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：US20130011922A1

公开(公告)日：2013-01-10

申请号：US13327545

申请日：2011-12-15

Applicant: STEVEN C. QUAY ,  JAMES MCSWIGGEN ,  NARENDRA K. VAISH ,  MOHAMMAD AHMADIAN

Inventor： STEVEN C. QUAY ,  JAMES MCSWIGGEN ,  NARENDRA K. VAISH ,  MOHAMMAD AHMADIAN

IPC: C07H21/02 ,  C12N5/071

CPC classification number: C12N15/111 ,  C12N2310/14 ,  C12N2310/533

Abstract: The present disclosure provides RNA molecules, for example, meroduplex ribonucleic acid molecules (mdRNA), and blunt ended double-stranded ribonucleic acid molecules capable of decreasing or silencing expression of a target gene. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target mRNA. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease or condition associated with the target gene.

Abstract translation: 本公开提供了RNA分子，例如，meroduplex核糖核酸分子（mdRNA）和能够降低或沉默靶基因表达的平端双链核糖核酸分子。 本公开的mdRNA包含至少三条链，其结合形成由切口或间隙分开的至少两个不重叠的双链区域，其中一条链与靶mRNA互补。 还提供减少细胞或受试者中靶基因表达以治疗与靶基因相关的疾病或病症的方法。

公开(公告)号：US20120190640A1

公开(公告)日：2012-07-26

申请号：US13189061

申请日：2011-07-22

Applicant: Steven C. QUAY ,  Peter C. Aprile ,  Zenaida O. Go ,  Anthony P. Sileno

Inventor： Steven C. QUAY ,  Peter C. Aprile ,  Zenaida O. Go ,  Anthony P. Sileno

IPC: A61K31/714 ,  A61P3/02

CPC classification number: A61K9/0043 ,  A61K9/08 ,  A61K31/7056 ,  A61K31/714 ,  A61K47/10 ,  A61K47/12 ,  A61K47/186

Abstract: A stable pharmaceutical mercury-free aqueous solution of cyanocobalamin comprised of cyanocobalamin and water wherein said solution of cyanocobalamin is suitable for intranasal administration, has a viscosity less than about 1000 cPs, and wherein said solution of cyanocobalamin has a bioavailability of cyanocobalamin when administered intranasally of at least about 7% relative to an intramuscular injection of cyanocobalamin with the proviso that the solution is essentially free of mercury and mercury-containing compounds. The present invention is also directed towards a method for elevating the vitamin B12 levels in the cerebral spinal fluid (CSF) comprising administering, intranasally a sufficient amount of a mercury-free cyanocobalamin solution so as to increase the average ratio of vitamin B12 in the CSF to that in the blood serum (B12 CSF/B12 Serum×100) to at least about 1.1 comprising intranasally administering an aqueous solution of a cyanocobalamin, wherein said solution of cyanocobalamin has a bioavailability of at least 7% relative to an intramuscular injection of a cyanocobalamin.

Abstract translation: 一种由氰钴胺素和水组成的稳定的药用无汞水溶液，其中所述氰钴胺溶液适合于鼻内给药，其粘度小于约1000cPs，其中所述氰钴胺溶液在鼻内给药时具有氰钴胺素的生物利用度 相对于肌内注射氰钴胺素至少约7％，条件是溶液基本上不含汞和含汞化合物。 本发明还涉及提高脑脊髓液（CSF）中的维生素B12水平的方法，其包括鼻内施用足量的无水银氰钴胺溶液，以增加CSF中维生素B12的平均比例 与血液中的血清（B12 CSF / B12血清×100）相比至至少约1.1，其包括鼻内施用氰钴胺水溶液，其中所述氰钴胺溶液相对于肌内注射的生物利用度为至少7％ 氰钴胺素

公开(公告)号：US08138149B2

公开(公告)日：2012-03-20

申请号：US12878936

申请日：2010-09-09

Applicant: Steven C. Quay ,  Jorge C. de Meireles ,  Arati Deshpande ,  Zenaida O. Go ,  Anthony P. Sileno

Inventor： Steven C. Quay ,  Jorge C. de Meireles ,  Arati Deshpande ,  Zenaida O. Go ,  Anthony P. Sileno

IPC: A61K38/23

CPC classification number: A61K9/0043 ,  A61K38/23

Abstract: An aqueous solution of calcitonin suitable for intranasal administration comprised of calcitonin, chlorobutanol at a concentration of less than 0.4% weight/weight, and water and having a pH of less than 4 with the proviso that benzalkonium chloride is not present in the solution. The aqueous solution of calcitonin can be used to treat osteoporosis, Paget's bone disease and hypercalcemia.

Abstract translation: 适于鼻内给药的降钙素水溶液包含浓度小于0.4重量％的降钙素，氯丁醇和水，pH小于4，条件是溶液中不存在苯扎氯铵。 降钙素水溶液可用于治疗骨质疏松症，佩吉特骨病和高钙血症。

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：US20110136233A1

公开(公告)日：2011-06-09

申请号：US13057743

申请日：2009-08-05

Applicant: Steven C. Quay ,  Narendra K. Vaish ,  Kathy L. Fosnaugh ,  Shaguna Seth

Inventor： Steven C. Quay ,  Narendra K. Vaish ,  Kathy L. Fosnaugh ,  Shaguna Seth

IPC: C12N5/00 ,  C07H21/02

CPC classification number: C12N15/1137 ,  C12N2310/14 ,  C12N2310/32 ,  C12N2310/533

Abstract: The present disclosure provides RNA molecules, for example, meroduplex ribonucleic acid molecules (mdRNA), capable of decreasing or silencing gene expression of PLK1 gene. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a PLK1 mRNA. Also provided are methods of decreasing expression of a PLK1 gene in a cell or in a subject to treat a PLK family member-related disease.

Abstract translation: 本公开提供了能够降低或沉默PLK1基因的基因表达的RNA分子，例如meroduplex核糖核酸分子（mdRNA）。 本公开的mdRNA包含至少三条链，其组合形成由切口或间隙分开的至少两个不重叠的双链区域，其中一条链与PLK1mRNA互补。 还提供减少细胞或受试者中PLK1基因表达以治疗PLK家族成员相关疾病的方法。

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：US07863245B2

公开(公告)日：2011-01-04

申请号：US12234547

申请日：2008-09-19

Applicant: Steven C. Quay

Inventor： Steven C. Quay

IPC: A61K38/22 ,  A61K38/17 ,  C07K14/435 ,  C07C217/28

CPC classification number: A61K9/0043 ,  A61K38/1709

Abstract: Pharmaceutical compositions comprising PYY(3-36) or Neuropeptide Y (NPY), a cyclodextrin, and a compound selected from phosphatidylcholine or diglyceride, wherein the PYY(3-36) or Neuropeptide Y (NPY) is present in an amount effective to alleviate one or more symptom(s) of obesity in a subject, and the cyclodextrin and the compound selected from phosphatidylcholine or diglyceride are present in an amount sufficient to enhance epithelial permeation.

Abstract translation: 包含PYY（3-36）或神经肽Y（NPY），环糊精和选自磷脂酰胆碱或甘油二酯的化合物的药物组合物，其中PYY（3-36）或神经肽Y（NPY）以有效缓解的量存在 受试者中一种或多种肥胖症状，以及环糊精和选自磷脂酰胆碱或甘油二酯的化合物以足以增加上皮渗透的量存在。

公开(公告)号：US20100055782A1

公开(公告)日：2010-03-04

申请号：US12529138

申请日：2008-03-03

Applicant: Steven C. Quay ,  James McSwiggen ,  Narendra K. Vaish ,  Mohammad Ahmadian

Inventor： Steven C. Quay ,  James McSwiggen ,  Narendra K. Vaish ,  Mohammad Ahmadian

IPC: C12N5/071 ,  C07H21/02 ,  C12N5/02

CPC classification number: C12N15/1135 ,  C12N2310/14

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing MYC gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-over-lapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a MYC mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine, a nucleoside replaced with a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a MYC gene in a cell or in a subject to treat a MYC-related disease.

Abstract translation: 本公开提供能够降低或沉默MYC基因表达的meroduplex核糖核酸分子（mdRNA）。 本公开的mdRNA包含至少三条链，其组合形成由切口或间隙分开的至少两个非重叠双链区域，其中一条链与MYC mRNA互补。 此外，meroduplex可以具有至少一个用5-甲基尿苷取代的尿苷，被锁定的核酸替代的核苷，或任选的其它修饰，以及它们的任何组合。 还提供减少细胞或受试者中MYC基因表达以治疗MYC相关疾病的方法。

公开(公告)号：US20100041140A1

公开(公告)日：2010-02-18

申请号：US12529011

申请日：2008-02-29

Applicant: Steven C. Quay ,  James McSwiggen ,  Narendra K. Vaish ,  Mohammad Ahmadian

Inventor： Steven C. Quay ,  James McSwiggen ,  Narendra K. Vaish ,  Mohammad Ahmadian

IPC: C12N5/07 ,  C07H21/02

CPC classification number: C12N15/1135 ,  C12N2310/14 ,  C12N2310/53

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing BCL2 gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-over-lapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a BCL2 mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a BCL2 gene in a cell or in a subject to treat a BCL2-related disease.

Abstract translation: 本公开提供能够降低或沉默BCL2基因表达的meroduplex核糖核酸分子（mdRNA）。 本公开的mdRNA包含至少三条链，其组合形成由切口或间隙分开的至少两个非重叠双链区域，其中一条链与BCL2 mRNA互补。 此外，meroduplex可以具有至少一个尿苷是5-甲基尿苷，核苷是锁定的核酸或任选的其它修饰，以及它们的任何组合。 还提供减少细胞或受试者中BCL2基因表达以治疗BCL2相关疾病的方法。