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31. 发明授权

US07419968B1 Methods for treating therapy-resistant tumors 失效
标题翻译：治疗耐药性肿瘤的方法
公开(公告)号：US07419968B1
公开(公告)日：2008-09-02
申请号：US10048033
申请日：2000-07-21
申请人： H. Michael Shepard
发明人： H. Michael Shepard
IPC分类号： A61K31/70
CPC分类号： G01N33/5011 , A61K47/556 , C12Q1/18
摘要： This invention provides methods for using novel substituted pyrimidine compounds, derivatives and analogs thereof to treat diseases such as cancer. Examples of compounds and derivatives for use in the methods are (E)-5-(2-bromovinyl)-2′-deoxy-5′-uridyl phenyl L-alaninylphosphoramidate and (E)-5-(2-bromovinyl)-2′-deoxy-5′-uridyl phenyl L-alaninyl monophosphate.
摘要翻译：本发明提供了使用新的取代嘧啶化合物，其衍生物和类似物来治疗诸如癌症的疾病的方法。用于该方法的化合物和衍生物的实例是（E）-5-（2-溴乙烯基）-2'-脱氧-5'-尿烷基苯基L-丙烯酰基磷酰胺酸酯和（E）-5-（2-溴乙烯基）-2 '脱氧-5'-尿苷酰基苯基L-丙烯酰基单磷酸酯。

32. 发明授权

US06683061B1 Enzyme catalyzed therapeutic activation 失效
标题翻译：酶催化治疗激活
公开(公告)号：US06683061B1
公开(公告)日：2004-01-27
申请号：US09856127
申请日：2001-10-10
申请人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
发明人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
IPC分类号： A01N4304
CPC分类号： C07H19/06
摘要： This invention provides novel substrate compounds that selectively inhibit the proliferation of pathological cells, for example, pathological calls that endogenously overexpress a target enzyme that confers resistance to biologic and chemotherapeutic agents. The enzyme acts on a substrate compound to 1) convert it to a cellular toxin and/or 2) release a toxic byproduct. In one embodiment, the activity of the target enzyme has been greatly enhanced in a target cell as a result of loss of tumor suppressor function and/or selection resulting from previous exposure to chemotherapy. In another embodiment, the pathological cell contains a target enzyme that is an expression product of an infectious agent in the cell. Further provided by this invention is a method for treating a subject by delivering to the subject a prodrug as described herein. The prodrugs of this invention may be used alone or in combination with other chemotherapeutics or alternative anti-cancer therapies such as radiation.
摘要翻译：本发明提供了选择性抑制病理细胞增殖的新型底物化合物，例如内源性过度表达赋予生物和化学治疗剂抗性的靶酶的病理学调节。该酶作用于底物化合物以1）将其转化为细胞毒素和/或2）释放有毒副产物。在一个实施方案中，由于先前暴露于化学疗法导致的肿瘤抑制功能和/或选择的丧失，靶细胞的活性已大大增强。在另一个实施方案中，病理细胞含有作为细胞中感染因子的表达产物的靶酶。本发明进一步提供的是通过向受试者递送本文所述的前药来治疗受试者的方法。本发明的前药可以单独使用或与其它化学治疗剂或替代的抗癌疗法如辐射一起使用。

33. 发明授权

US06399063B1 Monoclonal antibodies directed to the HER2 receptor 有权
标题翻译：针对HER2受体的单克隆抗体
公开(公告)号：US06399063B1
公开(公告)日：2002-06-04
申请号：US09152654
申请日：1998-09-14
申请人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
发明人： Robert M. Hudziak , H. Michael Shepard , Axel Ullrich , Brian M. Fendly
IPC分类号： A61K39395
CPC分类号： C07K16/32 , A61K38/00 , A61K39/395 , A61K47/6843 , A61K47/6849 , A61K2039/505 , C07K16/22 , C07K16/30 , C07K16/3015 , C07K2317/73 , A61K2300/00 , A61K38/217 , A61K38/2013 , A61K38/2006 , A61K38/191
摘要： A method of inhibiting growth of tumor cells which overexpress a growth factor receptor or growth factor by treatment of the cells with antibodies which inhibit the growth factor receptor function, is disclosed. A method of treating tumor cells with antibodies which inhibit growth factor receptor function, and with cytotoxic factor(s) such as tumor necrosis factor, is also disclosed. By inhibiting growth factor receptor functions tumor cells are rendered more susceptible to cytotoxic factors.
摘要翻译：公开了通过用抑制生长因子受体功能的抗体处理细胞来抑制过表达生长因子受体或生长因子的肿瘤细胞生长的方法。还公开了用抑制生长因子受体功能的抗体和细胞毒性因子如肿瘤坏死因子治疗肿瘤细胞的方法。通过抑制生长因子受体功能，肿瘤细胞对细胞毒性因子的敏感性更高。

34. 发明授权

US5710255A Characterization of a novel anti-p110.sup.RB monoclonal antibody 失效
标题翻译：新型抗p110RB单克隆抗体的表征
公开(公告)号：US5710255A
公开(公告)日：1998-01-20
申请号：US204329
申请日：1994-08-15
申请人： H. Michael Shepard , Shu Fen Wen
发明人： H. Michael Shepard , Shu Fen Wen
IPC分类号： G01N33/53 , A61K38/00 , A61K39/395 , A61P35/00 , C07K14/47 , C07K14/82 , C07K16/00 , C07K16/18 , C07K16/32 , C12N5/10 , C12N5/20 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577 , C12N5/00
CPC分类号： C07K16/18 , C07K14/4736 , A61K38/00 , C12N2799/026
摘要： This invention provides a family of monoclonal antibodies specific for epitopes of p110.sup.RB protein present in the nucleus. These antibodies have superior properties that prove useful for the detection of p110.sup.RB or its complexes with other cellular regulatory proteins in cells and in cell lysates. This invention also provides hybridoma cell lines that produce such monoclonal antibodies and methods of using these antibodies diagnostically, prognostically and therapeutically. Further, the invention provides a method for isolating proteins associated with p110.sup.RB proteins.
摘要翻译： PCT No.PCT / US92 / 05866 Sec。 371日期：1994年8月15日 102（e）日期1994年8月15日PCT提交1992年7月14日PCT公布。公开号WO94 / 01467 日期1994年1月20日本发明提供了对存在于细胞核中的p110RB蛋白的表位有特异性的单克隆抗体家族。这些抗体具有优异的性质，被证明可用于检测p110RB或其与细胞和细胞裂解物中其他细胞调节蛋白的复合物。本发明还提供了产生这种单克隆抗体的杂交瘤细胞系和在诊断，预后和治疗上使用这些抗体的方法。此外，本发明提供了分离与p110RB蛋白相关的蛋白质的方法。

35. 发明授权

US4963354A Use of tumor necrosis factor (TNF) as an adjuvant 失效
标题翻译：使用肿瘤坏死因子（TNF）作为佐剂
公开(公告)号：US4963354A
公开(公告)日：1990-10-16
申请号：US7075
申请日：1987-01-21
申请人： H. Michael Shepard , James E. Talmadge
发明人： H. Michael Shepard , James E. Talmadge
IPC分类号： A61K38/19 , A61K38/20 , A61K38/21 , A61K39/00
CPC分类号： A61K39/0011 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K2039/55522 , Y10S514/885
摘要： Tumor necrosis factors, alone or together with cytokines such as IL-1 or INF-.gamma., are capable of serving as non-toxic vaccine adjuvants.
摘要翻译：单独或与IL-1或INF-γ等细胞因子一起的肿瘤坏死因子能够作为无毒性疫苗佐剂。

36. 发明授权

US09447401B2 PH20 polypeptide variants, formulations and uses thereof 有权
标题翻译： PH20多肽变体，其制剂和用途
公开(公告)号：US09447401B2
公开(公告)日：2016-09-20
申请号：US13694731
申请日：2012-12-28
申请人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
发明人： Ge Wei , H. Michael Shepard , Qiping Zhao , Robert James Connor
IPC分类号： C12N9/26 , C12N15/00 , A61K38/47 , A61K38/28 , A61K45/06 , A61K9/00 , A61K47/10 , C12Q1/34 , A61K38/00
CPC分类号： C12N9/2474 , A61K9/0019 , A61K38/00 , A61K38/28 , A61K38/47 , A61K45/06 , A61K47/10 , C12Q1/34 , C12Y302/01035 , G01N2333/926 , G01N2333/928 , Y02A50/463 , A61K2300/00
摘要： Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.
摘要翻译：提供了修饰的PH20透明质酸酶多肽，包括表现出增加的稳定性和/或增加的活性的修饰的多肽。还提供了组合物及其制剂和用途。

37. 发明申请

US20130266579A1 Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof 审中-公开
标题翻译：有条件的活性抗表皮生长因子受体抗体及其使用方法
公开(公告)号：US20130266579A1
公开(公告)日：2013-10-10
申请号：US13815553
申请日：2013-03-08
申请人： Ge Wei , Gregory I. Frost , Lei Huang , H. Michael Shepard , Daniel Edward Vaughn
发明人： Ge Wei , Gregory I. Frost , Lei Huang , H. Michael Shepard , Daniel Edward Vaughn
IPC分类号： C07K16/28
CPC分类号： C07K16/2863 , A61K39/39558 , A61K47/6825 , A61K47/6849 , A61K47/6851 , A61K2039/505 , C07K16/30 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/92 , A61K39/00
摘要： Provided herein are modified anti-EGFR antibodies and nucleic acid molecules encoding modified anti-EGFR antibodies. Also provided are methods of treatment and uses using modified anti-EGFR antibodies.
摘要翻译：本文提供了修饰的抗EGFR抗体和编码修饰的抗EGFR抗体的核酸分子。还提供了使用修饰的抗EGFR抗体的治疗和使用的方法。

38. 发明申请

US20130202583A1 Companion diagnostic for anti-hyaluronan agent therapy and methods of use thereof 有权
标题翻译：抗透明质酸药物治疗的伴随诊断及其使用方法
公开(公告)号：US20130202583A1
公开(公告)日：2013-08-08
申请号：US13694071
申请日：2012-10-24
申请人： Ping Jiang , H. Michael Shepard , Lei Huang
发明人： Ping Jiang , H. Michael Shepard , Lei Huang
IPC分类号： G01N33/68 , A61K38/47
CPC分类号： C12N9/2474 , A61K38/47 , A61K47/10 , C07K14/47 , C07K2319/00 , C07K2319/30 , C07K2319/735 , G01N33/566 , G01N33/574 , G01N33/57488 , G01N33/6893 , G01N2333/705 , G01N2400/40 , G01N2800/52
摘要： Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.
摘要翻译：提供了用透明质酸药物如透明质酸降解酶进行癌症治疗的受试者鉴别的方法和诊断剂。提供用于检测和定量生物样品中透明质酸的诊断剂，并用抗透明质酸药物（例如透明质酸降解酶）监测癌症治疗。还提供了用于实施方法的组合和试剂盒。

39. 发明申请

US20100278801A1 COMPOSITIONS COMPRISING OPTIMIZED HER1 AND HER3 MULTIMERS AND METHODS OF USE THEREOF 审中-公开
标题翻译：包含优化的HER1和HER3多肽的组合物及其使用方法
公开(公告)号：US20100278801A1
公开(公告)日：2010-11-04
申请号：US12682584
申请日：2008-10-15
申请人： H. Michael Shepard , Pei Jin
发明人： H. Michael Shepard , Pei Jin
IPC分类号： A61K38/45 , C12N9/12 , C12N9/96 , A61P35/00
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/30
摘要： The invention provides for compositions comprising engineered Her3 multimers with improved binding affinity. Such multimers include, but are not limited to, Her1/Her 3 heterodimers in which the Her3 ligand binding domain has been optimized to increase binding to Her3. The composition also can include mixtures of Her 1 homodimers, Her 3 homodimers, and Her 1/Her 3 heterodimers.
摘要翻译：本发明提供包含具有改进的结合亲和力的工程化Her3多聚体的组合物。这样的多聚体包括但不限于Her1 / Her3异源二聚体，其中Her3配体结合结构域已被优化以增加与Her3的结合。组合物还可以包括Her1同型二聚体，Her 3同型二聚体和Her 1 / Her 3异二聚体的混合物。

40. 发明申请

US20100055093A1 PAN-CELL SURFACE RECEPTOR-SPECIFIC THERAPEUTICS 审中-公开
标题翻译： PAN细胞表面受体特异性治疗
公开(公告)号：US20100055093A1
公开(公告)日：2010-03-04
申请号：US12304467
申请日：2007-06-12
申请人： H. Michael Shepard , Pei Jin , Louis E. Burton , Malgorzata Beryt
发明人： H. Michael Shepard , Pei Jin , Louis E. Burton , Malgorzata Beryt
IPC分类号： A61K39/395 , C07K14/00 , C07K16/00 , C07H21/00 , C12N15/63 , C12N5/00 , A61K38/16 , A61K31/7052 , A61K35/12 , A61P35/00 , A61P9/00 , A61P13/10 , A61P11/00 , A61P29/00
CPC分类号： C07K14/71 , C07K2319/00
摘要： Provided are pan-cell surface receptor-specific therapeutics, methods for preparing them and methods of treatment using them. Among the pan-cell surface receptor-specific therapeutics are pan-HER-specific therapeutics that interact with at least two different HER receptor ligands and/or dimerize with or interact with two or more HER cell surface receptors. By virtue of these properties, the therapeutics modulate the activity of at least two cell surface receptors and are useful for therapeutic purposes.
摘要翻译：提供的是全细胞表面受体特异性治疗剂，其制备方法和使用它们的治疗方法。泛细胞表面受体特异性治疗剂是泛HER特异性治疗剂，其与至少两种不同的HER受体配体相互作用和/或与两种或多种HER细胞表面受体二聚化或相互作用。由于这些性质，治疗剂调节至少两种细胞表面受体的活性，并且可用于治疗目的。

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