 发明申请

WO2003101189A1 INDUCIBLE EUKARYOTIC EXPRESSION SYSTEM 审中-公开
标题翻译：可诱导的真核表达系统
公开(公告)号：WO2003101189A1
公开(公告)日：2003-12-11
申请号：PCT/US2003/016676
申请日：2003-05-28
申请人： REGENERON PHARMACEUTICALS, INC. , FANDL, James, P.
发明人： FANDL, James, P.
IPC分类号： A01K67/00
CPC分类号： C12N15/63 , A01K2217/05 , C07K2319/00 , C12N15/85 , C12N2830/00 , C12N2830/002 , C12N2830/15 , C12N2830/42 , C12N2840/20
摘要： Compositions and methods for the inducible expression of genes in eukaryotic cells. Expression of a nucleotide sequence of interest is controlled by a regulatory fusion protein that consists of a transcription blocking domain and a ligand-binding domain. When the cognate ligand for the ligandbinding 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 production of a desired product in eukaryotic cells.
摘要翻译：用于在真核细胞中诱导表达基因的组合物和方法。感兴趣的核苷酸序列的表达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。当存在配体结构域的同源配体时，所关注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产所需产物。

6. 发明申请

WO2017184832A1 COMPOSITIONS AND METHODS FOR MAKING ANTIBODIES BASED ON USE OF EXPRESSION-ENHANCING LOCI 审中-公开
标题翻译：基于使用表达增强型LOCI制备抗体的组合物和方法
公开(公告)号：WO2017184832A1
公开(公告)日：2017-10-26
申请号：PCT/US2017/028555
申请日：2017-04-20
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： BABB, Robert , BURAKOV, Darya , CHEN, Gang , FANDL, James, P.
IPC分类号： C07K16/00 , C07K16/46 , C12N15/90
CPC分类号： C07K16/468 , C07K16/00 , C12N15/85 , C12N15/907
摘要： This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific and bispecifc antibodies in eukaryotic cells, particularly Chinese hamster ( Cricetulus griseus ) cell lines, by employing multiple expression-enhancing locus.
摘要翻译：本发明涉及重组蛋白在真核细胞中的位点特异性整合和表达。具体而言，本发明包括通过使用多重表达增强基因座来改善真核细胞，特别是中国仓鼠（灰仓鼠）细胞系中抗原结合蛋白（包括单特异性和双特异性抗体）表达的组合物和方法

7. 发明申请

WO1992022665A1 PRODUCTION AND RECOVERY OF RECOMBINANT NEUROTROPHINS 审中-公开
标题翻译：重组神经营养因子的生产和恢复
公开(公告)号：WO1992022665A1
公开(公告)日：1992-12-23
申请号：PCT/US1992005006
申请日：1992-06-11
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： REGENERON PHARMACEUTICALS, INC. , PANAYOTATOS, Nikos , FANDL, James, P.
IPC分类号： C12P21/06
CPC分类号： C07K14/245 , C07K14/475 , C07K2319/02 , C12N15/70
摘要： We disclose a process for producing and recovering a recombinant neurotrophin comprising the steps of: (1) culturing a non-animal host cell transformed with a recombinant DNA molecule comprising an expression control sequence operatively linked to a DNA sequence encoding a neurotrophin; (2) solubilizing the neurotrophin in a solution comprising a protease inhibitor in an amount effective to inhibit degradation of the neurotrophin by proteases and a strong denaturing agent, said solution being essentially free of reducing agents; (3) exchanging the strong denaturing agent for a weak denaturing agent; (4) adjusting the solution to comprise a basic amino acid at a concentration effective to maintain the solubility of the neurotrophin in a nondenaturing environment; (5) removing the weak denaturing agent; and (6) purifying the neurotrophin. In a specific embodiment, also disclosed is the bacterial production of recombinant neurotrophin-4.
摘要翻译：我们公开了生产和回收重组神经营养蛋白的方法，包括以下步骤：（1）培养用包含与编码神经营养因子的DNA序列有效连接的表达控制序列的重组DNA分子转化的非动物宿主细胞; （2）将神经营养因子溶解在含有蛋白酶抑制剂的溶液中，所述溶液有效抑制蛋白酶和强变性剂对神经营养因子的降解，所述溶液基本上不含还原剂; （3）交换弱变性剂的强变性剂; （4）调节溶液以包含有效维持神经营养蛋白在非变性环境中的溶解度的碱性氨基酸; （5）去除弱变性剂; 和（6）纯化神经营养蛋白。在一个具体实施方案中，还公开了重组神经营养因子-4的细菌生产。

8. 发明申请

WO2017184831A1 COMPOSITIONS AND METHODS FOR MAKING ANTIBODIES BASED ON USE OF AN EXPRESSION-ENHANCING LOCUS 审中-公开
标题翻译：基于使用表达增强型基质制备抗体的组合物和方法
公开(公告)号：WO2017184831A1
公开(公告)日：2017-10-26
申请号：PCT/US2017/028552
申请日：2017-04-20
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： BABB, Robert , BURAKOV, Darya , CHEN, Gang , FANDL, James, P.
IPC分类号： C07K16/00 , C07K16/46 , C12N15/90
摘要： This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecifc antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing an expression-enhancing locus.
摘要翻译：本发明涉及重组蛋白在真核细胞中的位点特异性整合和表达。具体而言，本发明包括通过使用表达增强基因座来改善在真核细胞特别是中国仓鼠（灰仓鼠）细胞系中包括双特异抗体的抗体表达的组合物和方法。

9. 发明公开

EP2150617A1 ENHANCED EXPRESSION AND STABILITY REGIONS 有权
标题翻译：区以提高表达和稳定性
公开(公告)号：EP2150617A1
公开(公告)日：2010-02-10
申请号：EP08756678.2
申请日：2008-06-04
申请人： Regeneron Pharmaceuticals, Inc.
发明人： CHEN, Gang , BABB, Robert , FANDL, James, P.
IPC分类号： C12N15/85
CPC分类号： C12N15/85 , C07K16/00 , C07K2319/30 , C12N15/86 , C12N2740/10043 , C12N2800/30 , C12N2840/203 , C12P21/02
摘要： Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells.

10. 发明公开

EP1056856A1 MODIFIED CILIARY NEUROTROPHIC FACTOR, METHOD OF MAKING AND METHODS OF USE THEREOF 有权
标题翻译：改进睫状神经营养因子（CNTF），以及制造方法和用途
公开(公告)号：EP1056856A1
公开(公告)日：2000-12-06
申请号：EP99911020.8
申请日：1999-02-26
申请人： REGENERON PHARMACEUTICALS, INC.
发明人： FANDL, James, P. , STAHL, Neil
IPC分类号： C12N15/12 , C07K14/475 , A61K38/18
CPC分类号： G01N33/6842 , A61K38/185 , C07K14/475 , G01N33/68
摘要： Modified ciliary neurotrophic factor, methods for production and methods of use, especially in the treatment of Huntington's disease, obesity, and gestational or adult onset diabetes.

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