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1. 发明授权

US5523084A Enhancing the anti-tumor effect of melphalan by prior administration of L-amino acid oxidase with or without intermediate administration of anti-L-amino acid oxidase antibody 失效
标题翻译：通过事先给予L-氨基酸氧化酶，在或不加中间施用抗L-氨基酸氧化酶抗体的情况下，增强美法仑的抗肿瘤作用
公开(公告)号：US5523084A
公开(公告)日：1996-06-04
申请号：US301769
申请日：1994-09-07
申请人： Darell D. Bigner , Henry S. Friedman , Owen W. Griffith
发明人： Darell D. Bigner , Henry S. Friedman , Owen W. Griffith
IPC分类号： A61K38/44 , A61K37/48 , A61K31/195 , A61K37/50 , A61K39/395
CPC分类号： A61K38/44
摘要： L-amino acid oxidase is utilized to reduce plasma level of large neutral amino acids to allow the opportunity of increased melphalan transport into tumors and melphalan is administered when the plasma level of L-amino acid oxidase is sufficiently low so the gain from increased transport outweighs the loss from L-amino acid oxidase-mediated metabolism of melphalan. Preferably anti L-amino acid oxidase antibody is administered intermediate the L-amino acid oxidase and melphalan administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the melphalan transport improving plasma level reduction of large neutral amino acids thereby to reduce or eliminate degrading of melphalan by L-amino acid oxidase.
摘要翻译： L-氨基酸氧化酶被用于降低大中性氨基酸的血浆水平，以便当L-氨基酸氧化酶的血浆水平足够低时，给予美法仑输送到肿瘤中并且美法仑的机会被施用，因此增加运输的增益超过来自L-氨基酸氧化酶介导的美法仑代谢的损失。优选地，抗L-氨基酸氧化酶抗体在L-氨基酸氧化酶和美法仑给药之间施用，以在L-氨基酸氧化酶引起美法仑输送改善大中性氨基酸的血浆水平降低后消耗L-氨基酸氧化酶活性，从而通过L-氨基酸氧化酶降低或消除美法仑降解。

2. 发明授权

US5695751A Enhancing delivery of large neutral amino acid drugs 失效
标题翻译：加强大中性氨基酸药物的输送
公开(公告)号：US5695751A
公开(公告)日：1997-12-09
申请号：US531586
申请日：1995-09-21
申请人： Henry S. Friedman , Darell D. Bigner , Owen W. Griffith
发明人： Henry S. Friedman , Darell D. Bigner , Owen W. Griffith
IPC分类号： A61K38/44 , A61K31/195
CPC分类号： A61K38/44 , A61K31/198 , A61K31/221 , A61K39/3955 , A61K45/06 , C07K16/40 , C12Y104/03002 , A61K2039/545
摘要： L-amino acid oxidase is utilized to reduce the plasma level of large neutral amino acids to allow the opportunity of increased large neutral amino acid drug transport across the blood brain barrier. Preferably anti L-amino acid oxidase antibody is administered intermediate to the L-amino acid oxidase and large neutral amino acid drug administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the large neutral amino acid drug transport improving level plasma reduction of large neutral amino acids thereby to reduce or eliminate degrading of large neutral amino acid drugs by L-amino acid oxidase. The large neutral amino acid drugs include levodopa, melphalan, L-DON, azaserine, acivicin, L-alanosine and 3-(phosphonomethyl)phenylalanines. For treatment of brain tumors, the drug administration is preferably preceded by the administration of a large neutral amino acid glutathione depleting agent, e.g., L-buthionine-SR-sulfoximine. L-Amino acid oxidase is also utilized to enhance the transport of large neutral amino acid glutathione depleting agent across the blood brain barrier as an adjunct to radiation therapy of brain tumors.
摘要翻译：利用L-氨基酸氧化酶来降低大的中性氨基酸的血浆水平，以允许增加大的中性氨基酸药物在血脑屏障上的转运的机会。优选地，抗L-氨基酸氧化酶抗体在L-氨基酸氧化酶和大的中性氨基酸药物给药中间给药，以在L-氨基酸氧化酶引起大的中性氨基酸药物转运改善后消耗L-氨基酸氧化酶活性从而降低或消除大中性氨基酸药物由L-氨基酸氧化酶的降解。大的中性氨基酸药物包括左旋多巴，美法仑，L-DON，重氮丝氨酸，acivicin，L-脯氨酸和3-（膦酰基甲基）苯丙氨酸。为了治疗脑肿瘤，药物给药优选之前是施用大量中性氨基酸谷胱甘肽消耗剂，例如L-丁硫氨酸-SR-亚砜亚胺。 L-氨基酸氧化酶还用于增强大中性氨基酸谷胱甘肽消耗剂在血脑屏障上的转运，作为脑肿瘤放射治疗的辅助物质。

3. 发明授权

US5407925A Regional chemotherapy within the central nervous system with 4-hydroperoxycyclophosphamide 失效
标题翻译：用4-氢过氧环磷酰胺在中枢神经系统内进行区域化疗
公开(公告)号：US5407925A
公开(公告)日：1995-04-18
申请号：US788609
申请日：1991-11-06
申请人： Darell D. Bigner , Henry S. Friedman , O. Michael Colvin
发明人： Darell D. Bigner , Henry S. Friedman , O. Michael Colvin
IPC分类号： A61K31/675 , A61P35/00 , A61K31/66
CPC分类号： A61K31/675
摘要： A method of treating human tumors is provided in which tumors are regionally treated with a cytolytic, pre-activated, bifunctional alkylating agent, namely 4-hydroperoxycyclophosphamide. The treatment is effective against a variety of tumor types within the central nervous systems.
摘要翻译：提供了一种治疗人类肿瘤的方法，其中用细胞溶解的，预活化的双功能烷基化剂即4-氢过氧环磷酰胺处理肿瘤。该治疗对中枢神经系统内的多种肿瘤类型有效。

4. 发明申请

US20100290984A1 ANTI-MRP3 ANTIBODIES AND METHODS OF USE 有权
标题翻译：抗MRP3抗体及其使用方法
公开(公告)号：US20100290984A1
公开(公告)日：2010-11-18
申请号：US12516942
申请日：2007-11-30
申请人： Chien-Tsun Kuan , Darell D. Bigner
发明人： Chien-Tsun Kuan , Darell D. Bigner
IPC分类号： A61K51/10 , C07K16/18 , C07K16/46 , C07H21/04 , G01N33/566 , A61K9/127 , A61K39/395 , A61K49/00 , C12N5/07 , A61P35/00
CPC分类号： C07K16/28 , A61K2039/505 , C07K2317/34 , C07K2317/56 , C07K2317/622 , C07K2317/77 , C07K2317/92
摘要： An antibody having an antigen binding region capable of binding an epitope located in an extracellular portion of MRP3 and methods of utilizing same are provided. In particular, the invention provides antibodies targeted at a MRP3 antigen present on cells expressing MRP3 and methods useful in detecting or targeting cells expression the MRP3 antigen, as well as kits, nucleic acids, polypeptides, and cells for providing the antibodies.
摘要翻译：提供具有能够结合位于MRP3细胞外部分的表位的抗原结合区域的抗体及其利用方法。特别地，本发明提供靶向存在于表达MRP3的细胞上的MRP3抗原的抗体以及可用于检测或靶向表达MRP3抗原的细胞的方法，以及用于提供抗体的试剂盒，核酸，多肽和细胞。

5. 发明授权

US08900816B2 Assay for anti-EGFRvIII antibodies 有权
标题翻译：测定抗EGFRvIII抗体
公开(公告)号：US08900816B2
公开(公告)日：2014-12-02
申请号：US12669374
申请日：2008-07-21
申请人： Robert J. Schmittling , Gary E. Archer , John H. Sampson , Darell D. Bigner
发明人： Robert J. Schmittling , Gary E. Archer , John H. Sampson , Darell D. Bigner
IPC分类号： G01N33/537 , G01N33/571 , G01N33/574
CPC分类号： G01N33/57488 , G01N2333/485
摘要： Detection of human antibodies directed against the tumor-specific protein Epidermal Growth Factor Receptor variant Class III (EGFRvIII) provide information on tumor burden and vaccine response. The methods of the invention permit the specific identification of antibodies that are able to bind to EGFRvIII. The methods are useful in determining the presence of an EGFRvIII-expressing tumor and in detecting immune responses following immunization with EGFRvIII-derived peptide as part of a cancer immunotherapy regimen.
摘要翻译：检测针对肿瘤特异性蛋白质的人类抗体表皮生长因子受体变体III类（EGFRvIII）提供有关肿瘤负荷和疫苗反应的信息。本发明的方法允许特异性鉴定能够结合EGFRvIII的抗体。该方法可用于确定表达EGFRvIII的肿瘤的存在以及用EGFRvIII衍生的肽作为癌症免疫治疗方案的一部分免疫后检测免疫应答。

6. 发明申请

US20110217231A1 ANTI-TENASCIN MONOCLONAL ANTIBODY THERAPY FOR LYMPHOMA 审中-公开
标题翻译：抗淋巴细胞单克隆抗体治疗LYMPHOMA
公开(公告)号：US20110217231A1
公开(公告)日：2011-09-08
申请号：US11961840
申请日：2007-12-20
申请人： David Rizzieri , Darell D. Bigner , Michael Zalutsky
发明人： David Rizzieri , Darell D. Bigner , Michael Zalutsky
IPC分类号： A61K49/16 , A61K39/395 , A61P35/00
CPC分类号： A61K51/1018 , A61K51/1069 , A61K2039/505 , C07K16/30
摘要： A method of treating lymphoma in a subject comprises administering to a subject afflicted with lymphoma an antibody that binds to tenascin in a therapeutically effective amount. Preferably the antibody is monoclonal antibody 81C6 or an antibody that binds to the epitope bound by monoclonal antibody 81C6. Preferably the antibody is labeled with or conjugated to a chemotherapeutic agent, particularly a radioisotope such as 131I.
摘要翻译：治疗受试者淋巴瘤的方法包括向患有淋巴瘤的受试者施用治疗有效量的结合腱生蛋白的抗体。优选地，抗体是单克隆抗体81C6或与由单克隆抗体81C6结合的表位结合的抗体。优选地，抗体用化学治疗剂，特别是放射性同位素如131I标记或缀合。

7. 发明授权

US5558852A Methods of treating melanomas and gliomas with monoclonal antibody Me1-14 失效
标题翻译：用单克隆抗体Me1-14处理黑色素瘤和胶质瘤的方法
公开(公告)号：US5558852A
公开(公告)日：1996-09-24
申请号：US339582
申请日：1994-11-14
申请人： Darell D. Bigner , Michael R. Zalutsky
发明人： Darell D. Bigner , Michael R. Zalutsky
IPC分类号： A61K38/00 , A61K51/10 , C07K16/30 , A61K39/395 , A61K39/44
CPC分类号： A61K51/1066 , C07K16/3053 , A61K2121/00 , A61K38/00
摘要： Methods of treating solid or cystic tumors are disclosed. The method comprises administering to a human subject afflicted with a tumor an antibody in a therapeutically effective amount, wherein the antibody is monoclonal antibody Me1-14 or an antibody which binds to the epitope bound by monoclonal antibody Me1-14, and wherein the Fc receptor of the antibody is deleted. When the tumor is a brain tumor, the antibody may be administered by intrathecal injection. If the brain tumor is a cystic brain tumor, and the administering step may be carried out by depositing the antibody in the cyst cavity of the cystic brain tumor. Particularly preferred is a monoclonal antibody Me1-14 F(ab').sub.2 fragment coupled to .sup.131 I.
摘要翻译：公开了治疗固体或囊性肿瘤的方法。该方法包括以治疗有效量向患有肿瘤的人类受试者施用抗体，其中所述抗体是单克隆抗体Me1-14或与由单克隆抗体Me1-14结合的表位结合的抗体，并且其中Fc受体的抗体被删除。当肿瘤是脑肿瘤时，可以通过鞘内注射施用抗体。如果脑肿瘤是囊性脑肿瘤，并且施用步骤可以通过将抗体沉积在囊性脑肿瘤的囊腔中来进行。特别优选的是与131I偶联的单克隆抗体Me1-14F（ab'）2片段。

8. 发明授权

US09399662B2 Concurrent chemotherapy and immunotherapy 有权
标题翻译：并发化疗和免疫治疗
公开(公告)号：US09399662B2
公开(公告)日：2016-07-26
申请号：US12092180
申请日：2006-11-02
申请人： John H. Sampson , Darell D. Bigner , Duane Mitchell , Amy Heimberger
发明人： John H. Sampson , Darell D. Bigner , Duane Mitchell , Amy Heimberger
IPC分类号： C07K7/08 , A61K39/00 , A61K47/48 , C07K14/435
CPC分类号： C07K7/08 , A61K39/0005 , A61K39/0011 , A61K47/643 , A61K2039/55522 , A61K2039/6081 , C07K14/43504 , C07K2319/00
摘要： The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy, hi fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.
摘要翻译：由于担心诱导的淋巴细胞减少可以消除免疫治疗的治疗效果，化疗和免疫治疗的并发治疗被认为是禁忌症。替莫唑胺已被证明是恶性胶质瘤患者的有效化疗药物，并剥夺了该药物的胶质母细胞瘤（GBM）患者，以免疫疗法治疗是有争议的。尽管有常规的教条，我们证明化疗和免疫治疗可以同时递送，而不会消除免疫治疗的效果。实际上，替莫唑胺诱导的淋巴细胞减少实际上可能与肽疫苗协同作用。

9. 发明申请

US20090220551A1 CONCURRENT CHEMOTHERAPY AND IMMUNOTHERAPY 有权
标题翻译：同期化疗和免疫治疗
公开(公告)号：US20090220551A1
公开(公告)日：2009-09-03
申请号：US12092180
申请日：2006-11-02
申请人： John H. Sampson , Darell D. Bigner , Mitchell Duane , Amy Heimberger
发明人： John H. Sampson , Darell D. Bigner , Mitchell Duane , Amy Heimberger
IPC分类号： A61K39/00 , A61K38/10 , A61K38/17 , A61P35/00
CPC分类号： C07K7/08 , A61K39/0005 , A61K39/0011 , A61K47/643 , A61K2039/55522 , A61K2039/6081 , C07K14/43504 , C07K2319/00
摘要： The concurrent administration of chemotherapy and immunotherapy has been considered a contraindication because of the concern that the induced lymphopenia would ablate therapeutic efficacy of immunotherapy. Temozolomide has been shown to be an effective chemotherapeutic for patients with malignant gliomas and to deprive patients with glioblastoma (GBM) patients of this agent in order to treat with immunotherapy is controversial. Despite conventional dogma, we demonstrate that both chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy, in fact, the temozolomide induced lymphopenia may actually be synergistic with a peptide vaccine.
摘要翻译：由于担心诱导的淋巴细胞减少可以消除免疫治疗的治疗效果，化疗和免疫治疗的并发治疗被认为是禁忌症。替莫唑胺已被证明是恶性胶质瘤患者的有效化疗药物，并剥夺了该药物的胶质母细胞瘤（GBM）患者，以免疫疗法治疗是有争议的。尽管有常规的教条，我们证明化疗和免疫治疗可以同时进行，而不排除免疫治疗的效果，实际上，替莫唑胺诱导的淋巴细胞减少可能实际上与肽疫苗协同作用。

10. 发明授权

US5624659A Method of treating brain tumors expressing tenascin 失效
标题翻译：治疗表达腱生蛋白的脑肿瘤的方法
公开(公告)号：US5624659A
公开(公告)日：1997-04-29
申请号：US392419
申请日：1995-02-22
申请人： Darell D. Bigner , Michael R. Zalutsky
发明人： Darell D. Bigner , Michael R. Zalutsky
IPC分类号： A61K51/10 , C07K16/30 , A61K39/395 , C07K16/28
CPC分类号： C07K16/30 , A61K51/1066
摘要： Methods of treating solid and cystic tumors are disclosed. The method comprises administering to a subject afflicted with a cystic tumor an antibody which binds to tenascin in a therapeutically effective amount. The administering step is carried out by depositing the antibody in the cyst cavity of the cystic tumor. For solid tumors, disclosed is a method involving first, removing a solid tumor from a solid tissue organ of an afflicted subject; then forming an enclosed resection cavity in the organ of the subject at the location from which the solid tumor was removed; and then administering to the subject an antineoplastic agent by depositing the antineoplastic agent in the resection cavity. Particularly preferred for carrying out the foregoing is the monoclonal antibody 81C6 and antibodies which bind to the epitope bound by monoclonal antibody 81C6.
摘要翻译：公开了治疗固体和囊性肿瘤的方法。该方法包括向患有囊性肿瘤的受试者施用以治疗有效量结合腱生蛋白的抗体。施用步骤通过将抗体沉积在囊性肿瘤的囊腔中来进行。对于实体瘤，公开的方法是首先从受影响的受试者的固体组织器官去除实体瘤; 然后在移除实体瘤的位置形成被检体器官中的封闭切除腔; 然后通过将抗肿瘤剂沉积在切除腔中向受试者施用抗肿瘤剂。特别优选进行上述操作的是单克隆抗体81C6和与由单克隆抗体81C6结合的表位结合的抗体。

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