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CpG Oligonucleotide Prodrugs

Posted Jun 15 2010 5:00pm

Description of Invention:
Available for licensing and commercial development into prodrugs and methods of synthesizing the same are CpG oligonucleotides that include thermolabile substituent on at least one nucleotide. The invention also provides compositions that include carriers and therapeutically effective amounts of at least one CpG oligonucleotide prodrug. Therapeutic methods of using such thermolabile CpG oligonucleotide prodrugs are also provided (e.g., a prodrug that elicits an immune response). The thermolabile substituent is typically bonded to the non-bridging oxygen atom of at least one phosphate or phosphorothioate in the oligonucleotide.

The thermolabile CpG oligonucleotide prodrugs of the present invention can be administered to a patient as a prodrug of the parent CpG oligonucleotides in vivo. The thermolabile CpG oligonucleotide prodrugs of the present invention are rapidly internalized by immune cells (B cells, macrophages, dendritic cells, and monocytes) and localized in endocytic vesicles where they can interact with Toll-like receptor 9. This interaction triggers an immunostimulatory cascade characterized by B-cell proliferation, dendritic cell maturation, natural killer cell activation and the secretion of a variety of cytokines, chemokines and polyreactive immunoglobulins. Administration of the thermolabile CpG oligonucleotide prodrugs of the present invention to a host, for example, can improve the resistance of the host against infectious pathogenic microorganisms, e.g., parasites, bacteria, and viruses.



Inventors:
Daniela Verthelyi (FDA)
Serge L Beaucage (FDA)
Andrzej Grajkowski (FDA)


Patent Status:
HHS, Reference No. E-215-2004/0
US, Application No. 11/721,409 filed 11 Jun 2007



Portfolios:
Infectious Diseases
Infectious Diseases - Therapeutics
Infectious Diseases - Vaccines
In-vitro Data



For Additional Information Please Contact:
Michael Shmilovich Esq.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: shmilovm@mail.nih.gov
Phone: 301-435-5019
Fax: 301-402-0220


Ref No: 1057

Updated: 06/2010

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