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1. 发明申请

US20100120895A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
公开(公告)号：US20100120895A1
公开(公告)日：2010-05-13
申请号：US12598573
申请日：2008-05-02
申请人： India Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
发明人： India Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
IPC分类号： A61K31/7105 , C07H21/02 , A61P11/06 , A61P11/16
CPC分类号： C12N15/1137 , C12N2310/14 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/53 , C12Y301/04017 , C12N2310/3521
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-7, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

2. 发明申请

US20100197763A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
公开(公告)号：US20100197763A1
公开(公告)日：2010-08-05
申请号：US12598570
申请日：2008-05-02
申请人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
发明人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
IPC分类号： A61K31/713 , C07H21/02 , A61P11/00
CPC分类号： C12N15/1137 , A01K2207/05 , A01K2227/105 , A01K2267/0368 , C12N2310/14 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/3521
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-7, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

3. 发明申请

US20100137405A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
公开(公告)号：US20100137405A1
公开(公告)日：2010-06-03
申请号：US12598565
申请日：2008-05-02
申请人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
发明人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
IPC分类号： A61K31/7105 , C07H21/02 , A61P11/06 , A61P11/08
CPC分类号： C12N15/1137 , A01K2207/05 , A01K2227/105 , A01K2267/0368 , C12N2310/14 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/3521
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-I, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

4. 发明申请

US20100152278A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
公开(公告)号：US20100152278A1
公开(公告)日：2010-06-17
申请号：US12598566
申请日：2008-05-02
申请人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
发明人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
IPC分类号： A61K31/713 , C07H21/02
CPC分类号： C12N15/1137 , C12N2310/14 , C12N2310/315 , C12N2310/317 , C12N2310/321 , C12N2310/322 , C12N2310/332 , C12N2310/51 , C12N2310/52 , C12N2320/32 , C12N2310/3521
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-1, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-1, MMP -2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g., miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

5. 发明申请

US20100137406A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
公开(公告)号：US20100137406A1
公开(公告)日：2010-06-03
申请号：US12598576
申请日：2008-05-02
申请人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
发明人： Vasant Jadhav , Ivan Richards , Walter Strapps , Chandra Vargeese
IPC分类号： A61K31/7088 , C07H21/02 , A61P11/00
CPC分类号： C12N15/1137 , C12N2310/14 , C12Y301/04017
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-I, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-1, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g., miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

6. 发明申请

US20090137506A1 RNA Interference Mediated Inhibition of Cyclic Nucleotide Type 4 Phosphodiesterase (PDE4B) Gene Expression Using Short Interfering Nucleic Acid (siNA) 审中-公开
标题翻译： RNA干扰介导的使用短干扰核酸（siNA）的环型核苷酸4型磷酸二酯酶（PDE4B）基因表达的抑制作用
公开(公告)号：US20090137506A1
公开(公告)日：2009-05-28
申请号：US12114698
申请日：2008-05-02
申请人： Walter Strapps , Vasant Jadhav , Chandra Vargeese , Ivan Richards
发明人： Walter Strapps , Vasant Jadhav , Chandra Vargeese , Ivan Richards
IPC分类号： A61K31/7105 , C07H21/02
CPC分类号： C12N15/1137 , C12N2310/14 , C12Y301/04017
摘要： The invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3. The invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.
摘要翻译：本发明涉及用于研究，诊断和治疗响应于环核苷酸4型磷酸二酯酶（PDE4B）基因表达和/或活性的调节的性状，疾病和病症的化合物，组合物和方法，包括PDE4B1，PDE4B2，和PDE4B3。本发明涉及包括小核酸分子的双链核酸分子，例如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）和短发夹 RNA（shRNA）和能够介导针对环核苷酸4型磷酸二酯酶（PDE4B）基因表达的RNA干扰（RNAi）的多功能siNA分子，包括这种小核酸分子的这种小核酸分子的混合物和这种小核酸分子的脂质纳米颗粒（LNP）。这样的小核酸分子可用于例如提供预防，抑制或减少与受试者中PDE4B基因表达或活性相关的炎症，呼吸和自身免疫性疾病，性状和病症和/或其它疾病状态的组合物或生物体。

7. 发明申请

US20230089442A1 TECHNOLOGIES USEFUL FOR OLIGONUCLEOTIDE PREPARATION 有权
公开(公告)号：US20230089442A1
公开(公告)日：2023-03-23
申请号：US17439755
申请日：2020-03-19
申请人： Pachamuthu KANDASAMY , Mamoru SHIMIZU , David Charles Donnell BUTLER , Jayakanthan KUMARASAMY , Gopal Reddy BOMMINENI , Mohammed Rowshon ALAM , Sethumadhavan DIVAKARAMENON , Bijay Tilak BHATTARAI , Chandra VARGEESE , Keith Andrew BOWMAN , Stephany Michelle STANDLEY , WAVE LIFE SCIENCES LTD.
发明人： Pachamuthu Kandasamy , Mamoru Shimizu , David Charles Donnell Butler , Jayakanthan Kumarasamy , Gopal Reddy Bommineni , Mohammed Rowshon Alam , Sethumadhavan Divakaramenon , Bijay Tilak Bhattarai , Chandra Vargeese , Keith Andrew Bowman , Stephany Michelle Standley
IPC分类号： C07H1/02 , C07H21/00 , C07H19/04
摘要： Among other things, the present disclosure provides technologies for oligonucleotide preparation, particularly chirally controlled oligonucleotide preparation, which technologies provide greatly improved crude purity and yield, and significantly reduce manufacturing costs.

8. 发明申请

US20190249173A1 METHODS AND COMPOSITIONS OF BIOLOGICALLY ACTIVE AGENTS 审中-公开
公开(公告)号：US20190249173A1
公开(公告)日：2019-08-15
申请号：US16098658
申请日：2017-05-03
申请人： Chandra VARGEESE , Jason Jingxin ZHANG , Sethumadhavan DIVAKARAMENON , David Charles Donnell BUTLER , Genliang LU , Naoki IWAMOTO , Hailin YANG , Maria David FRANK-KAMENETSKY , Subramanian MARAPPAN , WAVE LIFE SCIENCES LTD.
发明人： Chandra Vargeese , Jason Jingxin Zhang , Sethumadhavan Divakaramenon , David Charles Donnell Butler , Genliang Lu , Naoki Iwamoto , Hailin Yang , Maria David Frank-Kamenetsky , Subramanian Marappan
IPC分类号： C12N15/11 , A61K31/7088 , A61K47/54
CPC分类号： C12N15/111 , A61K31/7088 , A61K47/542 , C12N2310/11 , C12N2310/14 , C12N2310/141 , C12N2310/16 , C12N2310/20 , C12N2310/315 , C12N2310/3515 , C12N2320/32
摘要： In some embodiments, the present disclosure pertains to compositions and methods related to delivery of a biologically active agent, wherein the compositions comprise a biologically active agent and a lipid. In various embodiments, the lipid is selected from: lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, alpha-linolenic acid, gamma-linolenic acid, docosa-hexaenoic acid (cis-DHA), turbinaric acid and dilinoleyl. In some embodiments, a composition and method are useful for delivery of a biologically active agent to a particular cell or tissue, e.g., a muscle cell or tissue.

9. 发明申请

US20180216108A1 OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF 审中-公开
公开(公告)号：US20180216108A1
公开(公告)日：2018-08-02
申请号：US15746220
申请日：2016-07-22
申请人： Chandra Vargeese , Meena , Nenad Svrzikapa , Susovan Mohapatra , Christopher J. Francis , Gregory L. Verdine , Anna Sokolovska
发明人： Chandra Vargeese , Meena , Nenad Svrzikapa , Susovan Mohapatra , Christopher J. Francis , Gregory L. Verdine , Anna Sokolovska
IPC分类号： C12N15/113 , A61P25/28
摘要： Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.

10. 发明授权

US09301923B2 Lipids, lipid compositions, and methods of using them 有权
标题翻译：脂质，脂质组成和使用它们的方法
公开(公告)号：US09301923B2
公开(公告)日：2016-04-05
申请号：US14197124
申请日：2014-03-04
申请人： Jeremy Baryza , Keith Bowman , Andrew Geall , Tanzina Labonte , Cameron Lee , Chandra Vargeese , Laura West , Junping Zhao
发明人： Jeremy Baryza , Keith Bowman , Andrew Geall , Tanzina Labonte , Cameron Lee , Chandra Vargeese , Laura West , Junping Zhao
IPC分类号： A61K31/575 , A61K47/06 , A61K9/127 , A61K31/7088 , A61K47/18 , A61K47/28 , A61K47/30 , C07J9/00 , C07J41/00 , C07J43/00 , A61K47/14 , C07J31/00
CPC分类号： A61K9/127 , A61K9/1272 , A61K31/7088 , A61K47/14 , A61K47/18 , A61K47/28 , A61K47/30 , A61K2300/00 , C07J9/00 , C07J31/006 , C07J41/0055 , C07J43/003
摘要： Disclosed are formulation and optimization protocols for delivery of therapeutically effective amounts of biologically active agents to liver, tumors, and/or other cells or tissues. Also provided are compositions and uses for cationic lipid compounds of formula (I). The invention also relates to compositions and uses for stealth lipids of formula (XI). Also provided are processes for making such compounds, compositions, and formulations, plus methods and uses of such compounds, compositions, and formulations to deliver biologically active agents to cells and/or tissues.
摘要翻译：公开了用于将治疗有效量的生物活性剂递送到肝，肿瘤和/或其它细胞或组织的制剂和优化方案。还提供了式（I）的阳离子脂质化合物的组合物和用途。本发明还涉及式（XI）的隐形脂质的组合物和用途。还提供了制备这种化合物，组合物和制剂以及这些化合物，组合物和制剂的方法和用途以将生物活性剂递送至细胞和/或组织的方法。

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