Methods Of Associating Genetic Variants With A Clinical Outcome In Patients Suffering From Age-Related Macular Degeneration Treated With Anti-VEGF

Patent metadata

Field	Value
Publication number	US-2021340605-A1
Application number	US-202117325498-A
Country	US
Kind code	A1
Filing date	May 20, 2021
Priority date	May 25, 2018
Publication date	Nov 4, 2021
Grant date	—

Abstract

Disclosed herein are methods and compositions for associating a genetic variant with intraretinal fluid. Also disclosed herein are methods and compositions for associating a genetic variant with visual acuity, anatomic outcomes or treatment frequency.

First claim

1 - 28 . (canceled)

29 . A method for treating a macular degeneration patient with aflibercept, comprising the steps of:
administering to the patient an initial treatment comprising intravitreal injection of about 2 mg of aflibercept about every 8 weeks; evaluating the patient for intraretinal fluid following the initial treatment with aflibercept; and if intraretinal fluid is present in the patient, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosage frequency of about every 4 to 7 weeks; or if intraretinal fluid is not present in the patient, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosage frequency of about every 9 to 12 weeks; wherein the patient has one or more genetic variants of human vascular endothelial growth factor (VEGF) selected from the group consisting of rs2056688, rs5962084, rs5962087, rs5915722, and rs5962095.

30 . The method of claim 29 , wherein the initial treatment comprises intravitreal injection of about 2 mg of aflibercept about every 8 weeks for about 9 months.

31 . The method of claim 29 , wherein the dosing frequency if intraretinal fluid is present in the patient is about 4 to 6 weeks.

32 . The method of claim 29 , wherein the patient is evaluated for intraretinal fluid using time domain optical coherence tomography (TD-OCT).

33 . A method for treating a macular degeneration patient with aflibercept, comprising the steps of:
evaluating the patient for intraretinal fluid; and if intraretinal fluid is present in the patient, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosing frequency of about every 4 to 7 weeks; or if intraretinal fluid is not present in the patient, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosing frequency of about every 9 to 16 weeks; wherein, prior to evaluating the patient for intraretinal fluid, the patient received an initial treatment comprising intravitreal injection with aflibercept; and wherein the patient has one or more genetic variants of human vascular endothelial growth factor (VEGF) selected from the group consisting of rs2056688, rs5962084, rs5962087, rs5915722, and rs5962095.

34 . The method of claim 33 , wherein, prior to evaluating the patient for intraretinal fluid, the patient received an initial treatment comprising intravitreal injection with aflibercept for at least about 3 months.

35 . The method of claim 34 , wherein the initial treatment comprises administering to the patient about 2 mg of aflibercept by intravitreal injection about every 8 weeks.

36 . The method of claim 34 , wherein, prior to evaluating the patient for intraretinal fluid, the patient received initial treatment comprising intravitreal injection with aflibercept for at least about one year.

37 . The method of claim 33 , wherein the dosing frequency if intraretinal fluid is present in the patient is about 4 to 6 weeks.

38 . The method of claim 33 , wherein the patient is evaluated for intraretinal fluid using time domain optical coherence tomography (TD-OCT).

39 . A method for treating a macular degeneration patient with aflibercept, comprising the steps of:
evaluating the level of intraretinal fluid in the patient about every 3 to 5 weeks; and if the level of intraretinal fluid in the patient has not decreased from the prior evaluation, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosing frequency of about every 4 to 7 weeks; or if the level of intraretinal fluid in the patient has decreased from the prior evaluation, then administering to the patient by intravitreal injection about 2 mg of aflibercept at a dosing frequency of about every 9 to 16 weeks; wherein, prior to evaluating the level of intraretinal fluid in the patient, the patient received an initial treatment comprising intravitreal injection with aflibercept; and wherein the patient has one or more genetic variants of human vascular endothelial growth factor (VEGF) selected from the group consisting of rs2056688, rs5962084, rs5962087, rs5915722, and rs5962095.

40 . The method of claim 39 , wherein, prior to evaluating the patient for intraretinal fluid, the patient received an initial treatment comprising intravitreal injection with aflibercept for at least about 3 months.

41 . The method of claim 40 , wherein the initial treatment comprises administering to the patient about 2 mg of aflibercept by intravitreal injection about every 8 weeks.

42 . The method of claim 39 , wherein, prior to evaluating the patient for intraretinal fluid, the patient received an initial treatment comprising intravitreal injection with aflibercept for at least about one year.

43 . The method of claim 39 , wherein the patient is evaluated for intraretinal fluid using time domain optical coherence tomography (TD-OCT).

44 . A method for treating a macular degeneration patient with aflibercept, comprising the steps of:
evaluating whether the patient has an anatomic outcome selected from the group consisting of resolution of intraretinal fluid, resolution of subretinal fluid, reduction in central retinal thickness, reduction in total neovascular lesion size, reduction in subretinal hyperreflectivity material (SHM), gain in ETDRS letters, lack of new or persistent leaks, or lack of macular hemorrhage; and if the anatomic outcome is present in the patient, then administering to the patient about 2 mg aflibercept at a dosing frequency of about every 9 to 12 weeks; or if the anatomic outcome is not present in the patient, then administering to the patient about 2 mg of aflibercept at a dosing frequency of about every 4 to 7 weeks to the patient; wherein, prior to evaluating whether the patient has the anatomic outcome, the patient has received an initial treatment comprising intravitreal injection with aflibercept; and wherein the patient has one or more genetic variants of human vascular endothelial growth factor (VEGF) selected from the group consisting of rs2056688, rs5962084, rs5962087, rs5915722, and rs5962095.

45 . The method of claim 44 , wherein, prior to evaluating the patient for the anatomic outcome, the patient received an initial treatment comprising intravitreal injection with aflibercept for at least about 3 months.

46 . The method of claim 44 , wherein the initial treatment with aflibercept comprises administering to the patient about 2 mg of aflibercept by intravitreal injection about every 8 weeks.

47 . The method of claim 44 , wherein, prior to evaluating the patient for intraretinal fluid, the patient received an initial treatment comprising intravitreal injection with aflibercept for at least about one year.

48 . The method of claim 44 , wherein the anatomic outcome is a reduction in central retinal thickness as measured by optical coherence tomography (OCT).

49 . The method of claim 44 , wherein the anatomic outcome is a resolution of subretinal fluid as measured by optical coherence tomography (OCT).

50 . The method of claim 44 , wherein the anatomic outcome is a reduction in total neovascular lesion size as measured by fluorescence angiography.

51 . The method of claim 44 , wherein the anatomic outcome is a reduction in subretinal hyperreflectivity material (SHM) as measured by optical coherence tomography (OCT).

52 . The method of claim 44

Assignees

• Regeneron Pharma

Inventors

• Perlee Lorah
• Hamon Sara

Classifications

• A61K39/001135

  Vascular endothelial growth factor [VEGF] · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• C12Q1/6827 Primary

  for detection of mutation or polymorphism · CPC title

• A61P27/00 Primary

  Drugs for disorders of the senses · CPC title