US 2016/0258930 A1 · METHODS OF DETERMINING INTERFERON HAVING DIRECT INHIBITORY EFFECTS ON TUMORS AND USES THEREOF

Abstract

The invention provides novel methods of determining or comparing potency of a test interferon relative to rSIFN-co (an interferon having therapeutic effects on solid tumors); methods of establishing substantial equivalence between a test interferon and rSIFN-co; methods for down-regulation of expression of Wnt-related receptors or co-receptors, such as LRP6/FZD6; down-regulation of expression of Wnt-related target genes, such as, Axin2, CD24, Survivin and/or ID2; inhibition of beta-catenin/TCF transcriptional activities; suppression of expression of beta-catenin; up-regulation of tumor suppressor genes, such as DKK-3, BATF2 and/or KLF4; inhibition of tumor cell viability in vitro; inhibition of tumor growth and metastases in vivo; inhibition of tumor cell migration, pseudopod formation, and colony formation in vitro; as well as methods for determining potency of a test interferon, kits for determination of such methods, and an interferon or an interferon substitute having said activities.

Claims21

Dependent claims

1-98. (canceled)

A method of determining or comparing potency of a test interferon relative to rSIFN-co or a rSIFN-co substitute, or establishing substantial equivalence between a test interferon and rSIFN-co or a rSIFN-co substitute, comprising the steps of:

1) providing the test interferon and rSIFN-co or rSIFN-co substitute;
and
2) determining one or more of the following activities on the test interferon and rSIFN-co or rSIFN-co substitute under the same specified conditions:
(a) inhibition of in vivo cancer cell growth in one or more tumor-bearing animal models;
(b) reduction in cancer cell viability;
(c) inhibition of cancer cell migration;
(d) inhibition of beta-catenin/TCF transcriptional activity in cancer cells;
(e) down-regulation of expression of LRP6 and/or FZD6 in cancer cells;
(f) inhibition of expression in cancer cells of one or more of:
Axin2, CD24, Survivin and ID2 in cancer cells;
(g) inhibition of pseudopod formation in cancer cells;
(h) inhibition of beta-catenin expression in cancer cells;
and
(i) up-regulation of expression of one or more of:
DKK-3, KLF-4, and BATF2 in cancer cells,
wherein the presence of one or more of the activities (a) to (f) in the test interferon in a statistically significant manner, and/or the presence of one or more of the activities (g) to (i) in the test interferon, indicates that the test interferon and rSIFN-co or rSIFN-co substitute have substantially the same potency, or that a substantial equivalence between the test interferon and rSIFN-co or rSIFN-co substitute is established.

13 more elements

Dependencies are inferred from the claim text.

Methods of determining interferon having direct inhibitory effects on tumors and uses thereof

Life of this patent

Methods of determining interferon having direct inhibitory effects on tumors and uses thereof

Life of this patent

Abstract

Claims21