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

Uniformed Services University of the Health Sciences, an Institution of Higher Learning Within the Department of Defense

Daniela Verthelyi

Dennis M Klinman

Mayda Gursel

Ken Ishii

Ihsan Gursel

Rainald Zeuner

James J Mond

Bruce Ivins

Serge L Beaucage

Andrzej Grajkowski

Ken Ishi

The present invention provides a CpG oligonucleotide prodrug that includes a thermolabile substituent on at least one nucleotide thereof. The present invention also provides compositions that include a carrier and a therapeutically effective amount of at least one CpG oligonucleotide prodrug. The present invention further provides therapeutic methods of using such thermolabile CpG oligonucleotide prodrugs and compositions thereof. The present invention further provides a method of inhibiting tetrad formation in a CpG oligonucleotide by functionalizing the CpG oligonucleotide with one or more thermolabile substituents.

CpG oligonucleotide prodrugs, compositions thereof and associated therapeutic methods

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating an immune-mediated disorder, such as, but not limited to, an autoimmune disease, by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide. Also disclosed are methods of suppressing an immune response in a subject by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

Suppressors of CpG oligonucleotides and methods of use

A substantially pure or isolated oligodeoxynucleotide of at least 10 nucleotides is disclosed, wherein the oligodeoxynucleotide comprised a sequence represented by either formula:5' NNNT-CpG-WNNN3&#x2032;wherein the CpG motif is unmethylated, W is A or T, and N, N, N, N, N, and Nare nucleotides, or the formula:5&#x2032; RY-CpG-RY 3&#x2032;wherein the central CpG motif is unmethylated, R is A or G, and Y is C or T, as well as an oligodeoxynucleotide delivery complex and a pharmacological composition comprising the present inventive oligodeoxynucleotide, and a method of inducing an immune response by administering the present inventive oligodeoxynucleotide to a host. In some embodiments, the oligodeoxynucleotide includes the nucleic acid sequences set forth as SEQ ID NO: 137.

Oligodeoxynucleotide and its use to induce an immune response

The present disclosure relates to oligodeoxynucleotides that suppress an immune response. Methods are disclosed for preventing or treating inflammatory arthropathies by administering a therapeutically effective amount of a suppressive oligodeoxynucleotide.

Method of treating inflammatory arthropathies with supressors of CPG oligonucleotides

The present disclosure relates to a method of preventing or treating an infection caused by a bioterrorism agent, specifically to a method of increasing an immune response to a bioterrorism agent using an oligodeoxynucleotide including a CpG motif, and a method of enhancing the immunogenicity of a vaccine against a bioterrorism agent using an oligodeoxynucleotide including a CpG motif.

Method of preventing infections from bioterrorism agents with immunostimulatory CpG oligonucleotides

A substantially pure or isolated oligodeoxynucleotide of at least 10 nucleotides is disclosed, wherein the oligodeoxynucleotide comprised a sequence represented by either formula:5'NNNT-CpG-WNNN3&#x2032;wherein the CpG motif is unmethylated, W is A or T, and N, N, N, N, N, and Nare nucleotides, or the formula:5&#x2032;RY-CpG-RY3&#x2032;wherein the central CpG motif is unmethylated, R is A or G, and Y is C or T, as well as an oligodeoxynucleotide delivery complex and a pharmacological composition comprising the present inventive oligodeoxynucleotide, and a method of inducing an immune response by administering the present inventive oligodeoxynucleotide to a host. In some embodiments, the oligodeoxynucleotide includes the nucleic acid sequences set forth as SEQ ID NO: 137.

Olioodeoxynucleotide and its use to induce an immune response

Method of treating inflammatory arthropathies with suppressors of CpG oligonucleotides

A method is disclosed herein for increasing an immune response to an opportunistic infection in an immunocompromised subject. In one embodiment, the subject is infected with a lentivirus. The method includes increasing an immune response to a pathogen using D oligodeoxynucleotides including a CpG motif.

Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides

Compositions including multiple oligodeoxynucleotides with a CpG motif are disclosed herein. The compositions can include either D or K type oligodeoxynucleotides. These compositions are of use in inducing an immune response in a large percentage of the individuals in a population.

Multiple CpG oligodeoxynucleotide and their use to induce an immune response

D type CpG oligodeoxynucleotides are provided herein that include a sequence represented by the following formula:5'XXXPuPyCpGPuPyXXX(W)(G)-3&#x2032;wherein the central CpG motif is unmethylated, Pu is a purine nucleotide, Py is a pyrimidine nucleotide, X and W are any nucleotide, M is any integer from 0 to 10, and N is any integer from 4 to 10. Methods of using these oligodeoxynucleotides to induce an immune response are provided.

The present invention provides a substantially pure or isolated oligodeoxynucleotide of at least about 10 nucleotides comprising a sequence represented by either the formula:5'NNNT-CpG-WNNNwherein the central CpG motif is unmethylated, W is A or T, and N, N, N, N, N, and Nare any nucleotides, or the formula:5&#x2032;RY-CpG-RYwherein the central CpG motif is unmethylated, R is. A or G, and Y is C or T, as well as an oligodeoxynucleotide delivery complex and a pharmacological composition comprising the present inventive oligodeoxynucleotide, and a method of inducing an immune response by administering the present inventive oligodeoxynucleotide to a host.

Novel methods of rapidly generating dendrtic cells are disclosed herein. The methods include contacting a dendritic cell precursor with a D ODN to generate a mature dendritic cell. In one specific, non-limiting example, the method includes contacting the dendritic cell precursor or the mature dendritic cell with an antigen. The methods are of use both in vitro and in vivo.

Method for rapid generation of mature dendritic cells

D type CpG oligodeoxynucleotides are provided herein that include a sequence represented by the following formula:5' XXXPuPyCpG PuPyXXX(W)(G)-3&#x2032;wherein the central CpG motif is unmethylated, Pu is a purine nucleotide, Py is a pyrimidine nucleotide, X and W are any nucleotide, M is any integer from 0 to 10, and N is any integer from 4 to 10. Methods of using these oligodeoxynucleotides to induce an immune response are provided.

Growing community of inventors

Potomac, MD, United States of America

Daniela Verthelyi