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BR0006019A - Oligonucleotìdeo de anti-sentido de adenosina baixo, composições, kit & método para tratamento de distúrbios de vias aéreas associados com broncoconstricção, inflamação pulmonar, alergia(s) & depleção de surfactante - Google Patents

Oligonucleotìdeo de anti-sentido de adenosina baixo, composições, kit & método para tratamento de distúrbios de vias aéreas associados com broncoconstricção, inflamação pulmonar, alergia(s) & depleção de surfactante

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Publication number
BR0006019A
BR0006019A BR0006019-4A BR0006019A BR0006019A BR 0006019 A BR0006019 A BR 0006019A BR 0006019 A BR0006019 A BR 0006019A BR 0006019 A BR0006019 A BR 0006019A
Authority
BR
Brazil
Prior art keywords
adenosine
antisense
mrna
compositions
low
Prior art date
Application number
BR0006019-4A
Other languages
English (en)
Inventor
Jonathan W Nyce
Original Assignee
Univ East Carolina
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 Univ East Carolina filed Critical Univ East Carolina
Publication of BR0006019A publication Critical patent/BR0006019A/pt

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    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
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    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
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    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
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    • 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
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Abstract

Patente de Invenção: <B>"OLIGONUCLEOTìDEO DE ANTI-SENTIDO DE ADENOSINA BAIXO, COMPOSIçõES, KIT & MéTODO PARA TRATAMENTO DE DISTúRBIOS DE VIAS AéREAS ASSOCIADOS COM BRONCOCONSTRICçãO, INFLAMAçãO PULMONAR, ALERGIA(S) & DEPLEçãO DE SURFACTANTE"<D>. Um método in vivo de distribuir seletivamente um ácido nucleico a um gen alvo ou mRNA, compreende a administração local, por exemplo, ao sistema respiratório, de um sujeito de uma quantidade terapêutica de um oligonucleotídeo (oligo) que é de anti-sentido ao códon de iniciação, a região de codificação, as regiões de flanco genómicas da extremidade 5' e da extremidade 3', junções de <B>introneção<D> de 5' e 3' ou regiões dentro de 2 a 10 nucleotídeos das junções do gen, ou anti-sentido a um mRNA complementar ao gen em uma quantidade efetiva para alcançar o polinucleotídeo alvo e reduzindo ou inibindo expressão. Além disso um método para tratar um efeito mediado de adenosina, compreende administrando localmente a um sujeito um oligo de anti-sentido em uma quantidade efetiva para tratar a doença respiratória, pulmonar, ou de vias aéreas. A fim de minimizar disparando receptores de adenosina por seus metabolismos, os oligos administrados têm um conteúdo baixo de ou são essencialmente livres de adenosina. Uma composição e formulações farmacêuticas compreendem o anti-sentido de oligo a um receptor de adenosina, genes e mRNAs codificando-os, regiões de flanco genómica e mRNA, margens intron e exon e todos segmentos reguladores e funcionalmente relacionados dos gens e mRNAs codificando os polipeptídeos, seus sais e misturas. Várias formulações contém um transportador necessário, e optativamente outros aditivos e agentes ativos biologicamente. O agente de adenosina baixa ou livre de adenosina (des-A) para praticar o método da invenção pode ser preparado selecionando um(s) gen(s) alvo, região(s) de flanco genómica(s), RNA(s) e/ou polipeptídeo(s) associados(s) com uma(s) doença(s) ou condição(s) afligindo vias respiratórias pulmonares, obtendo a sequência do(s) RNA(s) correspondendo ao(s) gen(s) alvo e/ou região(s) de flanco genómica(s), e/ou RNAs codificando o(s) polipeptídeo(s) alvo, selecionando pelo menos um segmento do mRNA o qual pode ser até 60% livre de timidina (T) e sintetizando um ou mais oligo-nucleotídeo(s) de anti-sentido aos segmentos de mRNA os quais são livres de adenosina (A) substituindo uma base universal por A quando presente no oligonucleotídeo. O agente pode ser preparado por seleção de sequências de ácidos nucleicos alvos com estiramento de passagem de GC, os quais têm conteúdo T baixo, e optativamente substituindo A nos oligonucleotídeos de anti-sentido com uma "Base universal ou alternativa". Os agentes, composições e formulações são usados para profilaticamente, tratamento preventivo e terapêutico de enfermidades associadas com respiração prejudicada, alergia(s) pulmonar e/ou inflamação ou depleção de surfactante pulmonar ou hiproprodução de surfactante, tais como vasoconstricção, inflamação, alergias, rinite alérgica, asma, respiração impedida, dor pulmonar, fibrose cística, broncoconstricção. O presente tratamento é adequado para administração em combinação com outros tratamentos, por exemplo, antes, durante e após outros tratamentos, inluindo radiação, quimioterapia, terapia de anticorpo e cirurgia, entr outros, Alternativamente, o agente presente é efetivamente administrado profilaticamente ou terapeuticamente por si só para condições sem terapias conhecidas ou como um substituto para terapias exibindo efeitos colaterais indesejados. O tratamento desta invenção pode ser administrado diretamente no sistema respiratório de um sujeito de modo que o agente tenha acesso direto aos pulmões, ou por rotas efetivas de administração, por exemplo localmente, transdermicamente, por implantação, etc. em uma quantidade efetiva para reduzir ou inibir os sintomas da enfermidade.
BR0006019-4A 1999-04-06 2000-03-24 Oligonucleotìdeo de anti-sentido de adenosina baixo, composições, kit & método para tratamento de distúrbios de vias aéreas associados com broncoconstricção, inflamação pulmonar, alergia(s) & depleção de surfactante BR0006019A (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US12795899P 1999-04-06 1999-04-06
PCT/US2000/008020 WO2000062736A2 (en) 1999-04-06 2000-03-24 Low adenosine anti-sense oligonucleotide, compositions, kit and method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) and surfactant depletion

Publications (1)

Publication Number Publication Date
BR0006019A true BR0006019A (pt) 2001-03-13

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Family Applications (1)

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BR0006019-4A BR0006019A (pt) 1999-04-06 2000-03-24 Oligonucleotìdeo de anti-sentido de adenosina baixo, composições, kit & método para tratamento de distúrbios de vias aéreas associados com broncoconstricção, inflamação pulmonar, alergia(s) & depleção de surfactante

Country Status (9)

Country Link
EP (1) EP1168919A4 (pt)
JP (1) JP2003515525A (pt)
CN (1) CN1330513A (pt)
AU (1) AU4031700A (pt)
BR (1) BR0006019A (pt)
CA (1) CA2330022A1 (pt)
HK (1) HK1042017A1 (pt)
IL (1) IL140054A0 (pt)
WO (1) WO2000062736A2 (pt)

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IL140054A0 (en) 2002-02-10
EP1168919A2 (en) 2002-01-09
HK1042017A1 (zh) 2002-08-02
CA2330022A1 (en) 2000-10-26
CN1330513A (zh) 2002-01-09
EP1168919A4 (en) 2002-03-06
WO2000062736A2 (en) 2000-10-26
AU4031700A (en) 2000-11-02
JP2003515525A (ja) 2003-05-07
WO2000062736A3 (en) 2001-10-11

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