公开(公告)号：US09134321B2

公开(公告)日：2015-09-15

申请号：US13183900

申请日：2011-07-15

申请人： Lieping Chen

发明人： Lieping Chen

IPC分类号： G01N33/68 ,  G01N33/53

CPC分类号： G01N33/6875 ,  G01N2800/10

摘要： Soluble H4 (sH4) levels have been discovered to correlate with the stage or severity of inflammatory disorders including autoimmune disorders. In particular, circulating levels of sH4 can be used as a diagnostic for determining the severity of an inflammatory disorder or the propensity for developing an inflammatory disorder. The severity of an inflammatory disorder can be determined by assaying the levels of sH4 in a subject and comparing the levels of sH4 to reference sH4 concentrations that correlate to specific stages of an inflammatory disorder. The therapeutic efficacy of treatments for inflammatory disorders can also be determined by comparing levels of sH4 before and during treatment. Methods and devices for measuring sH4 are also provided.

摘要翻译： 已经发现可溶性H4（sH4）水平与包括自身免疫性疾病在内的炎性疾病的阶段或严重程度相关。 特别地，sH4的循环水平可以用作诊断炎症性疾病的严重性或发展为炎性疾病的倾向。 炎症性疾病的严重程度可以通过测定受试者中sH4的水平并将sH4与参与sH4浓度的水平进行比较来确定，该浓度与炎症性疾病的特定阶段相关。 治疗炎症性疾病的治疗效果也可以通过比较治疗前和治疗期间sH4的水平来确定。 还提供了用于测量sH4的方法和装置。

公开(公告)号：US20120164168A1

公开(公告)日：2012-06-28

申请号：US13413990

申请日：2012-03-07

申请人： Lieping Chen

发明人： Lieping Chen

IPC分类号： A61K39/00 ,  A61P35/00 ,  A61P37/04

CPC分类号： C07K14/70532 ,  A61K38/00

摘要： Compositions and methods for costimulating T cells (i.e., increasing antigen-specific proliferation of T cells, enhancing cytokine production by T cells, stimulating differentiation ad effector functions of T cells and/or promoting T cell survival) are provided. Suitable compositions include variant B7-DC polypeptides, fragments and fusion proteins thereof. Variant B7-DC polypeptides have reduced binding affinity for the inhibitory PD-1 ligand and substantially retain the ability to costimulate T cells. Methods for using variant B7-DC polypeptides to stimulate immune responses in subjects in need thereof are provided.

摘要翻译： 提供了共刺激T细胞的组合物和方法（即，增加T细胞的抗原特异性增殖，增强T细胞的细胞因子产生，刺激T细胞的分化和效应子功能和/或促进T细胞存活）。 合适的组合物包括变体B7-DC多肽，其片段和融合蛋白。 变体B7-DC多肽具有降低的对抑制性PD-1配体的结合亲和力，并且基本上保持了共刺激T细胞的能力。 提供了使用变体B7-DC多肽刺激有需要的受试者的免疫应答的方法。

公开(公告)号：US20120064626A1

公开(公告)日：2012-03-15

申请号：US13280779

申请日：2011-10-25

申请人： Lieping CHEN

发明人： Lieping CHEN

IPC分类号： C12N5/0783 ,  C07K16/18

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2035/124 ,  C07K14/47 ,  C07K2317/24 ,  C07K2317/76

摘要： The invention provides novel polypeptides useful for co-stimulating T cells, isolated nucleic acid molecules encoding them, vectors containing the nucleic acid molecules, and cells containing the vectors. Also included are methods of making and using these co-stimulatory polypeptides.

摘要翻译： 本发明提供了可用于共刺激T细胞，编码它们的分离的核酸分子，含有核酸分子的载体和含有载体的细胞的新型多肽。 还包括制备和使用这些共刺激多肽的方法。

公开(公告)号：US20110200620A1

公开(公告)日：2011-08-18

申请号：US13012063

申请日：2011-01-24

申请人： Lieping CHEN ,  Scott E. STROME ,  Eugene D. KWON

发明人： Lieping CHEN ,  Scott E. STROME ,  Eugene D. KWON

IPC分类号： A61K39/395 ,  A61P35/00 ,  C12Q1/02 ,  G01N33/53 ,  C12Q1/68

CPC分类号： C07K16/2803 ,  A61K38/2013 ,  A61K38/2026 ,  A61K38/2066 ,  A61K38/208 ,  A61K38/2086 ,  A61K38/212 ,  A61K38/215 ,  A61K38/217 ,  A61K2039/505 ,  C07K16/2827 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/76 ,  C12N15/113 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2320/30 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/118 ,  C12Q2600/158 ,  G01N33/5088 ,  G01N33/5091 ,  G01N33/56972 ,  G01N33/57407 ,  G01N33/57438 ,  G01N33/57484

摘要： The invention features methods of diagnosis by assessing B7-H1 expression in a tissue from a subject that has, or is suspected of having, cancer, methods of treatment with agents that interfere with B7-H1-receptor interaction, methods of selecting candidate subjects likely to benefit from cancer immunotherapy, and methods of inhibiting expression of B7-H1.

摘要翻译： 本发明的特征在于通过评估来自具有或被怀疑患有癌症的受试者的组织中的B7-H1表达，以及干扰B7-H1受体相互作用的试剂的治疗方法，可能地选择候选对象的方法 受益于癌症免疫治疗，以及抑制B7-H1表达的方法。

公开(公告)号：US20110104049A1

公开(公告)日：2011-05-05

申请号：US12713731

申请日：2010-02-26

申请人： Scott E. Strome ,  Daniel Schindler ,  Lieping Chen ,  Harry M. Meade ,  Yann Echelard

发明人： Scott E. Strome ,  Daniel Schindler ,  Lieping Chen ,  Harry M. Meade ,  Yann Echelard

IPC分类号： A61K51/00 ,  A61P35/00 ,  A61P35/02 ,  A61P35/04

CPC分类号： A61K51/1096

摘要： The current invention relates to the development and methods of use of a recombinant agonistic antibody anti-human CD137, and glycosylation variants thereof. These antibodies act as anti-cancer agents and/or immune modulators that are effective in shrinking solid tumors or other cancerous indications and preventing their recurrence. The types of cancer for which the contemplated antibody is effective in treating also include leukemia and lymphoma. In a preferred embodiment the recombinant antibodies of the current invention were produced in and purified from the milk of transgenic animals. In another preferred embodiment of the current invention the agonistic anti-CD137 antibodies of the invention can be conjugated to radionuclides for radioimmunodetection or radioimmunotherapeutic purposes, or conjugated to a toxin for enhanced therapeutic treatment of various cancers.

摘要翻译： 本发明涉及重组激动抗体抗人CD137及其糖基化变体的开发和使用方法。 这些抗体作为有效减少实体瘤或其他癌症适应症并防止其复发的抗癌剂和/或免疫调节剂。 预期抗体对其治疗有效的癌症类型还包括白血病和淋巴瘤。 在优选的实施方案中，本发明的重组抗体在转基因动物的牛奶中制备并纯化。 在本发明的另一个优选实施方案中，本发明的激动性抗CD137抗体可以与放射性核素缀合以用于放射免疫检测或放射免疫治疗目的，或与毒素结合以增强各种癌症的治疗性治疗。

公开(公告)号：US20100285039A1

公开(公告)日：2010-11-11

申请号：US12811604

申请日：2009-01-05

申请人： Lieping Chen

发明人： Lieping Chen

IPC分类号： A61K39/395 ,  A61K38/02 ,  A61P35/00

CPC分类号： C07K16/2827 ,  A61K2039/505

摘要： Compositions and methods for restoring killing of cancer cells are provided. Preferably, the compositions are administered to a subject in an effective amount to antagonize, inhibit, reduce, or block B7-H1 mediated signal transduction in cancer cells expressing B7-H1. It has been discovered that B7-H1 transmits an anti-apoptotic signal in cancer cells that increases the resistance of the cancer cells to CTL mediated cytolysis and to Fas induced cell death. It is believed that blocking the transmission of the anti-apoptotic signal by B7-H1 increases the susceptibility of the cancer cells to apoptosis and CTL cytolysis thereby enhancing the death of cancer cells. Preferred compounds or B7-H1 antagonists include antibodies that bind to B7-H1, B7-H1 receptors, or ligands of B7-H1 such as PD-I or B7-1. Additional B7-H1 antagonists include small molecules, for example small molecules that bind the cytoplasmic portion of B7-H1 or the extracellular portion of B7-H1 and inhibit, reduce, block or interfere with B7-H1 signal transduction. Methods for treating one or more symptoms associated with cancer or hyperproliferation are also provided.

摘要翻译： 提供了恢复杀死癌细胞的组合物和方法。 优选地，组合物以有效量施用于受试者以拮抗，抑制，降低或阻断表达B7-H1的癌细胞中的B7-H1介导的信号转导。 已经发现B7-H1在癌细胞中传递抗细胞凋亡信号，其增加了癌细胞对CTL介导的细胞溶解和Fas诱导的细胞死亡的抗性。 据信，通过B7-H1阻断抗凋亡信号的传递增加了癌细胞对凋亡和CTL细胞溶解的敏感性，从而增强了癌细胞的死亡。 优选的化合物或B7-H1拮抗剂包括结合B7-H1，B7-H1受体或B7-H1的配体如PD-1或B7-1的抗体。 另外的B7-H1拮抗剂包括小分子，例如结合B7-H1的细胞质部分或B7-H1细胞外部分并抑制，减少，阻断或干扰B7-H1信号转导的小分子。 还提供了治疗与癌症或过度增生相关的一种或多种症状的方法。

公开(公告)号：US20090011444A1

公开(公告)日：2009-01-08

申请号：US12198014

申请日：2008-08-25

申请人： Lieping Chen

发明人： Lieping Chen

IPC分类号： G01N33/566

CPC分类号： G01N33/6875 ,  G01N2800/10

摘要： Soluble H4 (sH4) levels have been discovered to correlate with the stage or severity of inflammatory disorders including autoimmune disorders. In particular, circulating levels of sH4 can be used as a diagnostic for determining the severity of an inflammatory disorder or the propensity for developing an inflammatory disorder. The severity of an inflammatory disorder can be determined by assaying the levels of sH4 in a subject and comparing the levels of sH4 to reference sH4 concentrations that correlate to specific stages of an inflammatory disorder. The therapeutic efficacy of treatments for inflammatory disorders can also be determined by comparing levels of sH4 before and during treatment. Methods and devices for measuring sH4 are also provided.

摘要翻译： 已经发现可溶性H4（sH4）水平与包括自身免疫性疾病在内的炎性疾病的阶段或严重程度相关。 特别地，sH4的循环水平可以用作诊断炎症性疾病的严重性或发展为炎性疾病的倾向。 炎症性疾病的严重程度可以通过测定受试者中sH4的水平并将sH4与参与sH4浓度的水平进行比较来确定，该浓度与炎症性疾病的特定阶段相关。 治疗炎症性疾病的治疗效果也可以通过比较治疗前和治疗期间sH4的水平来确定。 还提供了用于测量sH4的方法和装置。

公开(公告)号：US07449300B2

公开(公告)日：2008-11-11

申请号：US10719477

申请日：2003-11-21

申请人： Lieping Chen ,  Scott E. Strome

发明人： Lieping Chen ,  Scott E. Strome

IPC分类号： G01N33/53

CPC分类号： C07K16/2827 ,  A61K2039/505 ,  C07K2317/74

摘要： The invention provides methods of removing B7-H1-specific antibodies from a body fluid (e.g., blood), methods of diagnosing and treating diseases and pathological conditions mediated by activated T cells, methods for screening for compounds that inhibit binding of a B7-H1-specific antibody to B7-H1, and methods of designing compounds that inhibit binding of a B7-H1-specific antibody to B7-H1.

摘要翻译： 本发明提供从体液（例如血液）中除去B7-H1特异性抗体的方法，诊断和治疗由活化的T细胞介导的疾病和病理状况的方法，筛选抑制B7-H1结合的化合物的方法 B7-H1的特异性抗体，以及设计抑制B7-H1特异性抗体与B7-H1结合的化合物的方法。

公开(公告)号：US07432351B1

公开(公告)日：2008-10-07

申请号：US10679775

申请日：2003-10-06

申请人： Lieping Chen

发明人： Lieping Chen

IPC分类号： C07K14/00 ,  C07K14/705 ,  G01N33/53

CPC分类号： C07K14/47 ,  C07K14/70532

摘要： Variant costimulatory polypeptides, nucleic acids encoding such polypeptides, and methods for using the polypeptides and nucleic acids to enhance a T cell response are provided herein.

摘要翻译： 本文提供了变体共刺激多肽，编码此类多肽的核酸，以及使用多肽和核酸来增强T细胞应答的方法。

公开(公告)号：US07235631B2

公开(公告)日：2007-06-26

申请号：US10072622

申请日：2002-02-07

申请人： Lieping Chen ,  Jürgen Bajorath

发明人： Lieping Chen ,  Jürgen Bajorath

IPC分类号： C07K14/47 ,  C07K14/725 ,  C07K16/46

CPC分类号： C07K14/70532 ,  A61K38/00

摘要： Purified ICOS polypeptides are described, as well as nucleic acids encoding the polypeptides, vectors including the nucleic acids, host cells containing the vectors, and methods for using the polypeptides, nucleic acids, and host cells.

摘要翻译： 描述了纯化的ICOS多肽，以及编码多肽的核酸，包括核酸的载体，含有载体的宿主细胞，以及使用多肽，核酸和宿主细胞的方法。