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1. 发明授权

US09333272B2 Fibrin binding peptide conjugates for diagnostic and therapeutic applications 有权
标题翻译：用于诊断和治疗应用的纤维蛋白结合肽缀合物
公开(公告)号：US09333272B2
公开(公告)日：2016-05-10
申请号：US12448102
申请日：2007-12-11
申请人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
发明人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
IPC分类号： A61K38/36 , A61K49/14 , A61K49/00 , A61K49/08 , A61K49/12 , C07K7/06 , G01N33/532 , G01N33/574 , G01N33/86
CPC分类号： A61K49/14 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/124 , C07K7/06 , G01N33/532 , G01N33/574 , G01N33/86 , G01N2500/04
摘要： The present invention relates to a novel class of diagnostically or therapeutically effective compounds comprising novel peptides able to bind fibrin, to a process for their preparation and to compositions thereof for use in therapy and diagnostics. The compounds of the invention bind, in particular, to fibrin present in the extracellular matrix (EC) of tumor or connective tissue of stroma thus acting as targeting moieties able to bring and successfully bound an active moiety linked thereto to fibrin depositions inside solid tumors.
摘要翻译：本发明涉及一类新的诊断或治疗有效化合物，其包含能够结合纤维蛋白的新肽，其制备方法及其组合物用于治疗和诊断。本发明的化合物特别结合存在于基质的肿瘤或结缔组织的细胞外基质（EC）中的纤维蛋白，因此作为能够使与其连接的活性部分与实质瘤内的纤维蛋白沉积成功结合的靶向部分。

2. 发明申请

US20100202967A1 FIBRIN BINDING PEPETIDE CONJUGATES FOR DIAGNOSTIC AND THERAPEUTIC APPLICATIONS 有权
标题翻译：用于诊断和治疗应用的纤维蛋白结合胶原蛋白
公开(公告)号：US20100202967A1
公开(公告)日：2010-08-12
申请号：US12448102
申请日：2007-12-11
申请人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
发明人： Silvio Aime , Linda Chaabane , Luciano Lattuada , Vito Lorusso , Edmund R. Marinelli , Pierfrancesco Morosini , Kondareddiar Ramalingam , Bo Song , Rolf E. Swenson , Fulvio Uggeri
IPC分类号： A61K49/00 , C07K7/08 , C07K7/50 , A61K38/10 , A61K38/16 , A61P35/00 , A61P35/04 , A61P29/00 , A61P7/02 , A61P9/00 , G01N33/50 , G01N33/567
CPC分类号： A61K49/14 , A61K49/0043 , A61K49/0056 , A61K49/085 , A61K49/124 , C07K7/06 , G01N33/532 , G01N33/574 , G01N33/86 , G01N2500/04
摘要： The present invention relates to a novel class of diagnostically or therapeutically effective compounds comprising novel peptides able to bind fibrin, to a process for their preparation and to compositions thereof for use in therapy and diagnostics. The compounds of the invention bind, in particular, to fibrin present in the extracellular matrix (EC) of tumor or connective tissue of stroma thus acting as targeting moieties able to bring and successfully bound an active moiety linked thereto to fibrin depositions inside solid tumors.
摘要翻译：本发明涉及一类新的诊断或治疗有效化合物，其包含能够结合纤维蛋白的新肽，其制备方法及其组合物用于治疗和诊断。本发明的化合物特别结合存在于基质的肿瘤或结缔组织的细胞外基质（EC）中的纤维蛋白，因此作为能够使与其连接的活性部分与实质瘤内的纤维蛋白沉积成功结合的靶向部分。

3. 发明申请

US20110256067A1 Contrast agents endowed with high relaxivity 有权
标题翻译：对比剂具有高的放松性
公开(公告)号：US20110256067A1
公开(公告)日：2011-10-20
申请号：US11630600
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61K49/10 , C07F5/00 , C07D243/10 , C07H15/26 , C07D243/08
CPC分类号： C07H15/26 , A61K49/085 , A61K49/124 , C07C237/08 , C07D243/08 , C07D243/10 , C07F9/3808 , C07F9/4006 , C07F9/5728 , C07H17/02
摘要： The present invention relates to a novel class of paramagnetic ion-based contrast agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhydroxylated chain, that show a pharmacokinetic profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity.
摘要翻译：本发明涉及式（I）的新型顺磁离子型造影剂，其中螯合骨架部分通过存在一个或多个多羟基化链而被高度官能化，其显示类似于常规的药代动力学特征使用T1一般血管外药物（NSA），但其进一步的特征是较高的松弛度。

4. 发明授权

US08540966B2 Contrast agents endowed with high relaxivity 有权
标题翻译：对比剂具有高的放松性
公开(公告)号：US08540966B2
公开(公告)日：2013-09-24
申请号：US11630600
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61K49/10 , C07D243/08
CPC分类号： C07H15/26 , A61K49/085 , A61K49/124 , C07C237/08 , C07D243/08 , C07D243/10 , C07F9/3808 , C07F9/4006 , C07F9/5728 , C07H17/02
摘要： The present invention relates to a novel class of paramagnetic ion-based contrast agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhydroxylated chain, that show a pharmacokinetic profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity.
摘要翻译：本发明涉及式（I）的新型顺磁离子型造影剂，其中螯合骨架部分通过存在一个或多个多羟基化链而被高度官能化，其显示类似于常规的药代动力学特征使用T1一般血管外药物（NSA），但其进一步的特征是较高的松弛度。

5. 发明授权

US07988950B2 Contrast agents endowed with high relaxivity for use in magnetic resonance imaging (MRI) which contain a chelating moiety with polyhydroxylated substituents 有权
标题翻译：对比剂具有高的放松性，用于磁共振成像（MRI），其含有具有多羟基化取代基的螯合部分
公开(公告)号：US07988950B2
公开(公告)日：2011-08-02
申请号：US11630605
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61B5/055 , A61K49/10 , C07F5/00
CPC分类号： C07H15/26 , A61K49/085 , A61K49/124 , C07C237/08 , C07D243/08 , C07D243/10 , C07F9/3808 , C07F9/4006 , C07F9/5728 , C07H17/02
摘要： The present invention relates to a novel class of paramagnetic ion-based contrast i agents of formula (I), wherein a chelating backbone moiety is highly functionalized by the presence of one or more polyhydroxylated chain, that show a pharmacokinetic i profile analogous to that of the commonly used T1-general extravascular agents (NSA) but are further characterized by a higher relaxivity. Formula (I): A(LR)v wherein: A is a linear or cyclic chelating backbone moiety; R is, independently, H or a C2-C70aminopolyol moiety comprising a ‘straight or branched alkyl chain substituted by from 2 to 30 hydroxyl groups, the said chain being optionally interrupted by one or more groups selected from -0-, —NH—, —N NCO—; and optionally substituted by one or more C4-C10 cyclic units; L is, independently, a direct bond or “a divalent straight or branched linker moiety between A and R, at most comprising 20 carbon atoms; V is a positive integer from 1 to 7; with the proviso that at least one of the R groups is other than H; or a physiologically acceptable salt of such ligand.
摘要翻译：本发明涉及一类新颖的式（I）的顺磁离子型对比剂，其中螯合骨架部分通过存在一个或多个多羟基化链而被高度官能化，其显示类似于常用的T1一般血管外药物（NSA），但其进一步特征在于较高的松弛度。式（I）：A（LR）v其中：A是直链或环状螯合骨架部分; R独立地是H或包含被2至30个羟基取代的“直链或支链烷基链”的C2-C70氨基多酚部分，所述链任选地被一个或多个选自-O-，-NH-， -N'， - CO - ， - CONH - ， - NHCO-，-CON'或> NCO-; 并任选地被一个或多个C 4 -C 10环单元取代; L独立地是直接键或“A和R之间的二价直链或支链连接体部分，最多包含20个碳原子; V是1到7的正整数; 条件是至少一个R基团不是H; 或这种配体的生理上可接受的盐。

6. 发明申请

US20070258905A1 Contrast Agents Endowed with High Relaxivity for Use in Magnetic Resonance Imaging (Mri) Which Contain a Chelating Moiety with Polyhydroxylated Substituents 有权
标题翻译：具有高松弛度的对比剂用于磁共振成像（Mri），其含有多羟基化取代基的螯合物
公开(公告)号：US20070258905A1
公开(公告)日：2007-11-08
申请号：US11630605
申请日：2005-06-28
申请人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
发明人： Silvio Aime , Matteo Galli , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri , Kondareddiar Ramalingam
IPC分类号： A61B5/055 , C07C211/00 , C07D211/00 , C07D243/00 , C07D243/08 , C07D255/04 , C07D315/00 , C07F9/02 , G01N24/08
CPC分类号： C07H15/26 , A61K49/085 , A61K49/124 , C07C237/08 , C07D243/08 , C07D243/10 , C07F9/3808 , C07F9/4006 , C07F9/5728 , C07H17/02
摘要： The present invention relates to a new class of paramagnetic ion-based contrast agents of molecular weight lower than 3.5 kDa that show a pharmacokinetic profile analogous to that of the commonly used T1-general extravascular agents and that are further characterized by a higher relaxivity.
摘要翻译：本发明涉及分子量低于3.5kDa的新型顺磁离子型造影剂，其显示类似于通常使用的T1-一般血管外试剂的药代动力学特征，并且其进一步特征在于较高的弛豫度。

7. 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。

8. 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。

9. 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。

10. 发明授权

US08642010B2 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：US08642010B2
公开(公告)日：2014-02-04
申请号：US12480578
申请日：2009-06-08
申请人： Aaron K. Sato , Daniel J. Sexton , Daniel T. Dransfield , Robert C. Ladner , Christophe Arbogast , Philippe Bussat , Hong Fan , Sudha Khurana , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Radhakrishna K. Pillai , Sibylle Pochon , Feng Yan , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf E. Swenson , Mathew A. Von Wronski
发明人： Aaron K. Sato , Daniel J. Sexton , Daniel T. Dransfield , Robert C. Ladner , Christophe Arbogast , Philippe Bussat , Hong Fan , Sudha Khurana , Karen E. Linder , Edmund R. Marinelli , Palaniappa Nanjappan , Adrian D. Nunn , Radhakrishna K. Pillai , Sibylle Pochon , Feng Yan , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf E. Swenson , Mathew A. Von Wronski
IPC分类号： A61K49/00 , A61B8/00
CPC分类号： A61K49/221 , A61K38/00 , A61K47/62 , A61K49/223 , A61K51/088 , C07K7/08 , C07K14/001 , C07K14/52 , C07K14/71 , C07K2319/00 , Y02A50/411 , Y02A50/58
摘要： The present invention provides polypeptides, peptide dimer, 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，以及包含这些多肽的二聚体和多聚体构建体。

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