Roche Innovation Center Copenhagen A/s

Santaris Pharma A/s

Other

Roche Diagnostics Gmbh

Dako A/s

Georgia Tech Research Corporation

Pna Diagnostics A/s

Troels Koch

Henrik Frydenlund Hansen

Christoph Rosenbohm

Daniel Sejer Pedersen

Signe M Christensen

Charlotte Albaek Thrue

Majken Westergaard

Miriam Frieden

Nikolaj Dam Mikkelsen

Hans-Georg Batz

Henrik Orum

Jesper Wengel

Claes Wahlestedt

Zicai Liang

Joacim Elmén

Mads Detlef Sørensen

Anders M Sorensen

Frank Bergmann

Yong Wu

Christoph Seidel

Konrad H Bleicher

Rupert Herrmann

Danith H Ly

Peter Hagedorn

Jacob Ravn

Jesper Worm

Erik Daa Funder

Nanna Albaek

Adrian Schaeublin

Sabine Sewing

Marcel Gubler

Annie Moisan

Bruce Alan Armitage

Gary B Schuster

Henrik O Slashedrum

Joerg Duschmalé

Henrik Ørum

Flemming Ressig Jensen

Mads Detlef Sorensen

Erich Koller

Lars Joenson

Konrad Bleicher

Martin Borre

Joachim Elmén

Mogens Havsteen Jacobsen

Gary B Shuster

Bruce A Armitage

Anders Malling Sørensen

Xi Shu

Meiling Li

Martina Brigitte Duschmalé

Christoph Rosenbohn

Jacob Jensen

Anders Sorensen

Daniel Pedersen

Charlotte Thrue

Joerg Jakob Andreas DuschmalÉ

Martina Brigitte DuschmalÉ

Anders Malling Sorensen

Joacim Elmen

The present invention relates to a compound of formula (II) or (IIb) Wherein X, Y, R, R, Rand Nu are as defined in the description and in the claims. The compound of formula (II) can be used in the manufacture of oligonucleotides. 

Thiophosphoramidites

The invention relates to a method of identifying stereodefined phosphorothioate oligonucleotide variants with reduced toxicity by creating and screening libraries of stereodefined chiral phosphorothioate variants for compounds with reduced toxicity, either in vitro or in vivo.

Chiral library screen

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

The present invention is directed to novel double-stranded short interfering (siRNA) analogs comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogs comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogs comprise at least one locked nucleic acid (LNA) monomer.

Short interfering RNA (siRNA) analogues

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

The present invention is directed to novel double-stranded short interfering (siRNA) analogues comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogues comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogues comprise at least one locked nucleic acid (LNA) monomer.

The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &#x3b1;--oxy-LNA, amino-LNA, &#x3b1;--amino-LNA, thio-LNA, &#x3b1;--thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues. 

Synthesis of locked nucleic acid derivatives

Methods are described for the synthesis of Locked Nucleic Acid (LNA) derivatives using certain nitrogen-containing nucleophiles.

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 invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as &#x3b1;--oxy-LNA, amino-LNA, &#x3b1;--amino-LNA, thio-LNA, &#x3b1;--thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilizing intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues. 

Growing community of inventors

Copenhagen, Denmark

Troels Koch