公开(公告)号：US08961995B2

公开(公告)日：2015-02-24

申请号：US13789215

申请日：2013-03-07

申请人： UAB Research Foundation

发明人： Ilya Frolov ,  Elena Frolova

IPC分类号： C07K14/18 ,  C12N15/86 ,  C12N7/01 ,  C12N15/40 ,  A61K35/76 ,  A61K39/00 ,  C12N7/00 ,  A61K39/12

CPC分类号： C12N15/86 ,  A61K39/12 ,  C12N2770/00 ,  C12N2770/36011 ,  C12N2770/36111 ,  C12N2770/36132 ,  C12N2770/36134 ,  C12N2770/36151

摘要： The present invention provides alphavirus replicons and methods of their use in producing heterologous protein.

摘要翻译： 本发明提供甲病毒复制子及其用于产生异源蛋白质的方法。

公开(公告)号：US08105578B2

公开(公告)日：2012-01-31

申请号：US11698947

申请日：2007-01-29

申请人： Michael S. Roberts ,  Robert M. Lorence ,  William S. Groene ,  Harvey Rabin ,  Reid W. von Borstel

发明人： Michael S. Roberts ,  Robert M. Lorence ,  William S. Groene ,  Harvey Rabin ,  Reid W. von Borstel

IPC分类号： A01N63/00 ,  C12N7/00

CPC分类号： C12N7/00 ,  A61K35/768 ,  A61K38/21 ,  A61K39/42 ,  C12N2760/18132 ,  C12N2770/36132 ,  A61K2300/00

摘要： The subject invention relates to viruses that are able to replicate and thereby kill neoplastic cells with a deficiency in the IFN-mediated antiviral response, and their use in treating neoplastic disease including cancer and large tumors. RNA and DNA viruses are useful in this regard. The invention also relates to methods for the selection, design, purification and use of such viruses for cancer therapy.

摘要翻译： 本发明涉及能够复制并因此杀死IFN介导的抗病毒应答缺陷的肿瘤细胞的病毒，以及它们在治疗包括癌症和大肿瘤的肿瘤疾病中的用途。 RNA和DNA病毒在这方面是有用的。 本发明还涉及用于癌症治疗的这种病毒的选择，设计，纯化和使用的方法。

公开(公告)号：US20080300394A1

公开(公告)日：2008-12-04

申请号：US12123790

申请日：2008-05-20

申请人： Alicia Hurtado ,  Daniel Meruelo

发明人： Alicia Hurtado ,  Daniel Meruelo

IPC分类号： C07H21/00

CPC分类号： C12N7/00 ,  A01K2267/0331 ,  A61K35/76 ,  C07K14/005 ,  C12N15/86 ,  C12N2770/36122 ,  C12N2770/36132 ,  C12N2770/36143 ,  C12N2770/36161 ,  C12N2840/203

摘要： Disclosed herein are new defective Sindbis viral vectors made from wild type Ar-339 Sindbis virus, with differences in replicase and envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are plasmids used for the production of the vectors, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.

摘要翻译： 本文公开了由野生型Ar-339辛德毕斯病毒制备的新的有缺陷的辛德比斯病毒载体，其在JT载体和共有的辛德比斯病毒序列之间以及JT和Ar-339载体之间具有复制酶和包膜蛋白的差异。 还公开了用于生产载体的质粒，用于生产载体的方法，用于治疗患有肿瘤的哺乳动物的方法和用于治疗方法的药物制剂。

公开(公告)号：US07303898B2

公开(公告)日：2007-12-04

申请号：US11392926

申请日：2006-03-28

申请人： Alicia Hurtado ,  Daniel Meruelo

发明人： Alicia Hurtado ,  Daniel Meruelo

IPC分类号： C12N15/64 ,  C12N15/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12N7/00 ,  A01K2267/0331 ,  A61K35/76 ,  C07K14/005 ,  C12N15/86 ,  C12N2770/36122 ,  C12N2770/36132 ,  C12N2770/36143 ,  C12N2770/36161 ,  C12N2840/203

摘要： Disclosed herein are new defective Sindbis viral vectors made from wild type Ar-339 Sindbis virus, with differences in replicase and envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are plasmids used for the production of the vectors, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.

公开(公告)号：US20160115458A1

公开(公告)日：2016-04-28

申请号：US14882216

申请日：2015-10-13

申请人： New York University

发明人： Daniel Meruelo ,  Jen-Chieh Tseng

IPC分类号： C12N7/00 ,  A61K38/45 ,  C12N15/86 ,  A61K48/00

CPC分类号： C12N7/00 ,  A61K35/768 ,  A61K38/00 ,  A61K38/45 ,  A61K48/0058 ,  A61K51/0491 ,  C12N9/1211 ,  C12N9/78 ,  C12N15/86 ,  C12N2770/36132 ,  C12N2770/36143 ,  C12N2770/36145 ,  C12N2770/36171 ,  C12N2830/007 ,  C12Y207/01021 ,  G01N33/574 ,  G01N2800/52 ,  A61K2300/00

摘要： Disclosed herein are methods for treating a mammal harboring a solid tumor which expresses higher levels of High Affinity Laminin Receptors (LAMR) than normal cells of the same lineage comprising systematically administering to a mammal in need of such treatment a therapeutically effective amount of a Replication Competent (RC) Sindbis virus vector, wherein said vector encodes a suicide gene.

公开(公告)号：US20120282225A1

公开(公告)日：2012-11-08

申请号：US13500010

申请日：2010-09-13

申请人： Samir El-Andaloussi ,  Gregory Heller ,  Ulo Langel ,  Taavi Lehto ,  Andres Merits ,  Liane Ulper

发明人： Samir El-Andaloussi ,  Gregory Heller ,  Ulo Langel ,  Taavi Lehto ,  Andres Merits ,  Liane Ulper

IPC分类号： A61K35/76 ,  A61P35/00 ,  C12N15/113

CPC分类号： A61K35/761 ,  A61K35/768 ,  C12N7/00 ,  C12N15/11 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/11 ,  C12N2320/33 ,  C12N2710/10332 ,  C12N2710/10343 ,  C12N2710/10361 ,  C12N2770/36132 ,  C12N2770/36143 ,  C12N2770/36161 ,  C12N2840/44

摘要： Viral vectors are potential tools for eliminating the viability of eukaryotic cells in anti-cancer therapies since they can efficiently destroy the cancer cells and trigger an immune response against tumours. Typically viruses are not specific to cancer cells and all methods known in art aiming to the construction of cancer-specific viruses suffer from serious problems. The present invention presents a universal method to overcome these problems and is usable for any DNA virus replicating in nucleus or for any layered vector of RNA viruses. In this method the viral gene expression and/or replication will be blocked by the introduction of one or more aberrantly spliced introns into crucial gene expression units of the virus or vector. Lethal effect of these mutations is reverted in a controlled manner by the delivery of splice-switch oligonucleotide (s) correcting the introduced defects and restoring the biological functionality of the virus or vector, including cytolytic properties.

摘要翻译： 病毒载体是消除抗癌治疗中真核细胞活力的潜在工具，因为它们可以有效地破坏癌细胞并引发针对肿瘤的免疫应答。 通常，病毒对癌细胞不是特异性的，并且用于构建癌症特异性病毒的艺术中已知的所有方法都遭受严重问题。 本发明提出了克服这些问题的通用方法，并且可用于在核中或任何分层RNA病毒载体中复制的任何DNA病毒。 在该方法中，通过将一个或多个异常剪接的内含子引入病毒或载体的关键基因表达单元中，病毒基因表达和/或复制将被阻断。 通过递送剪接切换寡核苷酸来校正引入的缺陷并恢复病毒或载体的生物学功能，包括细胞溶解性质，这些突变的致死作用以受控的方式被还原。

公开(公告)号：US08282916B2

公开(公告)日：2012-10-09

申请号：US12390096

申请日：2009-02-20

申请人： Daniel Meruelo ,  Jen-Chieh Tseng

发明人： Daniel Meruelo ,  Jen-Chieh Tseng

IPC分类号： A01N63/00 ,  A61K48/00

CPC分类号： C12N7/00 ,  A61K35/768 ,  A61K38/00 ,  A61K38/45 ,  A61K48/0058 ,  A61K51/0491 ,  C12N9/1211 ,  C12N9/78 ,  C12N15/86 ,  C12N2770/36132 ,  C12N2770/36143 ,  C12N2770/36145 ,  C12N2770/36171 ,  C12N2830/007 ,  C12Y207/01021 ,  G01N33/574 ,  G01N2800/52 ,  A61K2300/00

摘要： Disclosed herein are methods for treating a mammal harboring a solid tumor which expresses higher levels of High Affinity Laminin Receptors (LAMR) than normal cells of the same lineage comprising systematically administering to a mammal in need of such treatment a therapeutically effective amount of a Replication Competent (RC) Sindbis virus vector, wherein said vector encodes a suicide gene.

摘要翻译： 本文公开了用于治疗携带实体肿瘤的哺乳动物的方法，所述哺乳动物表达比相同谱系的正常细胞更高水平的高亲和层粘连蛋白受体（LAMR），包括系统地向需要这种治疗的哺乳动物施用治疗有效量的复制主管 （RC）辛德毕斯病毒载体，其中所述载体编码自杀基因。

公开(公告)号：US20080260698A1

公开(公告)日：2008-10-23

申请号：US12148172

申请日：2008-04-17

申请人： Scott C. Weaver ,  Ilya Frolov

发明人： Scott C. Weaver ,  Ilya Frolov

IPC分类号： A61K39/12 ,  C07H21/04 ,  C12N1/00 ,  C12Q1/70 ,  A61P31/12 ,  C12N7/04 ,  A61K35/76

CPC分类号： C12N7/00 ,  A61K39/12 ,  A61K39/193 ,  A61K2039/5254 ,  A61K2039/70 ,  C12N2770/36121 ,  C12N2770/36132 ,  C12N2770/36134 ,  C12N2770/36143 ,  C12Q1/70

摘要： The present invention discloses a chimeric alphavirus comprising a Sindbis virus cDNA fragment, an Eastern equine encephalitis virus cDNA fragment, a Western equine encephalitis virus cDNA fragment or a combination thereof. The present also discloses the use of this chimeric alphavirus as vaccines and in serological and diagnostic assays.

摘要翻译： 本发明公开了包含辛德毕斯病毒cDNA片段，东方马脑炎病毒cDNA片段，西马脑炎病毒cDNA片段或其组合的嵌合甲病毒。 本发明还公开了该嵌合甲病毒属作为疫苗和血清学和诊断测定法的用途。

公开(公告)号：US12097257B2

公开(公告)日：2024-09-24

申请号：US16977290

申请日：2019-03-04

申请人： NEW YORK UNIVERSITY

发明人： Daniel Meruelo ,  Alicia Hurtado Martinez ,  Christine Pampeno ,  Iris Scherwitzl

IPC分类号： A61K39/39 ,  A61K39/00 ,  A61P35/00 ,  C07K14/47 ,  C07K14/705 ,  C12N7/00

CPC分类号： A61K39/39 ,  A61K39/0011 ,  A61P35/00 ,  C07K14/4748 ,  C07K14/70521 ,  C07K14/70575 ,  C07K14/70578 ,  C12N7/00 ,  A61K2039/5256 ,  C07K2319/055 ,  C07K2319/30 ,  C12N2770/36132 ,  C12N2770/36143

摘要： Provided are polynucleotides and viral vectors, particularly, Alphavirus vectors such as Sindbis viral vectors, which encode an immune checkpoint protein, or a ligand binding portion of the checkpoint protein, or an immune checkpoint protein or ligand binding portion thereof fused to one or more immunoglobulin (Ig) domains, e.g., an Ig hinge region and an Ig heavy chain constant domain. Methods of treating a mammalian subject having a cancer or tumor are provided, in which the viral vectors, e.g., a Sindbis virus vector, encoding the immune checkpoint protein, a ligand binding portion thereof, or a checkpoint protein fusion protein as described, are administered to the subject, resulting in an anti-cancer or anti-tumor immune response, significant reduction in tumor growth in the treated subject and increased survivability.

公开(公告)号：US20240024394A1

公开(公告)日：2024-01-25

申请号：US18334449

申请日：2023-06-14

申请人： Massachusetts Institute of Technology ,  Ohio State Innovation Foundation

发明人： Darrell J. Irvine ,  Karl Dane Wittrup ,  Ron Weiss ,  Yingzhong Li ,  Noor Momin ,  Yizhou Dong

IPC分类号： A61K35/768 ,  A61P35/00 ,  A61K9/00 ,  C07K14/54 ,  C12N7/00

CPC分类号： A61K35/768 ,  A61P35/00 ,  A61K9/0019 ,  C07K14/5434 ,  C12N7/00 ,  C12N2770/36132

摘要： The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.