Roche Innovation Center Copenhagen A/s

Santaris Pharma A/s

Miriam Frieden

Charlotte Albaek Thrue

Majken Westergaard

Henrik Frydenlund Hansen

Troels Koch

Christoph Rosenbohm

Daniel Sejer Pedersen

Signe M Christensen

Nikolaj Dam Mikkelsen

Henrik Orum

Jens Bo Hansen

Henrik Ørum

Charlotte Thrue

Daniel Pedersen

Charlotte Albæck Thrue

A novel class of pharmaceuticals which comprises a Locked Nucleic Acid (LNA) which can be used in antisense therapy. These novel oligonucleotides have improved antisense properties. The novel oligonucleotides are composed of at least one LNA selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides.

Antisense design

Amino-LNA, thio-LNA and alpha-L-oxy-LN

The present invention is directed to novel oligonucleotides with improved antisense properties. The novel oligonucleotides comprise at least one Locked Nucleic Acid (LNA) selected from beta-D-thio/amino-LNA or alpha-L-oxy/thio/amino-LNA. The oligonucleotides comprising LNA may also include DNA and/or RNA nucleotides. The present invention also provides a new class of pharmaceuticals which comprise antisense oligonucleotides and are useful in antisense therapy.

Oligonucleotides with alternating segments of locked and non-locked nucleotides

The present invention provides improved oligomeric compound, in particular oligonucleotide compounds, and methods for modulating the expression of the Bcl-2 gene in humans. In particular, this invention relates to oligomeric compounds of 10-30 nucleobases in length which comprise a target binding domain that is specifically hybridizable to a region ranging from base position No. 1459 (5') to No. 1476 (3&#x2032;) of the human Bcl-2 mRNA, said target binding domain having the formula: 5&#x2032;-[(DNA/RNA)-(LNA/LNA*)-(DNA/RNA/LNA*)-(LNA/LNA*)-(DNA/RNA)]-3&#x2032; and said target binding domain comprising at least two LNA nucleotides or LNA analogue nucleotides linked by a phosphorothioate group (&#x2014;O&#x2014;P(O,S)&#x2014;O&#x2014;). In particular the oligo is predominantly or fully thiolated. The invention also provides the use of such oligomers or conjugates or chimera for the treatment of various diseases associated with the expression of the Bcl-2 gene, such as cancer.

Oligomeric compounds for the modulation of Bcl-2

Growing community of inventors

Copenhagen, Denmark

Miriam Frieden