Treatment for age-related macular degeneration (AMD) and pathogenic ocular neovascularization
AssigneesVegenics Pty Limited, The Schepens Eye Research Institute, Inc.
InventorsMegan E. Baldwin, Kameran Lashkari, Jie Ma
Life of this patent
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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.
Claims34
A method of prophylaxis or treatment of a disease or condition selected from macular degeneration and pathogenic ocular neovascularization, the method comprising:
- (a) measuring VEGF-C protein in a biological sample from a human subject to obtain a VEGF-C measurement,
- (b) determining from the VEGF-C protein measurement that VEGF-C protein is elevated in the subject, and
- (c) administering, to the eye of a subject identified as having elevated VEGF-C protein in the biological sample, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, said VEGF-C inhibitor comprising:
- (i) a polypeptide comprising a soluble fragment of human VEGFR-3, said fragment including immunoglobulin-like domains D1, D2, and D3 of said human VEGFR-3, wherein said VEGF-C inhibitor binds human VEGF-C;
- or
- (ii) the polypeptide of (i) with the proviso that positions of the polypeptide corresponding to positions 104-106 of SEQ ID NO:
- 4 are not identical to N-X-S or N-X-T, and wherein the polypeptide binds to human VEGF-C.
A method of monitoring and adjusting the dose of a prophylactic or therapeutic administered to a human subject for macular degeneration or for pathogenic ocular neovascularization, the method comprising:
- (a) administering to a human subject diagnosed with, or identified as having elevated risk for, a macular degeneration or pathogenic ocular neovascularization, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, said VEGF-C inhibitor comprising a polypeptide comprising:
- (i) a polypeptide comprising a soluble fragment of human VEGFR-3, said fragment including immunoglobulin-like domains D1, D2, and D3 of said human VEGFR-3, wherein said VEGF-C inhibitor binds human VEGF-C;
- or
- (ii) the polypeptide of (i) with the proviso that positions of the polypeptide corresponding to positions 104-106 of SEQ ID NO:
- 4 are not identical to N-X-S or N-X-T, and wherein the polypeptide binds to human VEGF-C;
- (b) measuring VEGF-C protein in a biological sample from the subject, after the administering, to obtain a VEGF-C protein measurement;
- (c) re-administering the composition to the subject:
- (i) wherein the VEGF-C protein 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 subject;
- or
- (ii) wherein the VEGF-C protein 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.
A method comprising
- obtaining an ocular tissue or fluid from a human subject,
- measuring VEGF-C protein in the ocular tissue or fluid;
- detecting an elevated VEGF-C protein measurement in the ocular tissue or fluid from the subject, compared to VEGF-C measurements from corresponding ocular tissue or fluid from apparently healthy control subjects;
- and
- administering to the eye of the subject a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, said VEGF-C inhibitor comprising:
- (i) a polypeptide comprising a soluble fragment of human VEGFR-3, said fragment including immunoglobulin-like domains D1, D2, and D3 of said human VEGFR-3, wherein said VEGF-C inhibitor binds human VEGF-C;
- or
- (ii) the polypeptide of (i) with the proviso that positions of the polypeptide corresponding to positions 104-106 of SEQ ID NO:
- 4 are not identical to N-X-S or N-X-T, and wherein the polypeptide binds to human VEGF-C.
A method comprising:
- (a) measuring VEGF-C protein in a biological sample from a human subject to obtain a VEGF-C protein measurement;
- (b) detecting elevated VEGF-C protein in the biological sample,
- (c) determining that the subject has an increased risk of developing macular degeneration or pathogenic ocular neovascularization from the elevated measurement of VEGF-C protein in the biological sample;
- (d) administering, to the eye of the subject determined to have the increased risk, a composition formulated for ophthalmic administration and comprising a VEGF-C inhibitor, said VEGF-C inhibitor comprising:
- (i) a polypeptide comprising a soluble fragment of human VEGFR-3, said fragment including immunoglobulin-like domains D1, D2, and D3 of said human VEGFR-3, wherein said VEGF-C inhibitor binds human VEGF-C;
- or
- (ii) the polypeptide of (i) with the proviso that positions of the polypeptide corresponding to positions 104-106 of SEQ ID NO:
- 4 are not identical to N-X-S or N-X-T, and wherein the polypeptide binds to human VEGF-C.
Dependencies are inferred from the claim text.