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1. 发明授权

US5756825A Hydroxamic acid-based bifunctional chelating compounds 失效
标题翻译：羟基恶唑基双功能螯合化合物
公开(公告)号：US5756825A
公开(公告)日：1998-05-26
申请号：US48869
申请日：1993-04-16
申请人： Ahmad Safavy , Donald J. Buchsbaum , Mohammad Bagher Kazaeli
发明人： Ahmad Safavy , Donald J. Buchsbaum , Mohammad Bagher Kazaeli
IPC分类号： A61K51/10 , C07C259/06 , C07K5/02 , C07C229/00 , C07C239/00
CPC分类号： C07C259/06 , A61K51/1093 , C07K5/022 , A61K2121/00 , A61K2123/00
摘要： The present disclosure details the preparation of hydroxamic-acid based bifunctional chelators and their use in conjugating metal ions to proteins and nucleic acids for tumor or tissue imaging or therapy purposes. Some preferred aspects of the disclosure involve the preparation of trisuccin, chemical name N-�tris(2-N- benzyloxyaminocarbonylethyl)! methylsuccinamic acid, which is a hydroxamic acid/succinate based structure that is particularly useful for binding radionuclides such as .sup.99m Tc, .sup.186 Re and .sup.67 Cu.
摘要翻译：本公开详细描述了基于异羟肟酸的双功能螯合剂的制备及其在将金属离子与用于肿瘤或组织成像或治疗目的的蛋白质和核酸结合的用途。本公开的一些优选方面涉及三琥珀，化学名称N- [三（2-N-苄氧基氨基羰基乙基）]甲基琥珀酸，其是特异可用于结合放射性核素如99mTc，186Re的异羟肟酸/琥珀酸酯基结构和67Cu。

2. 发明申请

US20110293515A1 HETEROFUNCTIONAL SEGMENT-POLY (ETHYLENE GLYCOL) POLYMERS AS DELIVERY VEHICLES 审中-公开
标题翻译：交联聚乙烯（乙烯甘油）聚合物
公开(公告)号：US20110293515A1
公开(公告)日：2011-12-01
申请号：US13144440
申请日：2010-01-12
申请人： Ahmad Safavy , James A. Bonner , Donald J. Buchsbaum
发明人： Ahmad Safavy , James A. Bonner , Donald J. Buchsbaum
IPC分类号： A61K51/06 , A61P35/00 , A61K49/00 , C08G69/48 , A61K47/48
CPC分类号： C08G69/44 , A61B5/055 , A61B5/411 , A61K47/59 , A61K47/60 , A61K47/645 , C08G69/10 , C08G69/40
摘要： Heterofunctional segment-poly(ethylene glycol) polymers, conjugates of these molecules with therapeutic and/or imaging agents, and methods for their use are disclosed. The heterofunctional segment-poly(ethylene glycol) polymers are useful as drug delivery conjugates, i.e., the heterofunctional segment-poly(ethylene glycol) polymers can be covalently attached to therapeutic agents (e.g., pharmaceutically active agents) and serve as delivery vehicles for the therapeutic agents. The heterofunctional segment-poly(ethylene glycol) polymers are also useful as imaging agent conjugates, i.e. the heterofunctional segment-poly(ethylene glycol) polymers can be covalently attached to imaging agents (e.g., tracers, imaging atoms, and imaging molecules) and serve as delivery vehicles for the imaging agents. Also disclosed are methods for treating a subject by administering to the subject an effective amount of the polymers conjugated to a therapeutic agent, an imaging agent, or a mixture thereof.
摘要翻译：公开了异功能段 - 聚（乙二醇）聚合物，这些分子与治疗和/或显像剂的缀合物及其使用方法。异源功能区段 - 聚（乙二醇）聚合物可用作药物递送缀合物，即异功能区段 - 聚（乙二醇）聚合物可以共价连接到治疗剂（例如药物活性剂）上，并用作治疗剂。异源功能片段 - 聚（乙二醇）聚合物也可用作显影剂缀合物，即异功能片段 - 聚（乙二醇）聚合物可以共价连接到成像剂（例如，示踪剂，成像原子和成像分子）并且用于作为成像剂的递送载体。还公开了通过向受试者施用有效量的与治疗剂，显像剂或其混合物缀合的聚合物来治疗受试者的方法。

3. 发明申请

US20110104143A1 Treating Basal-Like Genotype Cancers 有权
标题翻译：治疗基底样基因型癌症
公开(公告)号：US20110104143A1
公开(公告)日：2011-05-05
申请号：US12940746
申请日：2010-11-05
申请人： Donald J. Buchsbaum , Tong Zhou , Albert F. LoBuglio
发明人： Donald J. Buchsbaum , Tong Zhou , Albert F. LoBuglio
IPC分类号： A61K39/395 , C07K16/18 , A61P35/00 , G01N33/574
CPC分类号： C07K16/2878 , A61K9/0019 , A61K31/337 , A61K31/5517 , A61K31/704 , A61K39/3955 , A61K39/39558 , A61K47/42 , C07K2317/34 , C07K2317/73
摘要： Provided herein are methods of treating a subject with cancer comprising administering to the subject a death receptor agonist. Also provided herein are methods of screening a breast cancer cell for responsiveness to a DR5 agonist. Further provided herein are antibodies that selectively bind an N-terminal CARD of DDX3, a DDX3 lacking an N-terminal CARD, and an 80 kDa baculovirus TAP repeat (BIR).
摘要翻译：本文提供了用癌症治疗受试者的方法，包括向受试者施用死亡受体激动剂。本文还提供筛选乳腺癌细胞以响应DR5激动剂的方法。本文进一步提供选择性结合DDX3的N末端CARD，缺乏N端CARD的DDX3和80kDa杆状病毒TAP重复（BIR）的抗体。

4. 发明授权

US06703375B2 Molecular chemotherapy enhancement of radiotherapy 失效
标题翻译：分子化疗放疗增强
公开(公告)号：US06703375B2
公开(公告)日：2004-03-09
申请号：US10304436
申请日：2002-11-26
申请人： Donald J. Buchsbaum , C. Ryan Miller , G. Yancey Gillespie , Robert J. Garyer, Jr.
发明人： Donald J. Buchsbaum , C. Ryan Miller , G. Yancey Gillespie , Robert J. Garyer, Jr.
IPC分类号： A61K4800
CPC分类号： C12N15/86 , A61K38/45 , A61K38/50 , A61K41/00 , A61K48/00 , C12N2710/10343 , C12N2810/859 , Y02A50/473
摘要： The present invention provides a new approach for cancer treatment by utilizing gene therapy combined with radiation therapy to enhance cytotoxicity in malignant cells. Specifically, the present invention demonstrates that molecular chemotherapy with the cytosine deaminase gene and 5-fluorocytosine is an effective radiosensitizing strategy which may lead to substantial improvement in tumor control, with less normal tissue toxicity than conventional systemic administration of 5-fluorouracil, that would translate into improved cure rates and better survival. A noninvasive method is described for continuous in vivo monitoring of 5-fluorouracil production via magnetic resonance spectroscopy An adenovirus encoding cytosine deaminase gene which selectively replicates in tumor cells with a defective p53 pathway was constructed. Also provided is an adenovirus which encodes a fusion protein of cytosine deaminase and uracil phosphoribosyltransferase.
摘要翻译：本发明通过利用与放射治疗相结合的基因治疗来增强恶性细胞中的细胞毒性提供了一种新的癌症治疗方法。具体来说，本发明表明，具有胞嘧啶脱氨酶基因和5-氟胞嘧啶的分子化学疗法是一种有效的放射增敏策略，其可以导致肿瘤控制的显着改善，具有比常规全身施用5-氟尿嘧啶更少的正常组织毒性，这将翻译改善治愈率和更好的生存。描述了用于通过磁共振光谱法连续体内监测5-氟尿嘧啶的非侵入性方法。构建了在肿瘤细胞中选择性复制缺陷型p53途径的编码胞嘧啶脱氨酶基因的腺病毒。还提供了编码胞嘧啶脱氨酶和尿嘧啶磷酸核糖转移酶的融合蛋白的腺病毒。

5. 发明授权

US06468547B1 Enhancement of tumor cell chemosensitivity and radiosensitivity using single chain secretory antibodies 失效
标题翻译：使用单链分泌抗体增强肿瘤细胞化学敏感性和放射敏感性
公开(公告)号：US06468547B1
公开(公告)日：2002-10-22
申请号：US09499543
申请日：2000-02-07
申请人： Donald J. Buchsbaum , David T. Curiel , Murray Stackhouse
发明人： Donald J. Buchsbaum , David T. Curiel , Murray Stackhouse
IPC分类号： A61K3900
CPC分类号： C07K16/30 , A61K48/00 , A61K2039/505 , A61K2039/51 , C07K16/18 , C07K16/2863 , C07K16/32 , C07K16/40 , C07K2317/622 , C07K2317/73 , C12N2799/022
摘要： The present invention provides a method of enhancing the chemosensitivity and radiosensitivity of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the oncoprotein intracellularly in the endoplasmic reticulum of the cell. The present invention is also directed to a method for enhancing the inhibition of proliferation of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising the steps of: introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the protein intracellularly; and contacting said cell with an anti-neoplastic agent.
摘要翻译：本发明提供增强表达刺激细胞增殖的癌蛋白的肿瘤细胞的化学敏感性和放射敏感性的方法，包括将编码抗体同系物的核酸分子导入细胞，其中抗体同系物在细胞内表达并结合胞内胞内蛋白质细胞内质网。本发明还涉及一种用于增强表达癌细胞增殖的肿瘤细胞增殖抑制的方法，所述方法包括以下步骤：将编码抗体同系物的核酸分子导入细胞，其中所述抗体同源物在细胞内表达并在细胞内结合蛋白; 并使所述细胞与抗肿瘤剂接触。

6. 发明申请

US20130004521A1 TARGETING CANCER STEM CELLS 有权
标题翻译：靶向癌细胞
公开(公告)号：US20130004521A1
公开(公告)日：2013-01-03
申请号：US13634401
申请日：2011-03-18
申请人： Donald J. Buchsbaum , Albert F. Lobuglio , Tong Zhou , Kimberly Foreman
发明人： Donald J. Buchsbaum , Albert F. Lobuglio , Tong Zhou , Kimberly Foreman
IPC分类号： A61K39/395 , G01N33/573 , A61N5/10 , A61P35/00 , A61P35/04 , G01N33/574 , A61K31/7105
CPC分类号： C07K16/2878 , C07K2317/75
摘要： Provided is a method of determining the level of resistance or sensitivity of cancer stem cells to a death receptor agonist. The method includes detecting the level of IAP in one or more DR5/DDX3/IAP complexes in or from the cancer stem cells. Also provided is a method of killing cancer stem cells in a subject and a method of reducing the risk of cancer recurrence in a subject.
摘要翻译：提供了确定癌症干细胞对死亡受体激动剂的抗性或敏感性水平的方法。该方法包括检测在癌干细胞中或来自癌干细胞的一种或多种DR5 / DDX3 / IAP复合物中IAP的水平。还提供了一种杀死受试者中的癌症干细胞的方法和降低受试者中癌症复发风险的方法。

7. 发明授权

US6074640A Enhancement of tumor cell radiosensitivity using single chain intracellular antibodies 失效
标题翻译：使用单链细胞内抗体增强肿瘤细胞放射敏感性
公开(公告)号：US6074640A
公开(公告)日：2000-06-13
申请号：US961327
申请日：1997-10-30
申请人： David T. Curiel , Murray Stackhouse , Donald J. Buchsbaum
发明人： David T. Curiel , Murray Stackhouse , Donald J. Buchsbaum
IPC分类号： A61K48/00 , A61P35/00 , C07K16/18 , C07K16/30 , C07K16/32 , A61K39/395 , C07H21/04
CPC分类号： C07K16/32 , C07K16/18 , C07K16/30 , A61K2039/505 , A61K48/00 , C07K2317/622 , C07K2317/73
摘要： The present invention provides a method of enhancing the chemosensitivity and radiosensitivity of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the oncoprotein intracellularly in the endoplasmic reticulum of the cell. The present invention is also directed to a method for enhancing the inhibition of proliferation of a neoplastic cell expressing an oncoprotein that stimulates proliferation of the cell, comprising the steps of: introducing into the cell a nucleic acid molecule encoding an antibody homologue, wherein the antibody homologue is expressed intracellularly and binds to the protein intracellularly; and contacting said cell with an anti-neoplastic agent.
摘要翻译：本发明提供增强表达刺激细胞增殖的癌蛋白的肿瘤细胞的化学敏感性和放射敏感性的方法，包括将编码抗体同系物的核酸分子导入细胞，其中抗体同系物在细胞内表达并结合胞内胞内蛋白质细胞内质网。本发明还涉及一种用于增强表达癌细胞增殖的肿瘤细胞增殖抑制的方法，所述方法包括以下步骤：将编码抗体同系物的核酸分子导入细胞，其中所述抗体同源物在细胞内表达并在细胞内结合蛋白; 并使所述细胞与抗肿瘤剂接触。

8. 发明授权

US5981504A Genetic induction of receptors for targeted radiotherapy 失效
标题翻译：用于靶向放射治疗的受体的遗传诱导
公开(公告)号：US5981504A
公开(公告)日：1999-11-09
申请号：US948132
申请日：1997-10-09
申请人： Donald J. Buchsbaum , David Raben , Mohammad B. Khazaeli , David T. Curiel , Murray Stackhouse
发明人： Donald J. Buchsbaum , David Raben , Mohammad B. Khazaeli , David T. Curiel , Murray Stackhouse
IPC分类号： A61K51/08 , A61K51/10 , A61P35/00 , A61K48/00
CPC分类号： A61K51/1036 , A61K51/08 , A61K51/083 , A61K51/10 , A61K2123/00
摘要： The present invention provides a method to achieve radioisotopic localization at tumor sites, i.e., a method of enhancing radiolabeled ligand localization to a tumor in an individual in need of such treatment, comprising the steps of: transducing said tumor with a gene encoding a membrane expressed protein unique to said tumor; and administering to said individual a radiolabeled ligand which specifically binds to said protein. The use of gene therapy technology to induce expression of high affinity membrane molecules/receptors can enhance the specificity of radioisotope localization while the use of radioactive isotopes with the ability to deliver radiation damage across several cell diameters will compensate for less than perfect transduction efficiency.
摘要翻译：本发明提供了一种在肿瘤部位实现放射性同位素定位的方法，即在需要这种治疗的个体中增强对肿瘤的放射性标记配体定位的方法，包括以下步骤：用编码膜表达的基因转导所述肿瘤所述肿瘤独特的蛋白质; 并向所述个体施用特异性结合所述蛋白质的放射性标记的配体。使用基因治疗技术诱导高亲和力膜分子/受体的表达可以增强放射性同位素定位的特异性，而使用具有在几个细胞直径上传递辐射损伤的能力的放射性同位素将补偿不到完美的转导效率。

9. 发明授权

US08703712B2 Targeting cancer stem cells with DR5 agonists 有权
标题翻译：用DR5激动剂靶向癌症干细胞
公开(公告)号：US08703712B2
公开(公告)日：2014-04-22
申请号：US13634401
申请日：2011-03-18
申请人： Donald J. Buchsbaum , Albert F. Lobuglio , Tong Zhou , Kimberly Foreman
发明人： Donald J. Buchsbaum , Albert F. Lobuglio , Tong Zhou , Kimberly Foreman
IPC分类号： A61K39/00 , A61P35/00 , A61K39/395 , C12N5/095 , C07K16/30
CPC分类号： C07K16/2878 , C07K2317/75
摘要： Provided is a method of determining the level of resistance or sensitivity of cancer stem cells to a death receptor agonist. The method includes detecting the level of IAP in one or more DR5/DDX3/IAP complexes in or from the cancer stem cells. Also provided is a method of killing cancer stem cells in a subject and a method of reducing the risk of cancer recurrence in a subject.
摘要翻译：提供了确定癌症干细胞对死亡受体激动剂的抗性或敏感性水平的方法。该方法包括检测在癌干细胞中或来自癌干细胞的一种或多种DR5 / DDX3 / IAP复合物中IAP的水平。还提供了一种杀死受试者中的癌症干细胞的方法和降低受试者中癌症复发风险的方法。

10. 发明授权

US07981421B2 Combinations of antibodies selective for DR5 and other therapeutic agents 有权
标题翻译： DR5和其他治疗剂选择性抗体的组合
公开(公告)号：US07981421B2
公开(公告)日：2011-07-19
申请号：US12686659
申请日：2010-01-13
申请人： Tong Zhou , Kimihisa Ichikawa , Robert P. Kimberly , William J. Koopman , Jun Ohsumi , Albert F. LoBuglio , Donald J. Buchsbaum
发明人： Tong Zhou , Kimihisa Ichikawa , Robert P. Kimberly , William J. Koopman , Jun Ohsumi , Albert F. LoBuglio , Donald J. Buchsbaum
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30
CPC分类号： C07K16/2878 , A61K31/337 , A61K31/519 , A61K39/39541 , A61K41/00 , A61K45/06 , A61K2039/505 , C07K2317/24 , C07K2317/73 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.
摘要翻译：本发明的抗体与人DR5或与人DR4相互作用以在受体下游产生激动或拮抗作用，包括抑制细胞增殖和细胞凋亡。详细描述了任选与各种治疗剂组合的抗体的方法和用途，包括治疗凋亡相关疾病和治疗失调的细胞生长。

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