CA2692161C - Stabilized immune modulatory rna (simra) compounds - Google Patents

Stabilized immune modulatory rna (simra) compounds Download PDF

Info

Publication number
CA2692161C
CA2692161C CA2692161A CA2692161A CA2692161C CA 2692161 C CA2692161 C CA 2692161C CA 2692161 A CA2692161 A CA 2692161A CA 2692161 A CA2692161 A CA 2692161A CA 2692161 C CA2692161 C CA 2692161C
Authority
CA
Canada
Prior art keywords
vaccine
simra
adjuvant
disease
disorder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CA2692161A
Other languages
English (en)
French (fr)
Other versions
CA2692161A1 (en
Inventor
Ekambar R. Kandimalla
Tao Lan
Daqing Wang
Lakshmi Bhagat
Sudhir Agrawal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Idera Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Idera Pharmaceuticals Inc filed Critical Idera Pharmaceuticals Inc
Publication of CA2692161A1 publication Critical patent/CA2692161A1/en
Application granted granted Critical
Publication of CA2692161C publication Critical patent/CA2692161C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/7105Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/117Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55561CpG containing adjuvants; Oligonucleotide containing adjuvants
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/17Immunomodulatory nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/317Chemical structure of the backbone with an inverted bond, e.g. a cap structure
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/31Chemical structure of the backbone
    • C12N2310/318Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3183Diol linkers, e.g. glycols or propanediols
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/50Physical structure
    • C12N2310/51Physical structure in polymeric form, e.g. multimers, concatemers
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/50Methods for regulating/modulating their activity
    • C12N2320/51Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Pulmonology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Mycology (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA2692161A 2007-07-09 2008-07-07 Stabilized immune modulatory rna (simra) compounds Active CA2692161C (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US94852907P 2007-07-09 2007-07-09
US60/948,529 2007-07-09
US95719507P 2007-08-22 2007-08-22
US60/957,195 2007-08-22
US98116107P 2007-10-19 2007-10-19
US60/981,161 2007-10-19
US1528407P 2007-12-20 2007-12-20
US61/015,284 2007-12-20
PCT/US2008/069335 WO2009014887A2 (en) 2007-07-09 2008-07-07 Stabilized immune modulatory rna (simra) compounds

Publications (2)

Publication Number Publication Date
CA2692161A1 CA2692161A1 (en) 2009-01-29
CA2692161C true CA2692161C (en) 2015-09-29

Family

ID=40282076

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2692161A Active CA2692161C (en) 2007-07-09 2008-07-07 Stabilized immune modulatory rna (simra) compounds

Country Status (8)

Country Link
US (2) US8188261B2 (https=)
EP (3) EP2357231A2 (https=)
JP (1) JP5737937B2 (https=)
KR (1) KR101343489B1 (https=)
CN (2) CN102921003B (https=)
AU (1) AU2008279509B2 (https=)
CA (1) CA2692161C (https=)
WO (1) WO2009014887A2 (https=)

Families Citing this family (148)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA05013658A (es) * 2003-06-11 2006-03-02 Hybridon Inc Oligonucleotidos inmunomoduladores estabilizados.
MXPA06000619A (es) * 2003-07-15 2006-04-11 Hybridon Inc Estimulacion sinergistica del sistema inmune usando oligonucleotidos inmunoestimuladores y/o compuestos inmunomeros en conjunto con citocinas y/o agentes quimioterapeuticos o terapia de radiacion.
RU2572826C2 (ru) 2008-12-02 2016-01-20 Чиралджен, Лтд. Способ синтеза модифицированных по атому фосфора нуклеиновых кислот
CA2752694A1 (en) * 2009-02-10 2010-08-19 Idera Pharmaceuticals, Inc. Synthetic rna-based agonists of tlr7
KR101141544B1 (ko) 2009-03-13 2012-05-03 한국과학기술원 에스아이알엔에이 다중 접합체 및 이의 제조방법
CA2767253A1 (en) 2009-07-06 2011-01-13 Ontorii, Inc. Novel nucleic acid prodrugs and methods of use thereof
JP5868324B2 (ja) 2010-09-24 2016-02-24 株式会社Wave Life Sciences Japan 不斉補助基
AU2012284265B2 (en) 2011-07-19 2017-08-17 Wave Life Sciences Ltd. Methods for the synthesis of functionalized nucleic acids
HUE048622T2 (hu) 2011-11-18 2020-08-28 Alnylam Pharmaceuticals Inc RNSi szerek, készítmények és alkalmazási eljárások transztiretin (TTR) asszociált betegségek kezelésére
EP2780454A2 (en) 2011-11-18 2014-09-24 Alnylam Pharmaceuticals, Inc. Modified rnai agents
CA2873766A1 (en) * 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating atp2a2 expression
JP6453212B2 (ja) 2012-07-13 2019-01-16 ウェイブ ライフ サイエンシズ リミテッドWave Life Sciences Ltd. キラル制御
SG11201500239VA (en) 2012-07-13 2015-03-30 Wave Life Sciences Japan Asymmetric auxiliary group
CN104684923B (zh) * 2012-07-13 2018-09-28 株式会社新日本科学 手性核酸佐剂
WO2014022739A2 (en) 2012-08-03 2014-02-06 Alnylam Pharmaceuticals, Inc. Modified rnai agents
US9868955B2 (en) 2012-09-29 2018-01-16 Dynavax Technologies Corporation Human toll-like receptor inhibitors and methods of use thereof
US9228184B2 (en) 2012-09-29 2016-01-05 Dynavax Technologies Corporation Human toll-like receptor inhibitors and methods of use thereof
US10125369B2 (en) 2012-12-05 2018-11-13 Alnylam Pharmaceuticals, Inc. PCSK9 iRNA compositions and methods of use thereof
KR101898177B1 (ko) * 2013-01-08 2018-09-12 이데라 파마슈티칼즈, 인코포레이티드 톨-유사 수용체 기반 면역 반응을 조절하기 위한 면역 조절 올리고누클레오티드 (iro) 화합물
CA3216595A1 (en) 2013-03-14 2014-10-02 Kevin Fitzgerald Complement component c5 irna compositions and methods of use thereof
KR102486617B1 (ko) 2013-05-22 2023-01-12 알닐람 파마슈티칼스 인코포레이티드 Tmprss6 조성물 및 이의 사용 방법
TW201936624A (zh) 2013-05-22 2019-09-16 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法
TW201610151A (zh) 2013-09-23 2016-03-16 阿尼拉製藥公司 治療或預防與甲狀腺素運載蛋白相關疾病之方法
SG10201804960RA (en) 2013-12-12 2018-07-30 Alnylam Pharmaceuticals Inc Complement component irna compositions and methods of use thereof
WO2015106128A2 (en) 2014-01-09 2015-07-16 Alnylam Pharmaceuticals, Inc. MODIFIED RNAi AGENTS
JPWO2015108046A1 (ja) 2014-01-15 2017-03-23 株式会社新日本科学 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤
WO2015108047A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤
WO2015108048A1 (ja) 2014-01-15 2015-07-23 株式会社新日本科学 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤
ES2917473T3 (es) 2014-01-16 2022-07-08 Wave Life Sciences Ltd Diseño quiral
AU2015217301A1 (en) 2014-02-11 2016-08-25 Alnylam Pharmaceuticals, Inc. Ketohexokinase (KHK) iRNA compositions and methods of use thereof
TW201607559A (zh) 2014-05-12 2016-03-01 阿尼拉製藥公司 治療serpinc1相關疾患之方法和組成物
CA3215908A1 (en) 2014-05-22 2015-11-26 Alnylam Pharmaceuticals, Inc. Angiotensinogen (agt) irna compositions and methods of use thereof
AU2015269412B2 (en) 2014-06-04 2020-03-12 Exicure Operating Company Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
TWI864340B (zh) 2014-10-10 2024-12-01 美商艾爾妮蘭製藥公司 用於抑制hao1(羥酸氧化酶1(乙醇酸鹽氧化酶))基因表現的組合物及方法
TWI710633B (zh) 2014-11-10 2020-11-21 美商阿尼拉製藥公司 B型肝炎病毒(HBV)iRNA組成物及其用途方法
HK1244843A1 (zh) 2014-11-17 2018-08-17 Alnylam Pharmaceuticals, Inc. 载脂蛋白c3(apoc3)irna组合物及其使用方法
KR20170078843A (ko) 2014-11-21 2017-07-07 노오쓰웨스턴 유니버시티 구형 핵산 나노입자 접합체의 서열 특이적 세포 흡수
CA2970795A1 (en) 2014-12-18 2016-06-23 Alnylam Pharmaceuticals, Inc. Reversir compounds
WO2016130806A2 (en) 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
EP4365291A3 (en) 2015-06-12 2024-08-14 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions and methods of use thereof
IL316159A (en) 2015-06-15 2024-12-01 Mpeg La Llc Defined Oligonucleotide Multimers and Methods for Manufacture Thereof
US10494632B2 (en) 2015-07-10 2019-12-03 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (IGFALS) compositions and methods of use thereof
CN108135921B (zh) 2015-07-22 2023-10-17 波涛生命科学有限公司 寡核苷酸组合物及其方法
KR20250145703A (ko) 2015-09-02 2025-10-13 알닐람 파마슈티칼스 인코포레이티드 프로그램된 세포사 1 리간드 1 (PD-L1) iRNA 조성물 및 그의 사용 방법
FI3386518T3 (fi) 2015-12-07 2025-09-25 Genzyme Corp Menetelmiä ja koostumuksia serpinc1:een liittyvän häiriön hoitamiseksi
EP3469083A1 (en) 2016-06-10 2019-04-17 Alnylam Pharmaceuticals, Inc. COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
US11364304B2 (en) 2016-08-25 2022-06-21 Northwestern University Crosslinked micellar spherical nucleic acids
TW202313978A (zh) 2016-11-23 2023-04-01 美商阿尼拉製藥公司 絲胺酸蛋白酶抑制因子A1 iRNA組成物及其使用方法
AU2017376950B2 (en) 2016-12-16 2024-02-22 Alnylam Pharmaceuticals, Inc. Methods for treating or preventing TTR-associated diseases using transthyretin (TTR) iRNA compositions
EP3576752A4 (en) 2017-02-06 2020-12-16 Mpeg La, LLC MULTIMERIC OLIGONUCLEOTIDES WITH REDUCED RENAL CLEARANCE
WO2018209270A1 (en) 2017-05-11 2018-11-15 Northwestern University Adoptive cell therapy using spherical nucleic acids (snas)
UY37803A (es) 2017-07-10 2019-02-28 Genzyme Corp Métodos y composiciones para tratar un evento de sangrado en un sujeto que padece hemofilia
AU2018301477A1 (en) 2017-07-13 2020-02-27 Alnylam Pharmaceuticals Inc. Lactate dehydrogenase a (LDHA) iRNA compositions and methods of use thereof
US20200385719A1 (en) 2017-11-16 2020-12-10 Alnylam Pharmaceuticals, Inc. Kisspeptin 1 (kiss1) irna compositions and methods of use thereof
WO2019100039A1 (en) 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
JP2021508491A (ja) 2017-12-18 2021-03-11 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Alnylam Pharmaceuticals, Inc. 高移動度グループボックス−1(HMGB1)iRNA組成物及びその使用方法
WO2019217459A1 (en) 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
TWI851574B (zh) 2018-05-14 2024-08-11 美商阿尼拉製藥公司 血管收縮素原(AGT)iRNA組成物及其使用方法
WO2019226980A1 (en) * 2018-05-25 2019-11-28 Wake Forest University Health Sciences Cytotoxic fluoropyrimidine polymers and methods of use thereof
CA3105385A1 (en) 2018-09-18 2020-03-26 Alnylam Pharmaceuticals, Inc. Ketohexokinase (khk) irna compositions and methods of use thereof
WO2020069055A1 (en) 2018-09-28 2020-04-02 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
JP2022532652A (ja) 2019-05-17 2022-07-15 アルニラム ファーマスーティカルズ インコーポレイテッド オリゴヌクレオチドの経口送達
WO2021022108A2 (en) 2019-08-01 2021-02-04 Alnylam Pharmaceuticals, Inc. CARBOXYPEPTIDASE B2 (CPB2) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4007812A1 (en) 2019-08-01 2022-06-08 Alnylam Pharmaceuticals, Inc. Serpin family f member 2 (serpinf2) irna compositions and methods of use thereof
EP4013870A1 (en) 2019-08-13 2022-06-22 Alnylam Pharmaceuticals, Inc. Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof
EP4038189A1 (en) 2019-10-04 2022-08-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing ugt1a1 gene expression
WO2021076828A1 (en) 2019-10-18 2021-04-22 Alnylam Pharmaceuticals, Inc. Solute carrier family member irna compositions and methods of use thereof
TW202134435A (zh) 2019-10-22 2021-09-16 美商阿尼拉製藥公司 補體成分c3 irna組成物及其使用方法
CN119499394A (zh) 2019-11-01 2025-02-25 阿尔尼拉姆医药品有限公司 亨廷顿(HTT)iRNA药剂组合物及其使用方法
WO2021087325A1 (en) 2019-11-01 2021-05-06 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajb1-prkaca fusion gene expression
EP4055165A1 (en) 2019-11-06 2022-09-14 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases
CA3160329A1 (en) 2019-11-06 2021-05-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery
KR20220115946A (ko) 2019-11-13 2022-08-19 알닐람 파마슈티칼스 인코포레이티드 안지오텐시노겐 (agt) 관련 장애를 치료하기 위한 방법 및 조성물
WO2021102373A1 (en) 2019-11-22 2021-05-27 Alnylam Pharmaceuticals, Inc. Ataxin3 (atxn3) rnai agent compositions and methods of use thereof
EP4073251A1 (en) 2019-12-13 2022-10-19 Alnylam Pharmaceuticals, Inc. Human chromosome 9 open reading frame 72 (c9orf72) irna agent compositions and methods of use thereof
TW202138559A (zh) 2019-12-16 2021-10-16 美商阿尼拉製藥公司 含類PATATIN磷脂酶結構域3(PNPLA3)iRNA組成物及其使用方法
WO2021154941A1 (en) 2020-01-31 2021-08-05 Alnylam Pharmaceuticals, Inc. Complement component c5 irna compositions for use in the treatment of amyotrophic lateral sclerosis (als)
MX2022009763A (es) 2020-02-10 2022-09-09 Alnylam Pharmaceuticals Inc Composiciones y metodos para silenciar la expresion del factor de crecimiento endotelial vascular a (vegf-a).
KR20220143106A (ko) 2020-02-18 2022-10-24 알닐람 파마슈티칼스 인코포레이티드 아포지질단백질 C3 (APOC3) iRNA 조성물 및 이의 사용 방법
WO2021178607A1 (en) 2020-03-05 2021-09-10 Alnylam Pharmaceuticals, Inc. Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases
BR112022017822A2 (pt) 2020-03-06 2022-11-08 Alnylam Pharmaceuticals Inc Composições de irna de cetoexocinase (khk) e métodos de uso das mesmas
EP4121534A1 (en) 2020-03-18 2023-01-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating subjects having a heterozygous alanine-glyoxylate aminotransferase gene (agxt) variant
WO2021195307A1 (en) 2020-03-26 2021-09-30 Alnylam Pharmaceuticals, Inc. Coronavirus irna compositions and methods of use thereof
EP4127171A2 (en) 2020-03-30 2023-02-08 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajc15 gene expression
WO2021202902A1 (en) 2020-04-01 2021-10-07 Alnylam Pharmaceuticals, Inc. ALPHA-2A ADRENERGIC RECEPTOR (ADRA2A) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
EP4133078A1 (en) 2020-04-06 2023-02-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing myoc expression
WO2021206922A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof
CA3179678A1 (en) 2020-04-07 2021-10-14 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing scn9a expression
EP4133076A1 (en) 2020-04-07 2023-02-15 Alnylam Pharmaceuticals, Inc. Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof
KR20230018377A (ko) 2020-04-27 2023-02-07 알닐람 파마슈티칼스 인코포레이티드 아포지질단백질 e (apoe) irna 제제 조성물 및 이의 사용 방법
MX2022013606A (es) 2020-04-30 2023-01-16 Alnylam Pharmaceuticals Inc Composiciones de ácido ribonucleico interferente (arni) del factor b de complemento (cfb) y métodos de uso de las mismas.
CN115916978A (zh) * 2020-05-19 2023-04-04 哈德森医学研究所 寡核苷酸
WO2021237097A1 (en) 2020-05-21 2021-11-25 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting marc1 gene expression
WO2021252557A1 (en) 2020-06-09 2021-12-16 Alnylam Pharmaceuticals, Inc. Rnai compositions and methods of use thereof for delivery by inhalation
CN116075592A (zh) 2020-06-09 2023-05-05 阿尔尼拉姆医药品有限公司 用于沉默gpam(线粒体甘油-3-磷酸酰基转移酶1)表达的sirna组合物和方法
TW202214856A (zh) 2020-06-18 2022-04-16 美商阿尼拉製藥公司 黃嘌呤脫氫酶(XDH)iRNA組成物及其使用之方法
US20230257745A1 (en) 2020-07-10 2023-08-17 Alnylam Pharmaceuticals, Inc. Circular siRNAs
EP4217489A1 (en) 2020-09-24 2023-08-02 Alnylam Pharmaceuticals, Inc. Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof
EP4222262A1 (en) * 2020-09-30 2023-08-09 BioMarin Technologies B.V. Antisense oligonucleotides targeting the exon 51 of dystrophin gene
JP2023544413A (ja) 2020-10-05 2023-10-23 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 Gタンパク質共役受容体75(GPR75)iRNA組成物およびその使用方法
EP4232581A1 (en) 2020-10-21 2023-08-30 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating primary hyperoxaluria
EP4232582A1 (en) 2020-10-23 2023-08-30 Alnylam Pharmaceuticals, Inc. Mucin 5b (muc5b) irna compositions and methods of use thereof
KR20230107625A (ko) 2020-11-13 2023-07-17 알닐람 파마슈티칼스 인코포레이티드 응고 인자 V(F5) iRNA 조성물 및 이의 사용 방법
WO2022119873A1 (en) 2020-12-01 2022-06-09 Alnylam Pharmaceuticals, Inc. Methods and compositions for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
WO2022125490A1 (en) 2020-12-08 2022-06-16 Alnylam Pharmaceuticals, Inc. Coagulation factor x (f10) irna compositions and methods of use thereof
WO2022147214A2 (en) 2020-12-31 2022-07-07 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
EP4271695A2 (en) 2020-12-31 2023-11-08 Alnylam Pharmaceuticals, Inc. 2'-modified nucleoside based oligonucleotide prodrugs
EP4274896A1 (en) 2021-01-05 2023-11-15 Alnylam Pharmaceuticals, Inc. Complement component 9 (c9) irna compositions and methods of use thereof
WO2022174000A2 (en) 2021-02-12 2022-08-18 Alnylam Pharmaceuticals, Inc. Superoxide dismutase 1 (sod1) irna compositions and methods of use thereof for treating or preventing superoxide dismutase 1- (sod1-) associated neurodegenerative diseases
CN117222739A (zh) 2021-02-25 2023-12-12 阿尔尼拉姆医药品有限公司 朊病毒蛋白(prnp)irna组合物和其使用方法
TW202302847A (zh) 2021-02-26 2023-01-16 美商艾拉倫製藥股份有限公司 己酮糖激酶(KHK)iRNA組成物及其使用方法
IL305442A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
WO2022192519A1 (en) 2021-03-12 2022-09-15 Alnylam Pharmaceuticals, Inc. Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof
WO2022212231A2 (en) 2021-03-29 2022-10-06 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof
EP4314293A1 (en) 2021-04-01 2024-02-07 Alnylam Pharmaceuticals, Inc. Proline dehydrogenase 2 (prodh2) irna compositions and methods of use thereof
EP4323525A2 (en) * 2021-04-16 2024-02-21 Genentech, Inc. Optimized tlr7 ligands and uses thereof
MX2023012586A (es) 2021-04-26 2023-10-31 Alnylam Pharmaceuticals Inc Composiciones de acido ribonucleico de interferencia (arni) de serina 6, proteasa transmembranaria (tmprss6) y sus metodos de uso.
JP2024519293A (ja) 2021-04-29 2024-05-10 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 シグナル伝達兼転写活性化因子6(STAT6)iRNA組成物およびその使用方法
WO2022245583A1 (en) 2021-05-18 2022-11-24 Alnylam Pharmaceuticals, Inc. Sodium-glucose cotransporter-2 (sglt2) irna compositions and methods of use thereof
EP4347823A1 (en) 2021-06-02 2024-04-10 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
CN117561334A (zh) 2021-06-04 2024-02-13 阿尔尼拉姆医药品有限公司 人染色体9开放阅读框72(C9ORF72)iRNA药剂组合物和其使用方法
EP4351541A2 (en) 2021-06-08 2024-04-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating or preventing stargardt's disease and/or retinal binding protein 4 (rbp4)-associated disorders
IL309296A (en) 2021-06-30 2024-02-01 Alnylam Pharmaceuticals Inc Methods and compositions for the treatment of angiotensinogen-related disorder (AGT-)
WO2023283403A2 (en) 2021-07-09 2023-01-12 Alnylam Pharmaceuticals, Inc. Bis-rnai compounds for cns delivery
WO2023003805A1 (en) 2021-07-19 2023-01-26 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating subjects having or at risk of developing a non-primary hyperoxaluria disease or disorder
TW202421169A (zh) 2021-07-21 2024-06-01 美商艾拉倫製藥股份有限公司 代謝疾患相關的標靶基因iRNA組成物及其使用方法
CA3226878A1 (en) 2021-07-23 2023-01-26 Alnylam Pharmaceuticals, Inc. Beta-catenin (ctnnb1) irna compositions and methods of use thereof
JP2024529437A (ja) 2021-07-29 2024-08-06 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 3-ヒドロキシ-3-メチルグリタル-COAレダクターゼ(HMGCR)iRNA組成物およびその使用方法
CA3227852A1 (en) 2021-08-03 2023-02-09 Alnylam Pharmaceuticals, Inc. Transthyretin (ttr) irna compositions and methods of use thereof
IL310295A (en) 2021-08-04 2024-03-01 Alnylam Pharmaceuticals Inc iRNA compositions and methods for silencing angiotensinogen (AGT)
KR20240045300A (ko) 2021-08-13 2024-04-05 알닐람 파마슈티칼스 인코포레이티드 인자 XII (F12) iRNA 조성물 및 이의 사용 방법
WO2023034837A2 (en) 2021-08-31 2023-03-09 Alnylam Pharmaceuticals, Inc. Cell death-inducing dffa-like effector b (cideb) irna compositions and methods of use thereof
JP2024535850A (ja) 2021-09-17 2024-10-02 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 補体成分(C3)をサイレンシングするためのiRNA組成物および方法
AU2022345881A1 (en) 2021-09-20 2024-03-21 Alnylam Pharmaceuticals, Inc. Inhibin subunit beta e (inhbe) modulator compositions and methods of use thereof
KR20240067943A (ko) 2021-09-24 2024-05-17 알닐람 파마슈티칼스 인코포레이티드 미소관 연관 단백질 타우(MAPT) iRNA 제제 조성물 및 이의 사용 방법
MX2024004437A (es) 2021-10-15 2024-07-01 Alnylam Pharmaceuticals Inc Composiciones de inhibidor de la angiotensina-receptor neprilisina (arni) de administracion extrahepatica y metodos de uso de las mismas.
WO2023076450A2 (en) 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
TW202333749A (zh) 2021-10-29 2023-09-01 美商艾拉倫製藥股份有限公司 補體因子b(cfb)irna組成物及其使用方法
WO2023141314A2 (en) 2022-01-24 2023-07-27 Alnylam Pharmaceuticals, Inc. Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof
WO2024006999A2 (en) 2022-06-30 2024-01-04 Alnylam Pharmaceuticals, Inc. Cyclic-disulfide modified phosphate based oligonucleotide prodrugs
JP2025532593A (ja) 2022-09-15 2025-10-01 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 17b-ヒドロキシステロイドデヒドロゲナーゼ13型(hsd17b13)irna組成物およびその使用方法
JP2025532985A (ja) 2022-09-30 2025-10-03 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 修飾二本鎖rna剤
AU2024254919A1 (en) 2023-04-12 2025-10-30 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery of double-stranded rna agents
KR20260049597A (ko) 2023-08-04 2026-04-14 알닐람 파마슈티칼스 인코포레이티드 Ctnnb1-관련 질환을 치료하기 위한 방법 및 조성물
WO2025064660A2 (en) 2023-09-21 2025-03-27 Alnylam Pharmaceuticals, Inc. Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof
WO2025076031A2 (en) 2023-10-03 2025-04-10 Alnylam Pharmaceuticals, Inc. Peritoneal macrophages comprising a nanoparticle encapsulating a nucleic acid molecule and methods of use thereof
US12454693B1 (en) * 2024-09-27 2025-10-28 Dexcel Pharma Technologies Ltd. Nucleic acids for inhibiting expression of transferrin receptor 2

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5912332A (en) 1996-07-26 1999-06-15 Hybridon, Inc. Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides
EP0855184A1 (en) 1997-01-23 1998-07-29 Grayson B. Dr. Lipford Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination
US6248539B1 (en) * 1997-09-05 2001-06-19 The Scripps Research Institute Porous semiconductor-based optical interferometric sensor
US8153141B2 (en) * 2002-04-04 2012-04-10 Coley Pharmaceutical Gmbh Immunostimulatory G, U-containing oligoribonucleotides
MXPA05013658A (es) * 2003-06-11 2006-03-02 Hybridon Inc Oligonucleotidos inmunomoduladores estabilizados.
WO2005097993A2 (en) * 2004-02-19 2005-10-20 Coley Pharmaceutical Group, Inc. Immunostimulatory viral rna oligonucleotides
EP2371956A3 (en) * 2005-11-07 2012-01-04 Idera Pharmaceuticals Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides
US7776834B2 (en) * 2005-11-07 2010-08-17 Idera Pharmaceuticals, Inc. Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides
PL1957647T3 (pl) * 2005-11-25 2015-07-31 Zoetis Belgium S A Oligorybonukleotydy immunostymulujące
EP2021008B1 (en) * 2006-04-07 2015-12-02 Idera Pharmaceuticals, Inc. Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8

Also Published As

Publication number Publication date
US8362233B2 (en) 2013-01-29
JP2010532996A (ja) 2010-10-21
KR20100055413A (ko) 2010-05-26
CN102921003A (zh) 2013-02-13
AU2008279509B2 (en) 2011-07-21
EP2178567A2 (en) 2010-04-28
EP2357231A2 (en) 2011-08-17
EP2178567A4 (en) 2010-11-03
CN101795715A (zh) 2010-08-04
US20090053205A1 (en) 2009-02-26
KR101343489B1 (ko) 2013-12-20
WO2009014887A3 (en) 2009-12-30
US8188261B2 (en) 2012-05-29
EP2348112A3 (en) 2015-09-02
CN102921003B (zh) 2014-11-26
JP5737937B2 (ja) 2015-06-17
EP2348112B1 (en) 2018-11-28
AU2008279509A1 (en) 2009-01-29
EP2348112A2 (en) 2011-07-27
CA2692161A1 (en) 2009-01-29
US20120183530A1 (en) 2012-07-19
WO2009014887A2 (en) 2009-01-29

Similar Documents

Publication Publication Date Title
CA2692161C (en) Stabilized immune modulatory rna (simra) compounds
CA2648585C (en) Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8
US8202974B2 (en) Synthetic RNA-based agonists of TLR7
CA2624755C (en) Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response
CA2762206C (en) Potentiation of autoimmune and inflammatory disease treatments by immune regulatory oligonucleotide (iro) antagonists of tlr7 and tlr9
HK1159165B (en) Stabilized immune modulatory rna (simra) compounds
HK1159165A (en) Stabilized immune modulatory rna (simra) compounds
HK1127727B (en) Stabilized immune modulatory rna (simra) compounds for tlr7 and tlr8

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20130604

H11 Ip right ceased following rejected request for revival

Free format text: ST27 STATUS EVENT CODE: T-6-6-H10-H11-H101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: TIME LIMIT FOR REVERSAL EXPIRED

Effective date: 20250108