Pharmaceutical composition for preventing, stabilising and/or inhibiting blood and lymph vascularization
A pharmaceutical composition including as active agent, an antisens oligonucleotide having the sequence SEQ ID NO: 1 in a concentration from about 0.40 mg/ml to about 2 mg/ml and the use thereof for preventing, stabilizing and/or inhibiting blood and lymph vascularization.
1. A pharmaceutical composition, comprising as active agent an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
2. The pharmaceutical composition according to claim 1 , wherein said antisense oligonucleotide is in a concentration from about 0.80 mg/ml to about 1 mg/ml.
3. The pharmaceutical composition according to claim 1 , wherein said pharmaceutical composition is in a form of an aqueous solution, a suspension, a gel, an ointment, micelles or an emulsion.
4. The pharmaceutical composition according to claim 1 , wherein said pharmaceutical composition is in a form to be administrated topically, by intravitreal injection or by intraconjunctivial injection.
5. The pharmaceutical composition according to claim 1 , wherein said pharmaceutical composition is in a form to be administrated as an eye drop once, twice, or more per day.
6. The pharmaceutical composition according to claim 5 , wherein the amount of said antisense oligonucleotide to be administrated daily per eye is from about 40 μg to about 100 μg per drop.
7. The pharmaceutical composition according to a claim 1 , wherein the antisense oligonucleotide is in a form to be administrated daily to an eye in an amount of from about 8 μg to about 40 μg.
8. A unit dose container comprising the pharmaceutical composition according to claim 1 .
9. The unit dose container according to claim 8 , capable of dispensing eye drops.
10. A method for treating corneal graft rejection, comprising administering to a subject in need thereof a composition comprising as active agent, an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
11. A method for reducing the risk of immune rejection after corneal grafting, comprising administering to a subject in need thereof a composition comprising as active agent, an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
12. A method for treating glaucoma, comprising administering to a subject in need thereof a composition comprising as active agent, an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
13. The method according to claim 12 , wherein glaucoma is selected from the group consisting of: primary open angle glaucoma (POAG), primary angle closure glaucoma, normal tension glaucoma (NTG), pediatric glaucoma, pseudoexfoliative glaucoma, pigmentary glaucoma, traumatic glaucoma, neovascular glaucoma, and irido corneal endothelial glaucoma.
14. A method for treating retinopathy, comprising administering to a subject in need thereof a composition comprising as active agent, an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
15. A method for treating age related macular degeneration, comprising administering to a subject in need thereof a composition comprising as active agent, an antisense oligonucleotide having the sequence SEQ ID NO: 1 or any function-conservative sequence comprising from 9 to 30 nucleotides,
wherein said function-conservative sequence has at least 75% sequence identity compared to SEQ ID NO: 1 and conserves a capacity to inhibit IRS-1 gene expression,
said function-conservative sequence comprises the sequence SEQ ID NO: 20, and
said antisense oligonucleotide is present in the composition at a concentration of from about 0.40 mg/ml to about 2 mg/ml.
16. A method for treating, stabilizing and/or inhibiting blood and lymph vascularization, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition according to claim 1 .
17. The pharmaceutical composition according to claim 1 , wherein the antisense oligonucleotide comprises 9 to 30 nucleotides of SEQ ID NO: 1 and inhibits IRS-1 gene expression.
18. The pharmaceutical composition according to claim 1 , wherein the antisense oligonucleotide consists of 9 to 30 nucleotides of SEQ ID NO: 1 and inhibits IRS-1 gene expression.
19. The pharmaceutical composition according to claim 1 , wherein the antisense oligonucleotide comprises 12 to 30 nucleotides, comprises SEQ ID NO: 20, and inhibits IRS-1 gene expression.
20. The pharmaceutical composition according to claim 1 , wherein the antisense oligonucleotide comprises 25 to 30 nucleotides, comprises SEQ ID NO: 1, and inhibits IRS-1 gene expression.