Sting-dependent activators for treatment of disease
AssigneeUniversity of Miami
InventorGlen N. Barber
Life of this patent
Estimating the term…
Abstract
The present disclosure relates, in general, to oligonucleotides that stimulate STING (STimulator of INterferon Genes) activity and increase activity of immune cells. The disclosed STING activators (STAVs) are useful in the treatment of cancer and other immune-mediated conditions.
Claims21
A method of decreasing a size of a melanoma tumor in a subject in need thereof comprising administering intratumorally a composition comprising a STING (STimulator of INterferon Genes) activator comprising a double stranded DNA (dsDNA) comprising:
- a first strand comprising:
- between 70 nucleotides and 90 nucleotides with a modified 5′ end comprising one or more phosphorothioate linkages, where the first strand comprises 80 percent or more of guanine nucleotides;
- and
- a second strand comprising:
- between 70 nucleotides and 90 nucleotides, where the second strand comprises 80 percent or more of cytosine nucleotides, where the STING activator induces STING signaling, where the melanoma tumor is decreased in size by between:
- a lower limit of 25%;
- and
- an upper limit of 50%.
A method of treating a cancer in a subject in need thereof comprising administering a composition comprising a STING (STimulator of INterferon Genes) activator comprising a double stranded DNA (dsDNA) having a modified 5′ end comprising one or more phosphorothioate linkages and comprising between 70 and 90 nucleotides, where the STING activator induces STING signaling, where the STING activator induces Cxcl10 and/or type I IFN cytokine production to a melanoma tumor associated with the cancer thereby inhibiting the cancer.
A method of decreasing a size of a melanoma tumor in a subject in need thereof comprising administering intratumorally a composition comprising a STING (STimulator of INterferon Genes) activator comprising:
- a double stranded DNA (dsDNA) comprising:
- a first strand comprising:
- a modified 5′ end comprising one or more phosphorothioate linkages;
- a modified 3′ end comprising one or more phosphorothioate linkages;
- and
- between:
- 70 nucleotides and 90 nucleotides, where the first strand comprises 80 percent or more of adenine nucleotides;
- and
- a second strand comprising:
- a modified 5′ end comprising one or more phosphorothioate linkages;
- a modified 3′ end comprising one or more phosphorothioate linkages;
- and
- between:
- 70 nucleotides and 90 nucleotides, where second strand comprises 80 percent or more of thymine nucleotides,
- where the melanoma tumor is decreased in size by between:
- a lower limit of 25%;
- and
- an upper limit of 90%.
Dependencies are inferred from the claim text.