Compositions and methods of treating tissue damage
AssigneeSilver Creek Pharmaceuticals, Inc.
InventorsLaura D.J. Antipov, Shawdee Eshghi, Kristopher M. Kuchenbecker, Bjorn L. Millard, Matthew D. Onsum, Andrea D. Nickerson, Timothy R. Stowe, Yan Zhang
Life of this patent
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Abstract
Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue.
Claims18
A method to treat tissue damage, the method comprising:
- administering topically to the patient in need thereof a topical composition comprising (a) a therapeutically effective amount of the bi-specific protein having (i) an activator domain, wherein the activator domain comprises a variant of human insulin-like growth factor IGF-1 having at least 95% identity to wild type human IGF-1 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to E3, Y24, Y31, Y60, and combinations thereof, and (ii) a targeting domain, wherein the targeting domain comprises a variant of human Annexin A5 having at least 95% identity to wild type human Annexin A5 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160 and combinations thereof, and (b) a pharmaceutically acceptable carrier.
A method to promote tissue regeneration or tissue survival, the method comprising:
- administering topically to the patient in need thereof a topical composition comprising (a) a therapeutically effective amount of the bi-specific protein having (i) an activator domain, wherein the activator domain comprises a variant of human insulin-like growth factor IGF-1 having at least 95% identity to wild type human IGF-1 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to E3, Y24, Y31, Y60, and combinations thereof, and (ii) a targeting domain, wherein the targeting domain comprises a variant of human Annexin A5 having at least 95% identity to wild type human Annexin A5 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160 and combinations thereof, and (b) a pharmaceutically acceptable carrier.
A topical composition comprising (a) a therapeutically effective amount of the bi-specific protein having (i) an activator domain, wherein the activator domain comprises a variant of human insulin-like growth factor IGF-1 having at least 95% identity to wild type human IGF-1 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at one or more positions corresponding to E3, Y24, Y31, Y60, and combinations thereof, and (ii) a targeting domain, wherein the targeting domain comprises a variant of human Annexin A5 having at least 95% identity to wild type human Annexin A5 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160 and combinations thereof, and (b) a pharmaceutically acceptable carrier.
A topical composition comprising (a) a therapeutically effective amount of the bi-specific protein having (i) an activator domain, wherein the activator domain comprises a variant of human insulin-like growth factor IGF-1 comprising one or more mutations and having at least 95% identity to wild type human IGF-1, wherein the one or more mutations consists of an amino substitution at the position corresponding to position E3, an amino substitution at the position corresponding to position Y24, Y31 Y60, or combinations thereof, a deletion of amino acids 1-3, a deletion of amino acid R37, a deletion of amino acids 68-70, a 13-residue extension at the N-terminal or combinations thereof, and (ii) a targeting domain, wherein the targeting domain comprises a variant of human Annexin A5 having at least 95% identity to wild type human Annexin A5 and comprising one or more mutations, wherein the one or more mutations consist of a substitution at the position corresponding to C316 and optionally at one or more positions corresponding to R63, K70, K101, E138, D139, N160 and combinations thereof, and (b) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.