Use of a VEGF antagonist to treat angiogenic eye disorders

• US 9,254,338 B2
• Filed: 07/12/2013
• Issued: 02/09/2016
• Est. Priority Date: 01/13/2011
• Status: Active Grant

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Yancopoulos, George D.
• Primary Examiner(s): Saoud, Christine J
• Assistant Examiner(s): LOCKARD, JON MCCLELLAND
• Application Number:
  US13/940,370
• Publication Number:
  US 20130295094A1
• Time in Patent Office: 942 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/179 for growth factors; for growth regulators
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"

Abstract

The present invention provides methods for treating angiogenic eye disorders by sequentially administering multiple doses of a VEGF antagonist to a patient. The methods of the present invention include the administration of multiple doses of a VEGF antagonist to a patient at a frequency of once every 8 or more weeks. The methods of the present invention are useful for the treatment of angiogenic eye disorders such as age related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, branch retinal vein occlusion, and corneal neovascularization.

Claims

1. A method for treating an angiogenic eye disorder in a patient, said method comprising sequentially administering to the patient a single initial dose of a VEGF antagonist, followed by one or more secondary doses of the VEGF antagonist, followed by one or more tertiary doses of the VEGF antagonist;

wherein each secondary dose is administered 2 to 4 weeks after the immediately preceding dose; and

wherein each tertiary dose is administered at least 8 weeks after the immediately preceding dose;

wherein the VEGF antagonist is a VEGF receptor-based chimeric molecule comprising (1) a VEGFR1 component comprising amino acids 27 to 129 of SEQ ID NO;

2;

(2) a VEGFR2 component comprising amino acids 130-231 of SEQ ID NO;

2; and

(3) a multimerization component comprising amino acids 232-457of SEQ ID NO;

2.

2. The method of claim 1, wherein only a single secondary dose is administered to the patient, and wherein the single secondary dose is administered 4 weeks after the initial dose of the VEGF antagonist.

3. The method of claim 1, wherein only two secondary doses are administered to the patient, and wherein each secondary dose is administered 4 weeks after the immediately preceding dose.

4. The method of claim 3, wherein each tertiary dose is administered 8 weeks after the immediately preceding dose.

5. The method of claim 1, wherein at least 5 tertiary doses of the VEGF antagonist are administered to the patient, and wherein the first four tertiary doses are administered 8 weeks after the immediately preceding dose, and wherein each subsequent tertiary dose is administered 8 or 12 weeks after the immediately preceding dose.

6. The method of claim 1, wherein the angiogenic eye disorder is selected from the group consisting of:

age related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, branch retinal vein occlusion, and corneal neovascularization.

7. The method of claim 6, wherein the angiogenic eye disorder is age related macular degeneration.

8. The method of claim 1, wherein all doses of the VEGF antagonist are administered to the patient by topical administration or by intraocular administration.

9. The method of claim 8, wherein all doses of the VEGF antagonist are administered to the patient by intraocular administration.

10. The method of claim 9, wherein the intraocular administration is intravitreal administration.

11. The method of claim 10, wherein all doses of the VEGF antagonist comprise from about 0.5 mg to about 2 mg of the VEGF antagonist.

12. The method of claim 11, wherein all doses of the VEGF antagonist comprise 0.5 mg of the VEGF antagonist.

13. The method of claim 11, wherein all doses of the VEGF antagonist comprise 2 mg of the VEGF antagonist.

14. A method for treating an angiogenic eye disorder in a patient, said method comprising sequentially administering to the patient a single initial dose of a VEGF antagonist, followed by one or more secondary doses of the VEGF antagonist, followed by one or more tertiary doses of the VEGF antagonist;

wherein each secondary dose is administered 2 to 4 weeks after the immediately preceding dose; and

wherein each tertiary dose is administered at least 8 weeks after the immediately preceding dose;

wherein the VEGF antagonist is a VEGF receptor-based chimeric molecule comprising VEGFR1R2-FcΔ

C1(a) encoded by the nucleic acid sequence of SEQ ID NO;

1.

15. The method of claim 14, wherein only a single secondary dose is administered to the patient, and wherein the single secondary dose is administered 4 weeks after the initial dose of the VEGF antagonist.

16. The method of claim 14, wherein only two secondary doses are administered to the patient, and wherein each secondary dose is administered 4 weeks after the immediately preceding dose.

17. The method of claim 16, wherein each tertiary dose is administered 8 weeks after the immediately preceding dose.

18. The method of claim 17, wherein the angiogenic eye disorder is age related macular degeneration.

19. The method of claim 14, wherein at least 5 tertiary doses of the VEGF antagonist are administered to the patient, and wherein the first four tertiary doses are administered 8 weeks after the immediately preceding dose, and wherein each subsequent tertiary dose is administered 8 or 12 weeks after the immediately preceding dose.

20. The method of claim 14, wherein the angiogenic eye disorder is selected from the group consisting of:

age related macular degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein occlusion, branch retinal vein occlusion, and corneal neovascularization.

21. The method of claim 14, wherein all doses of the VEGF antagonist are administered to the patient by topical administration or by intraocular administration.

22. The method of claim 21, wherein all doses of the VEGF antagonist are administered to the patient by intraocular administration.

23. The method of claim 22, wherein the intraocular administration is intravitreal administration.

24. The method of claim 23, wherein all doses of the VEGF antagonist comprise from about 0.5 mg to about 2 mg of the VEGF antagonist.

25. The method of claim 24, wherein all doses of the VEGF antagonist comprise 0.5 mg of the VEGF antagonist.

26. The method of claim 24, wherein all doses of the VEGF antagonist comprise 2 mg of the VEGF antagonist.