公开(公告)号：WO2019116349A1

公开(公告)日：2019-06-20

申请号：PCT/IB2018/060138

申请日：2018-12-14

Applicant: CASEBIA THERAPEUTICS LLP

Inventor： TAKEUCHI, Ryo ,  NOMA, Akiko ,  HE, Shuying ,  SCARIA, Abraham

IPC: C12N15/90 ,  C12N9/22 ,  C12N15/113

CPC classification number: C12N15/907 ,  A61K48/005 ,  C12N9/22 ,  C12N9/88 ,  C12N15/1137 ,  C12N15/86 ,  C12N2310/20 ,  C12N2750/14143 ,  C12Y406/01002

Abstract: The present application provides materials and methods for treating a patient with autosomal dominant CORD, both ex vivo and in vivo ; materials and methods for editing a GUCY2D gene in a human cell; and materials and methods for editing a R838H, R838C, or R838S mutation in a GUCY2D gene in a human cell. The present application also provides one or more gRNAs or sgRNAs for editing a GUCY2D gene; one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene. The present application provides a therapeutic for treating a patient with autosomal dominant CORD. The present application also provides a kit for treating a patient with autosomal dominant CORD. In addition, the present application provides a self-inactivating CRISPR-Cas system.

公开(公告)号：WO2011133933A3

公开(公告)日：2012-01-05

申请号：PCT/US2011033669

申请日：2011-04-22

Applicant: UNIV FLORIDA ,  BOYE SHANNON ELIZABETH ,  HAUSWIRTH WILLIAM W ,  BOYE SANFORD LEON

Inventor： BOYE SHANNON ELIZABETH ,  HAUSWIRTH WILLIAM W ,  BOYE SANFORD LEON

IPC: C12N9/88 ,  C12N15/864

CPC classification number: C12N15/861 ,  A61K38/00 ,  A61K48/005 ,  C12N9/88 ,  C12N15/86 ,  C12N2750/14143 ,  C12N2830/008 ,  C12N2830/85 ,  C12Y406/01002

Abstract: Disclosed are viral vector compositions comprising polynucleotide sequences that express one or more biologically-active mammalian guanylate cyclase proteins. Also disclosed are methods for their use in preventing, treating, and/or ameliorating at least one or more symptoms of a disease, disorder, abnormal condition, or dysfunction resulting at least in part from a guanylate cyclase deficiency in vivo. In particular embodiments, the use of recombinant adeno-associated viral (rAAV) vectors to treat or ameliorate symptoms of Leber's congenital amaurosis, as well as other conditions caused by an absence or reduction in the expression of a functional retinal-specific guanylate cyclase 1 (retGC1).

Abstract translation: 公开了包含表达一种或多种生物活性哺乳动物鸟苷酸环化酶蛋白的多核苷酸序列的病毒载体组合物。 还公开了它们用于预防，治疗和/或改善至少部分由体内鸟苷酸环化酶缺陷导致的疾病，病症，异常状况或功能障碍的症状的方法。 在具体实施方案中，使用重组腺相关病毒（rAAV）载体来治疗或改善Leber先天性黑斑症的症状，以及由功能性视网膜特异性鸟苷酸环化酶1的表达的不存在或减少引起的其它病症（ retGC1）。

公开(公告)号：WO2015025217A3

公开(公告)日：2015-11-19

申请号：PCT/IB2014002029

申请日：2014-06-11

Applicant: PORTAGE PHARMACEUTICALS LTD ,  LITTMAN BRUCE H ,  THOMPSON JOHN F ,  MARCOUX FRANK W

Inventor： LITTMAN BRUCE H ,  THOMPSON JOHN F ,  MARCOUX FRANK W

IPC: A61K47/48

CPC classification number: A61K47/48246 ,  A61K38/1709 ,  A61K38/45 ,  A61K38/465 ,  A61K38/47 ,  A61K38/482 ,  A61K38/51 ,  A61K39/05 ,  A61K47/645 ,  C07K14/4702 ,  C07K2319/01 ,  C07K2319/10 ,  C12N9/12 ,  C12N9/16 ,  C12N9/2402 ,  C12N9/6424 ,  C12N9/88 ,  C12N15/1137 ,  C12N2310/3513 ,  C12Y207/1101 ,  C12Y301/06013 ,  C12Y302/01045 ,  C12Y302/01076 ,  C12Y304/21093 ,  C12Y406/01002

Abstract: Embodiments disclosed herein provide compositions for conjugates, including fusion proteins, and methods of using them to treat a variety of conditions. In some embodiments, the conjugates and/or fusion proteins incorporate a 60-amino acid human homeodomain (e.g., peptides derived from human HOX genes), to translocate functional and regulatory peptides and proteins or other biologically active molecules such as nucleic acids, which are not naturally associated with the human homeodomain, across cell and nuclear membranes to intended sites of action without provoking an unwanted immune response that may reduce exposure to the conjugate and/or result in a clinical adverse event. In further embodiments, disclosed conjugates and fusion proteins can pass through the blood-brain barrier to allow entry into the CNS. In various embodiments, the disclosed compositions are suitable for delivery into a cell (i) the expression product of a gene of interest and/or (ii) novel peptides or polynucleotides to regulate gene function.

Abstract translation: 本文公开的实施方案提供了用于缀合物的组合物，包括融合蛋白，以及使用它们治疗多种病症的方法。 在一些实施方案中，缀合物和/或融合蛋白掺入60个氨基酸的人同源结构域（例如，源自人HOX基因的肽），以易位功能和调节肽和蛋白质或其他生物活性分子如核酸， 不与人类同源结构域天然相关，穿过细胞膜和核膜到达预期的作用位置，而没有引起可能减少暴露于缀合物和/或导致临床不良事件的不需要的免疫应答。 在进一步的实施方案中，公开的缀合物和融合蛋白可以通过血脑屏障以允许进入CNS。 在各种实施方案中，所公开的组合物适合递送到细胞中（i）目的基因的表达产物和/或（ii）用于调节基因功能的新型肽或多核苷酸。

公开(公告)号：WO2015025217A2

公开(公告)日：2015-02-26

申请号：PCT/IB2014002029

申请日：2014-06-11

Applicant: PORTAGE PHARMACEUTICALS LTD ,  LITTMAN BRUCE H ,  THOMPSON JOHN F ,  MARCOUX FRANK W

Inventor： LITTMAN BRUCE H ,  THOMPSON JOHN F ,  MARCOUX FRANK W

IPC: A61K47/48

CPC classification number: A61K47/48246 ,  A61K38/1709 ,  A61K38/45 ,  A61K38/465 ,  A61K38/47 ,  A61K38/482 ,  A61K38/51 ,  A61K39/05 ,  A61K47/645 ,  C07K14/4702 ,  C07K2319/01 ,  C07K2319/10 ,  C12N9/12 ,  C12N9/16 ,  C12N9/2402 ,  C12N9/6424 ,  C12N9/88 ,  C12N15/1137 ,  C12N2310/3513 ,  C12Y207/1101 ,  C12Y301/06013 ,  C12Y302/01045 ,  C12Y302/01076 ,  C12Y304/21093 ,  C12Y406/01002

Abstract: Embodiments disclosed herein provide compositions for conjugates, including fusion proteins, and methods of using them to treat a variety of conditions. In some embodiments, the conjugates and/or fusion proteins incorporate a 60-amino acid human homeodomain (e.g., peptides derived from human HOX genes), to translocate functional and regulatory peptides and proteins or other biologically active molecules such as nucleic acids, which are not naturally associated with the human homeodomain, across cell and nuclear membranes to intended sites of action without provoking an unwanted immune response that may reduce exposure to the conjugate and/or result in a clinical adverse event. In further embodiments, disclosed conjugates and fusion proteins can pass through the blood-brain barrier to allow entry into the CNS. In various embodiments, the disclosed compositions are suitable for delivery into a cell (i) the expression product of a gene of interest and/or (ii) novel peptides or polynucleotides to regulate gene function.

Abstract translation: 本文公开的实施方案提供了用于缀合物的组合物，包括融合蛋白，以及使用它们来治疗各种病症的方法。 在一些实施方案中，缀合物和/或融合蛋白掺入60个氨基酸的人同源结构域（例如衍生自人HOX基因的肽），以移位功能和调节肽和蛋白质或其他生物活性分子，例如核酸，其为 不是天然地与人类同源结构域相关联，跨细胞和核膜到预期的作用位点，而不引发可能减少暴露于缀合物和/或导致临床不良事件的不需要的免疫应答。 在另外的实施方案中，所公开的缀合物和融合蛋白可以通过血脑屏障以允许进入CNS。 在各种实施方案中，所公开的组合物适于递送至细胞（i）感兴趣的基因的表达产物和/或（ii）新的肽或多核苷酸以调节基因功能。

公开(公告)号：WO2013079721A1

公开(公告)日：2013-06-06

申请号：PCT/EP2012/074247

申请日：2012-12-03

Applicant: BERGEN TEKNOLOGIOVERFØRING AS

Inventor： KNAPPSKOG, Per ,  FISKERSTRAND, Torunn

IPC: C07K14/435

CPC classification number: C12Y406/01002 ,  C12N9/88 ,  C12Q1/6883 ,  C12Q2600/156

Abstract: The present invention relates in a first aspect to new nucleic acid molecules and peptides identifying and diagnosing diarrhea syndrome including chronic diarrhea and bowel diseases. In addition, methods are provided for identifying or diagnosing a potential risk for developing or having a diarrhea syndrome comprising identifying in a sample from a subject the presence or absence of a mutation at position 2519 of the gene encoding GC-C. Moreover, a kit is provided allowing identification or diagnosing a diarrhea syndrome including probes allowing the detection of mutations at position 2519 of the nucleic acid sequence encoding GC-C or for detecting a mutation at position 840 of GC-C. Moreover, a method for screening and/or identifying candidate molecules useful in prophylactically or therapeutically treating said diseases is provided. Finally, the present invention relates to metformin and/or a pharmaceutically acceptable salts thereof for use in the prophylactic or therapeutic treatment of diarrhea syndrome.

Abstract translation: 本发明在第一方面涉及鉴定和诊断包括慢性腹泻和肠病的腹泻综合征的新的核酸分子和肽。 此外，提供了用于鉴定或诊断发展或具有腹泻综合征的潜在风险的方法，其包括在受试者的样品中识别编码GC-C的基因的位置2519处的突变的存在或不存在。 此外，提供了一种试剂盒，其允许鉴定或诊断腹泻综合征，包括允许检测编码GC-C的核酸序列的位置2519处的突变或用于检测GC-C位置840的突变的探针。 此外，提供了用于筛选和/或鉴定可用于预防或治疗所述疾病的候选分子的方法。 最后，本发明涉及用于预防或治疗腹泻综合征的二甲双胍和/或其药学上可接受的盐。

公开(公告)号：WO2011133933A2

公开(公告)日：2011-10-27

申请号：PCT/US2011/033669

申请日：2011-04-22

Applicant: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC. ,  BOYE, Shannon Elizabeth ,  HAUSWIRTH, William W. ,  BOYE, Sanford Leon

Inventor： BOYE, Shannon Elizabeth ,  HAUSWIRTH, William W. ,  BOYE, Sanford Leon

IPC: C12N7/00

CPC classification number: C12N15/861 ,  A61K38/00 ,  A61K48/005 ,  C12N9/88 ,  C12N15/86 ,  C12N2750/14143 ,  C12N2830/008 ,  C12N2830/85 ,  C12Y406/01002

Abstract: Disclosed are viral vector compositions comprising polynucleotide sequences that express one or more biologically-active mammalian guanylate cyclase proteins. Also disclosed are methods for their use in preventing, treating, and/or ameliorating at least one or more symptoms of a disease, disorder, abnormal condition, or dysfunction resulting at least in part from a guanylate cyclase deficiency in vivo. In particular embodiments, the use of recombinant adeno-associated viral (rAAV) vectors to treat or ameliorate symptoms of Leber's congenital amaurosis, as well as other conditions caused by an absence or reduction in the expression of a functional retinal-specific guanylate cyclase 1 (retGC1).

Abstract translation: 公开了包含表达一种或多种生物活性哺乳动物鸟苷酸环化酶蛋白的多核苷酸序列的病毒载体组合物。 还公开了它们用于预防，治疗和/或改善至少部分由体内鸟苷酸环化酶缺陷导致的疾病，病症，异常状况或功能障碍的症状的方法。 在具体实施方案中，使用重组腺相关病毒（rAAV）载体来治疗或改善Leber先天性黑斑症的症状，以及由功能性视网膜特异性鸟苷酸环化酶1的表达的不存在或减少引起的其它病症（ retGC1）。

公开(公告)号：WO2014197720A2

公开(公告)日：2014-12-11

申请号：PCT/US2014/041143

申请日：2014-06-05

Applicant: SYNERGY PHARMACEUTICALS, INC.

Inventor： SHAILUBHAI, Kunwar ,  COMISKEY, Stephen ,  FENG, Rong ,  BAI, Juncai ,  ZHANG, Ruoping ,  JIA, Jun ,  ZHOU, Junfeng ,  ZHAO, Qiao ,  ZHANG, Guoqing

IPC: C07K14/81

CPC classification number: C07K7/08 ,  B01D15/424 ,  C07K1/14 ,  C12N9/88 ,  C12Y406/01002

Abstract: The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

Abstract translation: 本发明提供了纯化包括选自本文所述的SEQ ID NO：1-251的GCC激动剂序列的肽的方法。 该方法包括在冷冻干燥（冻干）步骤之前的溶剂交换步骤。

公开(公告)号：WO2012037380A2

公开(公告)日：2012-03-22

申请号：PCT/US2011/051805

申请日：2011-09-15

Applicant: SYNERGY PHARMACEUTICALS INC. ,  COMISKEY, Stephen ,  FENG, Rong ,  FOSS, John ,  SHAILUBHAI, Kunwar

Inventor： COMISKEY, Stephen ,  FENG, Rong ,  FOSS, John ,  SHAILUBHAI, Kunwar

IPC: A61K38/16 ,  A61K38/10 ,  A61K9/16 ,  A61K9/20 ,  A61K9/48 ,  A61K47/48 ,  A61P35/00 ,  A61P3/00

CPC classification number: A61K38/10 ,  A61K9/0053 ,  A61K9/1623 ,  A61K9/1652 ,  A61K9/1676 ,  A61K9/2054 ,  A61K9/4858 ,  A61K9/4866 ,  A61K31/192 ,  A61K31/501 ,  A61K31/519 ,  A61K31/53 ,  A61K31/765 ,  A61K31/78 ,  A61K38/12 ,  A61K45/06 ,  A61K47/12 ,  A61K47/38 ,  C07K7/08 ,  C07K7/54 ,  C07K7/64 ,  C12Y406/01002 ,  A61K2300/00

Abstract: The invention provides low-dose formulations of guanylate cyclase-C ("GCC") agonist peptides and methods for their use. The formulations of the invention can be administered either alone or in combination with one or more additional therapeutic agents, preferably an inhibitor of cGMP-dependent phosphodiesterase or a laxative.

Abstract translation: 本发明提供了鸟苷酸环化酶-C（“GCC”）激动剂肽的低剂量制剂及其使用方法。 本发明的制剂可以单独施用或与一种或多种另外的治疗剂，优选cGMP依赖性磷酸二酯酶抑制剂或泻药一起施用。

公开(公告)号：WO2005113587A3

公开(公告)日：2006-05-18

申请号：PCT/EP2005005410

申请日：2005-05-18

Applicant: GANYMED PHARMACEUTICALS AG ,  TUERECI OEZLEM ,  SAHIN UGUR ,  KOSLOWSKI MICHAEL

Inventor： TUERECI OEZLEM ,  SAHIN UGUR ,  KOSLOWSKI MICHAEL

IPC: C07K14/47 ,  A61K39/395 ,  A61P35/00 ,  C07K14/705 ,  C07K16/30 ,  C12N9/88 ,  G01N33/574

CPC classification number: A61K6/00 ,  A61K47/486 ,  A61K47/48615 ,  A61K47/6851 ,  A61K49/00 ,  A61K2039/505 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C07K16/28 ,  C07K16/30 ,  C07K16/303 ,  C07K16/3046 ,  C07K16/3076 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/75 ,  C12N9/88 ,  C12Y406/01002 ,  G01N33/57496

Abstract: According to the invention, gene products expressed in a tumor-associated manner and the nucleic acids coding therefor were identified. The invention relates to the therapy and diagnosis of diseases wherein said gene products expressed in a tumor-associated manner are aberrantly expressed. The invention also relates to proteins, polypeptides and peptides which are expressed in a tumor associated manner and to nucleic acids coding therefor.

Abstract translation: 根据本发明，肿瘤相关基因产物表达，并识别编码它们的核酸。 本发明涉及一种其中这些肿瘤相关的基因产物被表达异常表达的疾病的治疗和诊断。 此外，本发明涉及表达肿瘤相关和核酸编码它们的蛋白质，多肽和肽。

公开(公告)号：WO2005113587A2

公开(公告)日：2005-12-01

申请号：PCT/EP2005/005410

申请日：2005-05-18

Applicant: GANYMED PHARMACEUTICALS AG ,  TÜRECI, Özlem ,  SAHIN, Ugur ,  KOSLOWSKI, Michael

Inventor： TÜRECI, Özlem ,  SAHIN, Ugur ,  KOSLOWSKI, Michael

IPC: C07K14/47

CPC classification number: A61K6/00 ,  A61K47/6851 ,  A61K49/00 ,  A61K2039/505 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C07K16/28 ,  C07K16/30 ,  C07K16/303 ,  C07K16/3046 ,  C07K16/3076 ,  C07K16/44 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/75 ,  C12N9/88 ,  C12Y406/01002 ,  G01N33/57496

Abstract: Erfindungsgemäss wurden Tumor-assoziiert exprimierte Genprodukte und die dafür kodierenden Nukleinsäuren identifiziert. Die vorliegende Erfindung betrifft die Therapie und Diagnose von Erkrankungen, bei denen diese Tumor-assoziiert exprimierten Genprodukte aberrant exprimiert werden. Des weiteren betrifft die Erfindung Proteine, Polypeptide und Peptide, die Tumor-assoziiert exprimiert werden und die dafür kodierenden Nukleinsäuren.

Abstract translation: 根据本发明，肿瘤相关基因产物表达，并识别编码它们的核酸。 本发明涉及一种其中这些肿瘤相关的基因产物被表达异常表达的疾病的治疗和诊断。 此外，本发明涉及表达肿瘤相关和核酸编码它们的蛋白质，多肽和肽。