Methods for increasing in vivo efficacy of oligonucleotides...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) A61K 31/7076 (2006.01) C07H 19/00 (2006.01) C07H 19/16 (2006.01) C07H 19/23 (2006.01) C07H 21/00 (2006.01) C07H 21/04 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2451738

The invention relates to the use of nucleotide substitutes for increasing the in vivo efficacy of nucleic acid molecules and also for inhibiting inflammation in mammals. More particularly, the present invention relates to the use of 2'6'diaminopurine (DAP) and analogs thereof per se in anti- inflammatory compositions, and also for preparing nucleic acid molecules having an increased in vivo physiological efficiency and a reduced toxicity as compared to conventional oligos. The invention is particularly useful for the preparation of antisense oligonucleotides for treating pulmonary/respiratory diseases such as cystic fibrosis, asthma, chronic bronchitis, chronic obstructive lung disease, eosinophilic bronchitis, allergies, allergic rhinitis, pulmonary fibrosis, adult respiratory distress syndrome, sinusitis, respiratory syncytial virus or other viral respiratory tract infection and cancer.

L'invention concerne l'utilisation de substituts nucléotidiques pour augmenter l'efficacité in vivo de molécules d'acide nucléique et également pour inhiber l'inflammation chez les mammifères. Plus particulièrement, la présente invention concerne l'utilisation de 2'6'diaminopurine (DAP) et d'analogues de celle-ci en soi dans des compositions anti-inflammatoires, ainsi que dans la préparation de molécules d'acide nucléique présentant une efficacité physiologique in vivo et une toxicité réduite si l'on compare avec les oligonucléotides classiques. L'invention est particulièrement utile dans la préparation d'oligonucléotides antisens servant à traiter des maladies pulmonaires/respiratoires telles que la mucoviscidose, l'asthme, la bronchite chronique, la broncho-pneumopathie chronique obstructive, la bronchite à éosinophiles, les allergies, la rhinite allergique, la fibrose pulmonaire, le syndrome de détresse respiratoire de l'adulte, la sinusite, l'infection virale syncytiale respiratoire ou une autre infection virale des voies respiratoires, et le cancer.

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