Hoechst Aktiengesellschaft

Aventis Pharma Deutschland, Gmbh

Coley Pharmaceutical Gmbh

Coley Pharmaceutical Group, Inc.

Sanofi-a Ventis Deutschland Gmbh

Translate Bio, Inc.

Pfizer Corporation

The General Hospital Corporation

Other

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Aventis Pharma S.a.

Hoechst Gmbh

University of Iowa Research Foundation

Miltenyi Biotec, Gmbh

Eugen Uhlmann

Gerhard Breipohl

Arthur Mertz Krieg

Anuschirwan Peyman

David William Will

Jörg Vollmer

Romesh R Subramanian

Marion Jurk

Irvin Winkler

Matthias Helsberg

Harald Debelak

Markus Weber

Jochen Knolle

Frank Jaschinski

Joachim Engels

Michel Janicot

Thomas Dino Rockel

Ulrike Samulowitz

Arno Schulz

Klaus Bartsch

Hubert Mullner

Paul Habermann

Peter Eckes

Holger Wallmeier

Rudolf Schneider

Brian Seed

Siegfried Stengelin

Wolfgang Konig

Gerard J O'Malley

Gerhard Kretzschmar

Grayson B Lipford

Wolfgang Ulmer

Jochen Huber

Matthias Mag

Steven Albert Benner

Arnold Ganser

Walter Arnold

Eckhard Strauch

Norbert Madry

Thomas Rockel

Eugen Leo

Robert Rankin

Waldemar Wetekam

Bernadus Uijtewaal

Niki Gunkel

Sandra Neumann

Carolin Carolus

Alfred Puhler

Wolfgang Wohlleben

Esther H Chang

Gunter Donn

Gerhard Seipke

Douglas Charles Hanson

Kathleen F Pirollo

Klaus-Peter Koller

Gunther J Riess

Christoph Meichsner

Michael Leineweber

Stephan Neuenhofer

Renate Alijah

Reinhard Kasmarker

Ralf Jockers

Cyril Couturier

Friedrich Wengenmayer

Grayson Lipford

Beate Greiner

Eberhard Unger

Gislinde Gothe

Marc Schwerdel

Bernhard O Noll

Karlheinz Budt

Friedrich Hein

Caroline Weiser

Heinz-Juergen Skrzipczyk

Michael Dörschug

Marion Jürk

Antonina Rait

Thomas Leutsch

Michael Lutz

Michaela Scherr

Chris Meier

Joerg Vollmer

Romesh Subramanian

Romualdas Smicius

Bernhard Noll

The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.

Multimeric oligonucleotide compounds having non-nucleotide based cleavable linkers

Multimeric oligonucleotide compounds

The invention refers to an oligonucleotide consisting of 10 to 20 nucleotides of selected regions of the TGF-beta1, TGF-beta2 or TGF-beta3 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2'-fluoro, 2&#x2032;-O-methoxy and/or 2&#x2032;-O-methyl modified nucleotides. The selected regions are preferably the region of nucleic acid no. 1380 to 1510, no. 1660 to 1680, no. 2390 to 2410, or no. 2740 to 2810 of the TGF-beta2 nucleic acid sequence of SEQ ID NO. 1, specific regions of the TGF-beta1 nucleic acid sequence of SEQ ID NO. 149, or specific regions of the TGF-beta3 nucleic acid sequence of SEQ ID No. 267. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in the prevention and/or treatment of a malignant and/or benign tumor, an immunologic disease, fibrosis, glaucoma, etc.

Modified TGF-beta oligonucleotides

The invention relates to oligonucleotides including at least one lipophilic substituted nucleotide analog and a pyrimidine-purine dinucleotide. The invention also relates to pharmaceutical compositions and methods of use thereof.

CpG oligonucleotide analogs containing hydrophobic T analogs with enhanced immunostimulatory activity

The invention refers to an oligonucleotide consisting of 10 to 20 nucleotides of selected regions of the TGF-beta1, TGF-beta2 or TGF-beta3 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2'-fluoro, 2&#x2032;-O-methoxy and/or 2&#x2032;-O-methyl modified nucleotides. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in a method for the prevention and/or treatment of glaucoma, posterior capsular opacification, dry eye, Marfan or Loeys-Dietz syndrome, riboblastoma, choroidcarcinoma, macular degeneration, such as age-related macular degeneration, diabetic macular endma, or cataract.

Modified TGF-beta oligonucleotide for use in a method of preventing and/or treating an ophthalmic disease

Multimetric oligonucleotide compounds

The invention refers to an oligonucleotide consisting of 10 to 18 nucleotides of selected regions of the TGF-beta2 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2'-fluoro, 2&#x2032;-O-methoxy and/or 2&#x2032;-O-methyl modified nucleotides. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in the prevention and/or treatment of a malignant and/or benign tumor, an immunologic disease, fibrosis, or an ophthalmic disease such as dry eye, glaucoma or posterior capsular opacification (PCO).

Modified TGF-beta2 oligonucleotides

Methods of delivering multiple targeting oligonucleotides to a cell using cleavable linkers

Multimeric oligonucleotides compounds having cleavable linkers

Multimeric oligonucleotides compounds

The invention relates to oligonucleotides including at least one backbone modification and a pyrimidine-purine dinucleotide. The invention also relates to pharmaceutical compositions and methods of use thereof.

Phosphate-modified oligonucleotide analogs with enhanced immunostimulatory activity

Growing community of inventors

Glashuetten, Germany

Eugen Uhlmann