Double-stranded synthetic oligonucleotides useful for...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Reexamination Certificate

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C536S023100, C536S024100, C536S024500

Reexamination Certificate

active

07659258

ABSTRACT:
The invention relates to a synthetic double-stranded oligonucleotide capable of modifying the molecular phenotype of osteoclasts and increasing the expression of the oestrogen alpha receptor gene. Pharmaceutical compositions comprising the oligonucleotide according to the invention are also described, as well as therapeutic applications of that oligonucleotide, in particular for the treatment of osteopenic diseases such as for example osteoporosis. The oligonucleotide according to the invention is characterized in that it comprises the sequence 5′-ATTTATTTTCAATACTGACT-3′ (SEQ ID NO: 1) or a fragment or a mutant thereof.

REFERENCES:
Lambertini, et al., “Osteoblastic Differentiation Induced by Transcription Factor Decoy against Estrogen Receptor α Gene,” Biochemical and Biophysical Research Communications 292, pp. 761-770 (2002).
Matsuzaki, et al., “Human Osteoclast-Like Cells Are Formed from Peripheral Blood Mononuclear Cells in a Coculture with SaOS-2 Cells Transfected with the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor Gene,” Endocrinology vol. 140, No. 2, pp. 925-932, copyright 1999 by The Endocrine Society.
Piva, et al., “Modulation of Estrogen Receptor Gene Transcription in Breast Cancer Cells by Liposome Delivered Decoy Molecules,” Journal of Steroid Biochemistry & Molecular Biology 75 (2000) pp. 121-128.
Boatright, et al., “Mechanisms of Caspase Activation,” Current Opinion in Cell Biology, 2003, pp. 725-731.
Lambertini E et al., “Modulation of gene expression in human osteoblasts by targeting a distal promoter region of human estrogen receptor-alpha gene”, Journal of Endocrinology, Mar. 2002, pp. 683-693, vol. 172, No. 3, XP002413954, ISSN: 0022-0795.
Penolaiii Letizia, et al., “Peptide nucleic acid-DNA decoy chimeras targeting NF-kappaB transcription factors: Induction of apoptosis in human primary osteoclasts”, International Journal of Molecular Medicine, Aug. 2004, pp. 145-152, vol. 14, No. 2, XP008073371, ISSN: 1107-3756.
Penolaiii Letizia, et al., “Cis element ‘decoy’ against the upstream promoter of human estrogen receptor gene”, Biochimica et Biophysica Acta. Gene Structure and Expression, Jul. 2000, pp. 560-567, vol. 1492, No. 2-3, XP004275731, ISSN: 0167-4781.
Penolaiii Letizia, et al., “Decoy oligodeoxynucleotides targeting NF-kappaB transcription factors: Induction of apoptosis in human primary osteoclasts.”, Biochemical Pharmacology, Oct. 2003, pp. 1189-1198, vol. 66, No. 7, XP002413955, ISSN: 0006-2952.
Piva R et al., “Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor [alpha]”, Apoptosis, An International Journal on Programmed Cell Death, Oct. 2005, pp. 1079-1094, vol. 10, No. 5, XP019204744, ISSN: 1573-675X.

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