US 12,005,097 B2
Aflibercept formulations and uses thereof
Bruce A. Kerwin, Bainbridge Island, WA (US); Julee A. Floyd, Seattle, WA (US); Alison J. Gillespie, Seattle, WA (US); and Christine C Siska, Seattle, WA (US)
Assigned to Just-Evotec Biologics, Inc., Seattle, WA (US)
Filed by Just-Evotec Biologics, Inc., Seattle, WA (US)
Filed on Oct. 3, 2021, as Appl. No. 17/492,649.
Application 17/492,649 is a continuation of application No. 16/462,527, granted, now 11,135,266, previously published as PCT/US2017/062521, filed on Nov. 20, 2017.
Claims priority of provisional application 62/497,584, filed on Nov. 21, 2016.
Prior Publication US 2022/0016210 A1, Jan. 20, 2022
Int. Cl. A61K 38/17 (2006.01); A61K 9/00 (2006.01); A61K 47/02 (2006.01); A61K 47/10 (2017.01); A61K 47/12 (2006.01); A61K 47/18 (2017.01); A61K 47/22 (2006.01); A61K 47/26 (2006.01); A61K 47/34 (2017.01)
CPC A61K 38/179 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0048 (2013.01); A61K 47/02 (2013.01); A61K 47/10 (2013.01); A61K 47/12 (2013.01); A61K 47/183 (2013.01); A61K 47/22 (2013.01); A61K 47/26 (2013.01); A61K 47/34 (2013.01)] 18 Claims
 
1. An ophthalmic formulation, comprising:
(a) aflibercept in a concentration of 5-100 mg/mL;
(b) a histidine buffer, wherein the histidine buffer concentration is 5-50 mM;
(c) a non-ionic surfactant selected from the group consisting of a polysorbate, a polyethylene glycol dodecyl ether, a poloxamer, 4-(1,1,3,3-Tetramethylbutyl)phenyl-polyethylene glycol, an alkylsaccharide and an alkylglycoside, at a concentration of 0.001% (w/v) to 5% (w/v);
(d) a tonicifying agent comprising a polyol or an amino acid selected from proline, arginine, aspartate, glutamate, glycine, histidine, isoleucine, and lysine, at a concentration of 2-4% (w/v), wherein the formulation has a final osmolality of 300±50 mOsm/kg;
(e) an additional amino acid stabilizing agent selected from the group consisting of proline, arginine, methionine, lysine and mixtures thereof; and
wherein the pH of the formulation is about pH 5.0 to about pH 6.5.