Pharmaceutical formulations of fcrn inhibitors suitable for subcutaneous administration

Abstract

Provided are various aqueous formulations of the neonatal Fc receptor (FcRn) antagonist ARGX-113, including formulations useful as pharmaceutical compositions, methods for their preparation, devices comprising the various formulations, and uses thereof. In certain embodiments the formulations are suitable and useful for administration of ARGX-113 to a human subject. In certain embodiments the formulations are suitable and useful for subcutaneous administration of ARGX-113 to a human subject. The formulations can be used in the treatment of any condition that would benefit from inhibition of FcRn-mediated antibody recycling. Such conditions can include any one or more of various antibody-mediated autoimmune diseases, including, for example and without limitation, myasthenia gravis (MG) and immune thrombocytopenia (ITP).

What is claimed is: 
     
         1 - 17 . (canceled) 
     
     
         18 . A packaged pharmaceutical product comprising a sterile container comprising a therapeutically effective amount of an aqueous formulation comprising about 100-200 mg/mL of a neonatal Fc receptor (FcRn) antagonist in 20-60 mM histidine/histidine HCl, 0-70 mM sucrose, 0-150 mM NaCl, 0-250 mM arginine HCl, 0.04% (w/v) polysorbate 20 or polysorbate 80, 0-15 mM L-methionine, pH 6.0-6.5, wherein the FcRn antagonist consists of a variant Fc region, and wherein the variant Fc region consists of two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. 
     
     
         19 . The packaged pharmaceutical product according to  claim 18 , comprising about 100-200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl. 
     
     
         20 . The packaged pharmaceutical product according to  claim 18 , comprising 150 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         21 . The packaged pharmaceutical product according to  claim 18 , comprising about 175 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         22 . The packaged pharmaceutical product according to  claim 18 , comprising 175 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         23 . The packaged pharmaceutical product according to  claim 18 , comprising about 200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         24 . The packaged pharmaceutical product according to  claim 18 , comprising 200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, and 100 mM NaCl, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         25 . The packaged pharmaceutical product according to  claim 18 , comprising about 100-200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine. 
     
     
         26 . The packaged pharmaceutical product according to  claim 18 , comprising about 165 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine. 
     
     
         27 . The packaged pharmaceutical product according to  claim 18 , comprising about 175 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         28 . The packaged pharmaceutical product according to  claim 18 , comprising 175 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         29 . The packaged pharmaceutical product according to  claim 18 , comprising about 200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         30 . The packaged pharmaceutical product according to  claim 18 , comprising 200 mg/mL of the FcRn antagonist in 20 mM histidine/histidine HCl, 60 mM sucrose, 100 mM NaCl, and 10 mM L-methionine, wherein the amino acid sequence of each of the Fc domains of the FcRn antagonist consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         31 . The packaged pharmaceutical product according to  claim 18 , wherein the packaged pharmaceutical product is presented as a single-use vial, a multi-use vial, or a pre-filled syringe. 
     
     
         32 . The packaged pharmaceutical product according to  claim 18 , wherein the packaged pharmaceutical product is presented as a single-use vial. 
     
     
         33 . A packaged pharmaceutical product comprising a sterile container comprising a therapeutically effective amount of an aqueous formulation comprising 100-200 mg/mL of an FcRn antagonist in 20 mM L-histidine/L-histidine HCl, 100 mM NaCl, 60 mM sucrose, 10 mM L-methionine, and 0.04% (w/v) polysorbate 20, pH 6.0-6.5, wherein the FcRn antagonist consists of a variant Fc region, and wherein the variant Fc region consists of two Fc domains which form a homodimer, wherein the amino acid sequence of each of the Fc domains consists of the amino acid sequence set forth in SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         34 . The packaged pharmaceutical product according to  claim 33 , wherein the amino acid sequence of each of the Fc domains consists of the amino acid sequence set forth in SEQ ID NO: 1. 
     
     
         35 . The packaged pharmaceutical product according to  claim 33 , wherein the aqueous formulation comprises about 180 mg/mL of the FcRn antagonist. 
     
     
         36 . The packaged pharmaceutical product according to  claim 33 , wherein the aqueous formulation comprises 180 mg/mL of the FcRn antagonist. 
     
     
         37 . The packaged pharmaceutical product according to  claim 33 , wherein the packaged pharmaceutical product is presented as a single-use vial, a multi-use vial, or a pre-filled syringe. 
     
     
         38 . The packaged pharmaceutical product according to  claim 33 , wherein the packaged pharmaceutical product is presented as a single-use vial.