Global Patent Index - EP 1168919 A4

EP 1168919 A4 20020306 - LOW ADENOSINE ANTI-SENSE OLIGONUCLEOTIDE, COMPOSITIONS, KIT AND METHOD FOR TREATMENT OF AIRWAY DISORDERS ASSOCIATED WITH BRONCHOCONSTRICTION, LUNG INFLAMMATION, ALLERGY(IES) AND SURFACTANT DEPLETION

Title (en)

LOW ADENOSINE ANTI-SENSE OLIGONUCLEOTIDE, COMPOSITIONS, KIT AND METHOD FOR TREATMENT OF AIRWAY DISORDERS ASSOCIATED WITH BRONCHOCONSTRICTION, LUNG INFLAMMATION, ALLERGY(IES) AND SURFACTANT DEPLETION

Title (de)

ANTISENSE OLIGONUKLEOTIDE MIT GERINGEM ADENOSIN GEHALT, ZUSAMMENSETZUNGEN, KIT UND BEHANDLUNGSMETHODE BEI ERKRANKUNG DER LUFTWEGE VERBUNDEN MIT BRONCHOKONSTRIKTION, LUNGENENTZÜNDUNG, ALLERGIEN UND SURFACTANTVERARMUNG

Title (fr)

OLIGONUCLEOTIDE ANTISENS A FAIBLE TENEUR EN ADENOSINE, COMPOSITIONS, KIT ET PROCEDE POUR LE TRAITEMENT D'AFFECTIONS DES VOIES AERIENNES ASSOCIEES A LA BRONCHOCONSTRICTION, A L'INFLAMMATION PULMONAIRE, AUX ALLERGIES ET A LA DEPLETION DE SURFACTANT

Publication

EP 1168919 A4 20020306 (EN)

Application

EP 00919668 A 20000324

Priority

  • US 0008020 W 20000324
  • US 12795899 P 19990406

Abstract (en)

[origin: WO0062736A2] An in vivo method of selectively delivering a nucleic acid to a target gene or mRNA, comprises the topical administration, e.g. to the respiratory system, of a subject of a therapeutic amount of an oligonucleotide (oligo) that is anti-sense to the initiation codon region, the coding region, the 5' or 3' inton-exon junctions or regions within 2 to 10 nucleotides of the junctions of the gene or antisense to a mRNA complementary to the gene in an amount effective to reach the target polynucleotide and reducing or inhibiting expression. In addition a method of treating and adenosine mediated effect, comprises topically administering to a subject an anti-sense oligo in an amount effective to treat the respiratory, pulmonary, or airway disease. In order to minimize triggering adenosine receptors by their metabolism, the administered oligos have a low content of or are essentially free of adenosine. A pharmaceutical composition and formulations comprise the oligo anti-sense to an adenosine receptor, genes and mRNAs encoding them, genomic and mRNA flanking regions, intron and exon borders and all regulatory and functionally related segments of the genes and mRNAs encoding the polypeptides, their salts and mixtures. Various formulations contain a requisite carrier, and optionally other additives and biologically active agents. The low adenosine or adenosine free (des-A) agent for practicing the method of the invention may be prepared by selecting a target gene(s), genomic flanking region(s), RNA(s) and/or polypeptide(s) associated with a disease(s) or condition(s) afflicting lung airways, obtaining the sequence of the mRNA(s) corresponding to the target gene(s) and/or genomic flanking region(s), and/or RNAs encoding the target polypeptide(s), selecting at least one segment of the mRNA which may be up to 60 % free of thymidine (T) and synthesizing one or more anti-sense oligonucleotide(s) to the mRNA segments which are free of adenosine (A) by substituting a universal base for A when present in the oligonucleotide. The agent may be prepared by selection of target nucleic acid sequences with GC running stretches, which have low T content, and by optionally replacing A in the anti-sense oligonucleotides with a "Universal or alternative base". The agent, composition and formulations are used for prophylactic, preventive and therapeutic treatment of ailments associated with impaired respiration, lung allergy(ies) and/or inflammation and depletion lung surfactant or surfactant hypoproduction, such as pulmonary vasoconstriction, inflammation, allergies, allergic rhynitis, asthma, impeded respiration, lung pain, cystic fibrosis, bronchoconstriction. The present treatment is suitable for administration in combination with other treatments, e.g. before, during and after other treatments, including radiation, chemotherapy, antibody therapy and surgery, among others. Alternatively, the present agent is effectively administered prophylactically or therapeutically by itself for conditions without known therapies or as a substitute for therapies exhibiting undesirable side effects. The treatment of this invention may be administered directly into the respiratory system of a subject so that the agent has direct access to the lungs, or by other effective routes of administration, e.g. topically, transdermally, by implantation, etc., in an amount effective to reduce or inhibit the symptoms of the ailment.

[origin: WO0062736A2] An in vivo method of selectively delivering a nucleic acid to a target gene or mRNA comprises the topical admistration, e.g. to the respiratory system, of a subject of a therapeutic amount of an oligonucleotide that is antisense to the initiation codon region, coding region, 5' or 3' inton-exon junctions or regions within 2 to 10 nucleotides of the junctions of the target gene, or antisense to a mRNA complementary to the target gene in an amount effective to reach the target polynucleotide and reducing or inhibiting expression. Additionally, a method of treating and adenosine mediated effect is described also utilizing the delivery of antisense and in order to minimize triggering adenosine receptors by their metabolism, the administered oligos have a low content of or are essentially free of adenosine. The agent, composition and formulations are used for prophlactic, preventive and therapeutic treatment of ailments associated with impaired respiration, lung allergies and/or vasoconstriction, inflammation, allergies, allergic rhynitis, asthma, impeded respiration, lung pain, cystic fibrosis and bronchoconstriction.

IPC 1-7

A61K 6/00

IPC 8 full level

C12N 1/15 (2006.01); A61K 9/02 (2006.01); A61K 9/08 (2006.01); A61K 9/10 (2006.01); A61K 9/12 (2006.01); A61K 9/127 (2006.01); A61K 9/14 (2006.01); A61K 9/28 (2006.01); A61K 9/48 (2006.01); A61K 9/70 (2006.01); A61K 9/72 (2006.01); A61K 31/7088 (2006.01); A61K 38/43 (2006.01); A61K 45/00 (2006.01); A61K 48/00 (2006.01); A61P 1/00 (2006.01); A61P 9/12 (2006.01); A61P 11/00 (2006.01); A61P 11/06 (2006.01); A61P 11/08 (2006.01); A61P 29/00 (2006.01); A61P 31/04 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); A61P 37/08 (2006.01); C12N 1/19 (2006.01); C12N 1/21 (2006.01); C12N 5/10 (2006.01); C12N 15/113 (2010.01); A61K 38/00 (2006.01)

CPC (source: EP)

A61P 1/00 (2017.12); A61P 9/12 (2017.12); A61P 11/00 (2017.12); A61P 11/06 (2017.12); A61P 11/08 (2017.12); A61P 29/00 (2017.12); A61P 31/04 (2017.12); A61P 35/00 (2017.12); A61P 35/02 (2017.12); A61P 37/08 (2017.12); C12N 15/113 (2013.01); C12N 15/1138 (2013.01); A61K 38/00 (2013.01); C12N 2310/18 (2013.01); C12N 2310/315 (2013.01); C12N 2310/33 (2013.01)

Citation (search report)

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  • [DA] RAHMAN M SAYEEDUR ET AL: "Nebularine (9-2'-deoxy-beta-D-ribofuranosylpurine) has the template characteristics of adenine in vivo and in vitro.", MUTATION RESEARCH, vol. 377, no. 2, 1997, pages 263 - 268, XP001024479, ISSN: 0027-5107
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  • [DA] OHTSUKA E ET AL: "AN ALTERNATIVE APPROACH TO DEOXYOLIGONUCLEOTIDES AS HYBRIDIZATION PROBES BY INSERTION OF DEOXYINOSINE AT AMBIGUOUS CODON POSITIONS", JOURNAL OF BIOLOGICAL CHEMISTRY. (MICROFILMS), vol. 260, no. 5, 10 March 1985 (1985-03-10), pages 2605 - 2608, XP002031938
  • [DA] NICHOLS R ET AL: "A UNIVERSAL NUCLEOSIDE FOR USE AT AMBIGOUS SITES IN DNA PRIMERS", NATURE, vol. 369, no. 6480, 9 June 1994 (1994-06-09), pages 492 - 493, XP000560346, ISSN: 0028-0836
  • [T] METZGER W JAMES ET AL: "Oligonucleotide therapy of allergic asthma.", JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 104, no. 2 PART 1, August 1999 (1999-08-01), pages 260 - 266, XP001024505, ISSN: 0091-6749
  • See references of WO 0062736A2

Designated contracting state (EPC)

AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

DOCDB simple family (publication)

WO 0062736 A2 20001026; WO 0062736 A3 20011011; AU 4031700 A 20001102; BR 0006019 A 20010313; CA 2330022 A1 20001026; CN 1330513 A 20020109; EP 1168919 A2 20020109; EP 1168919 A4 20020306; HK 1042017 A1 20020802; IL 140054 A0 20020210; JP 2003515525 A 20030507

DOCDB simple family (application)

US 0008020 W 20000324; AU 4031700 A 20000324; BR 0006019 A 20000324; CA 2330022 A 20000324; CN 00801046 A 20000324; EP 00919668 A 20000324; HK 02102615 A 20020408; IL 14005400 A 20000324; JP 2000611873 A 20000324