Methods of treating ophthalmic disorders

Abstract

The invention features methods of identifying patients as being likely to respond to anti-VEGF therapy. Furthermore, in those patients identified as failing to include one or more of the above ophthalmic response markers, the invention features treatment with an EPO antagonist (e.g., alone, or in combination with a VEGF antagonist).

1 - 16 . (canceled) 
     
     
         17 . A method of selectively treating a patient having an ophthalmic disorder with a VEGF antagonist, comprising:
 a) assaying a biological sample from the patient for one or more ophthalmic response markers selected from the group consisting of: a single allele having a nucleotide other than a thymine at the locus rs1617640, two alleles having a nucleotide other than a thymine at the locus rs1617640, a single allele having a guanine at the locus rs2010963, and two alleles having a guanine at the locus rs2010963;   b) thereafter, selecting the patient for treatment with the VEGF antagonist on the basis of the biological sample from the patient having one or more ophthalmic response markers selected from the group consisting of: a single allele having a nucleotide other than a thymine at the locus rs1617640, two alleles having a nucleotide other than a thymine at the locus rs1617640, a single allele having a guanine at the locus rs2010963, and two alleles having a guanine at the locus rs2010963; and   c) thereafter, administering a therapeutically effective amount of the VEGF antagonist.   
     
     
         18 . The method of  claim 17 , wherein said patient is selected on the basis of the biological sample having two alleles having a nucleotide other than a thymine at the locus rs1617640. 
     
     
         19 . The method of  claim 17 , wherein said patient is selected on the basis of the biological sample having a single allele having a guanine at the locus rs2010963. 
     
     
         20 . The method of  claim 17 , wherein said patient is selected on the basis of the biological sample having two alleles having a guanine at the locus rs2010963. 
     
     
         21 . A method of selectively treating a patient having an ophthalmic disorder with an EPO antagonist or a combination of a VEGF antagonist and an EPO antagonist, comprising:
 a) assaying a biological sample from the patient for at least one allele having a thymine at the locus rs1617640;   b) thereafter, selecting the patient for treatment with the combination of a VEGF antagonist and an EPO antagonist on the basis of the biological sample from the patient having at least one allele having a thymine at the locus rs1617640; and   c) thereafter, administering a therapeutically effective amount of the VEGF antagonist and/or EPO antagonist.   
     
     
         22 . A method of selectively treating a patient having an ophthalmic disorder with an EPO antagonist or a combination of a VEGF antagonist and an EPO antagonist, comprising:
 a) assaying a biological sample from the patient for at least two alleles having a thymine at the locus rs1617640;   b) thereafter, selecting the patient for treatment with the combination of a VEGF antagonist and an EPO antagonist on the basis of the biological sample from the patient having two alleles having a thymine at the locus rs161764; and   c) thereafter, administering a therapeutically effective amount of the VEGF antagonist and/or EPO antagonist.   
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 17 , wherein the biological sample is selected from the group consisting of synovial fluid, blood, serum, feces, plasma, urine, tear, saliva, cerebrospinal fluid, a leukocyte sample and a tissue sample. 
     
     
         25 . The method  claim 17 , wherein the step of assaying comprises a technique selected from the group consisting of polymerase chain reaction (PCR), TaqMan-based assays, direct sequencing, dynamic allele-specific hybridization, high-density oligonucleotide SNP arrays, restriction fragment length polymorphism (RFLP) assays, primer extension assays, oligonucleotide ligase assays, analysis of single strand conformation polymorphism, temperature gradient gel electrophoresis (TGGE), denaturing high performance liquid chromatography, high-resolution melting analysis, DNA mismatch-binding protein assays, SNPLex®, capillary electrophoresis, Southern Blot, flow cytometry, HPLC, and mass spectrometry. 
     
     
         26 - 43 . (canceled) 
     
     
         44 . The method of  claim 17 , wherein the ophthalmic disorder is macular degeneration. 
     
     
         45 . The method of  claim 44 , wherein said macular degeneration is age-related macular degeneration. 
     
     
         46 . The method or of  claim 17 , wherein the ophthalmic disorder is diabetic macular edema. 
     
     
         47 . The method of  claim 17 , wherein the ophthalmic disorder is diabetic retinopathy. 
     
     
         48 . The method of  claim 17 , wherein the VEGF antagonist is a VEGF binding molecule or VEGF receptor binding molecule. 
     
     
         49 . The method of  claim 48 , wherein the VEGF binding molecule or VEGF receptor binding molecule is VEGFA binding molecule. 
     
     
         50 . The method of  claim 49 , wherein the VEGFA binding molecule is an anti-VEGFA antibody or antigen-binding portion or derivative thereof. 
     
     
         51 . The method of  claim 50 , wherein said anti-VEGFA antibody or antigen-binding portion or derivative thereof is selected from the group consisting of: bevacizumab and ranibizumab. 
     
     
         52 . The method of  claim 51 , wherein said anti-VEGFA antibody or antigen binding portion or derivative thereof is ranibizumab. 
     
     
         53 . The method of  claim 50 , wherein said anti-VEGFA antibody or antigen-binding portion or derivative thereof is selected from the group consisting of: NVS4, NVS80, NVS81, NVS82, NVS83, NVS84 and NVS85 as described in U.S. Patent Application Publication 20120014958 or the VEGFA antibody or antigen-binding portion or derivative thereof described in U.S. Patent Application Publication 20140186350. 
     
     
         54 . The method  claim 21 , wherein said anti-EPO antagonist is an antibody or antigen-binding portion or derivative thereof. 
     
     
         55 . The method of  claim 54 , said anti-EPO antagonist is an antibody or antigen-binding portion or derivative thereof is selected from the group consisting of antibodies or derivatives thereof having the CDR sequences of Fabs NVS1, NVS2, NVS3, and NVS4 (including antibodies or derivatives thereof comprising the Fabs NVS1-4) as disclosed in U.S. Patent Application Publication No. 2014/0199306. 
     
     
         56 - 61 . (canceled)