US2021393530A1PendingUtilityA1

VEGF Antagonist Formulations

Assignee: REGENERON PHARMAPriority: Mar 25, 2005Filed: May 7, 2021Published: Dec 23, 2021
Est. expiryMar 25, 2025(expired)· nominal 20-yr term from priority
A61P 35/00A61K 47/26C07K 14/71A61K 31/7012A61P 7/00A61K 38/16A61K 9/19A61K 39/39591A61K 9/08A61P 43/00C07K 2318/20A61K 38/17A61K 38/179A61K 9/0019A61K 47/183A61K 47/12A61P 9/00A61K 31/4172A61K 47/02C07K 16/22C07K 2319/30A61K 47/22A61K 47/10Y02A50/30
80
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Claims

Abstract

Formulations of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist are provided including a pre-lyophilized formulation, a reconstituted lyophilized formulation, and a stable liquid formulation. Preferably, the fusion protein has the sequence of SEQ ID NO:4.

Claims

exact text as granted — not AI-modified
1 .- 20 . (canceled) 
     
     
         21 . A pre-filled syringe comprising a formulation comprising:
 10-50 mg/ml of a vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4,   a pH of 6.0-6.5,   an organic co-solvent,   a stabilizing agent comprising a sugar, an amino acid, or both, and   wherein said VEGF antagonist fusion protein exhibits less than 3% degradation after 15 months of storage at 5° C.   
     
     
         22 . The pre-filled syringe of  claim 21 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         23 . The pre-filled syringe of  claim 21 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         24 . The pre-filled syringe of  claim 23 , wherein said sugar comprises trehalose. 
     
     
         25 . The pre-filled syringe of  claim 23 , wherein said sugar comprises sucrose. 
     
     
         26 . The pre-filled syringe of  claim 23 , wherein said sugar comprises 5-30% sucrose. 
     
     
         27 . The pre-filled syringe of  claim 23 , wherein said sugar comprises 5-20% sucrose. 
     
     
         28 . The pre-filled syringe of  claim 25 , wherein said sugar further comprises trehalose. 
     
     
         29 . The pre-filled syringe of  claim 23 , wherein said co solvent comprises polysorbate. 
     
     
         30 . The pre-filled syringe of  claim 29 , wherein said co solvent comprises polysorbate 20. 
     
     
         31 . The pre-filled syringe of  claim 29 , wherein said pH is 6.2. 
     
     
         32 . The pre-filled syringe of  claim 31 , wherein said formulation further comprises a tonicity agent. 
     
     
         33 . The pre-filled syringe of  claim 32 , wherein said tonicity agent is sodium chloride. 
     
     
         34 . The pre-filled syringe of  claim 21 , wherein said stabilizing agent comprises an amino acid. 
     
     
         35 . The pre-filled syringe of  claim 34 , wherein said pH is 6.2. 
     
     
         36 . The pre-filled syringe of  claim 34 , wherein said co solvent comprises polysorbate. 
     
     
         37 . The pre-filled syringe of  claim 36 , wherein said co solvent comprises polysorbate 20. 
     
     
         38 . The pre-filled syringe of  claim 35 , wherein said formulation further comprises a tonicity agent. 
     
     
         39 . The pre-filled syringe of  claim 38 , wherein said tonicity agent is sodium chloride. 
     
     
         40 . The pre-filled syringe of  claim 21 , wherein said formulation comprises 40 mg/ml of said VEGF antagonist fusion protein. 
     
     
         41 . The pre-filled syringe of  claim 40 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         42 . The pre-filled syringe of  claim 40 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         43 . The pre-filled syringe of  claim 42 , wherein said sugar comprises trehalose. 
     
     
         44 . The pre-filled syringe of  claim 42 , wherein said sugar comprises sucrose. 
     
     
         45 . The pre-filled syringe of  claim 42 , wherein said sugar comprises 5-30% sucrose. 
     
     
         46 . The pre-filled syringe of  claim 42 , wherein said sugar comprises 5-20% sucrose. 
     
     
         47 . The pre-filled syringe of  claim 42 , wherein said co solvent comprises polysorbate. 
     
     
         48 . The pre-filled syringe of  claim 47 , wherein said co solvent comprises polysorbate 20. 
     
     
         49 . The pre-filled syringe of  claim 47 , wherein said pH is 6.2. 
     
     
         50 . The pre-filled syringe of  claim 49 , wherein said formulation further comprises a tonicity agent. 
     
     
         51 . The pre-filled syringe of  claim 50 , wherein said tonicity agent is sodium chloride. 
     
     
         52 . The pre-filled syringe of  claim 40 , wherein said stabilizing agent comprises an amino acid. 
     
     
         53 . The pre-filled syringe of  claim 52 , wherein said pH is 6.2. 
     
     
         54 . The pre-filled syringe of  claim 52 , wherein said co solvent comprises polysorbate. 
     
     
         55 . The pre-filled syringe of  claim 54 , wherein said co solvent comprises polysorbate 20. 
     
     
         56 . The pre-filled syringe of  claim 53 , wherein said formulation further comprises a tonicity agent. 
     
     
         57 . The pre-filled syringe of  claim 56 , wherein said tonicity agent is sodium chloride. 
     
     
         58 . A vial comprising a formulation comprising:
 10-50 mg/ml of a vascular endothelial growth factor (VEGF) antagonist fusion protein comprising amino acids 27-457 of SEQ ID NO: 4,   a pH of 6.0-6.5,   an organic co-solvent,   a stabilizing agent comprising a sugar, an amino acid, or both, and   wherein said VEGF antagonist fusion protein exhibits less than 3% degradation after 15 months of storage at 5° C.   
     
     
         59 . The vial of  claim 58 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         60 . The vial of  claim 58 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         61 . The vial of  claim 60 , wherein said sugar comprises trehalose. 
     
     
         62 . The vial of  claim 60 , wherein said sugar comprises sucrose. 
     
     
         63 . The vial of  claim 60 , wherein said sugar comprises 5-30% sucrose. 
     
     
         64 . The vial of  claim 60 , wherein said sugar comprises 5-20% sucrose. 
     
     
         65 . The vial of  claim 60 , wherein said cosolvent comprises polysorbate. 
     
     
         66 . The vial of  claim 65 , wherein said cosolvent comprises polysorbate 20. 
     
     
         67 . The vial of  claim 65 , wherein said pH is 6.2. 
     
     
         68 . The vial of  claim 67 , wherein said formulation further comprises a tonicity agent. 
     
     
         69 . The vial of  claim 68 , wherein said tonicity agent is sodium chloride. 
     
     
         70 . The vial of  claim 58 , wherein said stabilizing agent comprises an amino acid. 
     
     
         71 . The vial of  claim 70 , wherein said pH is 6.2. 
     
     
         72 . The vial of  claim 70 , wherein said cosolvent comprises polysorbate. 
     
     
         73 . The vial of  claim 72 , wherein said cosolvent comprises polysorbate 20. 
     
     
         74 . The vial of  claim 71 , wherein said formulation further comprises a tonicity agent. 
     
     
         75 . The vial of  claim 74  wherein said tonicity agent is sodium chloride. 
     
     
         76 . The vial of  claim 69 , wherein said formulation comprises 40 mg/ml of said VEGF antagonist fusion protein. 
     
     
         77 . The vial of  claim 76 , wherein said sugar comprises a sugar selected from group consisting of dextrose, ribose, fructose, mannitol, inositol, sorbitol, trehalose, sucrose, and lactose. 
     
     
         78 . The vial of  claim 76 , wherein said sugar comprises sucrose, trehalose, or mannitol. 
     
     
         79 . The vial of  claim 78 , wherein said sugar comprises trehalose. 
     
     
         80 . The vial of  claim 78 , wherein said sugar comprises sucrose. 
     
     
         81 . The vial of  claim 78 , wherein said sugar comprises 5-30% sucrose. 
     
     
         82 . The vial of  claim 78 , wherein said sugar comprises 5-20% sucrose. 
     
     
         83 . The vial of  claim 78 , wherein said cosolvent comprises polysorbate. 
     
     
         84 . The vial of  claim 83 , wherein said cosolvent comprises polysorbate 20. 
     
     
         85 . The vial of  claim 83 , wherein said pH is 6.2. 
     
     
         86 . The vial of  claim 85 , wherein said formulation further comprises a tonicity agent. 
     
     
         87 . The vial of  claim 86 , wherein said tonicity agent is sodium chloride. 
     
     
         88 . The vial of  claim 76 , wherein said stabilizing agent comprises an amino acid. 
     
     
         89 . The vial of  claim 88 , wherein said pH is 6.2. 
     
     
         90 . The vial of  claim 88 , wherein said cosolvent comprises polysorbate. 
     
     
         91 . The vial of  claim 90 , wherein said cosolvent comprises polysorbate 20. 
     
     
         92 . The vial of  claim 89 , wherein said formulation further comprises a tonicity agent. 
     
     
         93 . The vial of  claim 90 , wherein said tonicity agent is sodium chloride.

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