公开(公告)号：US11866710B2

公开(公告)日：2024-01-09

申请号：US18150827

申请日：2023-01-06

申请人： Alnylam Pharmaceuticals, Inc.

发明人： Aimee M. Deaton ,  John Michael Gansner ,  James D. McIninch ,  Mark K. Schlegel ,  Benjamin P. Garfinkel

IPC分类号： C07H21/04 ,  C12N15/113 ,  A61K47/54

CPC分类号： C12N15/1137 ,  A61K47/549 ,  C12Y304/21109 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/351

摘要： The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Transmembrane protease, serine 6 (TMPRSS6) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a TMPRSS6 gene and to methods of preventing and treating a TMPRSS6-associated disorder, e.g., a disorder associated with iron overload and/or a disorder of ineffective erythropoiesis, e.g., hereditary hemochromatosis, β-thalassemia (e.g., β-thalassemia major and β-thalassemia intermedia), polycythemia vera, myelodysplastic syndrome, congenital dyserythropoietic anemias, pyruvate kinase deficiency, erythropoietic porphyria, Parkinson's Disease, Alzheimer's Disease or Friedreich's Ataxia.

公开(公告)号：US20230323419A1

公开(公告)日：2023-10-12

申请号：US17973773

申请日：2022-10-26

申请人： Novartis AG

发明人： Holger Laux ,  Sandrine Romand ,  Ursula Bodendorf

IPC分类号： C12P21/00 ,  C12N15/90 ,  C12N5/00 ,  C12N9/64 ,  G01N15/14

CPC分类号： C12P21/00 ,  C12N15/907 ,  C12N5/00 ,  C12N9/6424 ,  C12Y304/21109 ,  G01N15/14 ,  C12N2510/02 ,  G01N2015/0065

摘要： The present application pertains inter alia to an isolated vertebrate cell suitable for recombinant expression of a polypeptide of interest, wherein the vertebrate cell is altered to impair the function of the endogenous protease matriptase and wherein said cell comprises at least one heterologous polynucleotide encoding a polypeptide of interest and wherein the polypeptide of interest is secreted by the cell. It was found that using respective vertebrate cells for producing a recombinant polypeptide of interest significantly reduces clipping of the polypeptide of interest that is secreted into the cell culture medium. Also provided are improved production and screening methods.

公开(公告)号：US20180105817A1

公开(公告)日：2018-04-19

申请号：US15562843

申请日：2016-04-04

申请人： Ionis Pharmaceuticals, Inc.

发明人： Shuling Guo ,  Mariam Aghajan ,  Eric E. Swayze

IPC分类号： C12N15/113 ,  A61P7/00 ,  A61P7/06

CPC分类号： C12N15/1137 ,  A61K47/549 ,  A61P7/00 ,  A61P7/06 ,  C07H21/00 ,  C12N15/113 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/334 ,  C12N2310/341 ,  C12N2310/351 ,  C12N2310/3525 ,  C12N2310/3527 ,  C12Y304/21109

摘要： Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as polycythemia, hemochromatosis or β-thalassemia can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to TMPRSS6.

公开(公告)号：US09290757B2

公开(公告)日：2016-03-22

申请号：US13506845

申请日：2012-05-18

申请人： Edwin L. Madison

发明人： Edwin L. Madison

IPC分类号： C12N9/64 ,  A61K38/00 ,  C12Q1/37 ,  G01N33/68 ,  C12N15/10 ,  C12N9/50 ,  C12N9/72

CPC分类号： C12N15/1037 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/21 ,  C07K2319/23 ,  C07K2319/30 ,  C07K2319/41 ,  C07K2319/42 ,  C12N9/50 ,  C12N9/6408 ,  C12N9/6462 ,  C12Q1/37 ,  C12Y304/21073 ,  C12Y304/21109 ,  G01N33/6842

摘要： Methods for identifying modified proteases with modified substrate specificity or other properties are provided. The methods screen candidate and modified proteases by contacting them with a substrate, such as a serpin, an alpha macroglobulins or a p35 family protein or modified serpins and modified p35 family members or modified alpha macroglobulins, that, upon cleavage of the substrate, traps the protease by forming a stable complex. Also provided are modified proteases.

公开(公告)号：US20140242062A1

公开(公告)日：2014-08-28

申请号：US14275772

申请日：2014-05-12

申请人： Edwin L. Madison ,  Jack Nguyen ,  Sandra Waugh Ruggles ,  Christopher Thanos

发明人： Edwin L. Madison ,  Jack Nguyen ,  Sandra Waugh Ruggles ,  Christopher Thanos

IPC分类号： A61K38/48

CPC分类号： A61K38/482 ,  A61K38/49 ,  C07K2319/00 ,  C12N9/6421 ,  C12N9/6424 ,  C12N9/6467 ,  C12Y304/21109

摘要： Provided are methods for and compounds for modulating the complement system. In particular, compounds are provided that inhibit complement activation and compounds are provided that promote complement activation. The compounds are therapeutics by virtue of their effects on the complement system. Hence, the compounds that inhibit complement activation can be used for treatment of ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, inflammatory diseases and diseases with an inflammatory component, including Alzheimer's Disease and other neurodegenerative disorders.

摘要翻译： 提供了用于调节补体系统的方法和化合物。 特别地，提供抑制补体活化的化合物，并提供促进补体活化的化合物。 这些化合物由于其对补体系统的作用而成为治疗剂。 因此，抑制补体活化的化合物可用于治疗缺血和再灌注障碍，包括心肌梗死和中风，败血症，自身免疫性疾病，炎症性疾病和具有炎性成分的疾病，包括阿尔茨海默病和其他神经变性疾病。

公开(公告)号：US20110250204A1

公开(公告)日：2011-10-13

申请号：US12901254

申请日：2010-10-08

申请人： Steve RUBEN ,  Paul A. MOORE ,  Tao HE ,  Candy N. LEE ,  Karen VAN ORDEN ,  Charles E. Birse ,  Mehdi Mesri ,  Elizabeth G. Joseloff

发明人： Steve RUBEN ,  Paul A. MOORE ,  Tao HE ,  Candy N. LEE ,  Karen VAN ORDEN ,  Charles E. Birse ,  Mehdi Mesri ,  Elizabeth G. Joseloff

IPC分类号： A61K39/395 ,  C07H21/02 ,  C07K16/00 ,  C07K16/18 ,  A61P35/00 ,  C12N5/071 ,  G01N33/53 ,  C12Q1/02 ,  A61K31/7088 ,  G01N33/68 ,  C07H21/04 ,  C12N5/16

CPC分类号： C07K16/3076 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K14/70546 ,  C07K14/70596 ,  C07K16/18 ,  C07K16/2839 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/303 ,  C07K16/40 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/732 ,  C07K2317/734 ,  C12N9/18 ,  C12N9/6424 ,  C12N15/113 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2320/30 ,  C12Q1/6886 ,  C12Q2600/158 ,  C12Y301/01 ,  C12Y304/21 ,  C12Y304/21109 ,  G01N33/57488 ,  G01N33/57492

摘要： Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (CAT). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods.

摘要翻译： 提供用于评估，治疗和预防使用癌症相关靶（CAT）的疾病，特别是癌症的方法和组合物。 还提供了用于确定或预测这些疾病的治疗或使用CAT选择治疗的有效性的方法和组合物。 还提供了使用CAT调节细胞功能的方法和组合物。 还提供了调节CAT（例如拮抗剂或激动剂）如抗体，蛋白质，小分子化合物和核酸试剂（例如RNAi和反义试剂）的组合物及其药物组合物。 进一步提供了筛选调节CAT的试剂的方法，以及通过这些筛选方法鉴定的试剂。

公开(公告)号：US20100189652A1

公开(公告)日：2010-07-29

申请号：US12758521

申请日：2010-04-12

申请人： SARAH POLLOCK ,  ANAT COHEN-DAYAG ,  OSNAT SELLA-TAVOR ,  SHIRLEY SAMEAH-GREENWALD ,  SHIRA WALACH ,  LILY BAZAK

发明人： SARAH POLLOCK ,  ANAT COHEN-DAYAG ,  OSNAT SELLA-TAVOR ,  SHIRLEY SAMEAH-GREENWALD ,  SHIRA WALACH ,  LILY BAZAK

IPC分类号： A61K39/395 ,  C07K16/18 ,  A61P35/00 ,  A61K49/00 ,  C12N9/96 ,  G01N33/53 ,  G01N33/566

CPC分类号： C12Y304/21109 ,  C12N9/6424 ,  C12Q1/6886 ,  C12Q2600/106

摘要： Novel splice variants as diagnostic markers, preferably membrane-bound. The novel variants according to the present invention may optionally be used for diagnosis of Marker-detectable disease as described herein, optionally through immunohistochemistry.

摘要翻译： 新型剪接变体作为诊断标记，优选膜结合。 根据本发明的新型变体可任选地通过免疫组织化学方法用于本文所述的可标记可检测疾病的诊断。

公开(公告)号：US11845801B2

公开(公告)日：2023-12-19

申请号：US16900677

申请日：2020-06-12

申请人： ASKGENE PHARMA, INC.

发明人： Yuefeng Lu ,  Chunxiao Yu ,  Jian-Feng Lu

IPC分类号： C07K16/00 ,  C07K16/28 ,  C07K14/81

CPC分类号： C07K16/2866 ,  C07K14/811 ,  C07K14/8146 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/55 ,  C07K2317/565 ,  C12Y304/21109 ,  C12Y304/24024 ,  C12Y304/24035

摘要： Provided herein are IL-15 cytokine prodrugs and methods of making and using thereof.

公开(公告)号：US11807882B2

公开(公告)日：2023-11-07

申请号：US17371980

申请日：2021-07-09

申请人： VERTEX PHARMACEUTICALS INCORPORATED

发明人： Edwin L. Madison ,  Vanessa Soros ,  Mikhail Popkov

IPC分类号： C12N9/64 ,  A61K31/397 ,  A61K45/06 ,  C07K14/435 ,  A61K38/00

CPC分类号： C12N9/6424 ,  A61K31/397 ,  A61K45/06 ,  C07K14/435 ,  C12Y304/21109 ,  A61K38/00 ,  A61K31/397

摘要： Provided are MTSP-1 polypeptides modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to inhibit its activity and thereby inhibit complement activation. The modified MTSP-1 polypeptides that inhibit complement activation can be used for treatment of diseases and conditions in which complement activation plays a role. Such diseases and conditions include inflammatory diseases and diseases with an inflammatory component. Exemplary of these disorders are ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, ophthalmic disorders, such as diabetic retinopathies and macular degeneration, including age-related macular degeneration (AMD), and transplanted organ rejection, such as renal delayed graft function (DGF).

公开(公告)号：US08486392B2

公开(公告)日：2013-07-16

申请号：US12901254

申请日：2010-10-08

申请人： Steve Ruben ,  Paul Moore ,  Tao He ,  Candy N. Lee ,  Karen Van Orden

发明人： Steve Ruben ,  Paul Moore ,  Tao He ,  Candy N. Lee ,  Karen Van Orden

IPC分类号： A61K39/395

CPC分类号： C07K16/3076 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/4748 ,  C07K14/705 ,  C07K14/70546 ,  C07K14/70596 ,  C07K16/18 ,  C07K16/2839 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/303 ,  C07K16/40 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/732 ,  C07K2317/734 ,  C12N9/18 ,  C12N9/6424 ,  C12N15/113 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2320/30 ,  C12Q1/6886 ,  C12Q2600/158 ,  C12Y301/01 ,  C12Y304/21 ,  C12Y304/21109 ,  G01N33/57488 ,  G01N33/57492

摘要： Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (CAT). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods.

摘要翻译： 提供用于评估，治疗和预防使用癌症相关靶（CAT）的疾病，特别是癌症的方法和组合物。 还提供了用于确定或预测这些疾病的治疗或使用CAT选择治疗的有效性的方法和组合物。 还提供了使用CAT调节细胞功能的方法和组合物。 还提供了调节CAT（例如拮抗剂或激动剂）如抗体，蛋白质，小分子化合物和核酸试剂（例如RNAi和反义试剂）的组合物及其药物组合物。 进一步提供了筛选调节CAT的试剂的方法，以及通过这些筛选方法鉴定的试剂。