公开(公告)号：US20170114341A1

公开(公告)日：2017-04-27

申请号：US15315608

申请日：2015-06-08

申请人： Curt W. BRADSHAW ,  Sukumar SAKAMURI ,  Laxman ELTEPU ,  Son LAM ,  Dingguo LIU ,  Bryan MEADE ,  Giuseppe Dello IACONO ,  Joseph STOCK ,  Bin LIU ,  Solstice Biologics, Ltd.

发明人： Curt W. BRADSHAW ,  Sukumar SAKAMURI ,  Laxman ELTEPU ,  Son LAM ,  Dingguo LIU ,  Bryan MEADE ,  Giuseppe Dello IACONO ,  Joseph STOCK ,  Bin LIU

IPC分类号： C12N15/113 ,  C07H19/20 ,  C07H21/02 ,  C07H19/10 ,  C12N15/85 ,  C07H21/04

CPC分类号： C12N15/113 ,  C07H19/10 ,  C07H19/20 ,  C07H21/02 ,  C07H21/04 ,  C12N15/85 ,  C12N2310/14 ,  C12N2310/31 ,  C12N2310/32 ,  C12N2310/346 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2330/30

摘要： The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3′-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5′-terminal, a 3′-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5′-terminal, a 3′-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.

公开(公告)号：US20190194655A1

公开(公告)日：2019-06-27

申请号：US16060171

申请日：2016-12-08

申请人： Curt W. Bradshaw ,  Sukumar Sakamuri ,  Bryan R. Meade ,  Laxman Eltepu ,  Giuseppe Dello Iacono ,  Son Lam ,  Joseph Stock ,  Dingguo Liu ,  Bin Liu ,  Solstice Biologics, Ltd.

发明人： Curt W. BRADSHAW ,  Sukumar SAKAMURI ,  Bryan R. MEADE ,  Laxman ELTEPU ,  Giuseppe Dello IACONO ,  Son LAM ,  Joseph STOCK ,  Dingguo LIU ,  Bin LIU

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K47/549 ,  C07F9/65515 ,  C07F9/65586 ,  C07F9/65616 ,  C12N2310/311 ,  C12N2310/312 ,  C12N2310/315 ,  C12N2310/351

摘要： The invention features a hybridized polynucleotide construct including a passenger strand, a guide strand loadable into a RISC complex, and one or more auxiliary moieties. At least one of the auxiliary moieties is non-bioreversibly linked to an internucleoside phosphate or phosphorothioate in the passenger strand. The invention further features methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell. The methods typically involve contacting the cell with the hybridized polynucleotide construct.

公开(公告)号：US20190202855A1

公开(公告)日：2019-07-04

申请号：US16326542

申请日：2017-08-17

申请人： Sukumar SAKAMURI ,  Curt W. BRADSHAW ,  Laxman ELTEPU ,  Bryan R. MEADE ,  Son LAM ,  Solstice Biologics, Ltd.

发明人： Sukumar SAKAMURI ,  Curt W. BRADSHAW ,  Laxman ELTEPU ,  Bryan R. MEADE ,  Son LAM

IPC分类号： C07H21/00 ,  C07F9/24 ,  C12N15/85 ,  C12N15/113

CPC分类号： C07H21/00 ,  C07F9/2408 ,  C07F9/65586 ,  C07F9/65616 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/85 ,  C12N2310/14

摘要： Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over ( )}enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

公开(公告)号：US20160257961A1

公开(公告)日：2016-09-08

申请号：US15034973

申请日：2014-11-06

申请人： Curt W. BRADSHAW ,  Laxman ELTEPU ,  Ayman KABAKIBI ,  Son LAM ,  Bin LIE ,  Dingguo LIE ,  Bryan R. MEADE ,  Sukumar SAKAMURI ,  SOLSTICE BIOLOGICS, LTD.

发明人： Curt W. BRADSHAW ,  Laxman ELTEPU ,  Ayman KABAKIBI ,  Son LAM ,  Bin LIU ,  Dingguo LIU ,  Bryan R. MEADE ,  Sukumar SAKAMURI

IPC分类号： C12N15/113

CPC分类号： C12N15/1137 ,  C07F9/65586 ,  C07F9/65616 ,  C07H21/00 ,  C12N2310/14 ,  C12N2310/311 ,  C12N2310/321 ,  C12N2310/351

摘要： The invention features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components is attached to an internucleotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains one or more bulky groups proximal to the disulfide group. The invention also features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components (i) is attached to an internucleotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains at least 4 atoms in a chain between the disulfide linkage and the phosphorus atom of the internucleotide bridging group or the terminal group; and where the chain does not contain a phosphate, an amide, an ester, or an alkenylene. The invention also features methods of delivering a polynucleotide to a cell using the polynucleotide constructs of the invention.

摘要翻译： 本发明的特征在于含有一种或多种组分（i）的多核苷酸构建体，其中所述组分（i）含有二硫键，其中所述一种或多种组分中的每一种与多核苷酸构建物的核苷酸间桥基团或末端基团连接，并且所述一种或多种组分 （i）含有一个或多个邻近二硫基的体积大的基团。 本发明还具有含有一种或多种组分（i）的多核苷酸构建体，其含有二硫键，其中所述一种或多种组分（i）中的每一个连接到多核苷酸构建体的核苷酸间桥基团或末端基团， 一个或多个组分（i）在二核苷酸桥连基团或末端基团的二硫键和磷原子之间的链中含有至少4个原子; 并且其中链不含有磷酸酯，酰胺，酯或亚烯基。 本发明还涉及使用本发明的多核苷酸构建体将多核苷酸递送至细胞的方法。

公开(公告)号：US20090098130A1

公开(公告)日：2009-04-16

申请号：US11969850

申请日：2008-01-04

申请人： Curt W. BRADSHAW ,  Sukumar Sakamuri ,  Yanwen Fu ,  Bryan Oates ,  Joel Desharnais ,  David Tumelty

发明人： Curt W. BRADSHAW ,  Sukumar Sakamuri ,  Yanwen Fu ,  Bryan Oates ,  Joel Desharnais ,  David Tumelty

IPC分类号： A61K39/44 ,  A61P3/10 ,  C07K19/00

CPC分类号： C07K14/605 ,  A61K47/6811 ,  A61K47/6843

摘要： The present invention provides GA targeting compounds which comprise GA targeting agent-linker conjugates linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to prevent or treat diabetes or diabetes-related conditions.

摘要翻译： 本发明提供了GA靶向化合物，其包含与抗体的结合位点连接的GA靶向剂 - 接头缀合物。 提供了化合物的各种用途，包括预防或治疗糖尿病或糖尿病相关病症的方法。

公开(公告)号：US20180346505A1

公开(公告)日：2018-12-06

申请号：US15534022

申请日：2015-12-10

申请人： SOLSTICE BIOLOGICS, LTD.

发明人： Curt W. BRADSHAW ,  Sukumar SAKAMURI ,  Dingguo LIU

IPC分类号： C07H19/10 ,  A61P31/14

CPC分类号： C07H19/11 ,  A61K31/712 ,  A61K47/54 ,  A61K47/549 ,  C07H19/10 ,  C07H19/213

摘要： The invention features a mononucleotide comprising a nucleobase bonded to a sugar having a 3′-carbon and a 5′-carbon, where the 5′-carbon is bonded to a phosphorus (V) atom of a phosphate group through an oxygen atom, the phosphorus (V) atom being bonded to (i) a disulfide bioreversible group through an oxygen atom; and (ii) (a) optionally substituted amino, optionally substituted alkoxy, optionally substituted aryloxy, or optionally substituted heteroaryloxy; or (b) the 3′-carbon through an oxygen atom. The invention also features methods of delivering the mononucleotide to a cell and methods of treating a subject having Hepatitis C.

公开(公告)号：US20110087010A1

公开(公告)日：2011-04-14

申请号：US12897594

申请日：2010-10-04

申请人： Curt W. BRADSHAW ,  Venkata Ramana DOPPALAPUDI ,  Jing-Yu LAI ,  John RIZZO

发明人： Curt W. BRADSHAW ,  Venkata Ramana DOPPALAPUDI ,  Jing-Yu LAI ,  John RIZZO

IPC分类号： C07K16/00 ,  C07D205/08

CPC分类号： C07K7/02 ,  A61K38/00 ,  C07K7/06 ,  C07K16/40 ,  C07K2319/30

摘要： The present invention provides AA targeting compounds which comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to treat disorders connected to abnormal angiogenesis.

摘要翻译： 本发明提供了AA靶向化合物，其包含与抗体的组合位点连接的AA靶向剂 - 接头缀合物。 提供了化合物的各种用途，包括治疗与异常血管发生相关的病症的方法。