High viscosity macromolecular compositions for treating ocular conditions

Abstract

Anti-angiogenesis compositions, and methods of using such compositions, useful for injection into the vitreous of human eyes are provided. Such compositions include MAAC solutions or particles present in a therapeutically effective amount, a viscosity-inducing component, and an aqueous carrier component. The compositions have viscosities at about 25° C. of at least about 10 cps or about 100 cps at a shear rate of 0.1/second. In a preferred embodiment, the viscosity at 25° C. is in the range of from about 80,000 cps to about 300,000 cps.

We claim: 
     
         1 . A method for treating an ocular condition, the method comprising:
 administering to the interior of an eye a composition comprising a therapeutically effective amount of a macromolecular anti-angiogenic component (MAAC) to a mammal suffering from an ocular condition, wherein the composition also comprises a viscosity inducing component in an amount effective to increase the viscosity of the composition to a viscosity at about 25° C. of at least about 10 cps at a shear rate of about 0.1/second, wherein said viscosity inducing component is injectable into the vitreous of a mammalian eye without permanently diminishing visual acuity.   
     
     
         2 . The method of  claim 2  wherein said composition comprises a solution. 
     
     
         3 . The method of  claim 1  wherein said composition comprises a gel. 
     
     
         4 . The method of  claim 1  wherein said composition comprises a suspension. 
     
     
         5 . The method of  claim 1  wherein a symptom of the ocular condition is angiogenesis and the MAAC comprises a direct or indirect inhibitor of a vascular endothelial growth factor (VEGF) activity. 
     
     
         6 . The method of  claim 5  wherein the MAAC comprises an agent selected from the group consisting of a nucleic acid (a oligonucleotide) and a polypeptide. 
     
     
         7 . The method of  claim 6  wherein said MAAC comprises a nucleic acid. 
     
     
         8 . The method of  claim 7  wherein said nucleic acid comprises a therapeutic agent selected from the group consisting of an aptamer, an RNAi, a ribozyme, and an antisense oligonucleotide. 
     
     
         9 . The method of  claim 8  wherein said MAAC comprises a therapeutic agent selected from the group consisting of siRNA Z, pegaptanib, and Cand5. 
     
     
         10 . The method of  claim 8  wherein said MAAC comprises at least one nucleic acid having a nucleic acid sequence having at least 80% identity to a nucleotide sequence selected from the group consisting of SEQ ID NO:1, 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, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:22, and SEQ ID NO:23, and nucleotide sequences corresponding to any of these containing at least one modified nucleotide. 
     
     
         11 . The method of  claim 10  wherein said nucleic acid has a nucleotide sequence having at least 90% identity to a nucleotide sequence selected from said group. 
     
     
         12 . The method of  claim 11  wherein said nucleic acid has a nucleotide sequence having at least 95% identity to a nucleotide sequence selected from said group. 
     
     
         13 . The method of  claim 11  wherein said nucleic acid has at least 95% identity to a nucleotide sequence selected from said group. 
     
     
         14 . The method of  claim 6  wherein said MAAC comprises a protein. 
     
     
         15 . The method of  claim 14  wherein said protein is selected from the group consisting of an antibody, an antibody mimic, an angiogenesis inhibitor and a receptor inhibitor. 
     
     
         16 . The method of  claim 14  wherein said protein comprises a therapeutic agent selected form the group consisting of ADNECTIN® CT-322, ADNECTIN® C7S100, ADNECTIN® C7C100, rambizumab, bevacizumab, urokinase peptide inhibitor A6, cisplatin, rapamycin, endostatin, angiostatin, tumstatin, pigment epithelium derived factor, and VEGF TRAP®, IMC-18F1 and IMC-1121 Fab. 
     
     
         17 . The method of  claim 14  wherein the peptide has an amino acid sequence having at least 80% identity to the amino acid sequence selected from the group consisting of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. 
     
     
         18 . The method of  claim 17  wherein said peptide has an amino acid sequence having at least 90% identity to a amino acid sequence selected from said group.