IGF-1 proteins and therapeutic uses thereof
View Patent ↗The present disclosure provides for techniques using pro-IGF-I for increasing IGF-I activity. Accordingly, the present disclosure provides for compositions and methods for treating or preventing a disease or disorder mediated by IGF-I. In addition, the present disclosure provides for kits for use in the treatment or prevention of a disease or disorder mediated by IGF-I.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a mutant pro-IGF-I protein, wherein the mutant pro-IGF-I protein comprises an amino acid sequence set forth in SEQ ID NO: 5, wherein the amino acid sequence comprises a combination of mutation K68G, a mutation at amino acid residue R71, and a mutation at amino acid residue R77.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises at least one of a pharmaceutically acceptable diluent, solubilizer, emulsifier, preservative, and adjuvant.
3. A kit comprising:
(a) a container;
(b) a pharmaceutically acceptable carrier and a mutant pro-IGF-I protein, wherein the mutant pro-IGF-I protein comprises a combination of mutation K68G, a mutation at amino acid residue R71, and a mutation at amino acid residue R77; and
(c) instructions for use.
4. The pharmaceutical composition of claim 1 , wherein
the mutant pro-IGF-I protein is glycosylation deficient.
5. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition comprises at least one of a pharmaceutically acceptable diluent, solubilizer, emulsifier, preservative, and adjuvant.
6. The kit of claim 3 , wherein the mutant pro-IGF-I protein is glycosylation deficient.
7. The pharmaceutical composition of claim 4 , wherein the mutant pro-IGF-I protein comprises a mutation at amino acid residues N92, N100, or a combination thereof.
8. The pharmaceutical composition of claim 7 , wherein the mutations are N92D, N100D, or any combination thereof.
9. A pharmaceutical composition comprising:
a pharmaceutically acceptable carrier; and
a nucleic acid molecule encoding a mutant pro-IGF-I protein, wherein the mutant pro-IGF-I protein comprises an amino acid sequence set forth in SEQ ID NO: 5, wherein the amino acid sequence comprises a combination of mutation K68G, a mutation at amino acid residue R71, and a mutation at amino acid residue R77.
10. A pharmaceutical composition of claim 9 , wherein the mutant pro-IGF-I protein is glycosylation deficient.
11. The pharmaceutical composition of claim 9 , wherein mutant pro-IGF-I protein comprises at least one mutation within a proprotein convertase cleavage site.
12. The pharmaceutical composition of claim 9 , wherein the amino acid sequence comprises mutations K68G, R71A, and R77A.
13. The pharmaceutical composition of claim 10 , wherein the mutant pro-IGF-I protein comprises a mutation at amino acid residue N92, N100, or a combination thereof.
14. The pharmaceutical composition of claim 13 , wherein the mutations are N92D, N100D, or any combination thereof.
15. A kit comprising:
(a) a container;
(b) a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a nucleic acid molecule encoding a mutant pro-IGF-I protein, wherein the mutant pro-IGF-I protein comprises an amino acid sequence set forth in SEQ ID NO: 5, wherein the amino acid sequence comprises a combination of mutation K68G, a mutation at amino acid residue R71, and a mutation at amino acid residue R77; and
(c) instructions for use.
16. A kit of claim 15 , wherein the mutant pro-IGF-I protein is glycosylation deficient.
17. The pharmaceutical composition of claim 1 , wherein the mutant pro-IGF-I protein is derived from a protein of SEQ ID NO: 1 that is mutated to become proprotein convertase cleavage deficiency.
18. The pharmaceutical composition of claim 1 , wherein the amino acid sequence comprises mutations K68G, R71A, and R77A.
19. The pharmaceutical composition of claim 7 , wherein the mutant pro-IGF-I protein comprises mutations at amino acid residues N92 and N100.
20. The pharmaceutical composition of claim 1 , wherein the mutant pro-IGF-I protein further comprises a mutation at amino acid residues N92, N100, or combinations thereof.
21. The pharmaceutical composition of claim 20 , wherein the mutant pro-IGF-I protein comprises mutations
K68G, R71A, and R77A; and
N92D, N100D, or combinations thereof.
22. The pharmaceutical composition of claim 1 , wherein the mutant pro-IGF-I protein is furin cleavage deficient, PACE4 cleavage deficient, or both.