US 2020/0246423 Al  26  Aug. 6, 2020  [0131]  Excipients include components of a pharmaceuti› cal formulation other than the active ingredient and are  typically added during formulation development for a spe› cific purpose, such as to stabilize the polypeptide while in  solution, change viscosity of the formulation, adjust tonicity,  and confer other desired properties to the formulation.  Excipients are well known in the art and are manufactured  by known methods and available from commercial suppli› ers. Excipients may include, for example, tonicity modifiers  ( e.g., any of the exemplary tonicity modifiers described  herein), stabilizers ( e.g., any of the exemplary stabilizers  described herein), salts (e.g., any of the exemplary salts  described herein), chelating agents (e.g., any of the exem› plary chelating agents described herein), sacrificial additives  and surfactants ( e.g., any of the exemplary additives or  surfactants described herein), and miscellaneous excipients  such as ammonium sulfate, magnesium sulfate, sodium  sulfate, trimethylamine N-oxide, betaine, metal ions (e.g.,  zinc,  copper,  calcium,  manganese,  and  magnesium),  CHAPS, monolaurate, 2-O-beta-mannoglycerate, and the  like. In one embodiment, the concentration of an excipient  in a formulation of the invention is between about 0.001 to  30 weight percent (e.g., about 0.001 to about 28 weight  percent, about 0.001 to about 26 weight percent, about 0.001  to about 24 weight percent, about 0.001 to about 22 weight  percent, about 0.001 to about 20 weight percent, about 0.001  to about 18 weight percent, about 0.001 to about 16 weight  percent, about 0.001 to about 14 weight percent, about 0.001  to about 12 weight percent, about 0.001 to about 10 weight  percent, about 0.001 to about 9 weight percent, about 0.001  to about 8 weight percent, about 0.001 to about 7 weight  percent, about 0.001 to about 6 weight percent, about 0.001  to about 5 weight percent, about 0.001 to about 4.5 weight  percent, about 0.001 to about 4.0 weight percent, about  0.001 to about 3.5 weight percent, about 0.001 to about 3.0  weight percent, about 0.001 to about 2.5 weight percent,  about 0.001 to about 2.0 weight percent, about 0.001 to  about 1.5 weight percent, about 0.001 to about 1.0 weight  percent, about 0.001 to about 0.5 weight percent, about  0.001 to about 0.1 weight percent, about 0.001 to about 0.01  weight percent, about 0.01 to about 30 weight percent, about  0.01 to about 28 weight percent, about 0.01 to about 26  weight percent, about 0.01 to about 24 weight percent, about  [0130]  C. Excipients Suitable for Use in Aflibercept For› mulations  [0129]  A person of ordinary skill in the art will understand  that the pH can be adjusted as necessary to maximize  stability and solubility of aflibercept in a particular formu› lation. For example, a strong acid ( e.g. HCl) or a strong base  (NaOH) can be added to a formulation to adjust the pH down  or up. Such adjustment to a target pH can be made in  buffer-free formulations and such formulations are still  considered buffer-free  about 6.4 to about 6.6, about 6.5 to about 7.0, about 6.5 to  about 6.9, about 6.5 to about 6.8, about 6.5 to about 6.7,  about 6.6 to about 7.0, about 6.6 to about 6.9, about 6.6 to  about 6.8, about 6.7 to about 7.0, about 6.7 to about 6.9, or  about 6.8 to about 7.0, or about 5.0, about 5.1, about 5.2,  about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about  5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3,  about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about  6.9, or about 7.0). In one embodiment, the pH is between 5.5  and 7.0. In another embodiment, the pH is between 6.0 and  6.5. In another embodiment, the pH is about 6.2.  about 5.1 to about 7.0, about 5.1 to about 6.9, about 5.1 to  about 6.8, about 5.1 to about 6.7, about 5.1 to about 6.6,  about 5.1 to about 6.5, about 5.1 to about 6.4, about 5.1 to  about 6.3, about 5.1 to about 6.2, about 5.1 to about 6.1,  about 5.1 to about 6.0, about 5.1 to about 5.9, about 5.1 to  about 5.8, about 5.1 to about 5.7, about 5.1 to about 5.6,  about 5.1 to about 5.5, about 5.1 to about 5.4, about 5.1 to  about 5.3, about 5.2 to about 7.0, about 5.2 to about 6.9,  about 5.2 to about 6.8, about 5.2 to about 6.7, about 5.2 to  about 6.6, about 5.2 to about 6.5, about 5.2 to about 6.4,  about 5.2 to about 6.3, about 5.2 to about 6.2, about 5.2 to  about 6.1, about 5.2 to about 6.0, about 5.2 to about 5.9,  about 5.2 to about 5.8, about 5.2 to about 5.7, about 5.2 to  about 5.6, about 5.2 to about 5.5, about 5.2 to about 5.4,  about 5.3 to about 7.0, about 5.3 to about 6.9, about 5.3 to  about 6.8, about 5.3 to about 6.7, about 5.3 to about 6.6,  about 5.3 to about 6.5, about 5.3 to about 6.4, about 5.3 to  about 6.3, about 5.3 to about 6.2, about 5.3 to about 6.1,  about 5.3 to about 6.0, about 5.3 to about 5.9, about 5.3 to  about 5.8, about 5.3 to about 5.7, about 5.3 to about 5.6,  about 5.3 to about 5.5, about 5.4 to about 7.0, about 5.4 to  about 6.9, about 5.4 to about 6.8, about 5.4 to about 6.7,  about 5.4 to about 6.6, about 5.4 to about 6.5, about 5.4 to  about 6.4, about 5.4 to about 6.3, about 5.4 to about 6.2,  about 5.4 to about 6.1, about 5.4 to about 6.0, about 5.4 to  about 5.9, about 5.4 to about 5.8, about 5.4 to about 5.7,  about 5.4 to about 5.6, about 5.5 to about 7.0, about 5.5 to  about 6.9, about 5.5 to about 6.8, about 5.5 to about 6.7,  about 5.5 to about 6.6, about 5.5 to about 6.5, about 5.5 to  about 6.4, about 5.5 to about 6.3, about 5.5 to about 6.2,  about 5.5 to about 6.1, about 5.5 to about 6.0, about 5.5 to  about 5.9, about 5.5 to about 5.8, about 5.5 to about 5.7,  about 5.6 to about 7.0, about 5.6 to about 6.9, about 5.6 to  about 6.8, about 5.6 to about 6.7, about 5.6 to about 6.6,  about 5.6 to about 6.5, about 5.6 to about 6.4, about 5.6 to  about 6.3, about 5.6 to about 6.2, about 5.6 to about 6.1,  about 5.6 to about 6.0, about 5.6 to about 5.9, about 5.6 to  about 5.8, about 5.7 to about 7.0, about 5.7 to about 6.9,  about 5.7 to about 6.8, about 5.7 to about 6.7, about 5.7 to  about 6.6, about 5.7 to about 6.5, about 5.7 to about 6.4,  about 5.7 to about 6.3, about 5.7 to about 6.2, about 5.7 to  about 6.1, about 5.7 to about 6.0, about 5.7 to about 5.9,  about 5.8 to about 7.0, about 5.8 to about 6.9, about 5.8 to  about 6.8, about 5.8 to about 6.7, about 5.8 to about 6.6,  about 5.8 to about 6.5, about 5.8 to about 6.4, about 5.8 to  about 6.3, about 5.8 to about 6.2, about 5.8 to about 6.1,  about 5.8 to about 6.0, about 5.9 to about 7.0, about 5.9 to  about 6.9, about 5.9 to about 6.8, about 5.9 to about 6.7,  about 5.9 to about 6.6, about 5.9 to about 6.5, about 5.9 to  about 6.4, about 5.9 to about 6.3, about 5.9 to about 6.2,  about 5.9 to about 6.1, about 6.0 to about 7.0, about 6.0 to  about 6.9, about 6.0 to about 6.8, about 6.0 to about 6.7,  about 6.0 to about 6.6, about 6.0 to about 6.5, about 6.0 to  about 6.4, about 6.0 to about 6.3, about 6.0 to about 6.2,  about 6.1 to about 7.0, about 6.1 to about 6.9, about 6.1 to  about 6.8, about 6.1 to about 6.7, about 6.1 to about 6.6,  about 6.1 to about 6.5, about 6.1 to about 6.4, about 6.1 to  about 6.3, about 6.2 to about 7.0, about 6.2 to about 6.9,  about 6.2 to about 6.8, about 6.2 to about 6.7, about 6.2 to  about 6.6, about 6.2 to about 6.5, about 6.2 to about 6.4,  about 6.3 to about 7.0, about 6.3 to about 6.9, about 6.3 to  about 6.8, about 6.3 to about 6.7, about 6.3 to about 6.6,  about 6.3 to about 6.5, about 6.4 to about 7.0, about 6.4 to  about 6.9, about 6.4 to about 6.8, about 6.4 to about 6.7, 