University of Iowa Research Foundation

Coley Pharmaceutical Group, Inc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Translate Bio, Inc.

Coley Pharmaceutical Gmbh

The General Hospital Corporation

Other

Checkmate Pharmaceuticals, Inc.

Pfizer Corporation

Ottawa Health Research Institute

Rana Therapeutics, Inc.

Adiutide Pharmaceuticals Gmbh

The General Hospital Corporation D/b/a Massachusetts General Hospital

Arthur Mertz Krieg

Eugen Uhlmann

Dennis M Klinman

Alfred D Steinberg

Romesh R Subramanian

Joel N Kline

James A McSwiggen

Jeannie T Lee

Jörg Vollmer

Heather Lynn Davis

Markus Weber

Ulrike Samulowitz

Thomas Dino Rockel

Joachim Schorr

Gunther Hartmann

Marion Jurk

Aaron Jay Morris

Grayson B Lipford

George J Weiner

Robert L Bratzler

Robert Rankin

Tong Wu

James G Barsoum

Douglas Charles Hanson

David A Schwartz

Grayson Lipford

George Weiher

Mohammed Milhem

David Mauro

Nicolai Lohse

Lars Ostergaard

Ole Schmeltz Sogaard

Schorr Joachim

Christian Schetter

Henrik Carl Schonheyder

Bernhard O Noll

Joerg Vollmer

Romesh Subramanian

Bernhard Noll

Provided are compositions and methods for treating cancer using administration of certain volumes of CpG oligonucleotides (CpG ODN) and, optionally, administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and/or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-a) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

Compositions and methods for tumor immunotherapy

The present disclosure relates to, inter alia, RNA molecules (e.g., RNA hairpin agonists) that bind to and agonize RIG-I-like receptors (RLRs), and to use of the molecules in methods for treating, or ameliorating one or more symptoms of, a disorder (e.g., cancer).

Synthetic RIG-I-like receptor agonists

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of MECP2. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of MECP2. Methods for modulating expression of MECP2 using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of MECP2.

Compositions and methods for modulating MECP2 expression

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

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of SMN1 or SMN2. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of SMN1 or SMN2 that comprises exon 7. Methods for modulating expression of SMN1 or SMN2 using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of SMN1 or SMN2.

Compositions and methods for modulating SMN gene family expression

Multimeric oligonucleotide compounds

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and/or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-&#x3b1;) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

Combination tumor immunotherapy

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of ATP2A2. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of ATP2A2. Methods for modulating expression of ATP2A2 using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of ATP2A2.

Compositions and methods for modulating ATP2A2 expression

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of hemoglobin genes (HBB, HBD, HBE1, HBG1 or HBG2). Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of hemoglobin genes. Methods for modulating expression of hemoglobin genes using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of hemoglobin genes.

Compositions and methods for modulating hemoglobin gene family expression

Methods for modulating expression of SMN1 and/or SMN2 in cells obtained from subjects having ALS or in subjects having ALS using single stranded oligonucleotides are provided. Methods for treating ALS using single stranded oligonucleotides are also provided.

Compositions and methods for treating amyotrophic lateral sclerosis

Multimetric oligonucleotide compounds

Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of UTRN. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of UTRN. Methods for modulating expression of UTRN using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of UTRN.

Compositions and methods for modulating UTRN expression

Growing community of inventors

Wellesley, MA, United States of America

Arthur Mertz Krieg