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1. 发明申请

US20120178906A1 CHELATION OF METALS TO THIOL GROUPS USING IN SITU REDUCTION OF DISULFIDE-CONTAINING COMPOUNDS BY PHOSPHINES 审中-公开
标题翻译：通过磷酸盐还原含有崩解剂的化合物将金属螯合到硫醇组合
公开(公告)号：US20120178906A1
公开(公告)日：2012-07-12
申请号：US13423751
申请日：2012-03-19
申请人： Aldo Cagnolini , Karen E. Linder , Kondareddiar Ramalingam , Hong (Helen) Fan
发明人： Aldo Cagnolini , Karen E. Linder , Kondareddiar Ramalingam , Hong (Helen) Fan
IPC分类号： C07K2/00
CPC分类号： A61K51/088
摘要： A method is disclosed for the syntheses of thiol-containing radiopharmaceuticals without the need for purification starting from chelators containing disulfide bonds. This is done by providing a method that reduces disulfide bonds on a precursor molecule or a precursor compound in the presence of phosphine compounds, thus freeing thiols for metal complexation.
摘要翻译：公开了用于合成含硫醇的放射性药物的方法，而不需要从含有二硫键的螯合剂开始纯化。这通过提供在膦化合物存在下还原前体分子或前体化合物上的二硫键的方法来实现，从而释放硫醇以进行金属络合。

2. 发明申请

US20090062509A1 CHELATION OF METALS TO THIOL GROUPS USING IN SITU REDUCTION OF DISULFIDE-CONTAINING COMPOUNDS BY PHOSPHINES 审中-公开
标题翻译：通过磷酸盐还原含有崩解剂的化合物将金属螯合到硫醇组合
公开(公告)号：US20090062509A1
公开(公告)日：2009-03-05
申请号：US12282766
申请日：2007-03-14
申请人： Aldo Cagnolini , Karen E. Linder , Kondareddiar Ramalingam , Hong Helen Fan
发明人： Aldo Cagnolini , Karen E. Linder , Kondareddiar Ramalingam , Hong Helen Fan
IPC分类号： C07K7/50 , C07K2/00 , C07K7/06 , C07K1/113 , C07K14/00
CPC分类号： A61K51/088
摘要： A method is disclosed for the syntheses of thiol-containing radiopharmaceuticals without the need for purification starting from chelators containing disulfide bonds. This is done by providing a method that reduces disulfide bonds on a precursor molecule or a precursor compound in the presence of phosphine compounds, thus freeing thiols for metal complexation.
摘要翻译：公开了用于合成含硫醇的放射性药物的方法，而不需要从含有二硫键的螯合剂开始纯化。这通过提供在膦化合物存在下还原前体分子或前体化合物上的二硫键的方法来实现，从而释放硫醇以进行金属络合。

3. 发明授权

US08420050B2 Gastrin releasing peptide compounds 失效
标题翻译：胃泌素释放肽化合物
公开(公告)号：US08420050B2
公开(公告)日：2013-04-16
申请号：US12137079
申请日：2008-06-11
申请人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle , Mary Ellen Maddalena
发明人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle , Mary Ellen Maddalena
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07K14/57572 , A61K49/085 , A61K49/122 , A61K49/14 , A61K51/088
摘要： Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer, said methods comprising the step of administering to a subject a dose comprising an amount of radioactively labeled L70, N-[4-[[[[[4,7,10-Tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetyl]amino]acetyl]amino]benzoyl]-L-glutaminyl-L-tryptophyl-L-alanyl-L-valyl-glycyl-L-histidyl-L-leucyl-L-methioninamide.
摘要翻译：还提供了治疗前列腺肿瘤或延缓前列腺肿瘤进展的新方法，包括治疗前列腺癌的治疗激素敏感性和激素难治性前列腺癌的骨或软组织转移的方法，延迟激素敏感性进展的方法前列腺癌，用于促进激素敏感性前列腺癌患者的联合治疗，并减少激素敏感性前列腺癌患者的异常血管通透性，所述方法包括向受试者施用包含一定量的放射性标记的L70，N- [4 - [[[[[[4,7,10-三（羧甲基）-1,4,7,10-四氮杂环十二烷-1-基]乙酰基]氨基]乙酰基]氨基]苯甲酰基] -L-谷氨酰胺基-L- 色氨酰-L-丙氨酰-L-缬氨酰 - 甘氨酰-L-组氨酰-L-亮氨酰-L-甲硫氨酰胺。

4. 发明申请

US20120009122A1 GASTRIN RELEASING PEPTIDE COMPOUNDS 失效
标题翻译： GASTRIN释放肽化合物
公开(公告)号：US20120009122A1
公开(公告)日：2012-01-12
申请号：US12958572
申请日：2010-12-02
申请人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle
发明人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle
IPC分类号： A61K51/08 , A61P35/00
CPC分类号： C07K14/57572 , A61K49/085 , A61K49/122 , A61K49/14 , A61K51/088
摘要： New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof.Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.
摘要翻译：用于具有式MN-O-PG的诊断成像或治疗的新的和改进的化合物，其中M是具有以下结构的金属螯合剂：其中R1-R5和FG如本文所定义（以与金属放射性核素复合的形式或不是），N-O-P是含有至少一个具有环状基团，至少一个取代的胆汁酸或至少一个非α氨基酸的非α氨基酸的接头，G是GRP受体靶向肽。在优选的实施方案中，M是Aazta金属螯合剂或其衍生物。还提供了使用本发明的化合物对患者成像和/或向患者提供放射治疗或光疗的方法。还提供了用于从该化合物制备诊断显像剂的方法和试剂盒。还提供了用于制备放射治疗剂的方法和试剂盒。

5. 发明申请

US20110262366A1 COMPOUNDS FOR TARGETING ENDOTHELIAL CELLS, COMPOSITIONS CONTAINING THE SAME AND METHODS FOR THEIR USE 审中-公开
标题翻译：用于靶向内皮细胞的化合物，包含其的组合物及其使用方法
公开(公告)号：US20110262366A1
公开(公告)日：2011-10-27
申请号：US12969327
申请日：2010-12-15
申请人： Mathew A. Von Wronski , Edmund R. Marinelli , Adrian D. Nunn , Radhakrishna K. Pillai , Kondareddiar Ramalingam , Michael F. Tweedle , Karen E. Linder , Palaniappa Nanjappan , Natarajan Raju , Feng Yan , Michel Schneider
发明人： Mathew A. Von Wronski , Edmund R. Marinelli , Adrian D. Nunn , Radhakrishna K. Pillai , Kondareddiar Ramalingam , Michael F. Tweedle , Karen E. Linder , Palaniappa Nanjappan , Natarajan Raju , Feng Yan , Michel Schneider
IPC分类号： A61K49/22 , C07K7/08 , C07K14/00 , C12N9/96 , A61P43/00 , C07K1/107 , A61K38/08 , A61K9/14 , A61K38/10 , A61K38/16 , C07K7/06 , C07K19/00
CPC分类号： A61K51/088 , A61K47/64 , A61K47/6925 , A61K49/006 , A61K49/0091 , A61K49/223 , A61K49/225 , A61K49/227 , B82Y5/00 , B82Y10/00 , B82Y30/00 , C07K7/06
摘要： The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-1 receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.
摘要翻译：本发明提供用于靶向表达NP-1受体的内皮细胞，肿瘤细胞或其他细胞的化合物，其含有该组合物的组合物及其使用方法。另外，本发明包括可用于可视化，治疗或放射治疗的诊断，治疗和放射治疗组合物。

6. 发明申请

US20090175786A1 Gastrin Releasing Peptide Compounds 失效
标题翻译：胃泌素释放肽化合物
公开(公告)号：US20090175786A1
公开(公告)日：2009-07-09
申请号：US12137079
申请日：2008-06-11
申请人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle , Mary Ellen Maddalena
发明人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael F. Tweedle , Mary Ellen Maddalena
IPC分类号： A61K51/08 , A61P35/04
CPC分类号： C07K14/57572 , A61K49/085 , A61K49/122 , A61K49/14 , A61K51/088
摘要： New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof.Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.Novel methods of treating prostate tumors or of delaying the progression of prostate tumors are also provided, including, methods of treating bone or soft tissue metastases of prostate cancer, methods for treating hormone sensitive and hormone refractory prostate cancer, methods for delaying the progression of hormone sensitive prostate cancer, for facilitating combination therapy in patients with hormone sensitive prostate cancer and for decreasing aberrant vascular permeability in patients with hormone sensitive prostate cancer.
摘要翻译：用于具有式MNOPG的诊断成像或治疗的新的和改进的化合物，其中M是具有以下结构的金属螯合剂：其中R1-R5和FG如本文所定义（以与金属放射性核素复合的形式），NOP 是含有至少一个具有环状基团，至少一个取代的胆汁酸或至少一个非α氨基酸的非α氨基酸的接头，G是GRP受体靶向肽。在优选的实施方案中，M是Aazta金属螯合剂或其衍生物。还提供了使用本发明的化合物对患者成像和/或向患者提供放射治疗或光疗的方法。还提供了用于从该化合物制备诊断显像剂的方法和试剂盒。还提供了用于制备放射治疗剂的方法和试剂盒。还提供了治疗前列腺肿瘤或延缓前列腺肿瘤进展的新方法，包括治疗前列腺癌骨或软组织转移的方法，治疗激素敏感性和激素难治性前列腺癌的方法，延迟激素进展的方法敏感前列腺癌，用于促进激素敏感性前列腺癌患者的联合治疗，并减少激素敏感性前列腺癌患者异常血管通透性。

7. 发明授权

US07556795B2 Radiopharmaceutical formulations 失效
标题翻译：放射性药物配方
公开(公告)号：US07556795B2
公开(公告)日：2009-07-07
申请号：US10513586
申请日：2003-05-05
申请人： Jianqing Chen , Karen E. Linder , Nannan Wang , Aldo Cagnolini
发明人： Jianqing Chen , Karen E. Linder , Nannan Wang , Aldo Cagnolini
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： A61K51/08 , A61K51/0478 , A61K51/088
摘要： Radiopharmaceutical compounds are disclosed having a radionuclide chelating moiety and a targeting ligand, and optionally a linker. Formulations of compositions useful for making the radiopharmaceutical compounds contain a chelating ligand, a reducing agent, an exchange ligand and a stabilizer.
摘要翻译：公开了具有放射性核素螯合部分和靶向配体以及任选的接头的放射性药物化合物。用于制备放射性药物化合物的组合物的制剂含有螯合配体，还原剂，交换配体和稳定剂。

8. 发明授权

US08444954B2 Gastrin releasing peptide compounds 失效
标题翻译：胃泌素释放肽化合物
公开(公告)号：US08444954B2
公开(公告)日：2013-05-21
申请号：US12958572
申请日：2010-12-02
申请人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael Tweedle
发明人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian Nunn , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael Tweedle
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07K14/57572 , A61K49/085 , A61K49/122 , A61K49/14 , A61K51/088
摘要： New and improved compounds for use in diagnostic imaging or therapy having the formula M-N—O—P-G, wherein M is a metal chelator having the structure: wherein R1-R5 and FG are as defined herein (in the form complexed with a metal radionuclide or not), N—O—P is the linker containing at least one non-alpha amino acid with a cyclic group, at least one substituted bile acid or at least one non-alpha amino acid, and G is the GRP receptor targeting peptide. In the preferred embodiment, M is an Aazta metal chelator or a derivative thereof. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound is further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.
摘要翻译：用于具有式MNOPG的诊断成像或治疗的新的和改进的化合物，其中M是具有以下结构的金属螯合剂：其中R1-R5和FG如本文所定义（以与金属放射性核素复合的形式），NOP 是含有至少一个具有环状基团，至少一个取代的胆汁酸或至少一个非α氨基酸的非α氨基酸的接头，G是GRP受体靶向肽。在优选的实施方案中，M是Aazta金属螯合剂或其衍生物。还提供了使用本发明的化合物对患者成像和/或向患者提供放射治疗或光疗的方法。还提供了用于从该化合物制备诊断显像剂的方法和试剂盒。还提供了用于制备放射治疗剂的方法和试剂盒。

9. 发明授权

US08420053B2 Gastrin releasing peptide compounds 失效
标题翻译：胃泌素释放肽化合物
公开(公告)号：US08420053B2
公开(公告)日：2013-04-16
申请号：US12551394
申请日：2009-08-31
申请人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael Tweedle
发明人： Enrico Cappelletti , Luciano Lattuada , Karen E. Linder , Edmund Marinelli , Palaniappa Nanjappan , Natarajan Raju , Kondareddiar Ramalingam , Rolf E. Swenson , Michael Tweedle
IPC分类号： A61K49/00
CPC分类号： C07K7/086 , A61K51/088
摘要： Improved compounds for use in diagnostic imaging or therapy having the formula M-N-O-P-G, wherein M is an optical label or a metal chelator (in the form complexed with a metal radionuclide or not), N-O-P is the linker, and G is the GRP receptor targeting peptide. Methods for imaging a patient and/or providing radiotherapy or phototherapy to a patient using the compounds of the invention are also provided. Methods and kits for preparing a diagnostic imaging agent from the compound are further provided. Methods and kits for preparing a radiotherapeutic agent are further provided.
摘要翻译：用于具有式MNOPG的诊断成像或治疗的改进的化合物，其中M是光学标记或金属螯合剂（以与金属放射性核素复合的形式），NOP是接头，G是GRP受体靶向肽。还提供了使用本发明的化合物对患者成像和/或向患者提供放射治疗或光疗的方法。还提供了用于从化合物制备诊断显像剂的方法和试剂盒。还提供了用于制备放射治疗剂的方法和试剂盒。

10. 发明申请

US20110097275A1 KDR AND VEGF/KDR BINDING PEPTIDES AND THEIR USE IN DIAGNOSIS AND THERAPY 有权
标题翻译： KDR和VEGF / KDR结合肽及其在诊断和治疗中的应用
公开(公告)号：US20110097275A1
公开(公告)日：2011-04-28
申请号：US12898119
申请日：2010-10-05
申请人： Christophe Arbogast , Philippe Bussat , Hong Fan , Sudha Khurana , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Radhakrishna K. Pillai , Sibylle Pochon , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf E. Swenson , Mathew A. Von Wronski , Feng Yan
发明人： Christophe Arbogast , Philippe Bussat , Hong Fan , Sudha Khurana , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Radhakrishna K. Pillai , Sibylle Pochon , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf E. Swenson , Mathew A. Von Wronski , Feng Yan
IPC分类号： A61K49/22 , A61P35/00
CPC分类号： A61K49/221 , A61K38/00 , A61K49/223 , A61K51/088 , C07K7/08 , C07K14/001 , C07K14/52 , C07K14/71 , C07K2319/00 , Y02A50/58
摘要： The present invention provides polypeptides, peptide dimers, and multimeric complexes comprising at least one binding moiety for KDR or VEGF/KDR complex, which have a variety of uses wherever treating, detecting, isolating or localizing angiogenesis is advantageous. Particularly disclosed are synthetic, isolated polypeptides capable of binding KDR or VEGF/KDR complex with high affinity (e.g., having a KD
摘要翻译：本发明提供了包含用于KDR或VEGF / KDR复合物的至少一个结合部分的多肽，肽二聚体和多聚体复合物，其具有各种用途，无论何处治疗，检测，分离或定位血管发生都是有利的。特别公开的是能够以高亲和力（例如具有KD <1μM）结合KDR或VEGF / KDR复合物的合成，分离的多肽，以及包含这些多肽，特别是造影剂的二聚体和多聚体构建体。还提供了使用本发明的造影剂监测和评估与血管生成或内皮细胞过度增殖相关的疾病（例如癌症）的治疗方案的治疗有效性的方法。

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