IP Library › Granted Patent US 12,338,274
Granted Patent B2
US 12,338,274 · App. 18/917,707 · Granted Jun 24, 2025

Anti-VEGF protein compositions and methods for producing the same

Inventors: Shunhai Wang (Scarsdale, NY); Ning Li (Greenwich, CT); Hunter Chen (New York, NY); Amardeep Singh Bhupender Bhalla (Montvale, NJ); Shawn M. Lawrence (Nyack, NY); Amy S. Johnson (Briarcliff Manor, NY); Meghan Casey (Ringwood, NJ); Jaimie Grapel (Waldwick, NJ)
Assignee: Regeneron Pharmaceuticals, Inc.
C07K14/71A61K38/1866C07K1/06C07K1/113C07K1/16C07K1/18C07K1/22C07K1/36C07K16/22C07K16/283C12N5/0018C12N5/0031C12N15/66C12P21/02C12P21/06G01N30/80C07K2317/622C07K2319/30C07K2319/33C12N2800/10G01N2030/027
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Quick Facts
Patent No.
US 12,338,274
App. No.
18/917,707
Granted
Jun 24, 2025
Kind
B2
Abstract

The present disclosure pertains to compositions comprising anti-VEGF proteins and methods for producing such compositions.

Claims (33)

1. A formulation comprising:

(a) 40 to 200 mg/ml of aflibercept produced in a cell culture media comprising a cell culture media wherein chemically defined media (CDM) is added to said cell culture media, wherein said aflibercept includes oxidized variants that have at least one oxidized amino acid residue selected from the group consisting of tryptophan, histidine, and a combination thereof,

(b) one or more pharmaceutically acceptable excipients selected from the group of buffering agents, preservatives, detergents and combinations thereof, and

(c) said formulation having a pH between 5.0 and 8.0.

2. The formulation of claim 1 , wherein said oxidized amino acid residue is histidine.

3. The formulation of claim 1 , wherein said oxidized amino acid residue is tryptophan.

4. The formulation of claim 2 , wherein said one or more excipients includes 5-40 mM of a buffer.

5. The formulation of claim 3 , wherein said one or more pharmaceutically acceptable excipients includes 5-40 mM of a buffer.

6. The formulation of claim 2 , wherein the pH is between 5.5 and 7.0.

7. The formulation of claim 3 , wherein the pH is between 5.5 and 7.0.

8. The formulation of claim 2 , further comprising 0.01% to 5.0% of an organic co-solvent.

9. The formulation of claim 3 , further comprising 0.01% to 5.0% of an organic co-solvent.

10. The formulation of claim 2 , further comprising 30 mM to 150 mM of a tonicity agent.

11. The formulation of claim 3 , further comprising 30 mM to 150 mM of a tonicity agent.

12. The formulation of claim 2 , wherein said oxidized histidine variants of aflibercept comprise less than 1.0% of the total amount of aflibercept.

13. The formulation of claim 2 , wherein said oxidized histidine variants of aflibercept comprise between 0.05% and 1.0% of the total amount of aflibercept.

14. The formulation of claim 3 , wherein said oxidized tryptophan variants of aflibercept comprise less than 1.0% of the total amount of aflibercept.

15. The formulation of claim 3 , wherein said oxidized tryptophan variants of aflibercept comprise between 0.2% and 1.0% of the total amount of aflibercept.

16. The formulation of claim 1 , wherein said formulation is stored under an inert gas.

17. The formulation of claim 1 , wherein said formulation is stored in a vial.

18. The formulation of claim 1 , wherein said formulation is stored in a syringe.

19. The formulation of claim 18 , wherein said formulation in said syringe is an autoinjector syringe.

20. A method of administering a pharmaceutically effective amount of aflibercept by intravitreal injection wherein said aflibercept is made in a cell culture media comprising a cell culture media wherein chemically defined media (CDM) is added to said cell culture media, and wherein said aflibercept includes oxidized variants that have at least one oxidized amino acid residue selected from the group consisting of tryptophan, histidine, and a combination thereof and one or more pharmaceutically acceptable excipients.

21. The method of claim 20 , wherein the pharmaceutically effective amount of aflibercept is 2 mg.

22. The method of claim 21 , wherein the pharmaceutically effective amount of aflibercept is administered by intravitreal injection once every 4 weeks.

23. The method of claim 21 , wherein the pharmaceutically effective amount of aflibercept is administered by intravitreal injection once every 4 weeks for the first 3 months, followed by 2 mg via intravitreal injection once every 8 weeks.

24. The method of claim 21 , wherein the pharmaceutically effective amount of aflibercept is administered by intravitreal injection every 4 weeks for the first 5 injections followed by 2 mg via intravitreal injection once every 8 weeks.

25. The method of claim 20 , further comprising the step of administering an anesthesia, an antiseptic and/or an antibiotic.

26. A method of treating Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), or Diabetic Retinopathy with aflibercept wherein said aflibercept is made in a cell culture media comprising a cell culture media wherein chemically defined media (CDM) is added to said cell culture media, and wherein said aflibercept includes oxidized variants that have at least one oxidized amino acid residue selected from the group consisting of tryptophan, histidine, and a combination thereof.

27. The method of claim 26 , further comprising a reduction in mean retinal thickness.

28. The method of claim 26 , further comprising an increase in visual acuity.

29. The method of claim 26 , further comprising a ≥2 step improvement on an Early Treatment of Diabetic Retinopathy Scale-Diabetic Retinopathy Severity Scale (ETDRS-DRSS) from baseline.

30. The method of claim 26 , further comprising a stabilization or elimination of one or more symptoms or indicia of Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), or Diabetic Retinopathy by any clinically measurable degree.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2025
From: WANG, SHUNHAI; LI, NING; CHEN, HUNTER; BHUPENDER BHALLA, AMARDEEP SINGH; LAWRENCE, SHAWN M.; JOHNSON, AMY S.; CASEY, MEGHAN E.; GRAPEL, JAIMIE
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 070070/0234 →
Continuity (13)
Continuation 18637124 · Apr 16, 2024
Continuation 18213779 · Jun 23, 2023
Continuation 18116166 · Mar 1, 2023
Continuation 17858724 · Jul 6, 2022
Continuation 17842286 · Jun 16, 2022
Continuation 17667298 · Feb 8, 2022
Continuation 17575425 · Jan 13, 2022
Division 17460578 · Aug 30, 2021
Continuation 17458519 · Aug 26, 2021
Continuation 16996293 · Aug 18, 2020
Provisional Application 63065012 · Aug 13, 2020
Provisional Application 62944635 · Dec 6, 2019
Related Publication 20250034231A1 · Jan 30, 2025
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