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11. 发明授权

US07105166B1 Soluble CTLA4 mutant molecules and uses thereof 有权
标题翻译：可溶性CTLA4突变体分子及其用途
公开(公告)号：US07105166B1
公开(公告)日：2006-09-12
申请号：US09609915
申请日：2000-07-03
申请人： Peter S. Linsley , Jeffrey A. Ledbetter , Jurgen Bajorath , Robert J. Peach , William Brady , Philip Wallace , Nitin Damle
发明人： Peter S. Linsley , Jeffrey A. Ledbetter , Jurgen Bajorath , Robert J. Peach , William Brady , Philip Wallace , Nitin Damle
IPC分类号： C07K16/46 , C07K14/705 , C07K14/725
CPC分类号： C07K16/247 , A61K38/00 , A61K2039/505 , C07K14/70521 , C07K14/7155 , C07K16/00 , C07K16/2818 , C07K16/2827 , C07K2317/34 , C07K2317/73 , C07K2319/00 , C07K2319/30 , Y10S514/885
摘要： The present invention provides soluble CTLA4 mutant molecules which bind CD80 and/or CD86 antigen.
摘要翻译：本发明提供结合CD80和/或CD86抗原的可溶性CTLA4突变分子。

12. 发明授权

US07094874B2 Soluble CTLA4 mutant molecules 有权
标题翻译：可溶性CTLA4突变体分子
公开(公告)号：US07094874B2
公开(公告)日：2006-08-22
申请号：US09865321
申请日：2001-05-23
申请人： Robert J. Peach , Joseph Roy Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert J. Peach , Joseph Roy Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： C07K14/725 , C07K16/46 , A61K38/17 , A61K39/395
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

13. 发明授权

US6090914A CTLA4/CD28Ig hybrid fusion proteins and uses thereof 失效
标题翻译： CTLA4 / CD28Ig杂合融合蛋白及其用途
公开(公告)号：US6090914A
公开(公告)日：2000-07-18
申请号：US228208
申请日：1994-04-15
申请人： Peter S. Linsley , Jeffrey A. Ledbetter , Jurgen Bajorath , Robert Peach , William Brady
发明人： Peter S. Linsley , Jeffrey A. Ledbetter , Jurgen Bajorath , Robert Peach , William Brady
IPC分类号： C12N15/00 , A61K38/00 , A61K39/395 , A61P29/00 , A61P31/12 , A61P31/14 , A61P31/18 , A61P35/00 , A61P37/00 , A61P37/02 , A61P37/06 , A61P37/08 , A61P43/00 , C07K14/52 , C07K14/54 , C07K14/705 , C07K14/715 , C07K14/725 , C07K16/00 , C07K16/18 , C07K16/24 , C07K16/28 , C07K16/46 , C07K19/00 , C12N5/00 , C12N5/10 , C12N15/01 , C12N15/09 , C12P21/02 , C12P21/08 , C12R1/91
CPC分类号： C07K14/7155 , C07K14/70503 , C07K14/70521 , A61K38/00 , C07K2317/73 , C07K2319/00 , C07K2319/30
摘要： The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins including CTLA4/CD28 chimeric proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.
摘要翻译：本发明鉴定CTLA4受体作为B7抗原的配体。提供编码人CTLA4受体基因的完整氨基酸序列。提供用于表达CTLA4作为免疫球蛋白融合蛋白的方法，用于制备包括CTLA4 / CD28嵌合蛋白的杂合CTLA4融合蛋白，并使用可溶性融合蛋白，其片段和衍生物，包括与B7和CTLA4反应的单克隆抗体来调节T 细胞相互作用和由这种相互作用介导的免疫应答。

14. 发明授权

US5637481A Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell 失效
标题翻译：编码双特异性融合蛋白的表达载体和在哺乳动物细胞中产生生物活性双特异性融合蛋白的方法
公开(公告)号：US5637481A
公开(公告)日：1997-06-10
申请号：US121054
申请日：1993-09-13
申请人： Jeffrey A. Ledbetter , Lisa K. Gilliland , Martha S. Hayden , Peter S. Linsley , Jurgen Bajorath , H. Perry Fell
发明人： Jeffrey A. Ledbetter , Lisa K. Gilliland , Martha S. Hayden , Peter S. Linsley , Jurgen Bajorath , H. Perry Fell
IPC分类号： C07K14/705 , A61K38/00 , C07K14/00 , C07K14/16 , C07K14/715 , C07K16/00 , C07K16/28 , C07K16/30 , C07K16/46 , C07K19/00 , C12N5/10 , C12N15/09 , C12N15/13 , C12N15/62 , C12P21/02 , C12P21/08 , C12R1/91 , G01N33/563 , G01N33/569 , G01N33/574 , C12N15/79 , C12P21/00
CPC分类号： C07K14/005 , C07K14/70521 , C07K14/7155 , C07K16/00 , C07K16/2809 , C07K16/2818 , C07K16/2827 , C07K16/30 , C07K16/468 , C12N15/62 , G01N33/563 , G01N33/56972 , G01N33/57492 , A61K2039/505 , A61K38/00 , C07K2317/31 , C07K2317/34 , C07K2317/622 , C07K2317/732 , C07K2317/734 , C07K2317/74 , C07K2319/00 , C07K2319/02 , C07K2319/30 , C07K2319/43 , C12N2740/16122 , G01N2333/705
摘要： The present invention provides an expression vector encoding monospecific or bispecific fusion protein. In one embodiment the expression vector encodes a monospecific fusion protein, which vector comprises a recombinant monospecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen.
摘要翻译：本发明提供编码单特异性或双特异性融合蛋白的表达载体。在一个实施方案中，表达载体编码单特异性融合蛋白，该载体包含重组单特异性单链盒，其包含编码能够结合细胞表面抗原的第一结合结构域的DNA序列。

15. 发明申请

US20100183612A1 METHODS OF TREATMENT USING CTLA4 MUTANT MOLECULES 审中-公开
标题翻译：使用CTLA4突变体分子进行治疗的方法
公开(公告)号：US20100183612A1
公开(公告)日：2010-07-22
申请号：US12694327
申请日：2010-01-27
申请人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： A61K39/395 , A61K39/00 , A61P37/06 , A61P35/02 , A61P35/00 , A61P3/10 , A61P17/06
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

16. 发明授权

US07439230B2 Methods of treatment using CTLA4 mutant molecules 有权
标题翻译：使用CTLA4突变体分子的治疗方法
公开(公告)号：US07439230B2
公开(公告)日：2008-10-21
申请号：US10980742
申请日：2004-11-03
申请人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
发明人： Robert J. Peach , Joseph R. Naemura , Peter S. Linsley , Jurgen Bajorath
IPC分类号： A61K38/16 , A61K39/395 , C07K14/00 , C07K14/725 , C07K16/46
CPC分类号： C07K14/7051 , A61K38/00 , A61K38/1774 , A61K39/39 , A61K39/3955 , A61K2039/505 , C07H21/04 , C07K14/70521 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.
摘要翻译：本发明提供与野生型CTLA4或非突变型CTLA4Ig相比，其结合比CD80和/或CD86抗原更高亲合力的可溶性CTLA4突变体分子。可溶性CTLA4分子具有包含CTLA4细胞外结构域的第一个氨基酸序列，其中S25-R33区域和M97-G107区域内的某些氨基酸残基被突变。本发明的突变分子还可以包括增加突变分子的溶解度的第二个氨基酸序列。

17. 发明授权

US06482919B2 Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell 失效
标题翻译：编码双特异性融合蛋白的表达载体和在哺乳动物细胞中产生生物活性双特异性融合蛋白的方法
公开(公告)号：US06482919B2
公开(公告)日：2002-11-19
申请号：US09813659
申请日：2001-03-21
申请人： Jeffrey A. Ledbetter , Martha S. Hayden , Peter S. Linsley , Jurgen Bajorath , H. Perry Fell , Lisa K. Gilliland
发明人： Jeffrey A. Ledbetter , Martha S. Hayden , Peter S. Linsley , Jurgen Bajorath , H. Perry Fell , Lisa K. Gilliland
IPC分类号： C07K1628
CPC分类号： C07K14/005 , A61K38/00 , A61K2039/505 , C07K16/2809 , C07K16/30 , C07K16/468 , C07K2317/31 , C07K2317/34 , C07K2317/622 , C07K2317/732 , C07K2317/734 , C07K2317/74 , C07K2319/00 , C07K2319/02 , C07K2319/30 , C07K2319/43 , C12N15/62 , C12N2740/16122 , G01N33/563 , G01N33/56972 , G01N33/57492 , G01N2333/705
摘要： The present invention provides novel soluble CTLA4Ig molecules having modified Ig domains.
摘要翻译：本发明提供具有修饰的Ig结构域的新的可溶性CTLA4Ig分子。

18. 发明申请

US20100035966A1 METHODS AND COMPOSITIONS FOR REGULATING CELL CYCLE PROGRESSION 有权
标题翻译：用于调节细胞周期进程的方法和组合物
公开(公告)号：US20100035966A1
公开(公告)日：2010-02-11
申请号：US12304968
申请日：2007-06-14
申请人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
发明人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
IPC分类号： A61K31/7105 , C12N5/10 , C12Q1/68 , C07H21/02
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/12 , C12N2330/10 , C12N2330/31
摘要： In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5′ end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5″end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.
摘要翻译：一方面，提供抑制哺乳动物细胞增殖的方法，包括向所述细胞中引入有效量的至少一种至少一种小干扰RNA试剂（iRNA），其中所述iRNA包含至少15个核苷酸的核苷酸序列，其中所述核苷酸序列包含由核苷酸位置1至12组成的种子区，其中位置1表示iRNA核苷酸序列的5'末端，并且其中所述种子区包含与六个互补的至少六个连续核苷酸的核苷酸序列其中位置1代表核苷酸序列的5'末端，其中所述核苷酸序列选自SEQ ID NO：1，SEQ ID NO：2，SEQ ID NO：2 SEQ ID NO：3，SEQ ID NO：4，SEQ ID NO：5，SEQ ID NO：6，SEQ ID NO：7和SEQ ID NO：8。在一些实施方案中，所述方法包括将至少一种抑制至少一种选自表5的miR-16应答基因的表达的iRNA引入到哺乳动物细胞中。

19. 发明授权

US07171311B2 Methods of assigning treatment to breast cancer patients 有权
标题翻译：为乳腺癌患者分配治疗方法
公开(公告)号：US07171311B2
公开(公告)日：2007-01-30
申请号：US10342887
申请日：2003-01-15
申请人： Hongyue Dai , Yudong He , Peter S. Linsley , Mao Mao , Christopher J. Roberts , Laura Johanna Van't Veer , Marc J. Van de Vijver , Rene Bernards , A. A. M. Hart
发明人： Hongyue Dai , Yudong He , Peter S. Linsley , Mao Mao , Christopher J. Roberts , Laura Johanna Van't Veer , Marc J. Van de Vijver , Rene Bernards , A. A. M. Hart
IPC分类号： G01N33/48 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158
摘要： The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also provides methods of classifying and treating patients based on prognosis. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the diagnostic, prognostic and statistical methods disclosed herein.
摘要翻译：本发明涉及其表达与乳腺癌相关的遗传标记。具体地，本发明提供了一组标志物，其表达模式可用于区分与乳腺癌相关的临床病症，例如雌激素受体ESR1和BRCA1和散发性肿瘤的存在或不存在，并提供关于肿瘤可能性的信息初步诊断五年内远处转移。本发明涉及使用这些标记来区分这些条件的方法。本发明还提供了基于预后对患者进行分类和治疗的方法。本发明还涉及包含即用型微阵列的试剂盒和用于使用本文公开的诊断，预后和统计学方法进行数据分析的计算机软件。

20. 发明授权

US06830937B1 Method for generating and identifying antibodies directed against a B7 失效
标题翻译：产生和鉴定针对B7的抗体的方法
公开(公告)号：US06830937B1
公开(公告)日：2004-12-14
申请号：US09666267
申请日：2000-09-21
申请人： Peter S. Linsley , Jeffrey A. Ledbetter , Nitin K. Damle , William Brady
发明人： Peter S. Linsley , Jeffrey A. Ledbetter , Nitin K. Damle , William Brady
IPC分类号： G01N3353
CPC分类号： G01N33/56972 , A61K38/00 , C07K14/705 , C07K14/70521 , C07K14/70532 , C07K16/2818 , C07K16/2827 , C07K2317/74 , C07K2319/00
摘要： The invention provides a method for generating and identifying antibodies directed against a B7 antigen having SEQ ID NO. 8 or a fragment of SEQ ID NO. 8, which antibodies inhibit B cells from binding CD28, comprising immunizing an animal with the B7 antigen so as to produce the antibodies; and screening the antibodies for antibodies that bind B7 and inhibit CD28 binding to B cells.
摘要翻译：本发明提供了产生和鉴定针对具有SEQ ID NO：1的B7抗原的抗体的方法。 8或SEQ ID NO.1的片段。 8，其抗体抑制B细胞结合CD28，包括用B7抗原免疫动物以产生抗体; 并筛选抗体结合B7并抑制CD28与B细胞结合的抗体。

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