Roche Innovation Center Copenhagen A/s

Santaris Pharma A/s

Other

Enzon Pharmaceuticals, Inc.

Roche Diagnostics Gmbh

Hoffmann-La Roche Inc.

Georgia Tech Research Corporation

Dako A/s

Lattec I/s

Pna Diagnostics A/s

F. Hoffmann-La Roche Ag

Henrik Frydenlund Hansen

Troels Koch

Charlotte Albaek Thrue

Majken Westergaard

Christoph Rosenbohm

Henrik Orum

Daniel Sejer Pedersen

Signe M Christensen

Nikolaj Dam Mikkelsen

Frank Winther Rasmussen

Hans-Georg Batz

Jacob Ravn

Peter Eigil Nielsen

Yong Wu

Philipp Hadwiger

Miriam Frieden

Nanna Albaek

Ellen Marie Straarup

Susanne Kammler

Leif Hoejslet Christensen

Jens Bo Rode Hansen

Konrad H Bleicher

Danith H Ly

Ole Buchardt

Peter Hagedorn

Maj Hedtjärn

Niels Fisker Nielsen

Søren Ottosen

Liam Good

Jesper Worm

Morten Lindow

Erik Daa Funder

Marie Wickstrom Lindholm

Adrian Schaeublin

Sabine Sewing

Marcel Gubler

Fei Chen

Bruce Alan Armitage

Annie Moisan

Gary B Schuster

Jens Bo Hansen

Henrik O Slashedrum

Henrik Ørum

Joerg Duschmalé

Charlotte Albæk Thrue

Gregroy Hardee

Meiling Li

Lars Joenson

Konrad Bleicher

Roald B Jensen

Martin Borre

Gary B Shuster

Bruce A Armitage

Carsten Schou

Martina Brigitte Duschmalé

Xi Shu

Flemming Larsen

Mark Turner

Frederik Beck

Margit Wissenbach

Leila Malik

Thomas Mathiasen

Birgit Kjaeldgaard Giwercman

Maj HEDTJÄRN

Marie Lindholm

Nanna ALBÆK

Daniel Pedersen

Charlotte Thrue

Martina Brigitte DuschmalÉ

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 the field of oligonucleotide therapeutics, and in particular to the use of a cleavable, e.g. a phosphodiester region covalently attached to a conjugate, a targeting group or blocking group to enhance the properties of the oligonucleotides, for example to improve the therapeutic index.

Oligonucleotide conjugates

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

The invention relates to the field of oligonucleotide therapeutics, and in particular to poly oligo oligonucleotides conjugates where two or more antisense oligonucleotides are covalently linked by physiologically labile linkers, and to a biocleavable functional group such as a conjugate group.

Poly oligomer compound with biocleavable conjugates

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 disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5'-()GGcaagcatccTG-3&#x2032; and 5&#x2032;-()TTactgccttcTT-3&#x2032;, wherein capital letters designate a beta-D-oxy-LNA nucleotide analog, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analog or a 2-deoxynucleotide, subscript 's' designates a phosphorothioate link between neighboring nucleotides/LNA nucleotide analogs, and subscript 'x' designates either a phosphorothioate link or a phosphorodiester link between neighboring nucleotides/LNA nucleotide analogs, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g. diabetic retinopathy, macular degeneration (ARMD), psoriasis, rheumatoid arthritis and other inflammatory diseases.

Potent LNA oligonucleotides for the inhibition of HIF-1A expression

The invention provides for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.

Oral delivery of therapeutically effective LNA oligonucleotides

The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5'-()GGcaagcatccTG-3&#x2032; and 5&#x2032;-()TTactgccttcTT-3&#x2032;, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript 's' designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues, and subscript 'x' designates either a phosphorothioate link or a phosphorodiester link between neighbouring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g. diabetic retinopathy, macular degeneration (ARMD), psoriasis, rheumatoid arthritis and other inflammatory diseases.

Potent LNA oligonucleotides for the inhibition of HIF-1a expression

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

Growing community of inventors

Rødovre, Denmark

Henrik Frydenlund Hansen