While oligonucleotides comprising 5'—C—phosphate—G—3 ' (CpG) sequences can effectively induce an immune response in human immune system cells, individuals respond with considerable heterogeneity depending on the specific CpG sequence. Unpredictable immune responses to CpGs present a challenge for inducing a consistent therapeutic immune response in all members of a diverse population using a single CpG sequence, even when that sequence is replicated in a CpG oligonucleotide.
FDA inventors discovered that using a mixture of multiple immune-activating oligonucleotides with different CpG motifs can induce a broad-based immunomodulatory response in a wide cross-section of subjects. These oligodeoxynucleotide mixtures comprise either different oligodeoxynucleotides expressing different CpG motifs or a single oligodeoxynucleotide containing multiple different motifs. These oligodeoxynucleotides also have the capacity to stimulate humoral, cell-mediated immune responses or both humoral and cell-mediated immune responses, depending on the motifs utilized.
|Potential Commercial Applications||Competitive Advantages|
Inventors: Dennis Klinman, Daniela Verthelyi, Ken Ishii
Klinman et al., "CpG Motifs Present in Bacterial DNA Rapidly Induce Lymphocytes to Secrete Interleukin 6, Interleukin 12 and Interferony.” Proc. Natl. Acad. Sci. USA 93: 2879-2883 (1996). PMID: 8610135
United States Patent No. 7,919,477 issued 04.05.2011
United States Patent No. 7,521,063 issued 04.21.2009
United States Patent No. 8,232,259 issued 12.01.2015
Product Area: Vaccine, adjuvant, therapeutic, allergy
FDA Reference No: E-2000-011
Ken Millburne, J.D.
FDA Technology Transfer Program