BR112020012427A8 - Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo - Google Patents

Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo

Info

Publication number
BR112020012427A8
BR112020012427A8 BR112020012427A BR112020012427A BR112020012427A8 BR 112020012427 A8 BR112020012427 A8 BR 112020012427A8 BR 112020012427 A BR112020012427 A BR 112020012427A BR 112020012427 A BR112020012427 A BR 112020012427A BR 112020012427 A8 BR112020012427 A8 BR 112020012427A8
Authority
BR
Brazil
Prior art keywords
oligonucleotide
oligonucleotides
conjugate
pharmaceutically acceptable
pharmaceutical composition
Prior art date
Application number
BR112020012427A
Other languages
English (en)
Other versions
BR112020012427A2 (pt
Inventor
Adrian Schaeublin
Erik Funder
Frydenlund Hansen Henrik
Jesper Worm
Joerg Duschmalé
Konrad Bleicher
Lars Joenson
Brigitte Duschmalé Martina
Meiling Li
Troels Koch
Xi Shu
Yong Wu
Original Assignee
Roche Innovation Ct Copenhagen As
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 Roche Innovation Ct Copenhagen As filed Critical Roche Innovation Ct Copenhagen As
Publication of BR112020012427A2 publication Critical patent/BR112020012427A2/pt
Publication of BR112020012427A8 publication Critical patent/BR112020012427A8/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/02—Phosphorylation
    • 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
    • C12N2310/313—Phosphorodithioates
    • 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
    • C12N2310/323—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
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

Abstract

oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo. a presente invenção refere-se a um oligonucleotídeo compreendendo pelo menos uma ligação internucleosídica de fosforoditioato de fórmula (i), conforme definido na descrição e nas reivindicações. o oligonucleotídeo da invenção pode ser usado como um medicamento.
BR112020012427A 2017-12-22 2018-12-21 Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo BR112020012427A8 (pt)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CNPCT/CN2017118040 2017-12-22
CN2017118040 2017-12-22
EP18198479 2018-10-03
EP18198479.0 2018-10-03
PCT/EP2018/086460 WO2019122279A1 (en) 2017-12-22 2018-12-21 Oligonucleotides comprising a phosphorodithioate internucleoside linkage

Publications (2)

Publication Number Publication Date
BR112020012427A2 BR112020012427A2 (pt) 2020-11-24
BR112020012427A8 true BR112020012427A8 (pt) 2024-04-02

Family

ID=65011984

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112020012427A BR112020012427A8 (pt) 2017-12-22 2018-12-21 Oligonucleotídeos, sal farmaceuticamente aceitável, conjugado, composição farmacêutica e processo para a fabricação de um oligonucleotídeo

Country Status (12)

Country Link
US (2) US20200339982A1 (pt)
EP (2) EP4074724A1 (pt)
JP (2) JP7476102B2 (pt)
KR (1) KR20200104345A (pt)
CN (1) CN111757936A (pt)
AU (1) AU2018386524A1 (pt)
BR (1) BR112020012427A8 (pt)
CA (1) CA3085406A1 (pt)
IL (1) IL275399A (pt)
MX (1) MX2020006430A (pt)
TW (1) TW201929870A (pt)
WO (1) WO2019122279A1 (pt)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117795069A (zh) * 2021-06-02 2024-03-29 阿塔兰塔治疗公司 用于将治疗性寡核苷酸递送至中枢神经系统的组合物和方法

Family Cites Families (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL90359A0 (en) * 1988-05-26 1989-12-15 University Patents Inc Nucleoside and polynucleotide thiophosphoramidite and phosphorodithioate compounds and their production
US5218088A (en) * 1989-11-02 1993-06-08 Purdue Research Foundation Process for preparing dithiophosphate oligonucleotide analogs via nucleoside thiophosphoramidite intermediates
ATE239484T1 (de) 1991-10-24 2003-05-15 Isis Pharmaceuticals Inc Derivatisierte oligonukleotide mit verbessertem aufnahmevermögen
WO1998008858A1 (en) * 1996-08-26 1998-03-05 Hybridon, Inc. Improved reagents and process for synthesis of oligonucleotides containing phosphorodithioate internucleoside linkages
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
CA2303299C (en) 1997-09-12 2016-02-23 Exiqon A/S Oligonucleotide analogues
NZ513402A (en) 1999-02-12 2003-06-30 Sankyo Co Novel nucleosides and oligonucleotide analogues
CA2372085C (en) 1999-05-04 2009-10-27 Exiqon A/S L-ribo-lna analogues
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
US7687617B2 (en) 2002-11-18 2010-03-30 Santaris Pharma A/S Oligonucleotides with alternating segments of locked and non-locked nucleotides
EP2535413A3 (en) 2005-11-10 2016-04-13 Roche Innovation Center Copenhagen A/S Splice switching oligomers for the TNF superfamily receptors and their use in treatment of disease
JP5342881B2 (ja) 2006-01-27 2013-11-13 アイシス ファーマシューティカルズ， インコーポレーテッド ６−修飾された二環式核酸類似体
KR101407707B1 (ko) 2006-04-03 2014-06-19 산타리스 팔마 에이/에스 Ａｎｔｉ-ｍｉｒｎａ 안티센스 올리고뉴클레오타이드를 함유하는 약학적 조성물
DK2015758T3 (da) 2006-05-05 2014-06-23 Isis Pharmaceuticals Inc Forbindelser og fremgangsmåder til modulering af ekspression af apob
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
US7547684B2 (en) 2006-05-11 2009-06-16 Isis Pharmaceuticals, Inc. 5′-modified bicyclic nucleic acid analogs
ES2377327T5 (es) 2006-10-18 2020-04-28 Ionis Pharmaceuticals Inc Compuestos antisentido
DK2149605T3 (da) 2007-03-22 2013-09-30 Santaris Pharma As Korte RNA antagonist forbindelser til modulering af det ønskede mRNA
JP2010524476A (ja) 2007-05-01 2010-07-22 サンタリス ファーマ アー／エス Ｔｎｆスーパーファミリー受容体についてのスプライススイッチオリゴマーおよび疾患の治療におけるそれらの使用方法
US8278425B2 (en) 2007-05-30 2012-10-02 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
WO2008154401A2 (en) 2007-06-08 2008-12-18 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
WO2009043354A2 (en) 2007-10-04 2009-04-09 Santaris Pharma A/S Combination treatment for the treatment of hepatitis c virus infection
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
DK2356129T3 (da) 2008-09-24 2013-05-13 Isis Pharmaceuticals Inc Substituerede alpha-L-bicykliske nukleosider
WO2011017521A2 (en) 2009-08-06 2011-02-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US8846637B2 (en) 2010-06-08 2014-09-30 Isis Pharmaceuticals, Inc. Substituted 2′-amino and 2′-thio-bicyclic nucleosides and oligomeric compounds prepared therefrom
JP6336755B2 (ja) 2010-11-12 2018-06-06 ザ ジェネラル ホスピタル コーポレイション ポリコームに関連する非コードｒｎａ
EP3067421B1 (en) 2011-02-08 2018-10-10 Ionis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
DK2742135T4 (da) 2011-08-11 2020-07-13 Ionis Pharmaceuticals Inc Bindingsmodificerede gapped oligomeriske forbindelser og anvendelser deraf
US10023861B2 (en) 2011-08-29 2018-07-17 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EP2753631A1 (en) 2011-09-07 2014-07-16 Marina Biotech, Inc. Synthesis and uses of nucleic acid compounds with conformationally restricted monomers
EP2850092B1 (en) 2012-04-09 2017-03-01 Ionis Pharmaceuticals, Inc. Tricyclic nucleic acid analogs
US10077443B2 (en) 2012-11-15 2018-09-18 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
PT2983721T (pt) 2013-04-12 2018-03-13 Evox Therapeutics Ltd Vesículas de entrega terapêutica
CA2921514C (en) 2013-05-01 2023-10-24 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating apolipoprotein c-iii 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
KR102287532B1 (ko) 2014-01-30 2021-08-11 에프. 호프만-라 로슈 아게 생분해성 컨쥬게이트를 갖는 폴리 올리고머 화합물
US9629867B2 (en) * 2014-03-11 2017-04-25 AM Biotechnologies, Inc. Methods and compositions of improved modified siRNA
EP3020813A1 (en) * 2014-11-16 2016-05-18 Neurovision Pharma GmbH Antisense-oligonucleotides as inhibitors of TGF-R signaling
WO2016079181A1 (en) * 2014-11-19 2016-05-26 Roche Innovation Center Copenhagen A/S Lna gapmer oligonucleotides comprising chiral phosphorothioate linkages
WO2016127000A1 (en) 2015-02-04 2016-08-11 Bristol-Myers Squibb Company Methods of selecting therapeutic molecules
EP3253871A1 (en) 2015-02-04 2017-12-13 Bristol-Myers Squibb Company Lna oligonucleotides with alternating flanks
WO2016172598A1 (en) 2015-04-22 2016-10-27 The Broad Institute Inc. Exosomes and uses thereof
EP3394258B1 (en) 2015-10-22 2021-09-22 Roche Innovation Center Copenhagen A/S In vitro toxicity screening assay
WO2017173034A1 (en) 2016-03-30 2017-10-05 The University Of North Carolina At Chapel Hill Biological agent-exosome compositions and uses thereof
WO2017216340A1 (en) 2016-06-17 2017-12-21 F. Hoffmann-La Roche Ag In vitro nephrotoxicity screening assay
SG10202005885VA (en) 2016-07-01 2020-07-29 Hoffmann La Roche Antisense oligonucleotides for modulating htra1 expression
JP2019522026A (ja) 2016-07-27 2019-08-08 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 非キラル３’−ｓ−または５’−ｓ−ホスホロチオエートヌクレオシド間結合を含むオリゴヌクレオチドの合成
CN110177544A (zh) 2016-11-29 2019-08-27 普尔泰克健康有限公司 用于递送治疗剂的外泌体
AU2018386527A1 (en) * 2017-12-22 2020-04-30 Roche Innovation Center Copenhagen A/S Gapmer oligonucleotides comprising a phosphorodithioate internucleoside linkage

Also Published As

Publication number Publication date
EP3728592A1 (en) 2020-10-28
TW201929870A (zh) 2019-08-01
KR20200104345A (ko) 2020-09-03
US20230002762A1 (en) 2023-01-05
JP7476102B2 (ja) 2024-04-30
AU2018386524A1 (en) 2020-07-02
CN111757936A (zh) 2020-10-09
BR112020012427A2 (pt) 2020-11-24
CA3085406A1 (en) 2019-06-27
IL275399A (en) 2020-07-30
MX2020006430A (es) 2020-09-17
EP4074724A1 (en) 2022-10-19
WO2019122279A1 (en) 2019-06-27
JP2021508690A (ja) 2021-03-11
JP2024041886A (ja) 2024-03-27
US20200339982A1 (en) 2020-10-29

Similar Documents

Publication Publication Date Title
BR112016017261A8 (pt) composto, composição farmacêutica, uso de um composto e processo para a fabricação de um composto
CL2019000107A1 (es) Composiciones de arni contra el componente c5 del complemento y métodos para su uso.(divisional solicitud 201702014)
DOP2023000252A (es) Compuestos de 6-azabencimidazol sustituidos como inhibidores de hpk1
BR112019008458A2 (pt) 1,2,4-triazolonas 2,4,5-trisubstituídas.
BR112017013806A2 (pt) composto, composição farmacêutica, utilização e processo para a fabricação de um composto
BR112017002221A2 (pt) 2-(morfolin-4-il)-1,7-naftiridinas
BR112013018920A2 (pt) composições de nanopartículas, formulações destas e seus usos
BR112014027571A2 (pt) métodos para o tratamento de retinopatia diabética e outras doenças oftalmológicas
UY37505A (es) Conjugados que comprenden un agonista dual de glp-1/glucagón, un conector y ácido hialurónico
DOP2016000253A (es) Nuevos compuestos
BR112015017069A2 (pt) processo para preparação de extrato a partir de meio de cultura de ceriporialacerata e composições farmacêuticas preparadas pelo que para prevenção ou tratamento de doenças diabéticas e complicações diabéticas, que contêm extrato de meio de cultura de ceriporialacerata como ingrediente ativo
BR112014018341A8 (pt) Compostos aza-heterocíclicos
UY32673A (es) Nuevas pirimidinas, composiciones farmaceuticas que las contienen, procedimientos de preparaciones y su aplicacion como medicamentos
DOP2016000118A (es) Tienopirimidinas como inhibidores mknk1 y mknk2
BR112017024727A2 (pt) cocristal, composição farmacêutica, método de tratamento de uma doença em um indivíduo e processo de produção de um cocristal
EA202090014A1 (ru) Гетероароматические соединения в качестве ингибиторов ванина
EA201690183A1 (ru) Замещенные пиразолопиридинамины
BR112014027582A8 (pt) composições oftalmicas com proteção e retenção de dessecação aperfeiçoada
BR112015007360A8 (pt) Composição farmacêutica, e, método para a preparação de uma droga de combinação
BR112015030431A2 (pt) formulação de liberação modificada
BR112019002007A2 (pt) composições farmacêuticas, processo para a fabricação de grânulos, processo para a fabricação de uma composição farmacêutica, processo para a preparação de monocloridrato de ipatasertib amorfo, método para o tratamento de distúrbios hiperproliferativos, utilização de uma composição farmacêutica e presente invenção
BR112017019750A2 (pt) processo para preparação de uma forma cristalina de menaquinol, forma cristalina de menaquinol, processo para preparação de uma forma sólida do menaquinol, composição farmacêutica ou nutracêutica e uso da forma cristalina de menaquinol
BR112015006363A2 (pt) combinações farmacêuticas compreendendo ligantes angiopoietina-2/dll4 duplos e agentes anti-vegf-r
BR112015030774A2 (pt) novos compostos para o tratamento de câncer
BR112016021656A2 (pt) inibidores das vias de sinalização de wnt

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]