Sarepta Therapeutics, Inc.

Avi Biopharma, Inc.

Anti-Gene Development Group

Antivirals Inc.

U.S. Army Medical Research and Material Command

The Scripps Research Institute

University of Nebraska

The United States of America as Represented by the Army Medical Research and Material Command

Anti-Gene Deveopment Group

Neu-Gene Development Group

Dwight D Weller

Patrick L Iversen

James E Summerton

David A Stein

Bao Zhong Cai

Gunnar J Hanson

Ming Zhou

Jed N Hassinger

Bruce L Geller

Lucas D Tilley

Sina Bavari

Dan V Mourich

Alan P Timmins

Eugene P Stirchak

Alexander Charles Rudolph

Richard Keith Bestwick

Robert Hudziak

Alvin W Smith

Yongfu Li

Randall E Brand

Jesse D Deere

Matthew Reeves

Douglas E Skilling

Benjamin Neuman

Michael Buchmeier

Charles Rudolph

Cornelis A Rijnbrand

Christina Mary Josephine Fox

Todime Muralimohan Reddy

John M Wages, Jr

Matthew Dale Reeves

Functionally-modified oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3' and/or 5&#x2032;-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Functionally-modified oligonucleotides and subunits thereof

Oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3' and/or 5&#x2032;-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Oligonucleotide analogues having modified intersubunit linkages and/or terminal groups

A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5' exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO:6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.

Antisense composition and method for treating muscle atrophy

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornaviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5'-terminal end 40 bases of the positive-sense RNA strand of the virus.

Antisense antiviral compound and method for treating ss/RNA viral infection

Oligonucleotide analogs comprising modified intersubunit linkages and/or modified 3' and/or 5&#x2032;-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

A method for enhancing, by at least 10 fold, the antibacterial activity of an antisense oligonucleotide composed of morpholino subunits linked by phosphorus-containing intersubunit linkages. The method includes one or both of: conjugating an arginine-rich carrier to a 3' or 5&#x2032; end of the oligonucleotide and modifying the oligonucleotide to contain 20%-50% intersubunit linkages that are positively charged at physiological pH. Also disclosed is an antisense oligonucleotide having enhanced antibacterial activity by virtue of one or both modifications.

Antibacterial antisense oligonucleotide and method

A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5' exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO: 6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.

The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

Antisense antiviral compounds and methods for treating a filovirus infection

Functionally-modified oligonucleotide analogs comprising modified intersubunit linkages and/or modified 3' and/or 5&#x2032;-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

A method and compound for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection are disclosed. The compound is an antisense oligonucleotide analog compound having a targeting sequence complementary to a preprocessed CTLA-4 mRNA region identified by SEQ ID NO: 22 in SEQ ID NO: 1, spanning the splice junction between intron 1 and exon 2 of the preprocessed mRNA of the subject. The compound is effective, when administered to a subject, to form within host cells, a heteroduplex structure (i) composed of the preprocessed CTLA-4 mRNA and the oligonucleotide compound, (ii) characterized by a Tm of dissociation of at least 45&#xb0; C., and (iii) resulting in an increased ratio of processed mRNA encoding ligand-independent CTLA-4 to processed mRNA encoding full-length CTLA-4.

Immunosuppression compound and treatment method

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Corvallis, OR, United States of America

Dwight D Weller