Pharmaceutical compositions comprising peptide variants and methods of use thereof

Abstract

Provided herein are pharmaceutical compositions, formulations and dosage forms comprising variants of fibroblast growth factor 19 (FGF19) proteins and peptide sequences (and peptidomimetics) and fusions of FGF19 and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), and variants of fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics). Methods of using the pharmaceutical compositions, formulations and dosage forms are also provided herein.

1 .- 131 . (canceled) 
     
     
         132 . A pharmaceutical composition comprising:
 a. a peptide having an amino acid sequence consisting of SEQ ID NO:70 is at a concentration of from 1 to 10 mg/mL, and   b. a pharmaceutically acceptable carrier comprising:
 i. Tris that is present in a range of 10 and 20 mM, 
 ii. from 9.2% to 9.3% (w/v) trehalose, and 
 iii. polysorbate-20 that is present in the range of 0.0075 to 0.25% (v/v). 
   
     
     
         133 . The pharmaceutical composition of  claim 132 , wherein the peptide is present at a concentration of 1 mg/mL. 
     
     
         134 . The pharmaceutical composition of  claim 132 , wherein the peptide is present at a concentration of 5 mg/mL. 
     
     
         135 . The pharmaceutical composition of  claim 132 , wherein the peptide is present at a concentration of 10 mg/mL. 
     
     
         136 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition has a pH in a range of 7.0 and 9.0 at 4° C. or 25° C. 
     
     
         137 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition has a pH in a range of 7.5 and 8.5 at 4° C. or 25° C. 
     
     
         138 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition has a pH of 8.0 at 4° C. 
     
     
         139 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition has a pH of 8.0 at 25° C. 
     
     
         140 . The pharmaceutical composition of  claim 132 , wherein the peptide is fused with an immunoglobulin Fc region. 
     
     
         141 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition does not comprise a salt. 
     
     
         142 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition does not comprise NaCl. 
     
     
         143 . The pharmaceutical composition of  claim 132 , wherein less than 10% of the peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         144 . The pharmaceutical composition of  claim 132 , wherein less than 10% of the peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         145 . The pharmaceutical composition of  claim 132 , wherein less than 5% of the peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         146 . The pharmaceutical composition of  claim 132 , wherein less than 5% of the peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         147 . The pharmaceutical composition of  claim 132 , wherein less than 2% of the peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         148 . The pharmaceutical composition of  claim 132 , wherein less than 2% of the peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         149 . The pharmaceutical composition of  claim 132 , wherein the pharmaceutical composition is in a liquid form. 
     
     
         150 . The pharmaceutical composition of  claim 149 , wherein less than 10% of the peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         151 . The pharmaceutical composition of  claim 149 , wherein less than 10% of the peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         152 . The pharmaceutical composition of  claim 149 , wherein less than 5% of the peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         153 . The pharmaceutical composition of  claim 149 , wherein less than 5% of the peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         154 . The pharmaceutical composition of  claim 149 , wherein less than 2% of peptide aggregates after a period of time of 4 weeks at 4° C. 
     
     
         155 . The pharmaceutical composition of  claim 149 , wherein less than 2% of peptide aggregates after a period of time of 4 weeks at 37° C. 
     
     
         156 . The pharmaceutical composition of  claim 132 , wherein the composition is provided in a single-use container. 
     
     
         157 . The pharmaceutical composition of  claim 132 , wherein the composition is provided in a syringe. 
     
     
         158 . The pharmaceutical composition of  claim 132 , wherein the composition is provided in an autoinjector. 
     
     
         159 . The pharmaceutical composition of  claim 132 , wherein the composition is provided in a multi-use container. 
     
     
         160 . The pharmaceutical composition of  claim 149 , wherein the composition is provided in a single-use container. 
     
     
         161 . The pharmaceutical composition of  claim 149 , wherein the composition is provided in a syringe. 
     
     
         162 . The pharmaceutical composition of  claim 149 , wherein the composition is provided in an autoinjector. 
     
     
         163 . The pharmaceutical composition of  claim 149 , wherein the composition is provided in a multi-use container.