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1. 发明授权

US09011853B2 B7-H4 fusion proteins and methods of use thereof 有权
标题翻译： B7-H4融合蛋白及其使用方法
公开(公告)号：US09011853B2
公开(公告)日：2015-04-21
申请号：US13392811
申请日：2010-08-31
申请人： Solomon Langermann , Linda Liu , Joseph R. Podojil , Stephen D. Miller , Shannon Marshall
发明人： Solomon Langermann , Linda Liu , Joseph R. Podojil , Stephen D. Miller , Shannon Marshall
IPC分类号： A61K38/16 , C07K14/705 , C07K16/46 , G01N33/68 , A61K38/17 , C07K16/28
CPC分类号： C07K14/70532 , A61K9/0019 , A61K38/00 , A61K38/1709 , A61K39/44 , C07K16/2827 , C07K2317/50 , C07K2317/56 , C07K2317/72 , C07K2319/30 , C07K2319/32 , G01N33/6863 , G01N33/6866 , G01N33/6869 , G01N2800/52
摘要： Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.
摘要翻译：公开了含有B7-H4多肽的融合蛋白。 B7-H4融合蛋白可以包括全长B7-H4多肽，或可以含有全长B7-H4多肽的片段，包括B7-H4多肽的一些或全部细胞外结构域。还公开了使用融合蛋白来下调T细胞活化和治疗炎性和自身免疫性疾病和病症的方法。 B7-H4融合蛋白可用于通过抑制或减少Th1，Th17，Th22和/或分泌或引起其他细胞的其他细胞的分化，增殖，活性和/或细胞因子产生和/或分泌来治疗炎症包括但不限于IL-1和bgr; TNF-α，TGF-β，IFN-γ，IL-17，IL-6，IL-23，IL-22，IL-21，和MMPs; 或增强Treg的IL-10分泌，增加Treg的分化，增加Treg的数量或其组合。

2. 发明申请

US20140044738A1 Antibodies And Other Molecules That Bind B7-H1 And PD-1 有权
标题翻译： B7-H1和PD-1的抗体和其他分子
公开(公告)号：US20140044738A1
公开(公告)日：2014-02-13
申请号：US14111402
申请日：2012-04-19
申请人： Solomon Langermann , Linda Liu , Shannon Marshall , Sheng Yao
发明人： Solomon Langermann , Linda Liu , Shannon Marshall , Sheng Yao
IPC分类号： C07K16/28 , G01N33/68 , A61K39/395
CPC分类号： C07K16/2827 , A61K39/3955 , C07K16/28 , C07K16/2803 , C07K16/2818 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/565 , C07K2317/75 , C07K2317/76 , G01N33/6854
摘要： The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.
摘要翻译：本发明涉及抗体及其抗原结合片段和能够免疫特异性结合B7-H1或PD-1的其它分子。在一些实施方案中，此类分子另外能够调节B7-H1或B7-DC结合PD-1或能够影响B7-H1或PD-1的信号传导活性的能力。本发明还涉及这些分子在诊断和治疗癌症和其它疾病中的用途。

3. 发明授权

US08609089B2 Compositions of PD-1 antagonists and methods of use 失效
标题翻译： PD-1拮抗剂的组合物和使用方法
公开(公告)号：US08609089B2
公开(公告)日：2013-12-17
申请号：US13332154
申请日：2011-12-20
申请人： Solomon Langermann , Linda Liu
发明人： Solomon Langermann , Linda Liu
IPC分类号： A61K39/395
CPC分类号： A61K38/177 , A61K31/675 , A61K45/06 , C07K14/70532 , C07K2319/33 , Y02A50/402 , Y02A50/409 , Y02A50/411 , Y02A50/423 , Y02A50/475 , Y02A50/478 , Y02A50/48 , A61K2300/00
摘要： Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.
摘要翻译：描述了使用治疗方案治疗癌症和感染性疾病的方法，其包括与增强剂（例如环磷酰胺）联合降低T细胞中的抑制性信号转导的化合物以产生有效的T细胞介导的应答。还公开了包含可用于本发明方法的PD-1拮抗剂和增效剂的组合物。

4. 发明申请

US20120177645A1 METHODS AND COMPOSITIONS FOR THE INHIBITION OF TRANSPLANT REJECTION 有权
标题翻译：抑制运输阻止剂的方法和组合物
公开(公告)号：US20120177645A1
公开(公告)日：2012-07-12
申请号：US13392399
申请日：2010-08-31
申请人： Solomon Langermann , Linda Liu
发明人： Solomon Langermann , Linda Liu
IPC分类号： A61K39/395 , A61P41/00 , C07K16/00
CPC分类号： C07K14/70532 , A61K9/0019 , A61K38/00 , A61K38/1709 , A61K39/44 , C07K16/2827 , C07K2317/50 , C07K2317/56 , C07K2317/72 , C07K2319/30 , C07K2319/32 , G01N33/6863 , G01N33/6866 , G01N33/6869 , G01N2800/52
摘要： Methods for modulating immune responses in a subject are provided. A preferred embodiment provides methods and compositions for reducing or inhibiting transplant rejection in a subject, preferably a human subject. Transplant rejection can be inhibited or reduced in a subject by administering an effective amount of B7-H4 polypeptide, fragments or fusions thereof to inhibit or reduce the biological activity of an immune cell or to reduce the amounts of proinflammatory molecules at a site of transplant. Th1, Th17 and Th22 cells are exemplary T cells that can be targeted for inhibition by B7-H4 polypeptides, fusion proteins or fragments thereof to inhibit or reduce inflammation.
摘要翻译：提供了调节受试者中免疫应答的方法。优选的实施方案提供用于减少或抑制受试者，优选人受试者的移植排斥的方法和组合物。通过施用有效量的B7-H4多肽，其片段或融合物来抑制或降低免疫细胞的生物活性或减少移植部位的促炎症分子的量，可以抑制或减少受试者的移植排斥反应。 Th1，Th17和Th22细胞是可被B7-H4多肽，融合蛋白或其片段抑制或减少炎症的靶向的示例性T细胞。

5. 发明授权

US06500434B1 Chaperone and adhesin proteins; vaccines, diagnostics and method for treating infections 有权
标题翻译：伴侣和粘附素蛋白; 疫苗，诊断和治疗感染的方法
公开(公告)号：US06500434B1
公开(公告)日：2002-12-31
申请号：US09298494
申请日：1999-04-23
申请人： Solomon Langermann , Scott J. Hultgren , Jerome S. Pinkner , Christine Gale Auguste
发明人： Solomon Langermann , Scott J. Hultgren , Jerome S. Pinkner , Christine Gale Auguste
IPC分类号： A61K39385
CPC分类号： A61K39/0258 , Y02A50/474
摘要： The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species with heteropolymeric protein complexes as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A novel vector for expressing the FimC-H complex at optimal levels is also disclosed.
摘要翻译：本发明提供用于给予人和非人动物以刺激免疫应答的细菌免疫原性试剂。它特别涉及用异源蛋白复合物对哺乳动物物种进行疫苗接种，作为刺激保护疫苗接受者免受病原菌种感染的抗体产生的机制。在另一方面，本发明提供了抗这种蛋白质和蛋白质复合物的抗体，其可以用作诊断和/或作为病原菌种的保护/治疗剂。还公开了用于以最佳水平表达FimC-H复合物的新载体。

6. 发明授权

US08709416B2 Compositions of PD-1 antagonists and methods of use 失效
标题翻译： PD-1拮抗剂的组合物和使用方法
公开(公告)号：US08709416B2
公开(公告)日：2014-04-29
申请号：US13332164
申请日：2011-12-20
申请人： Solomon Langermann , Linda Liu
发明人： Solomon Langermann , Linda Liu
IPC分类号： A61K39/395
CPC分类号： A61K38/177 , A61K31/675 , A61K45/06 , C07K14/70532 , C07K2319/33 , Y02A50/402 , Y02A50/409 , Y02A50/411 , Y02A50/423 , Y02A50/475 , Y02A50/478 , Y02A50/48 , A61K2300/00
摘要： Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.
摘要翻译：描述了使用治疗方案治疗癌症和感染性疾病的方法，其包括与增强剂（例如环磷酰胺）联合降低T细胞中的抑制性信号转导的化合物以产生有效的T细胞介导的应答。还公开了包含可用于本发明方法的PD-1拮抗剂和增效剂的组合物。

7. 发明申请

US20130230514A1 COMPOSITIONS OF PD-1 ANTAGONISTS AND METHODS OF USE 审中-公开
标题翻译： PD-1拮抗剂的组合物及其使用方法
公开(公告)号：US20130230514A1
公开(公告)日：2013-09-05
申请号：US13312201
申请日：2011-12-06
申请人： Solomon Langermann , Linda Liu
发明人： Solomon Langermann , Linda Liu
IPC分类号： A61K38/17 , A61K45/06 , A61K31/675
CPC分类号： A61K38/177 , A61K31/675 , A61K45/06 , C07K14/70532 , C07K2319/33 , Y02A50/402 , Y02A50/409 , Y02A50/411 , Y02A50/423 , Y02A50/475 , Y02A50/478 , Y02A50/48 , A61K2300/00
摘要： Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.
摘要翻译：描述了使用治疗方案治疗癌症和感染性疾病的方法，其包括与增强剂（例如环磷酰胺）联合降低T细胞中的抑制性信号转导的化合物以产生有效的T细胞介导的应答。还公开了包含可用于本发明方法的PD-1拮抗剂和增效剂的组合物。

8. 发明申请

US20100278838A1 EPHA2 MONOCLONAL ANTIBODIES AND METHODS OF USE THEREOF 审中-公开
标题翻译： EPHA2单克隆抗体及其使用方法
公开(公告)号：US20100278838A1
公开(公告)日：2010-11-04
申请号：US12755468
申请日：2010-04-07
申请人： Michael S. Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
发明人： Michael S. Kinch , Kelly Carles-Kinch , Peter Kiener , Solomon Langermann
IPC分类号： A61K39/395 , C07K16/00 , C12N15/13 , C12N15/63 , C12N5/00 , G01N33/567 , A61P35/00
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/56 , C07K2317/73 , C07K2317/75 , C07K2317/92
摘要： The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and agonizes EphA2, thereby increasing EphA2 phosphorylation and decreasing EphA2 levels. In other embodiments, the methods of the invention comprise the administration of an effective amount of an antibody that binds to EphA2 and inhibits cancer cell colony formation in soft agar, inhibits tubular network formation in three-dimensional basement membrane or extracellular matrix preparation, preferentially binds to an EphA2 epitope that is exposed on cancer cells but not non-cancer cells, and/or has a low Koff, thereby, inhibiting tumor cell growth and/or metastasis. The invention also provides pharmaceutical compositions comprising one or more EphA2 antibodies of the invention either alone or in combination with one or more other agents useful for cancer therapy.
摘要翻译：本发明涉及设计用于治疗，管理或预防癌症，特别是转移性癌症的方法和组合物。在一个实施方案中，本发明的方法包括施用有效量的结合EphA2并激动EphA2的抗体，从而增加EphA2磷酸化并降低EphA2水平。在其它实施方案中，本发明的方法包括施用有效量的结合EphA2的抗体并抑制软琼脂中的癌细胞集落形成，抑制三维基底膜或细胞外基质制剂中的管状网络形成，优先结合涉及暴露于癌细胞但不暴露于非癌细胞的EphA2表位，和/或具有低Koff，从而抑制肿瘤细胞生长和/或转移。本发明还提供包含本发明的一种或多种EphA2抗体的药物组合物，其单独或与一种或多种其它可用于癌症治疗的试剂组合。

9. 发明申请

US20100055102A1 COMPOSITIONS OF PD-1 ANTAGONISTS AND METHODS OF USE 有权
标题翻译： PD-1拮抗剂的组合物及其使用方法
公开(公告)号：US20100055102A1
公开(公告)日：2010-03-04
申请号：US12547129
申请日：2009-08-25
申请人： Solomon Langermann
发明人： Solomon Langermann
IPC分类号： A61K39/395
CPC分类号： A61K38/177 , A61K31/675 , A61K45/06 , C07K14/70532 , C07K2319/33 , Y02A50/402 , Y02A50/409 , Y02A50/411 , Y02A50/423 , Y02A50/475 , Y02A50/478 , Y02A50/48 , A61K2300/00
摘要： Methods of treating cancer and infectious diseases utilizing a treatment regimen comprising administering a compound that reduces inhibitory signal transduction in T cells, in combination with a potentiating agent, such as cyclophosphamide, to produce potent T cell mediated responses, are described. Compositions comprising the PD-1 antagonists and potentiating agents useful in the methods of the invention are also disclosed.
摘要翻译：描述了使用治疗方案治疗癌症和感染性疾病的方法，其包括与增强剂（例如环磷酰胺）联合降低T细胞中的抑制性信号转导的化合物以产生有效的T细胞介导的应答。还公开了包含可用于本发明方法的PD-1拮抗剂和增效剂的组合物。

10. 发明授权

US06737063B2 FimH adhesin proteins and methods of use 有权
标题翻译： FimH粘附素蛋白及其使用方法
公开(公告)号：US06737063B2
公开(公告)日：2004-05-18
申请号：US09900575
申请日：2001-07-06
申请人： Solomon Langermann , Andrew Revel , Christine Auguste , Jeanne Burlein
发明人： Solomon Langermann , Andrew Revel , Christine Auguste , Jeanne Burlein
IPC分类号： A61K3902
CPC分类号： C07K14/245 , A61K39/00
摘要： The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. Also provided are methods for vaccination of mammalian species, especially human patients, with variants of the E. coli FimH protein, said variants being derived from different strains of E. coli, and to production of antibodies that protect the vaccine recipient against infection by pathogenic bacterial species. In another aspect the invention provides antibodies against such proteins and protein complexes that may be used as diagnostics and/or as protective/treatment agents for pathogenic bacterial species. A plasmid-based method of producing polypeptides, especially fused polypeptides, such as the complex of a bacterial chaperone and a bacterial adhesin, is also disclosed.
摘要翻译：本发明提供用于给予人和非人动物以刺激免疫应答的细菌免疫原性试剂。还提供了用大肠杆菌FimH蛋白的变体对哺乳动物物种，特别是人类患者进行疫苗接种的方法，所述变体来自不同的大肠杆菌菌株，并且产生保护疫苗接受者免受致病性感染的抗体细菌种类。在另一方面，本发明提供了抗这种蛋白质和蛋白质复合物的抗体，其可以用作诊断和/或作为病原菌种的保护/治疗剂。还公开了一种基于质粒的产生多肽，特别是融合多肽的方法，例如细菌分子伴侣和细菌粘附素的复合物。

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