CA2794189C - Rna interference in dermal and fibrotic indications - Google Patents

Rna interference in dermal and fibrotic indications Download PDF

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Publication number
CA2794189C
CA2794189C CA2794189A CA2794189A CA2794189C CA 2794189 C CA2794189 C CA 2794189C CA 2794189 A CA2794189 A CA 2794189A CA 2794189 A CA2794189 A CA 2794189A CA 2794189 C CA2794189 C CA 2794189C
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seq
strand comprises
antisense strand
sense strand
nucleotides
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CA2794189A
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French (fr)
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CA2794189A1 (en
Inventor
Anastasia Khvorova
William Salomon
Joanne Kamens
Dmitry Samarsky
Tod M. Woolf
Pamela A. Pavco
Lyn Libertine
James Cardia
Karen G. Bulock
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Phio Pharmaceuticals Corp
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Phio Pharmaceuticals Corp
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • C12N2310/334—Modified C
    • C12N2310/3341—5-Methylcytosine
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
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    • C12N2320/30—Special therapeutic applications
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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/52—Methods for regulating/modulating their activity modulating the physical stability, e.g. GC-content

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  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Endocrinology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Gastroenterology & Hepatology (AREA)
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CA2794189A 2010-03-24 2011-03-24 Rna interference in dermal and fibrotic indications Active CA2794189C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US31725210P 2010-03-24 2010-03-24
US61/317,252 2010-03-24
US31763310P 2010-03-25 2010-03-25
US61/317,633 2010-03-25
PCT/US2011/029867 WO2011119887A1 (en) 2010-03-24 2011-03-24 Rna interference in dermal and fibrotic indications

Publications (2)

Publication Number Publication Date
CA2794189A1 CA2794189A1 (en) 2011-09-29
CA2794189C true CA2794189C (en) 2022-01-11

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ID=44673640

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CA2794189A Active CA2794189C (en) 2010-03-24 2011-03-24 Rna interference in dermal and fibrotic indications

Country Status (10)

Country Link
US (4) US9340786B2 (enExample)
EP (2) EP3560503B1 (enExample)
JP (4) JP6060071B2 (enExample)
KR (3) KR102453078B1 (enExample)
CN (3) CN103108642B (enExample)
AU (3) AU2011232365A1 (enExample)
BR (1) BR112012024049A2 (enExample)
CA (1) CA2794189C (enExample)
IL (1) IL265674B2 (enExample)
WO (1) WO2011119887A1 (enExample)

Families Citing this family (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2247729B1 (en) * 2008-02-11 2019-05-01 Phio Pharmaceuticals Corp. Modified rnai polynucleotides and uses thereof
EP2340309A2 (en) 2008-09-22 2011-07-06 Rxi Pharmaceuticals Corporation Neutral nanotransporters
US9074211B2 (en) 2008-11-19 2015-07-07 Rxi Pharmaceuticals Corporation Inhibition of MAP4K4 through RNAI
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
WO2011109248A1 (en) 2010-03-02 2011-09-09 Hapten Pharmaceuticals, Llc Effective sensitizing dose of a gelled immunomodulating topical composition
BR112012024049A2 (pt) 2010-03-24 2017-03-01 Rxi Pharmaceuticals Corp interferência de rna em indicações dérmicas e fibróticas
EP2550000A4 (en) 2010-03-24 2014-03-26 Advirna Inc RNAI COMPOUNDS OF REDUCED SIZE ADMINISTERING
CN106074591B (zh) 2010-03-24 2020-01-14 菲奥医药公司 眼部症候中的rna干扰
AU2015261583C1 (en) * 2010-10-14 2017-07-06 Mie University Preventative or therapeutic agent for fibrosis
AR083445A1 (es) 2010-10-14 2013-02-27 Univ Mie siARN CONTRA LA FIBROSIS
US8802839B2 (en) * 2011-07-15 2014-08-12 Fibrogen, Inc. Connective tissue growth factor antisense oligonucleotides
JP2015501844A (ja) * 2011-12-16 2015-01-19 モデルナ セラピューティクス インコーポレイテッドＭｏｄｅｒｎａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 修飾ヌクレオシド、ヌクレオチドおよび核酸組成物
WO2013177478A2 (en) * 2012-05-24 2013-11-28 Glaxosmithkline Intellectual Property (No.2) Limited Treatment method
US10006024B2 (en) 2012-11-29 2018-06-26 Gifu University RNA interference agent, method for producing same, and use therefor
EP3013958B1 (en) * 2013-06-25 2019-12-25 The United States of America, as represented by the Secretary, Department of Health and Human Services Glucan-encapsulated sirna for treating type 2 diabetes mellitus
EP3591053A1 (en) * 2013-07-05 2020-01-08 Bioneer Corporation Respiratory disease-related gene specific sirna, double-helical oligo rna structure containing sirna, compositon containing same for preventing or treating respiratory disease
CN106061488B (zh) 2013-12-02 2021-04-09 菲奥医药公司 癌症的免疫治疗
CA2932753A1 (en) 2013-12-04 2015-06-11 Rxi Pharmaceuticals Corporation Methods for treatment of wound healing utilizing chemically modified oligonucleotides
US10612020B2 (en) 2013-12-26 2020-04-07 Tokyo Medical University Artificial mimic miRNA for controlling gene expression, and use of same
WO2015099187A1 (ja) 2013-12-27 2015-07-02 株式会社ボナック 遺伝子発現制御のための人工マッチ型ｍｉＲＮＡおよびその用途
CN103933579A (zh) * 2014-04-03 2014-07-23 华侨大学 一种阳离子脂质体及其制备方法和应用
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
KR102506169B1 (ko) 2014-09-05 2023-03-08 피오 파마슈티칼스 코프. Tyr 또는 mmp1을 표적화하는 핵산을 사용한 노화 및 피부 장애의 치료 방법
CA2969590A1 (en) * 2014-12-03 2016-06-09 Rxi Pharmaceuticals Corporation Methods for the treatment of alopecia areata utilizing gene modulation approaches
US10337009B2 (en) 2014-12-15 2019-07-02 Bonac Corporation Single-stranded nucleic acid molecule for inhibiting TGF-β1 expression
ES2810375T3 (es) 2014-12-17 2021-03-08 Proqr Therapeutics Ii Bv Edición direccionada de ARN
US11027023B2 (en) 2014-12-27 2021-06-08 Bonac Corporation Natural type miRNA for controlling gene expression, and use of same
US11142769B2 (en) 2015-03-27 2021-10-12 Bonac Corporation Single-stranded nucleic acid molecule having delivery function and gene expression regulating ability
WO2016161388A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Fully stabilized asymmetric sirna
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
WO2017030973A1 (en) 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
CN109563509B (zh) 2015-10-19 2022-08-09 菲奥医药公司 靶向长非编码rna的减小尺寸的自递送核酸化合物
US10751426B2 (en) * 2015-10-30 2020-08-25 Bonac Corporation Composition stably containing single-stranded nucleic acid molecule that suppresses expression of TGF-β1 gene
US10478503B2 (en) 2016-01-31 2019-11-19 University Of Massachusetts Branched oligonucleotides
WO2017178883A2 (en) * 2016-04-11 2017-10-19 Olix Pharmaceuticals, Inc. Treatment of idiopathic pulmonary fibrosis using rna complexes that target connective tissue growth factor
EP3475424A1 (en) 2016-06-22 2019-05-01 ProQR Therapeutics II B.V. Single-stranded rna-editing oligonucleotides
US11753638B2 (en) 2016-08-12 2023-09-12 University Of Massachusetts Conjugated oligonucleotides
WO2018035046A1 (en) 2016-08-15 2018-02-22 President And Fellows Of Harvard College Treating infections using idsd from proteus mirabilis
CA3035293A1 (en) 2016-09-01 2018-03-08 Proqr Therapeutics Ii B.V. Chemically modified single-stranded rna-editing oligonucleotides
EP3571300A1 (en) 2017-01-19 2019-11-27 ProQR Therapeutics II B.V. Oligonucleotide complexes for use in rna editing
IL269517B2 (en) 2017-04-05 2025-01-01 Silence Therapeutics Gmbh Nucleic acids for inhibiting expression of a target gene in a cell, conjugates thereof, compositions containing them, and medical uses thereof
JP7167059B2 (ja) 2017-04-19 2022-11-08 フィオ ファーマシューティカルズ コーポレーション 核酸化合物の局所送達
WO2019103857A1 (en) 2017-11-22 2019-05-31 Iovance Biotherapeutics, Inc. Expansion of peripheral blood lymphocytes (pbls) from peripheral blood
CA3064590A1 (en) 2017-06-23 2018-12-27 University Of Massachusetts Two-tailed self-delivering sirna and related methods
CN111601883B (zh) 2017-11-17 2024-06-21 艾欧凡斯生物治疗公司 由细针抽吸物和小活检物扩增til
WO2019136459A1 (en) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Processes for generating til products enriched for tumor antigen-specific t-cells
KR102956273B1 (ko) 2018-01-08 2026-04-24 이오반스 바이오테라퓨틱스, 인크. 종양 항원-특이적 t-세포에 대해 풍부화된 til 생성물의 생성 방법
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
CN112512532B (zh) * 2018-07-31 2024-11-08 雷莫内克斯生物制药有限公司 用于抑制ctgf表达的组合物
WO2020027640A1 (ko) * 2018-07-31 2020-02-06 주식회사 레모넥스 Ctgf 발현 억제용 조성물
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
CA3118493A1 (en) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Expansion of tils utilizing akt pathway inhibitors
CR20210295A (es) 2018-11-05 2021-07-09 Iovance Biotherapeutics Inc Procesos para la producción de linfocitos infiltrantes de tumor y usos de estos en inmunoterapia
TW202039829A (zh) 2018-11-05 2020-11-01 美商艾歐凡斯生物治療公司 改善之腫瘤反應性ｔ細胞的選擇
TW202039831A (zh) 2018-11-05 2020-11-01 美商艾歐凡斯生物治療公司 對抗ｐｄ－１抗體呈現難治性之非小細胞肺癌（ｎｓｃｌｃ）病患之治療
WO2020131547A1 (en) 2018-12-19 2020-06-25 Iovance Biotherapeutics, Inc. Methods of expanding tumor infiltrating lymphocytes using engineered cytokine receptor pairs and uses thereof
WO2020150636A1 (en) 2019-01-18 2020-07-23 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
KR20210136050A (ko) 2019-03-01 2021-11-16 이오반스 바이오테라퓨틱스, 인크. 액상 종양으로부터의 종양 침윤 림프구의 확장 및 그의 치료 용도
WO2020232029A1 (en) 2019-05-13 2020-11-19 Iovance Biotherapeutics, Inc. Methods and compositions for selecting tumor infiltrating lymphocytes and uses of the same in immunotherapy
KR102512292B1 (ko) 2019-06-21 2023-03-22 엘지전자 주식회사 모터 어셈블리 및 그 제조 방법
KR102171452B1 (ko) 2019-06-21 2020-10-29 엘지전자 주식회사 모터 어셈블리 및 그 제조 방법
CA3149835A1 (en) 2019-08-09 2021-02-18 University Of Massachusetts Chemically modified oligonucleotides targeting snps
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
KR102757180B1 (ko) * 2019-11-22 2025-01-21 (주)바이오니아 Ctgf 유전자 특이적 이중가닥 올리고뉴클레오티드 및 이를 포함하는 섬유증 관련 질환 및 호흡기 관련 질환 예방 및 치료용 조성물
WO2021118990A1 (en) 2019-12-11 2021-06-17 Iovance Biotherapeutics, Inc. Processes for the production of tumor infiltrating lymphocytes (tils) and methods of using the same
MX2019015708A (es) * 2019-12-19 2021-06-21 Centro De Retina Medica Y Quirurgica S C Composición farmaceutica en la forma de un vector génico conteniendo un shrna para regular la expresion de los receptores cannabinoides cb1 para el tratamiento de enfermedades que cursan con fibrosis en cualquier mamífero.
EP4146793A1 (en) 2020-05-04 2023-03-15 Iovance Biotherapeutics, Inc. Selection of improved tumor reactive t-cells
CA3176826A1 (en) 2020-05-04 2021-11-11 Iovance Biotherapeutics, Inc. Processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy
AU2020450890B2 (en) * 2020-05-26 2025-04-10 Olix Pharmaceuticals, Inc. RNAi agent targeting MyD88 and use thereof
EP4157289A4 (en) 2020-05-26 2024-06-26 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
WO2022076606A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
EP4225330A1 (en) 2020-10-06 2023-08-16 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
CA3201818A1 (en) 2020-12-11 2022-06-16 Maria Fardis Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors
CA3202483A1 (en) 2020-12-17 2022-06-23 Maria Fardis Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors
US20240123067A1 (en) 2020-12-17 2024-04-18 Iovance Biotherapeutics, Inc. Treatment of cancers with tumor infiltrating lymphocyte therapies
CN114854738A (zh) * 2021-02-04 2022-08-05 纳肽得(青岛)生物医药有限公司 用于治疗与TGFβ1表达相关的疾病的siRNA
WO2022204564A2 (en) 2021-03-25 2022-09-29 Iovance Biotherapeutics, Inc. Methods and compositions for t-cell coculture potency assays and use with cell therapy products
KR20240037185A (ko) 2021-04-19 2024-03-21 이오반스 바이오테라퓨틱스, 인크. 키메라 공동자극 수용체, 케모카인 수용체, 및 세포 면역치료에서의 이의 용도
AR126207A1 (es) 2021-06-23 2023-09-27 Univ Massachusetts Compuestos de oligonucleotidos anti-flt1 optimizados para el tratamiento de la preeclampsia y otros desordenes angiogénicos
WO2022270071A1 (ja) * 2021-06-24 2022-12-29 国立大学法人北海道大学 肝線維化抑制のための剤及び医薬組成物
WO2023009716A1 (en) 2021-07-28 2023-02-02 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors
CA3235824A1 (en) 2021-10-27 2023-05-04 Frederick G. Vogt Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy
US20250032618A1 (en) 2021-11-10 2025-01-30 Iovance Biotherapeutics, Inc. Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes
WO2023201369A1 (en) 2022-04-15 2023-10-19 Iovance Biotherapeutics, Inc. Til expansion processes using specific cytokine combinations and/or akti treatment
EP4565683A1 (en) 2022-08-01 2025-06-11 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
WO2024098024A1 (en) 2022-11-04 2024-05-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
WO2025101484A1 (en) 2023-11-06 2025-05-15 Iovance Biotherapeutics, Inc. Treatment of endometrial cancers with tumor infiltrating lymphocyte therapies
WO2025260042A1 (en) * 2024-06-14 2025-12-18 Amgen Inc. Rnai constructs and methods for inhibiting cnr1 expression

Family Cites Families (360)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4201860A (en) 1978-05-09 1980-05-06 Bristol-Myers Company Purine derivatives
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US5643889A (en) 1984-07-11 1997-07-01 Temple University-Of The Commonwealth System Of Pennsylvania Cholesterol conjugates of 2'5'-oligoadenylate derivatives and antiviral uses thereof
US5028703A (en) 1988-03-11 1991-07-02 Massachusetts Institute Of Technology Glucan composition and process for preparation thereof
US4810646A (en) 1984-11-28 1989-03-07 Massachusetts Institute Of Technology Glucan compositions and process for preparation thereof
US5082936A (en) 1984-11-28 1992-01-21 Massachusetts Institute Of Technology Glucan composition and process for preparation thereof
US4992540A (en) 1984-11-28 1991-02-12 Massachusetts Institute Of Technology Glucan composition and process for preparation thereof
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
DE3529497A1 (de) 1985-08-17 1987-02-26 Boehringer Mannheim Gmbh N(pfeil hoch)6(pfeil hoch)-disubstituierte purinderivate, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel
US4737323A (en) 1986-02-13 1988-04-12 Liposome Technology, Inc. Liposome extrusion method
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5750666A (en) 1988-05-26 1998-05-12 Competitve Technologies, Inc. Polynucleotide phosphorodithioate compounds
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
ZA902710B (en) 1989-05-22 1991-12-24 Univ Georgia Res Found Enzyme luminescence assay
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5032401A (en) 1989-06-15 1991-07-16 Alpha Beta Technology Glucan drug delivery system and adjuvant
ATE153856T1 (de) 1989-09-08 1997-06-15 Alpha Beta Technology Zusammensetzung zur stimulierung des immunsystems
CA2066172A1 (en) 1989-09-08 1991-03-09 Alpha Beta Technology, Inc. Method for producing soluble glucans
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5495009A (en) 1989-10-24 1996-02-27 Gilead Sciences, Inc. Oligonucleotide analogs containing thioformacetal linkages
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
DK0942000T3 (da) 1989-10-24 2004-11-01 Isis Pharmaceuticals Inc 2'-modificerede oligonukleotider
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US6153737A (en) 1990-01-11 2000-11-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US6399754B1 (en) 1991-12-24 2002-06-04 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5914396A (en) 1990-01-11 1999-06-22 Isis Pharmaceuticals, Inc. 2'-O-modified nucleosides and phosphoramidites
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US6358931B1 (en) 1990-01-11 2002-03-19 Isis Pharmaceuticals, Inc. Compositions and methods for modulating RNA
US5514786A (en) 1990-01-11 1996-05-07 Isis Pharmaceuticals, Inc. Compositions for inhibiting RNA activity
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5658731A (en) 1990-04-09 1997-08-19 Europaisches Laboratorium Fur Molekularbiologie 2'-O-alkylnucleotides as well as polymers which contain such nucleotides
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
US5151510A (en) 1990-04-20 1992-09-29 Applied Biosystems, Inc. Method of synethesizing sulfurized oligonucleotide analogs
AU7979491A (en) 1990-05-03 1991-11-27 Vical, Inc. Intracellular delivery of biologically active substances by means of self-assembling lipid complexes
CA2040374C (en) 1990-07-06 1998-06-16 Gunnar Rorstad Process for enhancing the resistance of aquatic animals to disease
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
DE69126530T2 (de) 1990-07-27 1998-02-05 Isis Pharmaceutical, Inc., Carlsbad, Calif. Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
DE69133511T2 (de) 1990-08-13 2006-09-28 Isis Pharmaceuticals, Inc., Carlsbad Zuckermodifizierte oligonukleotide zum erkennen und steuern der genexpression
EP0547142A1 (en) 1990-08-28 1993-06-23 Epoch Pharmaceuticals, Inc. Solid support synthesis of 3'-tailed oligonucleotides via a linking molecule
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
GB9022560D0 (en) 1990-10-17 1990-11-28 G B Biotechnology Limited Processing of waste
WO1994008003A1 (en) 1991-06-14 1994-04-14 Isis Pharmaceuticals, Inc. ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE
US5419966A (en) 1991-06-10 1995-05-30 Microprobe Corporation Solid support for synthesis of 3'-tailed oligonucleotides
US5214135A (en) 1991-08-30 1993-05-25 Chemgenes Corporation N-protected-2'-O-methyl-ribonucleosides and N-protected 2'-O-methyl-3'-cyanoethyl-N-,N-diisopropyl phosphoramidite ribonucleosides
US7384634B2 (en) 1991-08-30 2008-06-10 University Of South Florida Connective tissue growth factor
US5770209A (en) 1991-08-30 1998-06-23 University Of South Florida Acceleration of wound healing using connective tissue growth factor
US5525719A (en) 1991-08-30 1996-06-11 Chemgenes Corporation N-protected-2'-O-methyl-and N-protected-3'-O-methyl-ribonucleosides and their phosphoramidite derivatives
US5599797A (en) 1991-10-15 1997-02-04 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5607923A (en) 1991-10-15 1997-03-04 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity
US5661134A (en) 1991-10-15 1997-08-26 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5856455A (en) 1991-12-24 1999-01-05 Isis Pharmaceuticals, Inc. Gapped 2'-modified oligonucleotides
IL104461A (en) 1992-01-22 2001-05-20 Hoechst Ag Oligonucleotide analogs, their preparation and pharmaceutical compositions containing them
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5817781A (en) 1992-06-01 1998-10-06 Gilead Sciences, Inc. Modified internucleoside linkages (II)
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US6346614B1 (en) 1992-07-23 2002-02-12 Hybridon, Inc. Hybrid oligonucleotide phosphorothioates
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
CN1124980A (zh) 1993-03-31 1996-06-19 海布里顿公司 具有改良抗流感活性的经修饰寡核苷酸
CA2159629A1 (en) 1993-03-31 1994-10-13 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
DK0626387T3 (da) 1993-05-12 1999-09-27 Novartis Ag Nukleosider og oligonukleotider med 2'-ethergrupper
FR2705099B1 (fr) 1993-05-12 1995-08-04 Centre Nat Rech Scient Oligonucléotides phosphorothioates triesters et procédé de préparation.
US6015886A (en) 1993-05-24 2000-01-18 Chemgenes Corporation Oligonucleotide phosphate esters
US5428149A (en) 1993-06-14 1995-06-27 Washington State University Research Foundation Method for palladium catalyzed carbon-carbon coulping and products
US5580972A (en) 1993-06-14 1996-12-03 Nexstar Pharmaceuticals, Inc. Purine nucleoside modifications by palladium catalyzed methods
US5534259A (en) 1993-07-08 1996-07-09 Liposome Technology, Inc. Polymer compound and coated particle composition
US5532130A (en) 1993-07-20 1996-07-02 Dyad Pharmaceutical Corporation Methods and compositions for sequence-specific hybridization of RNA by 2'-5' oligonucleotides
US5417978A (en) 1993-07-29 1995-05-23 Board Of Regents, The University Of Texas System Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use
US5614621A (en) 1993-07-29 1997-03-25 Isis Pharmaceuticals, Inc. Process for preparing oligonucleotides using silyl-containing diamino phosphorous reagents
WO1995006731A2 (en) 1993-09-02 1995-03-09 Ribozyme Pharmaceuticals, Inc. Non-nucleotide containing enzymatic nucleic acid
CA2170869C (en) 1993-09-03 1999-09-14 Phillip Dan Cook Amine-derivatized nucleosides and oligonucleosides
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
ES2127948T3 (es) 1993-10-27 1999-05-01 Ribozyme Pharm Inc Oligonucleotidos modificados en la posicion 2'-amido y 2'-peptido.
NZ277616A (en) 1993-11-16 1997-12-19 Genta Inc Synthetic oligomers having phosphonate internucleosidyl linkages of undefined chirality mixed with non-phosphate internucleosidyl linkages
ATE315939T1 (de) 1993-11-19 2006-02-15 Univ Sydney Verfahren zur prophylaxe oder kontrolle des katarakts
US5652359A (en) 1993-12-02 1997-07-29 Epoch Pharmaceuticals, Inc. Oligonucleotides containing n-methyl thiolated bases having antiviral activity
CA2179168A1 (en) 1993-12-17 1995-06-22 Douglas A. Kniss Antisense oligonucleotides to suppress eicosanoid formation
AU1878895A (en) 1994-02-18 1995-09-04 Hybridon, Inc. Oligonucleotides with anti-respiratory syncytial virus activity
US5646126A (en) 1994-02-28 1997-07-08 Epoch Pharmaceuticals Sterol modified oligonucleotide duplexes having anticancer activity
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5651981A (en) 1994-03-29 1997-07-29 Northwestern University Cationic phospholipids for transfection
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5777153A (en) 1994-07-08 1998-07-07 Gilead Sciences, Inc. Cationic lipids
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5591721A (en) 1994-10-25 1997-01-07 Hybridon, Inc. Method of down-regulating gene expression
US5681940A (en) 1994-11-02 1997-10-28 Icn Pharmaceuticals Sugar modified nucleosides and oligonucleotides
US5767099A (en) 1994-12-09 1998-06-16 Genzyme Corporation Cationic amphiphiles containing amino acid or dervatized amino acid groups for intracellular delivery of therapeutic molecules
US5948767A (en) 1994-12-09 1999-09-07 Genzyme Corporation Cationic amphiphile/DNA complexes
US5716824A (en) 1995-04-20 1998-02-10 Ribozyme Pharmaceuticals, Inc. 2'-O-alkylthioalkyl and 2-C-alkylthioalkyl-containing enzymatic nucleic acids (ribozymes)
US5830430A (en) 1995-02-21 1998-11-03 Imarx Pharmaceutical Corp. Cationic lipids and the use thereof
AUPN166195A0 (en) 1995-03-13 1995-04-06 Norvet Research Pty Limited Process for glucan extraction
US6420549B1 (en) 1995-06-06 2002-07-16 Isis Pharmaceuticals, Inc. Oligonucleotide analogs having modified dimers
EP0874910A4 (en) 1995-06-07 1999-04-21 Life Technologies Inc ENHANCED CATIONIC LIPID TRANSFECTION BY PEPTIDES
CA2222328C (en) 1995-06-07 2012-01-10 Inex Pharmaceuticals Corporation Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5851548A (en) 1995-06-07 1998-12-22 Gen-Probe Incorporated Liposomes containing cationic lipids and vitamin D
US6221911B1 (en) 1995-06-07 2001-04-24 Karo Bio Ab Uses for thyroid hormone compounds or thyroid hormone-like compounds
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
AUPN398295A0 (en) 1995-07-05 1995-07-27 Carlton And United Breweries Limited Chemical compounds and processes for their production
US5734041A (en) 1995-10-20 1998-03-31 Mcgill University Preparation of chiral phosphorothioate oligomers
US5705621A (en) 1995-11-17 1998-01-06 Isis Pharmaceuticals, Inc. Oligomeric phosphite, phosphodiester, Phosphorothioate and phosphorodithioate compounds and intermediates for preparing same
US5684143A (en) 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
US6331617B1 (en) 1996-03-21 2001-12-18 University Of Iowa Research Foundation Positively charged oligonucleotides as regulators of gene expression
US6444806B1 (en) 1996-04-30 2002-09-03 Hisamitsu Pharmaceutical Co., Inc. Conjugates and methods of forming conjugates of oligonucleotides and carbohydrates
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20080119427A1 (en) 1996-06-06 2008-05-22 Isis Pharmaceuticals, Inc. Double Strand Compositions Comprising Differentially Modified Strands for Use in Gene Modulation
US5789416B1 (en) 1996-08-27 1999-10-05 Cv Therapeutics Inc N6 mono heterocyclic substituted adenosine derivatives
US6111085A (en) 1996-09-13 2000-08-29 Isis Pharmaceuticals, Inc. Carbamate-derivatized nucleosides and oligonucleosides
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
US6248878B1 (en) 1996-12-24 2001-06-19 Ribozyme Pharmaceuticals, Inc. Nucleoside analogs
US7504493B2 (en) 1997-01-23 2009-03-17 The John Hopkins University Characterization of the yeast transcriptome
WO1998051278A2 (en) 1997-05-14 1998-11-19 Inex Pharmaceuticals Corporation High efficiency encapsulation of charged therapeutic agents in lipid vesicles
WO1998053319A2 (en) 1997-05-21 1998-11-26 The Johns Hopkins University Gene expression profiles in normal and cancer cells
ATE347911T1 (de) 1997-09-15 2007-01-15 Genetic Immunity Llc Zusammensetzungen für die zufuhr von genen an antigen-präsentierende zellen der haut
US6028183A (en) 1997-11-07 2000-02-22 Gilead Sciences, Inc. Pyrimidine derivatives and oligonucleotides containing same
AU1507199A (en) 1997-12-15 1999-07-05 Yamanouchi Pharmaceutical Co., Ltd. Novel pyrimidine-5-carboxamide derivatives
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
US6562618B1 (en) 1997-12-25 2003-05-13 Japan Tobacco, Inc. Monoclonal antibody against connective tissue growth factor and medicinal uses thereof
US6020475A (en) 1998-02-10 2000-02-01 Isis Pharmeuticals, Inc. Process for the synthesis of oligomeric compounds
WO1999054459A2 (en) 1998-04-20 1999-10-28 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
US20040241845A1 (en) 1998-05-22 2004-12-02 Luc Desgroseillers Mammalian staufen and use thereof
US6242589B1 (en) 1998-07-14 2001-06-05 Isis Pharmaceuticals, Inc. Phosphorothioate oligonucleotides having modified internucleoside linkages
US6277967B1 (en) 1998-07-14 2001-08-21 Isis Pharmaceuticals, Inc. Carbohydrate or 2′-modified oligonucleotides having alternating internucleoside linkages
US6271358B1 (en) 1998-07-27 2001-08-07 Isis Pharmaceuticals, Inc. RNA targeted 2′-modified oligonucleotides that are conformationally preorganized
US20040009938A1 (en) 1998-08-07 2004-01-15 Muthiah Manoharan Methods of enhancing renal uptake of oligonucleotides
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
US6344323B1 (en) * 1998-09-16 2002-02-05 Vitagenix, Inc. Compositions and methods for inhibiting cox-2 expression and treating cox-2 associated disorders by using cox-2 antisense oligonucleotides
US6020483A (en) 1998-09-25 2000-02-01 Nexstar Pharmaceuticals, Inc. Nucleoside modifications by palladium catalyzed methods
US6475490B1 (en) 1998-10-19 2002-11-05 Fordham University Compositions and methods for promoting tissue repair using heat shock proteins
CN1660911A (zh) 1998-12-14 2005-08-31 迈阿密大学 结缔组织生长因子片段及其方法和用途
US7115390B1 (en) 1998-12-14 2006-10-03 Fibrogen, Inc. Connective tissue growth factor fragments and methods and uses thereof
US6455586B1 (en) 1998-12-15 2002-09-24 Leonard L. Kaplan Topical immunomodulating compositions for treatment of aids, Hepatitis B & C, other infectious diseases, and cancer
CA2361251C (en) 1999-01-27 2011-03-08 David L. Becker Formulations comprising antisense nucleotides to connexins
DE19956568A1 (de) 1999-01-30 2000-08-17 Roland Kreutzer Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens
US6465628B1 (en) 1999-02-04 2002-10-15 Isis Pharmaceuticals, Inc. Process for the synthesis of oligomeric compounds
PT1152009E (pt) 1999-02-12 2005-03-31 Sankyo Co Novos analogos de nucleosidos e oligonucleotidos
US6207819B1 (en) 1999-02-12 2001-03-27 Isis Pharmaceuticals, Inc. Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds
US6121437A (en) 1999-03-16 2000-09-19 Isis Pharmaceuticals, Inc. Phosphate and thiophosphate protecting groups
US6706491B1 (en) 1999-04-09 2004-03-16 The Board Of Trustees Of The University Of Illinois Reagents and methods for identifying and modulating expression of genes regulated by p21
US6492497B1 (en) 1999-04-30 2002-12-10 Cambridge Antibody Technology Limited Specific binding members for TGFbeta1
EP1190044A2 (en) 1999-06-16 2002-03-27 The John Hopkins University Characterization of the yeast transcriptome
US6593466B1 (en) 1999-07-07 2003-07-15 Isis Pharmaceuticals, Inc. Guanidinium functionalized nucleotides and precursors thereof
GB9925459D0 (en) 1999-10-27 1999-12-29 Plant Bioscience Ltd Gene silencing
US8017742B2 (en) 1999-11-10 2011-09-13 Japan Science And Technology Agency Gene carrier
JP2001206899A (ja) 1999-11-18 2001-07-31 Japan Tobacco Inc ＴＧＦ−βＩＩ型受容体に対するヒトモノクローナル抗体及びその医薬用途
US20040072785A1 (en) 1999-11-23 2004-04-15 Wolff Jon A. Intravascular delivery of non-viral nucleic acid
DE10160151A1 (de) 2001-01-09 2003-06-26 Ribopharma Ag Verfahren zur Hemmung der Expression eines vorgegebenen Zielgens
US7829693B2 (en) 1999-11-24 2010-11-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
US7098030B2 (en) 1999-12-31 2006-08-29 Mirus Bio Corporation Polyampholytes for delivering polyions to a cell
US20050032733A1 (en) 2001-05-18 2005-02-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SiNA)
WO2001068836A2 (en) 2000-03-16 2001-09-20 Genetica, Inc. Methods and compositions for rna interference
ATE450621T2 (de) 2000-03-30 2009-12-15 Whitehead Biomedical Inst Mediatoren von rns-interferenz, die rns- sequenzspezifisch sind
WO2001085941A2 (en) 2000-05-11 2001-11-15 Academisch Ziekenhuis Bij De Universiteit Van Amsterdam Myc targets
US7108721B2 (en) 2000-05-11 2006-09-19 Massachusetts Institute Of Technology Tissue regrafting
US7175844B2 (en) 2000-07-18 2007-02-13 Joslin Diabetes Center, Inc. Methods of modulating fibrosis
JP5154728B2 (ja) 2000-07-24 2013-02-27 クレニツキー・ファーマシューティカルズ，インコーポレイテッド 神経栄養活性を有する置換５−アルキニルピリミジン
EP1307557A2 (en) 2000-08-02 2003-05-07 The Johns Hopkins University Endothelial cell expression patterns
CA2418030C (en) 2000-08-03 2010-10-26 Martin Sauter Isolation of glucan particles and uses thereof
US6794137B2 (en) 2000-09-08 2004-09-21 New York University Gene markers useful for detecting skin damage in response to ultraviolet radiation
WO2002022176A1 (en) 2000-09-15 2002-03-21 Genvec, Inc. Method of modulating neovascularization
US20020132788A1 (en) 2000-11-06 2002-09-19 David Lewis Inhibition of gene expression by delivery of small interfering RNA to post-embryonic animal cells in vivo
US6476003B1 (en) 2000-11-06 2002-11-05 Immusonic, Inc. Method for preparing small particle size glucan in a dry material
KR100872437B1 (ko) 2000-12-01 2008-12-05 막스-플랑크-게젤샤프트 츄어 푀르더룽 데어 비쎈샤프텐 에.파우. Ｒｎａ 간섭을 매개하는 작은 ｒｎａ 분자
FR2818642B1 (fr) 2000-12-26 2005-07-15 Hoechst Marion Roussel Inc Nouveaux derives de la purine, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilistion
WO2002059300A2 (en) 2000-12-28 2002-08-01 J & J Research Pty Ltd Double-stranded rna-mediated gene suppression
DE10100127A1 (de) 2001-01-03 2002-10-02 Henkel Kgaa Verfahren zur Bestimmung der Homeostase der Haut
DE10100121A1 (de) 2001-01-03 2002-08-01 Henkel Kgaa Verfahren zur Bestimmung des Hautstreß oder der Hautalterung in vitro
US7044945B2 (en) 2001-03-30 2006-05-16 Sand Bruce J Prevention of regression in thermal ciliary muscle tendinoplasty
EP1572867B1 (en) 2001-04-11 2014-07-23 The Johns Hopkins University Endothelial cell expression patterns
US20030077829A1 (en) 2001-04-30 2003-04-24 Protiva Biotherapeutics Inc.. Lipid-based formulations
WO2003070884A2 (en) 2002-02-20 2003-08-28 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF MDR P-GLYCOPROTEIN GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20070032441A1 (en) 2001-05-18 2007-02-08 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina)
CA2526831C (en) 2001-05-18 2012-07-31 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina)
US20060211642A1 (en) 2001-05-18 2006-09-21 Sirna Therapeutics, Inc. RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
US20050233997A1 (en) 2001-05-18 2005-10-20 Sirna Therapeutics, Inc. RNA interference mediated inhibition of matrix metalloproteinase 13 (MMP13) gene expression using short interfering nucleic acid (siNA)
DE10131458A1 (de) 2001-06-29 2003-01-09 Aventis Pharma Gmbh Verfahren zur Identifizierung von Verbindungen zur Therapie von Alterungsprozessen des Herz-Kreislauf Systems
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
DE10133858A1 (de) 2001-07-12 2003-02-06 Aventis Pharma Gmbh Synthetische doppelsträngige Oligonucleotide zur gezielten Hemmung der Genexpression
AU2002329667A1 (en) 2001-07-30 2003-02-17 Uta Griesenbach Specific inhibition of gene expression by small double stranded rnas
JP4226471B2 (ja) 2001-09-18 2009-02-18 ファイブローゲン、インコーポレーテッド 結合組織増殖因子の分析方法
US7786094B2 (en) 2001-10-09 2010-08-31 Biopolymer Engineering, Inc. Use of beta-glucans against biological warfare weapons and pathogens including anthrax
US20040248835A1 (en) 2001-10-26 2004-12-09 Anja Krebs Use of a double-stranded ribonucleic acid for treating an infection with a positivestrand rna-virus
WO2003035083A1 (de) * 2001-10-26 2003-05-01 Ribopharma Ag Medikament zur behandlung einer fibrotischen erkrankung durch rna interferenz
US20040063654A1 (en) 2001-11-02 2004-04-01 Davis Mark E. Methods and compositions for therapeutic use of RNA interference
AU2002368202B2 (en) 2001-11-02 2008-06-05 Insert Therapeutics, Inc Methods and compositions for therapeutic use of RNA interference
US6965025B2 (en) 2001-12-10 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
AU2002366641A1 (en) 2001-12-11 2003-06-23 Fibrogen, Inc. Methods for inhibiting ocular processes
EP3415625A1 (en) 2002-02-01 2018-12-19 Life Technologies Corporation Double-stranded oligonucleotides
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
WO2003064621A2 (en) 2002-02-01 2003-08-07 Ambion, Inc. HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES
ES2318106T3 (es) 2002-02-01 2009-05-01 Mcgill University Oligonucleotidos que comprenden segmentos alternos y usos de los mismos.
US6923833B2 (en) 2002-04-09 2005-08-02 Ray C. Wasielewski Biologically reabsorbable acetabular constraining components and materials for use with a hip replacement prosthesis and bioreabsorbable materials to augment hip replacement stability and function
WO2003099840A1 (en) 2002-05-24 2003-12-04 Isis Pharmaceuticals, Inc. Oligonucleotides having modified nucleoside units
FR2840217B1 (fr) 2002-06-03 2005-06-24 Oreal Compositions cosmetiques comprenant au moins un oligonucleotide d'arn double brin (dsrna)et leurs utilisations
US20040005263A1 (en) * 2002-06-05 2004-01-08 Exxonmobil Research And Engineering Company Process for reducing NOx in waste gas streams using sodium chlorite
ES2280826T5 (es) 2002-08-05 2017-08-03 Silence Therapeutics Gmbh Nuevas formas adicionales de moléculas de ARN de interferencia
DE10238298A1 (de) 2002-08-21 2004-03-04 Beiersdorf Ag Verwendung von Antisense-Oligonucleotiden zur Behandlung von degenerativen Hauterscheinungen
WO2004027030A2 (en) 2002-09-18 2004-04-01 Isis Pharmaceuticals, Inc. Efficient reduction of target rna’s by single- and double-stranded oligomeric compounds
EP1556402B1 (en) 2002-09-25 2011-06-22 University of Massachusetts In vivo gene silencing by chemically modified and stable sirna
CA2502649A1 (en) 2002-10-18 2004-04-29 Nucleonics Inc. Double-stranded rna structures and constructs, and methods for generating and using the same
US7309361B2 (en) 2002-10-23 2007-12-18 Wasielewski Ray C Biologic modular tibial and femoral component augments for use with total knee arthroplasty
AU2003304386A1 (en) 2002-10-30 2005-02-25 The Center For Blood Research, Inc. Methods for treating and preventing apoptosis-related diseases using rna interfering agents
ATE443764T1 (de) 2002-11-04 2009-10-15 Univ Massachusetts Allelspezifische rna-interferenz
US9150605B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
WO2006006948A2 (en) * 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
JP2006507841A (ja) 2002-11-14 2006-03-09 ダーマコン， インコーポレイテッド 機能的ｓｉＲＮＡおよび超機能的ｓｉＲＮＡ
US7655785B1 (en) 2002-11-14 2010-02-02 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof
DE10254214A1 (de) 2002-11-20 2004-06-09 Beiersdorf Ag Oligoribonukleotide zur Behandlung von degenerativen Hauterscheinungen durch RNA-Interferenz
ATE465255T1 (de) 2002-11-26 2010-05-15 Univ Massachusetts Verabreichung von sirnas
US7790867B2 (en) 2002-12-05 2010-09-07 Rosetta Genomics Inc. Vaccinia virus-related nucleic acids and microRNA
WO2004065600A2 (en) 2003-01-17 2004-08-05 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Rna interference by palindromic or modified rna molecules
DE10302421A1 (de) 2003-01-21 2004-07-29 Ribopharma Ag Doppelsträngige Ribonukleinsäure mit verbesserter Wirksamkeit
CA2514912A1 (en) 2003-02-05 2004-08-26 University Of Massachusetts Rnai targeting of viruses
US20040162235A1 (en) 2003-02-18 2004-08-19 Trubetskoy Vladimir S. Delivery of siRNA to cells using polyampholytes
US20040167090A1 (en) 2003-02-21 2004-08-26 Monahan Sean D. Covalent modification of RNA for in vitro and in vivo delivery
US20050026286A1 (en) 2003-03-05 2005-02-03 Jen-Tsan Chi Methods and compositions for selective RNAi mediated inhibition of gene expression in mammal cells
WO2004080406A2 (en) 2003-03-07 2004-09-23 Alnylam Pharmaceuticals Therapeutic compositions
EP1604014A4 (en) 2003-03-20 2008-03-26 Dana Farber Cancer Inst Inc GENE EXPRESSION IN BREAST CANCER
WO2004090105A2 (en) 2003-04-02 2004-10-21 Dharmacon, Inc. Modified polynucleotides for use in rna interference
JP4597976B2 (ja) 2003-04-17 2010-12-15 アルナイラム ファーマシューティカルズ インコーポレイテッド 修飾ｉＲＮＡ剤
US7462602B2 (en) 2003-05-01 2008-12-09 University Of Florida Research Foundation, Inc. Anti-scarring ribozymes and methods
US20060178327A1 (en) 2003-05-30 2006-08-10 Yeung Wah Hin A Inhibition of gene expression by delivery of specially selected double stranded or other forms of small interfering RNA precursors enabling the formation and function of small interfering RNA in vivo and in vitro
US7750144B2 (en) 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
AU2004252442B2 (en) 2003-06-02 2010-04-08 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of FNAi
US7405274B2 (en) 2003-06-04 2008-07-29 Fibrogen, Inc. Connective tissue growth factor antibodies
WO2005014782A2 (en) * 2003-06-13 2005-02-17 Alnylam Europe Ag., Double-stranded ribonucleic acid with increased effectiveness in an organism
US20050026823A1 (en) 2003-06-20 2005-02-03 Biomarin Pharmaceutical Inc. Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues
SG190613A1 (en) 2003-07-16 2013-06-28 Protiva Biotherapeutics Inc Lipid encapsulated interfering rna
WO2005019430A2 (en) 2003-08-22 2005-03-03 Research Development Foundation In vitro selection of aptamer beacons
US20050118625A1 (en) 2003-10-02 2005-06-02 Mounts William M. Nucleic acid arrays for detecting gene expression associated with human osteoarthritis and human proteases
WO2005038013A1 (en) 2003-10-07 2005-04-28 Isis Pharmaceuticals, Inc. Artisense oligonucleotides optimized for kidney targeting
NZ546983A (en) 2003-11-24 2009-05-31 Canji Inc Reduction of dermal scarring
WO2005059133A2 (en) * 2003-12-19 2005-06-30 Antisense Pharma Gmbh Combination therapy associating a tgf-breta antagonist with a chemiotherapeutic agent
US20080254487A1 (en) 2004-01-16 2008-10-16 Fibrogen, Inc. Connective Tissue Growth Factor Signaling
EP2123759B1 (en) 2004-02-06 2014-01-15 Thermo Fisher Scientific Biosciences Inc. Stabilized RNAS as transfection controls and silencing reagents
US20060069050A1 (en) 2004-02-17 2006-03-30 University Of Massachusetts Methods and compositions for mediating gene silencing
EP1731615A1 (en) 2004-02-20 2006-12-13 National Institute of Advanced Industrial Science and Technology Cytoplasmic localization dna and rna
US20060058255A1 (en) 2004-03-01 2006-03-16 Jianzhu Chen RNAi-based therapeutics for allergic rhinitis and asthma
US8569474B2 (en) 2004-03-09 2013-10-29 Isis Pharmaceuticals, Inc. Double stranded constructs comprising one or more short strands hybridized to a longer strand
WO2005098041A2 (en) 2004-03-26 2005-10-20 University Of Florida Research Foundation, Inc. Detection and treatment of fibrotic disorders
KR101147147B1 (ko) 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Ｒｎａ 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드
US20050265957A1 (en) 2004-04-08 2005-12-01 Monahan Sean D Polymerized formamides for use in delivery of compounds to cells
CA2564616C (en) 2004-04-20 2016-08-30 Nastech Pharmaceutical Company Inc. Methods and compositions for enhancing delivery of double-stranded rna or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells
US8168600B2 (en) 2004-04-23 2012-05-01 Isis Pharmaceuticals, Inc. Compositions and methods for topical delivery of oligonucleotides
US7687616B1 (en) 2004-05-14 2010-03-30 Rosetta Genomics Ltd Small molecules modulating activity of micro RNA oligonucleotides and micro RNA targets and uses thereof
PL2338332T3 (pl) 2004-05-20 2014-07-31 Eden Research Plc Cząsteczka glukanu kapilarnego lub cząsteczka ściany komórkowej zamykająca składnik terpenowy
ATE536418T1 (de) 2004-06-07 2011-12-15 Protiva Biotherapeutics Inc Lipidverkapselte interferenz-rna
US7740861B2 (en) 2004-06-16 2010-06-22 University Of Massachusetts Drug delivery product and methods
HUE033977T2 (en) 2004-08-23 2018-02-28 Sylentis Sau Treatment of eye disorders with siRNAs characterized by increased intraocular pressure
US20060211766A1 (en) 2004-09-30 2006-09-21 Kaplan Leonard L Gelled immunomodulating topical compositions and a method of treating warts and other human papilloma virus skin infections
EP1796732B1 (en) 2004-10-01 2013-10-30 Novartis Vaccines and Diagnostics, Inc. Modified small interfering rna molecules and methods of use
US20100069620A1 (en) 2004-12-02 2010-03-18 Rxi Pharmaceuticals Corp. Novel compositions of chemically modified small interfering rna
WO2006065601A2 (en) 2004-12-15 2006-06-22 Merck & Co., Inc. Inhibitors of akt activity
TWI386225B (zh) 2004-12-23 2013-02-21 Alcon Inc 用於治療眼睛病症的結締組織生長因子（ＣＴＧＦ）ＲＮＡ干擾（ＲＮＡｉ）抑制技術
US20060142228A1 (en) 2004-12-23 2006-06-29 Ambion, Inc. Methods and compositions concerning siRNA's as mediators of RNA interference
US20060171943A1 (en) 2005-02-01 2006-08-03 Amgen Inc. Compositions and methods of treating fibrotic disorders
WO2006128141A2 (en) 2005-05-27 2006-11-30 Sirna Therapeutics, Inc. Rna interference mediated inhibition of stromal cell-derived factor-1 (sdf-1) gene expression using short interfering nucleic acid (sina)
US20090018097A1 (en) 2005-09-02 2009-01-15 Mdrna, Inc Modification of double-stranded ribonucleic acid molecules
EP1948245B1 (en) 2005-10-24 2011-10-05 University of Massachusetts Compositions and their uses for gene therapy of bone conditions
JP2009514898A (ja) 2005-11-07 2009-04-09 タイタン ファーマシューティカルズ インコーポレイテッド ガリウムを使用する、肝臓の有害状態の処置および予防
FR2894582B1 (fr) 2005-12-12 2008-02-22 Fabre Pierre Dermo Cosmetique Sirna anti myosine va et depigmentation de la peau
WO2007069068A2 (en) 2005-12-16 2007-06-21 Diatos Cell penetrating peptide conjugates for delivering nucleic acids into cells
WO2007079224A2 (en) 2005-12-30 2007-07-12 Wei-Wu He Sirna compositions promoting scar-free wound healing of skin and methods for wound treatment
US7825099B2 (en) * 2006-01-20 2010-11-02 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
CN101374528A (zh) * 2006-01-20 2009-02-25 夸克医药公司 Rtp801的治疗用途
EP1981543A1 (en) 2006-01-23 2008-10-22 Abbott Laboratories Chemically modified polycation polymer for sirna delivery
CA2638906A1 (en) 2006-01-26 2007-08-16 University Of Massachusetts Rna interference agents for therapeutic use
US20100286233A1 (en) 2006-03-09 2010-11-11 University Of Rochester Peripheral and neural inflammatory crosstalk
EP2261333B1 (en) 2006-04-03 2016-03-30 Roche Innovation Center Copenhagen A/S Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides
DK2021472T3 (da) 2006-05-05 2011-09-19 Isis Pharmaceuticals Inc Forbindelser og fremgangsmåder til modulering af genekspression
US9878043B2 (en) 2006-06-23 2018-01-30 Engeneic Molecular Delivery Pty Ltd Targeted delivery of drugs, therapeutic nucleic acids and functional nucleic acids to mammalian cells via intact killed bacterial cells
US20080039415A1 (en) 2006-08-11 2008-02-14 Gregory Robert Stewart Retrograde transport of sirna and therapeutic uses to treat neurologic disorders
BRPI0715375A2 (pt) 2006-08-18 2013-06-18 Hoffmann La Roche policonjugados para distribuiÇço in vivo de polinucleotÍdeos
US8809514B2 (en) 2006-09-22 2014-08-19 Ge Healthcare Dharmacon, Inc. Tripartite oligonucleotide complexes and methods for gene silencing by RNA interference
JP2010507387A (ja) 2006-10-25 2010-03-11 クアーク・ファーマスーティカルス、インコーポレイテッド 新規のｓｉＲＮＡおよびその使用方法
US20080193443A1 (en) 2006-10-30 2008-08-14 Oxana Beskrovnaya Methods and compositions for the treatment of polycystic diseases
US8039010B2 (en) 2006-11-03 2011-10-18 Allergan, Inc. Sustained release intraocular drug delivery systems comprising a water soluble therapeutic agent and a release modifier
US20090010948A1 (en) 2006-12-15 2009-01-08 The University Of Hong Kong Anti-tumor vaccines delivered by dendritic cells devoid of interleukin-10
WO2008109353A1 (en) 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting map2k gene expression and uses thereof
WO2008109105A2 (en) 2007-03-06 2008-09-12 Flagship Ventures Methods and compositions for improved therapeutic effects with sirna
WO2009005813A1 (en) 2007-07-02 2009-01-08 Wyeth Modulators of axl for use in treating bone disorders
US9884899B2 (en) 2007-07-06 2018-02-06 Promedior, Inc. Methods for treating fibrosis using CRP antagonists
WO2009020344A2 (en) 2007-08-06 2009-02-12 Postech Acad Ind Found Small interfering rnas (sirnas) controlling multiple target genes and method for preparing the same
US20090043367A1 (en) 2007-08-09 2009-02-12 Yitzhak Zilberman Apparatus and methods for removing an electronic implant from a body
CA2697043A1 (en) * 2007-08-21 2009-02-26 Virginia Commonwealth University Intellectual Property Foundation Methods and compositions for treatment or prevention of radiation-induced fibrosis
EP2193140B1 (en) 2007-08-27 2016-11-02 1Globe Health Institute LLC Compositions of asymmetric interfering rna and uses thereof
WO2009043392A1 (en) * 2007-10-02 2009-04-09 Telefonaktiebolaget L M Ericsson (Publ) Method and arrangement in a telecommunication system
CA2702028A1 (en) 2007-10-02 2009-04-09 Rxi Pharmaceuticals Corp. Tripartite rnai constructs
CN103898110A (zh) 2007-10-03 2014-07-02 夸克制药公司 新siRNA结构
CN102006890A (zh) 2007-12-04 2011-04-06 阿尔尼拉姆医药品有限公司 靶向脂质
KR100949791B1 (ko) 2007-12-18 2010-03-30 이동기 오프-타겟 효과를 최소화하고 ＲＮＡｉ 기구를 포화시키지않는 신규한 ｓｉＲＮＡ 구조 및 그 용도
BRPI0907008A2 (pt) 2008-01-31 2015-07-07 Alnylam Pharmaceuticals Inc Métodos otimizados para liberação de dsrna alvejando o gene pcsk9
EP2247729B1 (en) * 2008-02-11 2019-05-01 Phio Pharmaceuticals Corp. Modified rnai polynucleotides and uses thereof
EP2268811A1 (en) 2008-03-07 2011-01-05 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
EP3604533A1 (en) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
WO2010006237A2 (en) 2008-07-11 2010-01-14 Alnylam Pharmaceuticals, Inc. Phosphorothioate oligonucleotides non-nucleosidic phosphorothiotes as delivery agents for irna agents
CA2728467A1 (en) * 2008-07-15 2010-01-21 F. Hoffmann-La Roche Ag Compositions and methods for inhibiting expression of tgf-beta receptor genes
WO2010008582A2 (en) 2008-07-18 2010-01-21 Rxi Pharmaceuticals Corporation Phagocytic cell drug delivery system
EP2318528A1 (en) 2008-07-24 2011-05-11 Rxi Pharmaceuticals Corporation Rnai constructs and uses therof
SG196769A1 (en) 2008-08-25 2014-02-13 Excaliard Pharmaceuticals Inc Antisense oligonucleotides directed against connective tissue growth factor and uses thereof
US8946172B2 (en) 2008-08-25 2015-02-03 Excaliard Pharmaceuticals, Inc. Method for reducing scarring during wound healing using antisense compounds directed to CTGF
WO2010027830A2 (en) 2008-08-25 2010-03-11 Excaliard Pharmaceuticals, Inc. Methods for modulation of connective tissue growth factor expression by administering antisense oligonucleotides through a delivery system so as to reduce scarring from wound healing and threat fibrotic diseases
ES2657696T3 (es) 2008-08-25 2018-03-06 Excaliard Pharmaceuticals, Inc. Método para reducir la cicatrización durante la curación de una herida utilizando compuestos antisentido dirigidos al CTGF
EP2340309A2 (en) * 2008-09-22 2011-07-06 Rxi Pharmaceuticals Corporation Neutral nanotransporters
EP3067359A1 (en) 2008-09-23 2016-09-14 Scott G. Petersen Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating rna interference
WO2010036962A1 (en) * 2008-09-25 2010-04-01 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene
US9074211B2 (en) 2008-11-19 2015-07-07 Rxi Pharmaceuticals Corporation Inhibition of MAP4K4 through RNAI
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
US8486909B2 (en) 2009-06-24 2013-07-16 Board Of Regents Of The University Of Nebraska Compositions and methods for the diagnosis and treatment of inflammatory disorders and fibrotic disease
MX2012004247A (es) 2009-10-06 2012-06-25 Angiochem Inc Composiciones y metodos para el transporte de agentes terapeuticos.
WO2011109248A1 (en) 2010-03-02 2011-09-09 Hapten Pharmaceuticals, Llc Effective sensitizing dose of a gelled immunomodulating topical composition
WO2011109698A1 (en) 2010-03-04 2011-09-09 Rxi Pharmaceuticals Corporation Formulations and methods for targeted delivery to phagocyte cells
CN106074591B (zh) 2010-03-24 2020-01-14 菲奥医药公司 眼部症候中的rna干扰
EP2550000A4 (en) 2010-03-24 2014-03-26 Advirna Inc RNAI COMPOUNDS OF REDUCED SIZE ADMINISTERING
BR112012024049A2 (pt) 2010-03-24 2017-03-01 Rxi Pharmaceuticals Corp interferência de rna em indicações dérmicas e fibróticas
SI2670411T1 (sl) 2011-02-02 2019-06-28 Excaliard Pharmaceuticals, Inc. Protismiselne spojine, ki so usmerjene na rastni faktor veznega tkiva (CTGF), za uporabo v postopku zdravljenja keloidov ali hipertrofnih brazgotin
US20140072613A1 (en) 2012-09-10 2014-03-13 Cynthia Lander Compositions and Methods for Treating Cutaneous Scarring
CN106061488B (zh) 2013-12-02 2021-04-09 菲奥医药公司 癌症的免疫治疗
CA2932753A1 (en) 2013-12-04 2015-06-11 Rxi Pharmaceuticals Corporation Methods for treatment of wound healing utilizing chemically modified oligonucleotides
US11279934B2 (en) 2014-04-28 2022-03-22 Phio Pharmaceuticals Corp. Methods for treating cancer using nucleic acids targeting MDM2 or MYCN
WO2015168605A1 (en) 2014-05-01 2015-11-05 Rxi Pharmaceuticals Corporation Methods for treatment of disorders in the front of the eye utilizing nucleic acid molecules
KR102506169B1 (ko) 2014-09-05 2023-03-08 피오 파마슈티칼스 코프. Tyr 또는 mmp1을 표적화하는 핵산을 사용한 노화 및 피부 장애의 치료 방법
CA2969590A1 (en) 2014-12-03 2016-06-09 Rxi Pharmaceuticals Corporation Methods for the treatment of alopecia areata utilizing gene modulation approaches
WO2016161388A1 (en) 2015-04-03 2016-10-06 University Of Massachusetts Fully stabilized asymmetric sirna
JP7009356B2 (ja) 2015-04-03 2022-01-25 ユニバーシティ・オブ・マサチューセッツ ハンチンチンｍＲＮＡをターゲティングするオリゴヌクレオチド化合物
EP3277815B1 (en) 2015-04-03 2021-09-22 University of Massachusetts Oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
US10808247B2 (en) 2015-07-06 2020-10-20 Phio Pharmaceuticals Corp. Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
EP3347000A4 (en) 2015-09-11 2019-03-27 Phio Pharmaceuticals Corp. METHODS OF TREATING DISORDERS AND SKIN DISORDERS USING HAPTENES
AU2016322934A1 (en) 2015-09-14 2018-04-12 Compass Therapeutics Llc Compositions and methods for treating cancer via antagonism of the CD155/TIGIT pathway and TGF-beta
CN109563509B (zh) 2015-10-19 2022-08-09 菲奥医药公司 靶向长非编码rna的减小尺寸的自递送核酸化合物
JP7167059B2 (ja) 2017-04-19 2022-11-08 フィオ ファーマシューティカルズ コーポレーション 核酸化合物の局所送達

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