Enzymatic nucleic acid-mediated treatment of ocular diseases or conditions related to levels of vascular endothelial growth factor receptor (VEGF-R)
View Patent ↗The present invention relates to nucleic acid molecules such as ribozymes, DNAzymes, and antisense which modulate the synthesis, expression and/or stability of an mRNA encoding one or more receptors of vascular endothelial growth factor, such as flt-1 and KDR. Nucleic acid molecules and methods for the inhibition of angiogenesis and treatment of cancer and ocular diseases are provided, optionally in conjunction with other therapeutic agents.
1. A compound having Formula II: (SEQ ID NO: 13488)
5′-u s a s c s a s au ucU GAu Gag gcg aaa gcc Gaa Aag aca aB-3′ wherein each a is 2′-O-methyl adenosine nucleotide, each g is a 2′-O-methyl guanosine nucleotide, each c is a 2′-O-methyl cytidine nucleotide, each u is a 2′-O-methyl uridine nucleotide, each A is adenosine, each G is guanosine, each s individually represents a phosphorothioate internucleotide linkage, U is 2′-deoxy-2′-C-allyl uridine, and B is an inverted deoxyabasic moiety.
2. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
3. A method of locally or intraconjunctivally administering to a cell the compound of claim 1 comprising contacting said cell with the compound under conditions suitable for said administration.
4. The method of claim 3 , wherein said cell is a mammalian cell.
5. The method of claim 3 , wherein said cell is a human cell.
6. The method of claim 3 , wherein said administration is in the presence of a delivery reagent.
7. The method of claim 6 , wherein said delivery reagent is a lipid.
8. The method of claim 7 , wherein said lipid is a cationic lipid.
9. The method of claim 7 , wherein said lipid is a phospholipid.
10. The method of claim 6 , wherein said delivery reagent is a liposome.
11. A method of inhibiting ocular angiogenesis in a patient comprising the step of locally or intraconjunctivally administering the compound of claim 1 to the patient under conditions suitable for said inhibition.
12. The method of claim 11 , wherein said ocular angiogenesis is associated with diabetic retinopathy.
13. The method of claim 11 , wherein said ocular angiogenesis is associated with age related diabetic retinopathy.
14. A method of locally or intraconjunctivally administering to a mammal the compound of claim 1 comprising contacting said mammal with the compound under conditions suitable for said administration.
15. The method of claim 14 , wherein said mammal is a human.
16. The method of claim 14 , wherein said administration is in the presence of a delivery reagent.
17. The method of claim 16 , wherein said delivery reagent is a lipid.
18. The method of claim 17 , wherein said lipid is a cationic lipid.
19. The method of claim 17 , wherein said lipid is a phospholipid.
20. The method of claim 16 , wherein said delivery reagent is a liposome.