Treatment for age-related macular degeneration (amd)

Abstract

The present application is directed to the use of a VEGF-C inhibitor, a VEGFR-2 inhibitor and/or a VEGFR-3 inhibitor as a prophylactic or therapeutic for the treatment of eye disorders such as a maculopathy and pathogenic ocular neovascularisation. The application is also directed to the use of a VEGF-C measurement from a biological sample from a mammalian subject as a predictive marker, a selected marker, a responsive marker or a tracking marker for a disease or condition selected from the group consisting of a maculopathy and pathogenic ocular neovascularization.

1 - 3 . (canceled) 
     
     
         4 . A method comprising
 (a) measuring VEGF-C in a biological sample from a mammalian subject to obtain a VEGF-C measurement, and   (b) using the VEGF-C measurement to
 (i) assess the risk of the subject developing a disease or condition selected from a maculopathy and pathogenic ocular neovascularization; 
 (ii) assess the risk of a disease or condition selected from a maculopathy and pathogenic ocular neovascularization in the subject progressing to a more serious or advanced disease or condition; 
 (iii) select a prophylactic or therapeutic to inhibit a disease or condition selected from a maculopathy and pathogenic ocular neovascularization; or 
 (iv) monitor and adjust the dose of a prophylactic or therapeutic for a disease or condition selected from a maculopathy and pathogenic ocular neovascularization. 
   
     
     
         5 . A method according to  claim 4  of assessing risk of a subject developing a maculopathy or pathogenic ocular neovascularization, the method comprising:
 (a) measuring VEGF-C in a biological sample from a mammalian subject to obtain a VEGF-C measurement, and 
 (b) determining an increased risk of the subject developing the maculopathy or the pathogenic ocular neovascularization from an elevated measurement of VEGF-C in the biological sample, or determining a normal or decreased risk of the subject developing the maculopathy or the pathogenic ocular neovascularization from the absence of the elevated measurement. 
 
     
     
         6 . The method according to  claim 5  that comprises detecting elevated VEGF-C in the biological sample, and determining that the subject has an increased risk of developing the maculopathy or the pathogenic ocular vascularisation, attributable to the elevated measurement of VEGF-C. 
     
     
         7 . The method according to  claim 5  further comprising administering, to the eye of a subject determined to have the increased risk, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, a VEGFR-2 inhibitor, or a VEGFR-3 inhibitor. 
     
     
         8 . The method according to  claim 5 , wherein determining the risk comprises calculating a risk score for the subject developing the maculopathy or the pathogenic ocular neovascularization based on the measurement of the VEGF-C in the sample. 
     
     
         9 . The method according to  claim 8 , wherein the risk score comprises an odds ratio, a relative risk, an overall risk over a period of time for the subject developing the maculopathy or the pathogenic ocular neovascularization. 
     
     
         10 . The method according to  claim 5 , further comprising communicating the risk to the subject, to a guardian for the subject, to a healthcare worker or organization involved in eye care for the subject, or to an insurer. 
     
     
         11 . The method according to  claim 5 , further comprising generating a communication containing the risk, wherein the communication is printed to a tangible report or stored in a non-transient computer readable memory or medium and made accessible to the subject, to a healthcare worker or organization involved in eye care for the subject, or to an insurer. 
     
     
         12 . A method according to  claim 4  for assessing the risk of a maculopathy in the mammalian subject progressing to a more advanced or sever maculopathy, the method comprising:
 (a) measuring VEGF-C in a biological sample from the mammalian subject at a first time point to obtain a first VEGF-C measurement, wherein the mammalian subject is identified as having at least one symptom of a maculopathy; 
 (b) measuring VEGF-C in a biological sample from the mammalian subject at a second time point, after the first time point, to obtain a second VEGF-C measurement; and 
 (c) comparing the first and second VEGF-C measurements to determine if the amount of VEGF-C is changing in the subject between the time points. 
 
     
     
         13 . The method according to  claim 12 , further comprising administering, to the eye of a subject in whom the VEGF-C measurements have increased from the first time point to the second time point, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, a VEGFR-2 inhibitor, or a VEGFR-3 inhibitor. 
     
     
         14 . A method of prophylaxis or treatment of a disease or condition selected from a maculopathy and pathogenic ocular neovascularization according to  claim 4 , the method comprising:
 (a) measuring VEGF-C in a biological sample from a mammalian subject to obtain a VEGF-C measurement,   (b) determining from the VEGF-C measurement that VEGF-C is elevated in the mammalian subject, and   (c) administering, to the eye of a subject identified as having elevated VEGF-C in the biological sample, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, a VEGFR-2 inhibitor, or a VEGFR-3 inhibitor, in a therapeutically effective amount.   
     
     
         15 . The method according to  claim 14 , wherein the mammalian subject has been diagnosed with the disease or condition, and the composition is administered in a therapeutically effective amount. 
     
     
         16 . A method according to  claim 4  of monitoring and adjusting the dose of a prophylactic or therapeutic for a maculopathy or for pathogenic ocular neovascularization, the method comprising:
 (a) administering to a mammalian subject diagnosed with, or identified as having elevated risk for, a maculopathy or pathogenic ocular neovascularization, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, a VEGFR-2 inhibitor, or a VEGFR-3 inhibitor; 
 (b) measuring VEGF-C in a biological sample from the mammalian subject, after the administering, to obtain a VEGF-C measurement; 
 (c) re-administering the composition to the mammalian subject. 
 
     
     
         17 . The method according to  claim 16 , wherein the VEGF-C measurement from step (b) is elevated, and wherein the re-administering is performed with a greater dose and/or a more frequent dosing schedule to further reduce the VEGF-C in the mammalian subject. 
     
     
         18 . The method according to  claim 16 , wherein the VEGF-C measurement from step (b) is normal or below normal compared to apparently healthy subjects, and wherein the re-administering is performed with a smaller dose and/or a less frequent dosing schedule. 
     
     
         19 . The method according to  claim 16 , comprising repeating steps (b) and (c). 
     
     
         20 . A method comprising obtaining an ocular tissue or fluid from a mammalian subject,
 measuring VEGF-C in the ocular tissue or fluid; and   detecting an elevated VEGF-C measurement in the tissue or fluid from the subject, compared to VEGF-C measurements from corresponding ocular tissue or fluid from apparently healthy control subjects.   
     
     
         21 . The method according to  claim 20 , further comprising communicating the measurement of the VEGF-C to the subject, to a healthcare worker for the subject, or to an insurer. 
     
     
         22 . The method according to  claim 20 , further comprising administering to the eye of the subject a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, a VEGFR-2 inhibitor, or a VEGFR-3 inhibitor. 
     
     
         23 - 43 . (canceled)