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1. 发明授权

US08927207B2 miRNAs as therapeutic targets in cancer 有权
标题翻译： miRNA作为癌症治疗靶点
公开(公告)号：US08927207B2
公开(公告)日：2015-01-06
申请号：US12996249
申请日：2009-06-05
申请人： Jingfang Ju , Bo Song , Yuan Wang
发明人： Jingfang Ju , Bo Song , Yuan Wang
IPC分类号： C12Q1/68 , C12N15/113
CPC分类号： C12N15/1137 , A61K31/7088 , A61K45/06 , C12N15/113 , C12N15/1135 , C12N2310/113 , C12N2310/14 , C12N2320/31 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178
摘要： MicroRNAs (miRNAs) are a class of non-coding small RNA molecules that regulate gene expression at the post-transcriptional level by interacting with 3′ untranslated regions (UTRs) of their target mRNAs. The invention relates to the application of miR-192 and miR-215. Both of these miRNAs impact cellular proliferation through the p53-miRNA circuit, and interact with dihydrofolate reductase (DHFR) and thymidylate synthase (TS). Particularly, upregulation of these miRNAs reduces cellular proliferation. The invention relates to this discovery. For example, inhibiting miR-192 and/or miR-215 sensitizes a neoplasm or a subject with a neoplasm to chemotherapeutic agents. Furthermore, measuring the levels of miR-192 and/or miR-215 provides one with information regarding whether the neoplasm or subject will respond to chemotherapeutic agents. Accordingly, the invention relates to composition and methods relating to the identification, characterization and modulation of the expression of miR-192 and miR-215.
摘要翻译：微RNA（miRNA）是一类非编码小RNA分子，通过与其靶mRNA的3'非翻译区（UTR）相互作用，在转录后水平调节基因表达。本发明涉及miR-192和miR-215的应用。这两种miRNA通过p53-miRNA电路影响细胞增殖，并与二氢叶酸还原酶（DHFR）和胸苷酸合酶（TS）相互作用。特别地，这些miRNA的上调减少细胞增殖。本发明涉及这一发现。例如，抑制miR-192和/或miR-215使肿瘤或具有肿瘤的受试者对化学治疗剂敏感。此外，测量miR-192和/或miR-215的水平提供了关于肿瘤或受试者是否将对化学治疗剂作出反应的信息。因此，本发明涉及与miR-192和miR-215的表达的鉴定，表征和调节相关的组合物和方法。

2. 发明申请

US20110166201A1 MIRNAS AS THERAPEUTIC TARGETS IN CANCER 有权
标题翻译： MIRNAS作为癌症中的治疗目标
公开(公告)号：US20110166201A1
公开(公告)日：2011-07-07
申请号：US12996249
申请日：2009-06-05
申请人： Jingfang Ju , Bo Song , Yuan Wang
发明人： Jingfang Ju , Bo Song , Yuan Wang
IPC分类号： A61K31/7052 , C12N5/00 , C12Q1/68 , C07H21/00 , A61P35/00
CPC分类号： C12N15/1137 , A61K31/7088 , A61K45/06 , C12N15/113 , C12N15/1135 , C12N2310/113 , C12N2310/14 , C12N2320/31 , C12Q1/6886 , C12Q2600/136 , C12Q2600/178
摘要： MicroRNAs (miRNAs) are a class of non-coding small RNA molecules that regulate gene expression at the post-transcriptional level by interacting with 3′ untranslated regions (UTRs) of their target mRNAs. The invention relates to the application of miR-192 and miR-215. Both of these miRNAs impact cellular proliferation through the p53-miRNA circuit, and interact with dihydrofolate reductase (DHFR) and thymidylate synthase (TS). Particularly, upregulation of these miRNAs reduces cellular proliferation. The invention relates to this discovery. For example, inhibiting miR-192 and/or miR-215 sensitizes a neoplasm or a subject with a neoplasm to chemotherapeutic agents. Furthermore, measuring the levels of miR-192 and/or miR-215 provides one with information regarding whether the neoplasm or subject will respond to chemotherapeutic agents. Accordingly, the invention relates to composition and methods relating to the identification, characterization and modulation of the expression of miR-192 and miR-215.
摘要翻译：微RNA（miRNA）是一类非编码小RNA分子，通过与其靶mRNA的3'非翻译区（UTR）相互作用，在转录后水平调节基因表达。本发明涉及miR-192和miR-215的应用。这两种miRNA通过p53-miRNA电路影响细胞增殖，并与二氢叶酸还原酶（DHFR）和胸苷酸合酶（TS）相互作用。特别地，这些miRNA的上调减少细胞增殖。本发明涉及这一发现。例如，抑制miR-192和/或miR-215使肿瘤或具有肿瘤的受试者对化学治疗剂敏感。此外，测量miR-192和/或miR-215的水平提供了关于肿瘤或受试者是否将对化学治疗剂作出反应的信息。因此，本发明涉及与miR-192和miR-215的表达的鉴定，表征和调节相关的组合物和方法。

3. 发明申请

US20120087992A1 miRNAS AS THERAPEUTIC TARGETS IN CANCER 审中-公开
标题翻译： miRNA作为癌症中的治疗目标
公开(公告)号：US20120087992A1
公开(公告)日：2012-04-12
申请号：US13257836
申请日：2010-03-22
申请人： Jingfang Ju , Yuan Wang , Bo Song
发明人： Jingfang Ju , Yuan Wang , Bo Song
IPC分类号： A61K31/7088 , A61K33/24 , A61N5/00 , C07H21/02 , C12Q1/68 , C12N5/00 , A61K31/704
CPC分类号： C12Q1/6886 , A61K31/7088 , A61K45/06 , C12Q1/6809 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178 , A61K2300/00 , C12Q2525/207
摘要： Methods for modulating expression of a component of a cell, comprising contacting the cell with a nucleic acid comprising an miR-140 nucleic acid sequence in an amount sufficient to modulate the cellular component are provided. Overexpression of miR-140 inhibits cell proliferation in both U-2 OS (wt-p53) and HCT 116 (wt-p53) cell lines. Cells transfected with miR-140 are more resistant to chemotherapeutic agent methotrexate, mi-140 expression is related to HDAC4 protein expression. The claimed methods reduce the protein expression level of HDAC4 without degrading the target mRNA.
摘要翻译：提供了调节细胞成分表达的方法，包括使细胞与含有足以调节细胞成分的量的miR-140核酸序列的核酸接触。 miR-140的过表达抑制U-2 OS（wt-p53）和HCT 116（wt-p53）细胞系中的细胞增殖。用miR-140转染的细胞对化学治疗剂甲氨蝶呤更具抗性，mi-140表达与HDAC4蛋白表达有关。所要求的方法降低HDAC4的蛋白质表达水平，而不降解靶mRNA。

4. 发明授权

US08551450B2 Targeting vector-phospholipid conjugates 有权
标题翻译：靶向载体 - 磷脂缀合物
公开(公告)号：US08551450B2
公开(公告)日：2013-10-08
申请号：US12782783
申请日：2010-05-19
申请人： Philippe Bussat , Samir Cherkaoui , Hong (Helen) Fan , Bernard Lamy , Palaniappa Nanjappan , Radhakrishna Pillai , Sibylle Pochon , Bo Song , Rolf E. Swenson
发明人： Philippe Bussat , Samir Cherkaoui , Hong (Helen) Fan , Bernard Lamy , Palaniappa Nanjappan , Radhakrishna Pillai , Sibylle Pochon , Bo Song , Rolf E. Swenson
IPC分类号： A61K49/00 , A61B8/00
CPC分类号： A61K49/223 , A61K38/00 , A61K47/544 , A61K47/60 , A61K47/62 , A61K49/227 , C07K7/08 , C07K14/001 , C07K14/52 , C07K14/71 , C07K2319/00 , Y02A50/58
摘要： Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.
摘要翻译：提供具有高KDR结合亲和力的肽载体和用于制备此类载体的方法。肽载体可以与磷脂结合并包含在超声造影剂组合物中。这样的超声造影剂在治疗和诊断方法中是特别有用的，例如在成像含KDR组织和评估和治疗与肿瘤病症相关的血管发生过程中。本发明还提供大规模生产高纯度二聚体和单体肽磷脂共轭物以及用于形成缀合物的前体材料的方法。本发明还提供了大规模生产含有非常低水平的TFA的高纯度肽磷脂缀合物的方法。

5. 发明授权

US08466107B2 Fibrin-binding peptides and conjugates thereof 有权
标题翻译：纤维蛋白结合肽及其缀合物
公开(公告)号：US08466107B2
公开(公告)日：2013-06-18
申请号：US13598811
申请日：2012-08-30
申请人： Philippe Bussat , Bernard Lamy , Edmund R. Marinelli , Sibylle Pochon , Bo Song , Rolf E. Swenson
发明人： Philippe Bussat , Bernard Lamy , Edmund R. Marinelli , Sibylle Pochon , Bo Song , Rolf E. Swenson
IPC分类号： A61K38/36
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： Fibrin-binding peptides having high binding affinity and excellent physical characteristics compared to previously known fibrin-binding peptides are provided. These fibrin-binding peptides may be conjugated to a detectable label or a therapeutic agent and used to detect and facilitate treatment of pathological conditions associated with the presence of fibrin such as thrombic, angiogenic and neoplastic conditions. These peptides may be used in imaging processes such as MRI, ultrasound and nuclear medicine imaging (e.g. PET, scintigraphic imaging, etc.). The peptides may also be used therapeutically. The present invention also provides processes and methods for making and using such peptides and conjugates thereof.
摘要翻译：提供了与先前已知的纤维蛋白结合肽相比具有高结合亲和力和优异物理特性的纤维蛋白结合肽。这些纤维蛋白结合肽可以缀合到可检测标记或治疗剂，并用于检测和促进治疗与血纤维蛋白如血栓形成和血管生成和肿瘤状况有关的病理状况。这些肽可以用于诸如MRI，超声和核医学成像（例如PET，闪烁照相成像等）的成像过程中。肽也可以在治疗上使用。本发明还提供了制备和使用这些肽及其缀合物的方法和方法。

6. 发明申请

US20120328512A1 Fibrin-Binding Peptides and Conjugates Thereof 有权
标题翻译：纤维蛋白结合肽及其缀合物
公开(公告)号：US20120328512A1
公开(公告)日：2012-12-27
申请号：US13598811
申请日：2012-08-30
申请人： Philippe Bussat , Bernard Lamy , Edmund R. Marinelli , Sibylle Pochon , Bo Song , Rolf E. Swenson
发明人： Philippe Bussat , Bernard Lamy , Edmund R. Marinelli , Sibylle Pochon , Bo Song , Rolf E. Swenson
IPC分类号： A61K38/10 , C07K14/00 , A61K38/17 , A61P35/04 , A61K51/08 , A61P35/00 , A61P7/02 , A61P29/00 , C07K7/08 , A61K49/00
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： Fibrin-binding peptides having high binding affinity and excellent physical characteristics compared to previously known fibrin-binding peptides are provided. These fibrin-binding peptides may be conjugated to a detectable label or a therapeutic agent and used to detect and facilitate treatment of pathological conditions associated with the presence of fibrin such as thrombic, angiogenic and neoplastic conditions. These peptides may be used in imaging processes such as MRI, ultrasound and nuclear medicine imaging (e.g. PET, scintigraphic imaging, etc.). The peptides may also be used therapeutically. The present invention also provides processes and methods for making and using such peptides and conjugates thereof.
摘要翻译：提供了与先前已知的纤维蛋白结合肽相比具有高结合亲和力和优异物理特性的纤维蛋白结合肽。这些纤维蛋白结合肽可以缀合到可检测标记或治疗剂，并用于检测和促进治疗与血纤维蛋白如血栓形成和血管生成和肿瘤状况有关的病理状况。这些肽可以用于诸如MRI，超声和核医学成像（例如PET，闪烁照相成像等）的成像过程中。肽也可以在治疗上使用。本发明还提供了制备和使用这些肽及其缀合物的方法和方法。

7. 发明授权

US07794693B2 Targeting vector-phospholipid conjugates 有权
标题翻译：靶向载体 - 磷脂缀合物
公开(公告)号：US07794693B2
公开(公告)日：2010-09-14
申请号：US11608395
申请日：2006-12-08
申请人： Philippe Bussat , Samir Cherkaoui , Hong (Helen) Fan , Bernard Lamy , Palaniappa Nanjappan , Radhakrishna Pillai , Sibylle Pochon , Bo Song , Rolf E. Swenson
发明人： Philippe Bussat , Samir Cherkaoui , Hong (Helen) Fan , Bernard Lamy , Palaniappa Nanjappan , Radhakrishna Pillai , Sibylle Pochon , Bo Song , Rolf E. Swenson
IPC分类号： A61K49/00 , A61B8/00
CPC分类号： A61K49/223 , A61K38/00 , A61K47/544 , A61K47/60 , A61K47/62 , A61K49/227 , C07K7/08 , C07K14/001 , C07K14/52 , C07K14/71 , C07K2319/00 , Y02A50/58
摘要： Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.
摘要翻译：提供具有高KDR结合亲和力的肽载体和用于制备此类载体的方法。肽载体可以与磷脂结合并包含在超声造影剂组合物中。这样的超声造影剂在治疗和诊断方法中是特别有用的，例如在成像含KDR组织和评估和治疗与肿瘤病症相关的血管生成过程中。本发明还提供大规模生产高纯度二聚体和单体肽磷脂共轭物以及用于形成缀合物的前体材料的方法。本发明还提供了大规模生产含有非常低水平的TFA的高纯度肽磷脂缀合物的方法。

9. 发明申请

US20050250700A1 KDR and VEGF/KDR binding peptides 审中-公开
标题翻译： KDR和VEGF / KDR结合肽
公开(公告)号：US20050250700A1
公开(公告)日：2005-11-10
申请号：US10939890
申请日：2004-09-13
申请人： Aaron Sato , Daniel Sexton , Daniel Dransfield , Robert Ladner , Christophe Arbogast , Phillipe Bussat , Hong Fan , Sudha Khurana , Karen Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian Nunn , Radhakrishna Pillai , Sibylle Pochon , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf Swenson , Mathew Von Wronski
发明人： Aaron Sato , Daniel Sexton , Daniel Dransfield , Robert Ladner , Christophe Arbogast , Phillipe Bussat , Hong Fan , Sudha Khurana , Karen Linder , Edmund Marinelli , Palaniappa Nanjappan , Adrian Nunn , Radhakrishna Pillai , Sibylle Pochon , Kondareddiar Ramalingam , Ajay Shrivastava , Bo Song , Rolf Swenson , Mathew Von Wronski
IPC分类号： A61K38/00 , A61K38/10 , C07K7/06 , C07K7/08 , C07K14/00 , G01N33/574 , G01N33/68
CPC分类号： C07K7/08 , A61K38/00 , C07K7/06 , C07K14/001 , G01N33/574 , G01N33/6872 , G01N2333/515 , G01N2500/00 , Y02A50/411 , Y02A50/58
摘要： The present invention provides, inter alia, peptides, 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：本发明尤其提供了包含至少一个KDR或VEGF / KDR复合物结合部分的肽，肽二聚体和多聚体复合物，其在治疗，检测，分离或定位血管发生的任何地方都具有多种用途。特别公开的是能够以高亲和力结合KDR或VEGF / KDR复合物的合成的分离的多肽（例如，具有K SUB D <1μM），以及包含这些多肽的二聚体和多聚体构建体。

10. 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。

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