Compositions and Methods for the Treatment of Ophthalmic Disease

Abstract

Compositions and methods of treating ocular disorders comprising CXCR4 inhibitory compositions.

1 - 38 . (canceled) 
     
     
         39 ) A method of treating a retinal disorder, comprising:
 administering to the retinal tissue of a mammal in need of such treating a composition comprising an oligonucleotide inhibitor of CXCR4 activity.   
     
     
         40 ) The method of  claim 39  wherein said CXCR4 inhibitor comprises an RNAi oligonucleotide. 
     
     
         41 ) The method of  claim 40  wherein said RNAi oligonucleotide is administered directly to ocular tissues. 
     
     
         42 ) The method of  claim 41  wherein said RNAi oligonucleotide is administered by placement of nucleic acid into the posterior segment of the eye. 
     
     
         43 ) The method of  claim 42  wherein said nucleic acid is injected into the posterior segment of the eye. 
     
     
         44 ) The method of  claim 41  wherein said siRNA is administered by subconjunctival delivery. 
     
     
         45 ) The method of  claim 41  wherein said siRNA is administered by subretinal delivery. 
     
     
         46 ) The method of  claim 41  wherein said siRNA is administered in a vehicle selected from the group consisting of an implant, a microsphere, and a liquid. 
     
     
         47 ) The method of  claim 46  wherein said siRNA is administered in a vehicle selected from the group consisting of a biodegradable implant and a biodegradable microsphere. 
     
     
         48 ) The method of  claim 47  wherein said siRNA is administered intravitreally. 
     
     
         49 ) The method of  claim 47  wherein said siRNA is administered subconjunctivally. 
     
     
         50 ) The method of  claim 47  wherein said siRNA is administered subretinally. 
     
     
         51 ) The method of  claim 41  wherein said RNAi comprises a nucleotide sequence complementary to a nucleotide sequence region of at least 12 contiguous nucleotides of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         52 ) The method of  claim 41  wherein said RNAi comprises a nucleotide sequence complementary to a nucleotide sequence region of at least 18 contiguous nucleotides of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         53 ) The method of  claim 41  wherein said RNAi comprises a nucleotide sequence complementary to a nucleotide sequence region of at least 22 contiguous nucleotides of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         54 ) The method of  claim 42  wherein said RNAi comprises a nucleotide sequence complementary to a nucleotide sequence region of at least 25 contiguous nucleotides of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9. 
     
     
         55 ) The method of any one of  claims 51 - 54  wherein said nucleotide sequence region is comprised in SEQ ID NO: 2 or SEQ ID NO: 3. 
     
     
         56 ) The method of  claim 55  wherein said nucleotide sequence region is at least partially contained in an open reading frame encoding a CXCR4 polypeptide. 
     
     
         57 ) The method of  claim 56  wherein said nucleotide sequence region is not contained in an open reading frame encoding a CXCR4 polypeptide. 
     
     
         58 ) The method of any one of  claims 51 - 55  wherein said nucleotide sequence region is comprised in SEQ ID NO: 7, SEQ ID NO: 8 or SEQ ID NO: 9. 
     
     
         59 ) The method of  claim 58  wherein said nucleotide sequence region is at least partially contained in an open reading frame encoding a SDF-1 polypeptide. 
     
     
         60 ) The method of  claim 59  wherein said nucleotide sequence region is not contained in an open reading frame encoding a SDF-1 polypeptide. 
     
     
         61 ) The method of  claim 42  wherein said nucleic acid comprises an expression vector that expresses said RNAi in situ. 
     
     
         62 ) The method of  claim 42  wherein said nucleic acid in contained in an intraocular implant. 
     
     
         63 ) The method of  claim 62  wherein said intraocular implant is at least partially biodegradable. 
     
     
         64 ) The method of  claim 61  wherein said nucleic acid comprises siRNA having a nucleotide sequence selected from the group consisting of: SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, and SEQ ID NO: 55. 
     
     
         65 - 96 . (canceled)