BR112018068410A2 - oligonucleotídeos para redução da expressão de pd-l1 - Google Patents

oligonucleotídeos para redução da expressão de pd-l1

Info

Publication number
BR112018068410A2
BR112018068410A2 BR112018068410A BR112018068410A BR112018068410A2 BR 112018068410 A2 BR112018068410 A2 BR 112018068410A2 BR 112018068410 A BR112018068410 A BR 112018068410A BR 112018068410 A BR112018068410 A BR 112018068410A BR 112018068410 A2 BR112018068410 A2 BR 112018068410A2
Authority
BR
Brazil
Prior art keywords
oligonucleotides
expression
reducing
liver
present
Prior art date
Application number
BR112018068410A
Other languages
English (en)
Inventor
Javanbakht Hassan
PEDERSEN Lykke
Jackerott Malene
Ottosen Soren
Luangsay Souphalone
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of BR112018068410A2 publication Critical patent/BR112018068410A2/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/1131—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 viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/1138—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 receptors or cell surface proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511—Organic adjuvants
    • A61K2039/55516—Proteins; Peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/26—Infectious diseases, e.g. generalised sepsis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

refere-se a presente invenção a oligonucleotídeos anti -sentido que são capazes de reduzir a expressão de pd-l1 em uma célula alvo. os oligonucleotídeos proporcionam a hibridização com o arnm de pd-l1. a presente invenção refere-se ainda aos conjugados do oligonucleotídeo e composições farmacêuticas e métodos para o tratamento de infecções virais do fígado tais como hbv, hcv e hdv; infecções por parasitas, tais como malária, toxoplasmose, leishmaniose e tripanossomíase, ou câncer de fígado ou metástases no fígado utilizando-se o oligonucleotídeo.
BR112018068410A 2016-03-14 2017-03-14 oligonucleotídeos para redução da expressão de pd-l1 BR112018068410A2 (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16160149 2016-03-14
PCT/EP2017/055925 WO2017157899A1 (en) 2016-03-14 2017-03-14 Oligonucleotides for reduction of pd-l1 expression

Publications (1)

Publication Number Publication Date
BR112018068410A2 true BR112018068410A2 (pt) 2019-01-15

Family

ID=58314191

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112018068410A BR112018068410A2 (pt) 2016-03-14 2017-03-14 oligonucleotídeos para redução da expressão de pd-l1

Country Status (31)

Country Link
US (5) US20170283496A1 (pt)
EP (2) EP3786297A1 (pt)
JP (4) JP6748219B2 (pt)
KR (4) KR20230136689A (pt)
CN (4) CN114717235A (pt)
AR (2) AR108038A1 (pt)
AU (3) AU2017235278C1 (pt)
BR (1) BR112018068410A2 (pt)
CA (2) CA3120687A1 (pt)
CL (4) CL2018002570A1 (pt)
CO (1) CO2018007761A2 (pt)
CR (2) CR20200119A (pt)
DK (1) DK3430141T3 (pt)
ES (1) ES2857702T3 (pt)
HR (1) HRP20210315T1 (pt)
HU (1) HUE053172T2 (pt)
IL (4) IL303077A (pt)
LT (1) LT3430141T (pt)
MX (2) MX2018010830A (pt)
MY (1) MY194912A (pt)
PE (3) PE20230157A1 (pt)
PH (1) PH12018501964A1 (pt)
PL (1) PL3430141T3 (pt)
PT (1) PT3430141T (pt)
RS (1) RS61528B1 (pt)
RU (1) RU2747822C2 (pt)
SG (1) SG11201807854SA (pt)
SI (1) SI3430141T1 (pt)
TW (3) TWI794662B (pt)
UA (1) UA127432C2 (pt)
WO (1) WO2017157899A1 (pt)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2744987C (en) 2008-12-02 2018-01-16 Chiralgen, Ltd. Method for the synthesis of phosphorus atom modified nucleic acids
BR112012000828A8 (pt) 2009-07-06 2017-10-10 Ontorii Inc Novas pró-drogas de ácido nucleico e métodos de uso das mesmas
US10428019B2 (en) 2010-09-24 2019-10-01 Wave Life Sciences Ltd. Chiral auxiliaries
RU2014105311A (ru) 2011-07-19 2015-08-27 Уэйв Лайф Сайенсес Пте. Лтд. Способы синтеза функционализованных нуклеиновых кислот
JP6268157B2 (ja) 2012-07-13 2018-01-24 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ 不斉補助基
SG10201912895PA (en) 2012-07-13 2020-02-27 Wave Life Sciences Ltd Chiral control
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
JPWO2015108047A1 (ja) 2014-01-15 2017-03-23 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
KR102423317B1 (ko) 2014-01-16 2022-07-22 웨이브 라이프 사이언시스 리미티드 키랄 디자인
JP2018520688A (ja) 2015-07-21 2018-08-02 ザ チルドレンズ メディカル センター コーポレーション Ｐｄ−ｌ１発現造血幹細胞およびその使用
AU2017235278C1 (en) 2016-03-14 2022-03-10 F. Hoffmann-La Roche Ag Oligonucleotides for reduction of PD-L1 expression
US20220354888A1 (en) * 2016-08-03 2022-11-10 Aalborg Universitet ANTISENSE OLIGONUCLEOTIDES (ASOs) DESIGNED TO INHIBIT IMMUNE CHECKPOINT PROTEINS
WO2018065589A1 (en) 2016-10-07 2018-04-12 Secarna Pharmaceuticals Gmbh & Co. Kg Novel approach for treating cancer
US11879137B2 (en) 2017-09-22 2024-01-23 The Children's Medical Center Corporation Treatment of type 1 diabetes and autoimmune diseases or disorders
CN111511914B (zh) * 2017-10-16 2023-11-17 豪夫迈·罗氏有限公司 减少PAPD5和PAPD7 mRNA的核酸分子用于治疗乙型肝炎感染
WO2019140236A1 (en) * 2018-01-12 2019-07-18 Bristol-Myers Squibb Company Antisense oligonucleotides targeting alpha-synuclein and uses thereof
WO2020007772A1 (en) * 2018-07-02 2020-01-09 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting gbp-1
WO2020011653A1 (en) * 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
US20210380978A1 (en) * 2018-10-15 2021-12-09 The Brigham And Women`S Hospital, Inc. The long non-coding RNA INCA1 and Homo sapiens heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) as therapeutic targets for immunotherapy
WO2020178258A1 (en) * 2019-03-05 2020-09-10 F. Hoffmann-La Roche Ag Intracellular targeting of molecules
US20220177894A1 (en) 2019-04-02 2022-06-09 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for immunotherapy
JP2022531415A (ja) 2019-05-03 2022-07-06 セカルナ・ファーマシューティカルズ・ゲーエムベーハー・ウント・コ・カーゲー 腫瘍の処置に使用するためのｐｄ－ｌ１アンチセンスオリゴヌクレオチド
CN114901821A (zh) * 2019-12-19 2022-08-12 豪夫迈·罗氏有限公司 Sept9抑制剂用于治疗乙型肝炎病毒感染的用途
CN114829601A (zh) * 2019-12-19 2022-07-29 豪夫迈·罗氏有限公司 Sbds抑制剂用于治疗乙型肝炎病毒感染的用途
WO2021123086A1 (en) * 2019-12-20 2021-06-24 F. Hoffmann-La Roche Ag Enhanced oligonucleotides for inhibiting scn9a expression
WO2021173812A1 (en) * 2020-02-28 2021-09-02 Aligos Therapeutics, Inc. Methods and compositions for targeting pd-l1
IL300340A (en) 2020-08-05 2023-04-01 Hoffmann La Roche Treatment with oligonucleotides in hepatitis B patients
WO2023011597A1 (en) * 2021-08-04 2023-02-09 Hepagene Therapeutics (HK) Limited Ligand conjugates for delivery of therapeutically active agents
CN113789324B (zh) * 2021-08-17 2023-08-25 广东省大湾区华南理工大学聚集诱导发光高等研究院 一种aie探针及其制备方法与在荧光定量pcr方法中的应用
WO2023083906A2 (en) 2021-11-11 2023-05-19 F. Hoffmann-La Roche Ag Pharmaceutical combinations for treatment of hbv
WO2024011109A2 (en) * 2022-07-06 2024-01-11 Adverum Biotechnologies, Inc. Compositions and methods for treatment of achromotopsia

Family Cites Families (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
CA2095212A1 (en) 1990-11-08 1992-05-09 Sudhir Agrawal Incorporation of multiple reporter groups on synthetic oligonucleotides
RU2123528C1 (ru) * 1990-11-08 1998-12-20 Чирон Корпорейшн Способ получения белков hcv, пригодных для использования в вакцине или иммуноанализе, асиалогликопротеин (варианты), композиция для использования в вакцине или в иммуноанализе (варианты), способ очистки асиалогликопротеина и способ понижения содержания или элиминации hcv
ATE239484T1 (de) 1991-10-24 2003-05-15 Isis Pharmaceuticals Inc Derivatisierte oligonukleotide mit verbessertem aufnahmevermögen
NL9201440A (nl) 1992-08-11 1994-03-01 Univ Leiden Triantennaire clusterglycosiden, hun bereiding en toepassing.
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
AU3999495A (en) 1994-10-06 1996-05-02 Buchardt, Dorte Peptide nucleic acid conjugates
US5684142A (en) 1995-06-07 1997-11-04 Oncor, Inc. Modified nucleotides for nucleic acid labeling
CN1120707C (zh) 1995-11-22 2003-09-10 约翰斯·霍普金斯大学 增强生物分子的细胞摄取的配体
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
US5770716A (en) 1997-04-10 1998-06-23 The Perkin-Elmer Corporation Substituted propargylethoxyamido nucleosides, oligonucleotides and methods for using same
EP0975370B9 (en) 1997-05-21 2004-11-03 The Board Of Trustees Of The Leland Stanford Junior University Composition and method for enhancing transport across biological membranes
CN1273476C (zh) 1997-09-12 2006-09-06 埃克西康有限公司 寡核苷酸类似物
US6096875A (en) 1998-05-29 2000-08-01 The Perlein-Elmer Corporation Nucleotide compounds including a rigid linker
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6335432B1 (en) 1998-08-07 2002-01-01 Bio-Red Laboratories, Inc. Structural analogs of amine bases and nucleosides
US6335437B1 (en) 1998-09-07 2002-01-01 Isis Pharmaceuticals, Inc. Methods for the preparation of conjugated oligomers
ES2234563T5 (es) 1999-02-12 2018-01-17 Daiichi Sankyo Company, Limited Nuevos análogos de nucleósidos y oligonucleótidos
NZ514348A (en) 1999-05-04 2004-05-28 Exiqon As L-ribo-LNA analogues
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
WO2005007855A2 (en) 2003-07-14 2005-01-27 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF B7-H1 GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20060276422A1 (en) 2001-05-18 2006-12-07 Nassim Usman RNA interference mediated inhibition of B7-H1 gene expression using short interfering nucleic acid (siNA)
US20040142325A1 (en) 2001-09-14 2004-07-22 Liat Mintz Methods and systems for annotating biomolecular sequences
EP3287144A1 (en) * 2002-07-03 2018-02-28 ONO Pharmaceutical Co., Ltd. Immunopotentiating compositions
EP1569661B1 (en) 2002-11-18 2009-09-09 Santaris Pharma A/S Antisense design
BRPI0411219A (pt) 2003-06-12 2006-07-18 Nucleonics Inc seqüências de hbv e hcv conservadas úteis para silenciamento de gene
DK1495769T3 (da) 2003-07-11 2008-06-23 Lbr Medbiotech B V Mannose-6-phosphat-receptormedieret gentransfer til muskelceller
JP5303146B2 (ja) 2004-10-06 2013-10-02 メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ Ｂ７−ｈ１ならびに癌の診断、予後診断および処置の方法
ZA200703482B (en) * 2004-10-06 2008-09-25 Mayo Foundation B7-H1 and methods of diagnosis, prognosis, and treatment of cancer
US20120122801A1 (en) 2005-01-05 2012-05-17 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
SI1907000T2 (sl) 2005-06-08 2020-07-31 Dana-Farber Cancer Institute Postopki in sestavki za zdravljenje persistentne HIV infekcije z inhibicijo programiranih celični smrtnih 1 (PD-1) poti
WO2007031091A2 (en) 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
PL2314594T3 (pl) 2006-01-27 2014-12-31 Isis Pharmaceuticals Inc Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych
WO2007134014A2 (en) 2006-05-05 2007-11-22 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of gcgr
DK2066684T3 (da) 2006-05-11 2012-10-22 Isis Pharmaceuticals Inc 5´-Modificerede bicycliske nukleinsyreanaloge
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
EP2133365B1 (en) 2006-12-27 2017-05-17 Emory University Compositions and methods for the treatment of infections and tumors
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede mRNA
ES2388590T3 (es) 2007-05-30 2012-10-16 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos con puente aminometileno N-sustituido.
ES2386492T3 (es) 2007-06-08 2012-08-21 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos carbocíclicos
ES2376507T5 (es) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos 6-disustituidos
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
WO2009124238A1 (en) 2008-04-04 2009-10-08 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising neutrally linked terminal bicyclic nucleosides
WO2009126933A2 (en) 2008-04-11 2009-10-15 Alnylam Pharmaceuticals, Inc. Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
EP2356129B1 (en) 2008-09-24 2013-04-03 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
MX2011005691A (es) 2008-11-28 2011-07-20 Univ Emory Metodos para el tratamiento de infecciones y tumores.
US9181525B2 (en) * 2009-03-06 2015-11-10 Mie University Method for enhancing a function of a T cell
KR101835889B1 (ko) * 2009-05-06 2018-03-08 큐알엔에이, 인크. 지질 수송 및 대사 유전자에 대한 천연 안티센스 전사체의 억제에 의해 지질 수송 및 대사 유전자 관련된 질환의 치료
CN103221541B (zh) * 2009-05-28 2017-03-01 库尔纳公司 通过抑制抗病毒基因的天然反义转录物来治疗抗病毒基因相关疾病
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
EP2555778A4 (en) 2010-04-06 2014-05-21 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR INHIBITING CD274 / PD-L1 GENE EXPRESSION
WO2011156202A1 (en) 2010-06-08 2011-12-15 Isis Pharmaceuticals, Inc. Substituted 2 '-amino and 2 '-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
KR102072631B1 (ko) 2010-08-17 2020-02-03 시르나 쎄러퓨틱스 인코퍼레이티드 짧은 간섭 핵산 （ｓｉＮＡ）을 사용한 Ｂ형 간염 바이러스 （ＨＢＶ） 유전자 발현의 ＲＮＡ 간섭 매개 억제
PL3124610T3 (pl) 2010-10-28 2019-09-30 Benitec Biopharma Limited Leczenie hbv
KR20130132475A (ko) 2010-12-17 2013-12-04 애로우헤드 리서치 코오포레이션 ｓｉＲＮＡ의 갈락토오스 클러스터-약동학적 조절제 표적 물질
BR122020024388B1 (pt) 2010-12-29 2021-09-21 F. Hoffmann-La Roche Ag Oligonucleotídeo e composição farmacêutica
RU2667524C2 (ru) 2011-04-21 2018-09-21 Ионис Фармасьютикалз, Инк. Модулирование экспрессии вируса гепатита b (hbv)
CN113430196A (zh) 2011-06-30 2021-09-24 箭头药业股份有限公司 用于抑制乙型肝炎病毒的基因表达的组合物和方法
RU2014105311A (ru) 2011-07-19 2015-08-27 Уэйв Лайф Сайенсес Пте. Лтд. Способы синтеза функционализованных нуклеиновых кислот
EP3453761A1 (en) 2011-08-29 2019-03-13 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
CN104136451A (zh) 2011-09-07 2014-11-05 玛瑞纳生物技术有限公司 具有构象限制的单体的核酸化合物的合成和用途
WO2013049307A2 (en) 2011-09-30 2013-04-04 University Of Miami Enhanced immune memory development by aptamer targeted mtor inhibition of t cells
WO2013154798A1 (en) 2012-04-09 2013-10-17 Isis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
WO2013159109A1 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Modulation of hepatitis b virus (hbv) expression
WO2013173635A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
US10174323B2 (en) * 2012-05-16 2019-01-08 The General Hospital Corporation Compositions and methods for modulating ATP2A2 expression
JP6268157B2 (ja) 2012-07-13 2018-01-24 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ 不斉補助基
MY173826A (en) 2012-11-15 2020-02-24 Roche Innovation Ct Copenhagen As Oligonucleotide conjugates
BR112015012644A2 (pt) 2012-11-30 2017-12-19 Hoffmann La Roche método para determinar a necessidade de um paciente com câncer, método de tratamento do câncer, composição farmacêutica, uso de um ácido nucleico ou anticorpo e kit;
WO2014118272A1 (en) * 2013-01-30 2014-08-07 Santaris Pharma A/S Antimir-122 oligonucleotide carbohydrate conjugates
BR112015018161A2 (pt) * 2013-01-30 2017-08-22 Hoffmann La Roche Conjugado de oligômeros antisense de lna, composição farmacêutica e uso de um conjugado de oligômeros antisense de lna
IL284593B2 (en) 2013-05-01 2023-02-01 Ionis Pharmaceuticals Inc Compositions and methods for modulation of hbv and ttr expression
CN112263682A (zh) 2013-06-27 2021-01-26 罗氏创新中心哥本哈根有限公司 靶向pcsk9的反义寡聚体和缀合物
WO2015114146A1 (en) * 2014-02-03 2015-08-06 Sividon Diagnostics Gmbh Method for predicting the response to an anti-her2 containing therapy and/or chemotherapy in patients with breast cancer
US20170216403A1 (en) 2014-08-12 2017-08-03 Massachusetts Institute Of Technology Synergistic tumor treatment with il-2, a therapeutic antibody, and an immune checkpoint blocker
AU2015329974B2 (en) 2014-10-10 2019-06-20 F. Hoffmann-La Roche Ag GaINAc phosphoramidites, nucleic acid conjugates thereof and their use
US9828601B2 (en) 2015-02-27 2017-11-28 Idera Pharmaceuticals, Inc. Compositions for inhibiting checkpoint gene expression and uses thereof
GB201507926D0 (en) 2015-05-08 2015-06-24 Proqr Therapeutics N V Improved treatments using oligonucleotides
JP6893505B2 (ja) * 2015-10-02 2021-06-23 ロシュ イノベーション センター コペンハーゲン エーエス オリゴヌクレオチドコンジュゲーション方法
PL3377510T3 (pl) 2015-11-16 2021-05-04 F. Hoffmann-La Roche Ag Amidofosforyn klastra GalNAc
EP3387131A4 (en) 2015-12-09 2019-08-07 Alnylam Pharmaceuticals, Inc. POLYNUCLEOTIDE AGENTS TARGETING LIGAND 1 OF PROGRAMMED CELL DEATH 1 (PD-L1) AND THEIR METHODS OF USE
AU2017235278C1 (en) 2016-03-14 2022-03-10 F. Hoffmann-La Roche Ag Oligonucleotides for reduction of PD-L1 expression

Also Published As

Publication number Publication date
KR102580776B1 (ko) 2023-09-20
WO2017157899A1 (en) 2017-09-21
AR118719A2 (es) 2021-10-27
PE20181892A1 (es) 2018-12-11
AU2017235278A8 (en) 2018-08-16
RU2018134379A3 (pt) 2020-06-23
JP2022034059A (ja) 2022-03-02
KR20210120131A (ko) 2021-10-06
KR102306797B1 (ko) 2021-10-05
TWI794662B (zh) 2023-03-01
ES2857702T3 (es) 2021-09-29
MY194912A (en) 2022-12-22
CR20180432A (es) 2018-11-21
US20230331837A1 (en) 2023-10-19
DK3430141T3 (da) 2021-03-01
CN114085836B (zh) 2024-01-26
KR20230136689A (ko) 2023-09-26
TW202128998A (zh) 2021-08-01
AR108038A1 (es) 2018-07-11
TWI790485B (zh) 2023-01-21
CN114736900A (zh) 2022-07-12
PE20201499A1 (es) 2020-12-29
IL290294B (en) 2022-10-01
PL3430141T3 (pl) 2022-02-28
KR20220100095A (ko) 2022-07-14
US20200048344A1 (en) 2020-02-13
RU2018134379A (ru) 2020-04-15
KR102417646B1 (ko) 2022-07-07
US10745480B2 (en) 2020-08-18
CL2020000865A1 (es) 2020-08-28
RU2747822C2 (ru) 2021-05-14
CN108779465B (zh) 2022-05-13
CL2020001127A1 (es) 2020-08-28
HRP20210315T1 (hr) 2021-04-16
CL2018002570A1 (es) 2018-12-28
IL296483A (en) 2022-11-01
CA3013683C (en) 2021-07-13
IL290294A (en) 2022-04-01
TW201734209A (zh) 2017-10-01
EP3430141A1 (en) 2019-01-23
AU2021236439A1 (en) 2021-10-14
CL2020001126A1 (es) 2020-08-28
IL260759B (en) 2022-03-01
TWI721128B (zh) 2021-03-11
KR20180120702A (ko) 2018-11-06
IL303077A (en) 2023-07-01
JP2024029180A (ja) 2024-03-05
CR20200119A (es) 2021-04-19
CN114085836A (zh) 2022-02-25
AU2021236439B2 (en) 2022-06-16
US20170283496A1 (en) 2017-10-05
LT3430141T (lt) 2021-03-25
EP3786297A1 (en) 2021-03-03
PT3430141T (pt) 2021-02-25
UA127432C2 (uk) 2023-08-23
JP7447073B2 (ja) 2024-03-11
TW202128997A (zh) 2021-08-01
CO2018007761A2 (es) 2018-08-10
JP2019512498A (ja) 2019-05-16
TW202328448A (zh) 2023-07-16
IL290294B2 (en) 2023-02-01
CN114717235A (zh) 2022-07-08
US10829555B2 (en) 2020-11-10
IL296483B2 (en) 2023-10-01
AU2017235278B2 (en) 2021-11-11
RS61528B1 (sr) 2021-04-29
HUE053172T2 (hu) 2021-06-28
JP7002603B2 (ja) 2022-02-10
US20200247884A1 (en) 2020-08-06
AU2017235278C1 (en) 2022-03-10
AU2022202479A1 (en) 2022-05-12
CA3013683A1 (en) 2017-09-21
SG11201807854SA (en) 2018-10-30
SI3430141T1 (sl) 2021-04-30
CA3120687A1 (en) 2017-09-21
EP3430141B1 (en) 2020-12-30
MX2018010830A (es) 2019-02-07
JP2020172488A (ja) 2020-10-22
PH12018501964A1 (en) 2019-06-24
PE20230157A1 (es) 2023-02-01
CN108779465A (zh) 2018-11-09
IL296483B1 (en) 2023-06-01
US20210147535A1 (en) 2021-05-20
CN114736901A (zh) 2022-07-12
JP6748219B2 (ja) 2020-08-26
AU2017235278A1 (en) 2018-08-09
US11466081B2 (en) 2022-10-11
MX2022012221A (es) 2022-10-27

Similar Documents

Publication Publication Date Title
BR112018068410A2 (pt) oligonucleotídeos para redução da expressão de pd-l1
CY1122946T1 (el) Μεθοδοι για θεραπεια filoviridαε ιου μολυνσεων
UY37353A (es) Agentes de iarn para la infección por el virus de la hepatitis b
BR112017008868A2 (pt) composições de irna do vírus da hepatite b (hbv) e métodos de seu uso
CL2018003561A1 (es) Moléculas de ácido nucleico para la reducción de arnm de papd5 o papd7 para tratar la infección por hepatitis b
CY1123289T1 (el) Ενωσεις ολιγονουκλεοτιδιων για τη στοχευση του huntingtin mrna
BR112018011450A2 (pt) métodos e composições para o tratamento de um transtorno associado à serpinc1
BR112017018318A2 (pt) composição farmacêutica para tratar câncer compreendendo microrna como ingrediente ativo
BR112017013028A2 (pt) nucleosídeos, nucleotídeos e análogos dos mesmos substituídos
BR112017021021A2 (pt) inibidores de indolamina-2,3-dioxigenase para o tratamento de câncer
CL2016000493A1 (es) Inhibidores de polimerasa hcv.
BR112019010342A2 (pt) composições do irna de serpina1 e métodos de uso destas
ECSP15031144A (es) Nucleósidos sustituidos, nucleótidos y análogos de los mismos
BR112013005872A2 (pt) compostos, composição farmacêutica e respectivos usos
BR112017012859A2 (pt) fosforamidatos para o tratamento do vírus da hepatite b
AR100840A1 (es) COMPOSICIONES Y MÉTODOS PARA INHIBIR LA EXPRESIÓN DEL GEN DE a-1 ANTITRIPSINA
BR112017025698A2 (pt) composições e métodos para inibir a expressão do gene de hif2alfa
PE20170440A1 (es) Derivados de isoindolina
BR112016007226A2 (pt) composições e métodos para inibição da expressão do gene alas1
BR112018009946A2 (pt) pró-fármacos de ácido nucleico
UY37936A (es) AGENTES iARN Y COMPOSICIONES PARA INHIBIR LA EXPRESIÓN DEL RECEPTOR DE ASIALOGLICOPROTEÍNA 1
BR112019008856A2 (pt) rnas de fita dupla quimicamente modificados pós-transcricionalmente
CL2016002737A1 (es) Nucleasa efectora tal para la inactivación específica del correceptor del vih ccr5
EA202191771A1 (ru) КОМПОЗИЦИИ НА ОСНОВЕ RNAi ПРОТИВ ВИРУСА ГЕПАТИТА В (HBV) И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
AR105532A1 (es) Composiciones y métodos para silenciar la expresión génica del virus de la hepatitis b

Legal Events

Date Code Title Description
B350 Update of information on the portal [chapter 15.35 patent gazette]
B06W Patent application suspended after preliminary examination (for patents with searches from other patent authorities) chapter 6.23 patent gazette]
B154 Notification of filing of divisional application [chapter 15.50 patent gazette]

Free format text: O PEDIDO FOI DIVIDIDO NO BR122022026376-3 PROTOCOLO 870220121112 EM 22/12/2022 15:54.O PEDIDO FOI DIVIDIDO NO BR122022026389-5 PROTOCOLO 870220121153 EM 22/12/2022 16:21.

B06A Patent application procedure suspended [chapter 6.1 patent gazette]