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1. 发明申请

US20130045492A1 Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain 审中-公开
标题翻译：使用普通轻链制备全人类双特异性抗体的方法
公开(公告)号：US20130045492A1
公开(公告)日：2013-02-21
申请号：US13488628
申请日：2012-06-05
申请人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号： C12P21/00 , G01N21/64 , G01N33/566
CPC分类号： C07K16/468 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/28 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/515 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C07K2319/30 , C12N15/8509 , C12N2800/204
摘要： A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.
摘要翻译：提供遗传修饰的小鼠，其中小鼠表达免疫球蛋白轻链总谱，其特征在于有限数量的轻链可变结构域。提供的小鼠在其种系中仅来自有限谱系的一个或几个免疫球蛋白轻链可变结构域。提供了使用如本文所述的小鼠制备具有通用轻链的双特异性抗体的方法，包括人轻链可变区。提供了适合用于多特异性结合蛋白（例如双特异性抗体）和宿主细胞的人可变区的方法。提供了能够结合第一和第二抗原的双特异性抗体，其中第一和第二抗原是单个蛋白质的分离表位或两种不同蛋白质上的分离表位。

2. 发明申请

US20120192300A1 Common Light Chain Mouse 审中-公开
标题翻译：普通轻链鼠标
公开(公告)号：US20120192300A1
公开(公告)日：2012-07-26
申请号：US13412936
申请日：2012-03-06
申请人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人： Robert Babb , John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号： A01K67/027
摘要： A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making light chain variable regions in mice, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, are provided.
摘要翻译：提供遗传修饰的小鼠，其中小鼠表达免疫球蛋白轻链总谱，其特征在于有限数量的轻链可变结构域。提供的小鼠在其种系中仅来自有限谱系的一个或几个免疫球蛋白轻链可变结构域。提供了在小鼠中制备轻链可变区的方法，包括人轻链可变区。提供了适用于多特异性结合蛋白（例如双特异性抗体）的人可变区的方法。

3. 发明申请

US20120021409A1 Common Light Chain Mouse 审中-公开
公开(公告)号：US20120021409A1
公开(公告)日：2012-01-26
申请号：US13093156
申请日：2011-04-25
申请人： John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人： John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号： C12Q1/68 , G01N33/566 , A01K67/027
摘要： A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making light chain variable regions in mice, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, are provided.

4. 发明申请

US20130198879A1 Humanized Universal Light Chain Mice 审中-公开
标题翻译：人性化通用轻链小鼠
公开(公告)号：US20130198879A1
公开(公告)日：2013-08-01
申请号：US13566765
申请日：2012-08-03
申请人： John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
发明人： John McWhirter , Lynn MacDonald , Sean Stevens , Samuel Davis , David R. Buckler , Karolina A. Hosiawa , Andrew J. Murphy
IPC分类号： A01K67/027
CPC分类号： A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/2833 , C07K16/40 , C07K2317/21 , C07K2317/24 , C07K2317/515 , C07K2317/76 , C07K2317/92 , C07K2319/30 , C12N9/6489 , C12N15/8509 , C12N2800/204 , C12N2800/30
摘要： Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.
摘要翻译：提供了包含人源化重链免疫球蛋白基因座，表达通用轻链的人源化轻链基因座和编码ADAM6或直系同源物或其同系物或功能片段的基因的小鼠，组织，细胞和遗传物质。提供表达包含人可变结构域的人源化重链的小鼠，并且其表达包含人可变结构域的人源化轻链，其中轻链来自不超过一个或不超过两个轻链V和J或重排的V / J序列。提供了表达具有通用轻链和人源化重链的抗体的肥沃雄性小鼠。提供了制备双特异性结合蛋白的方法和组合物。

5. 发明授权

US07205148B2 Genome mutation by intron insertion into an embryonic stem cell genome 有权
标题翻译：通过内含子插入到胚胎干细胞基因组中的基因组突变
公开(公告)号：US07205148B2
公开(公告)日：2007-04-17
申请号：US10865424
申请日：2004-06-10
申请人： Aris N. Economides , David M. Valenzuela , Samuel Davis , George Yancopoulos
发明人： Aris N. Economides , David M. Valenzuela , Samuel Davis , George Yancopoulos
IPC分类号： C12N15/87 , C12N15/05 , C12N15/00
CPC分类号： C12N15/85 , A01K67/0275 , A01K2217/05 , A01K2217/075 , A61D19/04 , C12N15/907 , C12N2800/30 , C12N2830/42 , C12N2840/44
摘要： Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.
摘要翻译：通过将内含子通过同源重组插入到基因组外显子中而在基因组外显子中产生突变的方法。此外，提供了通过将内含子通过同源重组插入到基因组外显子中而将修饰引入基因组外显子的方法，从而提供了从包含基因组外显子的基因组的基因组区域产生的成熟mRNA转录物不含修饰。所述方法提供了用于将任何类型的突变和/或修饰引入哺乳动物细胞基因组的快速方法。

6. 发明申请

US20060197680A1 Remote telemetry device 失效
公开(公告)号：US20060197680A1
公开(公告)日：2006-09-07
申请号：US11411524
申请日：2006-04-26
申请人： Samuel Davis , Reiner Gerdes , Mark Johnson
发明人： Samuel Davis , Reiner Gerdes , Mark Johnson
IPC分类号： G08C19/16
CPC分类号： H04Q9/00 , H04Q2209/10 , H04Q2209/40 , H04Q2209/60
摘要： The systems and methods disclosed herein relate to digital data communication systems, and more particularly, the systems and methods relate to systems and methods for facilitating digital communication between a modem equipped meter and a central data acquisition system. In one example, the system has the central data acquisition system, a first telemetry device that utilizes a modem for data communication, and a second telemetry device with a processor for communicating with the first telemetry device, and a digital cellular radio for communicating with the processor. The processor relays digital meter data from the first telemetry device to the digital cellular radio and the digital cellular radio transmits the digital meter data to the central data acquisition system. This system allows the utility company to transmit the reading of utility consumption by a consumer without the use of telephone lines.

7. 发明申请

US20050163798A1 Modified chimeric polypeptides with improved pharmacokinetic properties and methods of making and using thereof 有权
公开(公告)号：US20050163798A1
公开(公告)日：2005-07-28
申请号：US11016097
申请日：2004-12-17
申请人： Nicholas Papadopoulos , Samuel Davis , George Yancopoulos
发明人： Nicholas Papadopoulos , Samuel Davis , George Yancopoulos
IPC分类号： A61K38/00 , C07K14/71 , C07H21/04 , A61K39/00
CPC分类号： C07K14/71 , A61K38/00 , C07K16/22 , C07K19/00 , C07K2319/00 , C07K2319/30
摘要： Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.

8. 发明申请

US20050100906A1 TIE-2 ligands, methods of making and uses thereof 失效
标题翻译： TIE-2配体，其制备方法和用途
公开(公告)号：US20050100906A1
公开(公告)日：2005-05-12
申请号：US10603293
申请日：2003-06-25
申请人： Samuel Davis , George Yancopoulos
发明人： Samuel Davis , George Yancopoulos
IPC分类号： A61K31/00 , C07H21/04 , C07K14/705 , C12Q1/68
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0306
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptorbody which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention further provides for a ligandbody which specifically binds TIE-2 receptor. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth, differentiation or migration of cells expressing the TIE-2 receptor, including, but not limited to, hematopoietic precursor cells, a method of blocking the growth, differentiation or migration of cells expressing the TIE-2 receptor including, but not limited to, hematopoietic precursor cells, and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供人TIE-2的拮抗剂。本发明进一步提供了特异性结合TIE-2受体的配体体。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE-2受体的细胞的生长，分化或迁移的方法，包括但不限于，造血前体细胞，阻断表达TIE-2受体的细胞的生长，分化或迁移的方法，包括但不限于造血前体细胞，以及减弱或预防人类肿瘤生长的方法。

9. 发明授权

US5879672A Tie-2 ligand 1 失效
标题翻译： Tie-2配体1
公开(公告)号：US5879672A
公开(公告)日：1999-03-09
申请号：US348492
申请日：1994-12-02
申请人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
发明人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
IPC分类号： C12N15/12 , A61K38/00 , A61K38/17 , A61P43/00 , C07K14/47 , C07K14/515 , C07K16/28 , C12N5/02 , C12N5/07 , C12N15/85 , C12P21/00 , A61K38/19 , C07K14/52
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds human TIE-2 ligand. The invention also provides an antibody which specifically binds human TIE-2 ligand. The invention further provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization and a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法和促进表达TIE-2受体的细胞的生长或分化的方法。

10. 发明申请

US20180282411A1 Heavy Chain Constant Regions with Reduced Binding to Fc Gamma Receptors 审中-公开
公开(公告)号：US20180282411A1
公开(公告)日：2018-10-04
申请号：US15562881
申请日：2016-03-30
申请人： Samuel Davis , Eric Smith , Tong Zhang , Supriya Patel
发明人： Samuel Davis , Eric Smith , Tong Zhang , Supriya Patel
IPC分类号： C07K16/28
CPC分类号： C07K16/2809 , C07K16/2803 , C07K16/2887 , C07K2317/24 , C07K2317/31 , C07K2317/526 , C07K2317/53 , C07K2317/71 , C07K2317/732 , C07K2317/90
摘要： The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fcγ receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and/or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fcγ receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

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