公开(公告)号：US09751909B2

公开(公告)日：2017-09-05

申请号：US14343607

申请日：2012-09-07

Applicant: Tracy J. Matray ,  Iwona M. Maciagiewicz ,  Michael E. Houston, Jr.

Inventor： Tracy J. Matray ,  Iwona M. Maciagiewicz ,  Michael E. Houston, Jr.

IPC: C07H21/04 ,  C07H19/04 ,  C07H19/16 ,  C07H19/00 ,  C07H19/06 ,  C07H23/00 ,  C07H19/10 ,  C12N15/113

CPC classification number: C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H23/00 ,  C12N15/113

Abstract: Processes for synthesis of conformationally restricted nucleomonomers (CRN) by ozonolysis or oxidation of a 2′-vinyl substituted nucleoside precursor with protected 3′-hydroxyl, 4′-hydroxymethyl and 5′-hydroxyl positions. The CRN nucleomonomers can be used to prepare nucleic acid compounds. CRN nucleomonomers for nucleic acid compounds can be prepared in high yields and in multi-gram scale. The nucleic acid compounds can be of various regulatory classes such as antisense RNA for therapeutic modalities useful for treating or preventing diseases or disorders by up- or down-regulating the expression of genes and other nucleic acid based regulatory systems in a cell.

公开(公告)号：US08501824B2

公开(公告)日：2013-08-06

申请号：US13076158

申请日：2011-03-30

Applicant: Steven C. Quay ,  Michael E. Houston, Jr. ,  Pierrot Harvie ,  Roger C. Adami ,  Renata Fam ,  Mary G. Prieve ,  Kathy L. Fosnaugh ,  Shaguna Seth

Inventor： Steven C. Quay ,  Michael E. Houston, Jr. ,  Pierrot Harvie ,  Roger C. Adami ,  Renata Fam ,  Mary G. Prieve ,  Kathy L. Fosnaugh ,  Shaguna Seth

IPC: A61K47/22 ,  A61K48/00 ,  C07D233/64

CPC classification number: A61K47/183 ,  A61K9/127 ,  A61K9/1271 ,  A61K9/1272 ,  A61K31/7088 ,  A61K47/18 ,  A61K47/22 ,  A61K47/28 ,  A61K47/44 ,  A61K48/0025 ,  A61K48/0033 ,  C07C235/02 ,  C07C279/12 ,  C07C279/14 ,  C07D213/40 ,  C07D213/56 ,  C07D233/26 ,  C07D233/64 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1131 ,  C12N15/1138 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  Y10S514/943

Abstract: This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract translation: 本公开提供了一系列用于药物递送，治疗以及疾病和病症的诊断和治疗的氨基酸脂质化合物和组合物。 氨基酸脂质化合物和组合物可用于向细胞，组织，器官和受试者递送各种试剂，例如核酸治疗剂。

公开(公告)号：US08063178B2

公开(公告)日：2011-11-22

申请号：US11955207

申请日：2007-12-12

Applicant: Steven C. Quay ,  Douglas L. Badders ,  Richard E. Herman ,  Michael E. Houston, Jr. ,  Paul Hickok Johnson

Inventor： Steven C. Quay ,  Douglas L. Badders ,  Richard E. Herman ,  Michael E. Houston, Jr. ,  Paul Hickok Johnson

IPC: A61K38/00 ,  C07H21/02 ,  C40B40/02 ,  C12Q1/70

CPC classification number: C12N15/1037 ,  A61K38/00

Abstract: Trp cage binding domains polypeptides are disclosed. The Trp cage binding domains have the generic formulae of SEQ ID NO: 2, 7, 10 or 11. They can be efficiently produced and screened using phage display technology.

Abstract translation: 公开了Trp结构域结合域多肽。 Trp结构域具有SEQ ID NO：2，7，10或11的通式。它们可以使用噬菌体展示技术有效地生产和筛选。

公开(公告)号：US20110130327A1

公开(公告)日：2011-06-02

申请号：US12954827

申请日：2010-11-26

Applicant: MICHAEL E. HOUSTON, JR. ,  ROGER C. ADAMI ,  STEVEN C. QUAY ,  PHUONG NGUYEN ,  HARRY C. WANG ,  DIANE E. FRANK

Inventor： MICHAEL E. HOUSTON, JR. ,  ROGER C. ADAMI ,  STEVEN C. QUAY ,  PHUONG NGUYEN ,  HARRY C. WANG ,  DIANE E. FRANK

IPC: A61K38/10 ,  C07C229/26 ,  A61K31/197 ,  A61K31/225 ,  C07C233/36 ,  A61K31/16 ,  C07K7/08 ,  C07K9/00 ,  C07D403/14 ,  A61K31/4178 ,  C07D403/12 ,  A61K31/7088 ,  A61K31/713 ,  A61P31/12 ,  A61P19/02 ,  A61P35/00 ,  A61P1/16 ,  A61P31/16 ,  C12N5/071

CPC classification number: G01N33/50 ,  A61K9/0043 ,  A61K9/0073 ,  A61K47/6911 ,  C12Q1/02

Abstract: Multi-arm amine compounds and compositions for enhancing intracellular, in vitro, and in vivo delivery of drug, active, and therapeutic substances including ribonucleic acids. This disclosure provides novel compounds and compositions for making and using delivery materials and carriers which increase the efficiency of delivery of biologically active and pharmacologically active molecules. Embodiments of this disclosure may further provide delivery of various therapeutic agents including nucleic acid therapeutics such as regulatory RNA, interfering RNA, and agents for RNAi, as well as other protein and peptide therapeutics. In some aspects, this disclosure provides multi-arm amine compounds and compositions which can enhance permeation of a drug substance.

Abstract translation: 用于增强药物，活性和治疗物质（包括核糖核酸）的细胞内，体外和体内递送的多臂胺化合物和组合物。 本公开提供了用于制备和使用递送材料和载体的新型化合物和组合物，其提高了生物活性和药理学活性分子的递送效率。 本公开的实施方案还可以提供各种治疗剂的递送，包括核酸治疗剂，例如调节RNA，干扰RNA和用于RNAi的试剂，以及其它蛋白质和肽治疗剂。 在一些方面，本公开提供了可以增强药物物质渗透性的多臂胺化合物和组合物。

公开(公告)号：US20100240731A1

公开(公告)日：2010-09-23

申请号：US12750622

申请日：2010-03-30

Applicant: Roger C. Adami ,  Michael E. Houston ,  Rachel E. Johns

Inventor： Roger C. Adami ,  Michael E. Houston ,  Rachel E. Johns

IPC: A61K31/713 ,  C07K14/00 ,  C07K7/08 ,  C07K7/06 ,  A61P35/00 ,  A61P3/00 ,  A61P29/00 ,  A61P31/12 ,  C07K5/10 ,  C07K5/08

CPC classification number: A61K47/42 ,  A61K31/713 ,  A61K47/543 ,  A61K47/544 ,  A61K47/6455 ,  A61K48/00 ,  A61K48/0033 ,  A61K48/0041 ,  C07K7/08 ,  C07K14/00 ,  C07K14/001 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14

Abstract: Lipopeptide compounds comprising a peptide having 2 to 100 amino acid residues, and having a lipophilic group attached to at least one terminus of the peptide or to at least one amino acid residue of the peptide, and salts and uses thereof. The lipophilic group may be attached to the N-terminus, C-terminus or both termini of the peptide. The lipophilic group may be attached to at least one interal amino acid residue (i.e., an amino acid residue that is not the N-terminus or the C-terminus amino acid residue of the peptide). The lipophilic group may be attached to either termini or both and at least one internal amino acid residue.

Abstract translation: 包含具有2至100个氨基酸残基并且具有连接至该肽的至少一个末端或该肽的至少一个氨基酸残基的亲脂基团的脂肽化合物及其盐和用途。 亲脂基团可以连接到肽的N末端，C末端或两个末端。 亲脂基团可以连接到至少一个间氨基酸残基（即，不是肽的N-末端或C末端氨基酸残基的氨基酸残基）。 亲脂基团可以连接到末端或两者和至少一个内部氨基酸残基。

公开(公告)号：US20100113332A1

公开(公告)日：2010-05-06

申请号：US11576139

申请日：2005-09-27

Applicant: Lishan Chen ,  Kunyuan Cui ,  Michael E. Houston, JR. ,  Yuching Chen

Inventor： Lishan Chen ,  Kunyuan Cui ,  Michael E. Houston, JR. ,  Yuching Chen

IPC: A61K38/14 ,  C07H21/02 ,  A61K31/7052 ,  C07K9/00 ,  A61P29/00 ,  A61P37/00 ,  A61P17/06

CPC classification number: C12N15/1136 ,  A61K47/64 ,  A61K2121/00 ,  C07K14/001 ,  C07K14/43572 ,  C07K14/47 ,  C12N15/111 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/3513 ,  C12N2320/32

Abstract: What is disclosed is the use of a formulation comprising double stranded ribonucleic acid (dsRNA) in the manufacture of a medicament for treating an inflammatory disease in a mammal and inhibiting production of tumor necrosis factor-α (TNF-α) in the mammal.

Abstract translation: 所公开的是使用包含双链核糖核酸（dsRNA）的制剂在制备用于治疗哺乳动物炎症性疾病和抑制哺乳动物肿瘤坏死因子-α（TNF-α）产生的药物中的用途。

公开(公告)号：US20080261304A1

公开(公告)日：2008-10-23

申请号：US12013274

申请日：2008-01-11

Applicant: Mohammad Ahmadian ,  Kunyuan Cui ,  Lishan Chen ,  Shu-Chih Chen ,  Michael E. Houston

Inventor： Mohammad Ahmadian ,  Kunyuan Cui ,  Lishan Chen ,  Shu-Chih Chen ,  Michael E. Houston

IPC: C12N5/02 ,  C07H21/02

CPC classification number: A61K45/06 ,  A61K31/713 ,  A61K38/00 ,  A61K47/554 ,  A61K48/005 ,  C07K14/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1137 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2320/30 ,  C12N2320/32 ,  C12Y302/01023

Abstract: A double-stranded RNA, preferably a small, interfering (si)RNA or a siHybrid, to which cholesterol moieties are linked.

Abstract translation: 胆固醇部分连接的双链RNA，优选小的干扰（si）RNA或siHybrid。

公开(公告)号：US5824483A

公开(公告)日：1998-10-20

申请号：US491527

申请日：1995-06-16

Applicant: Michael E. Houston, Jr. ,  Robert S. Hodges

Inventor： Michael E. Houston, Jr. ,  Robert S. Hodges

IPC: G01N33/53 ,  B01J19/00 ,  C07K1/04 ,  C07K7/00 ,  C07K14/00 ,  C07K14/705 ,  C40B40/10 ,  C40B60/14

CPC classification number: C07K1/047 ,  B01J19/0046 ,  C07K14/001 ,  C07K14/705 ,  C40B80/00 ,  G01N33/53 ,  A61K2039/6031 ,  A61K2039/622 ,  A61K2039/64 ,  B01J2219/00315 ,  B01J2219/0059 ,  B01J2219/00592 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00628 ,  B01J2219/0063 ,  B01J2219/00659 ,  B01J2219/00725 ,  C07K2319/00 ,  C40B40/10 ,  C40B60/14

Abstract: Combinatorial libraries of different-sequence peptide members is disclosed. The libraries are comprised of stabilized, alpha-helical polypeptides having a similar tertiary structure but different amino acid residues at specific, "variable" positions in the sequence. The polypeptides are stabilized through coiled-coil interactions with other .alpha.-helical polypeptides and/or via intrahelical lactam bridges. Also disclosed are methods for using such libraries to screen for selected macromolecular ligands.

Abstract translation: 公开了不同序列肽成员的组合文库。 文库由稳定的α-螺旋多肽组成，其具有相似的三级结构，但序列中特定的“可变”位置具有不同的氨基酸残基。 通过与其它α-螺旋多肽和/或经由内耳内酰胺桥接的螺旋线圈相互作用来稳定多肽。 还公开了使用这些文库筛选选定的大分子配体的方法。

公开(公告)号：US20130190383A1

公开(公告)日：2013-07-25

申请号：US13643180

申请日：2011-04-26

Applicant: Narendra K. Vaish ,  Kathy L. Fosnaugh ,  Shaguna Seth ,  Michael E. Houston, JR. ,  Michael V. Templin

Inventor： Narendra K. Vaish ,  Kathy L. Fosnaugh ,  Shaguna Seth ,  Michael E. Houston, JR. ,  Michael V. Templin

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N15/111 ,  C12N15/1135 ,  C12N15/1136 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/3231 ,  C12N2310/533 ,  C12N2320/30 ,  C12N2320/51 ,  C12Y103/99005 ,  C12Y203/0102 ,  C12Y207/01153 ,  C12Y207/11001 ,  C12Y207/11021 ,  C12Y207/11024 ,  C12Y304/21021

Abstract: This disclosure provides single-stranded and multi-stranded nucleic acid compounds having one or more double-stranded regions that regulate the function or expression of nucleic acid molecules expressed in a cell or a cell regulatory system dependent upon a nucleic acid. The disclosure provides a range of nucleic acid compounds having one or more conformationally restricted nucleomonomers (CRN). Certain nucleic acid compounds may have one or more conformationally restricted nucleomonomers and one or more hydroxymethyl substituted nucleomonomers (UNA). The nucleic acid compounds are useful in various therapeutic modalities.

Abstract translation: 本公开提供具有调节在细胞中表达的核酸分子的功能或表达的一个或多个双链区域的单链和多链核酸化合物或依赖于核酸的细胞调节系统。 本公开提供了一系列具有一个或多个构象限制性核单体（CRN）的核酸化合物。 某些核酸化合物可以具有一个或多个构象限制的核小体单体和一个或多个羟甲基取代的核子单体（UNA）。 核酸化合物可用于各种治疗方式。

公开(公告)号：US20130039970A1

公开(公告)日：2013-02-14

申请号：US13527723

申请日：2012-06-20

Applicant: Barry A. Polisky ,  Roger C. Adami ,  Michael V. Templin ,  Pierrot Harvie ,  Rachel E. Johns ,  Jaya S. Giyanani ,  Michael E. Houston, JR.

Inventor： Barry A. Polisky ,  Roger C. Adami ,  Michael V. Templin ,  Pierrot Harvie ,  Rachel E. Johns ,  Jaya S. Giyanani ,  Michael E. Houston, JR.

IPC: A61K9/127 ,  A61K38/02 ,  A61K31/7105 ,  A61K31/711 ,  A61K31/713 ,  A61P35/00 ,  A61P3/06 ,  A61P29/00 ,  A61P3/00 ,  A61P19/02 ,  A61P25/00 ,  A61P19/08 ,  A61P9/00 ,  A61P31/12 ,  A61K31/7088

CPC classification number: A61K9/127 ,  A61K9/1271 ,  A61K9/1277 ,  C12N15/111 ,  C12N15/113 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32

Abstract: Processes and compositions for liposomal delivery of therapeuticals prepared by contacting an aqueous solution of an active agent with a solution of liposome-forming components containing one or more DILA2 amino acid compounds or lipids in organic solvent to form an impinging stream. A protocol including flow rates, pH, and an incubation period are used to control formation of liposomal components for therapeutic applications. The impinging stream may be collected and incubated to prepare a liposomal formulation which encapsulates the active agent. The composition can be quenched with buffer and filtered by tangential flow and diafiltration and other means for finishing as a pharmaceutical composition.

Abstract translation: 通过使活性剂的水溶液与含有一种或多种DILA2氨基酸化合物或脂质的脂质体形成成分的溶液在有机溶剂中接触以形成冲击流而制备的治疗剂的脂质体递送的方法和组合物。 使用包括流速，pH和潜伏期的方案来控制用于治疗应用的脂质体组分的形成。 可以收集冲击流并将其温育以制备包封活性剂的脂质体制剂。 组合物可以用缓冲液淬火并通过切向流动和渗滤过滤，以及用作药物组合物的其它装置。