Solution Formulations of Engineered Anti-IL-23p19 Antibodies

Abstract

The present invention provides high concentration solution formulations of anti-human interleukin-23 p19 (IL-23p19) antibody huml3B8-b, and their use in treating various disorders.

1 . A solution formulation comprising an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1, wherein at least 99% of the anti-IL-23p19 antibody hum13B8-b is present as a monomer following storage at about 5° C. for about 6 months as measured by high-pressure size exclusion chromatography (HP-SEC). 
     
     
         2 . The solution formulation of  claim 1  comprising at least 100 mg/mL anti-IL-23p19 antibody hum13B8-b. 
     
     
         3 . The solution formulation of  claim 1  further comprising a buffer, a surfactant, and an amount of a tonicity adjustment agent to render the solution isotonic. 
     
     
         4 . The solution formulation of  claim 3 , wherein the buffer is histidine or acetate. 
     
     
         5 . The solution formulation of  claim 3 , wherein the surfactant is polysorbate 80, polysorbate 20, or poloxamer 188. 
     
     
         6 . The solution formulation of  claim 3 , wherein the tonicity adjustment agent is sucrose, trehlose, or mannitol. 
     
     
         7 . The solution formulation of  claim 3 , wherein the buffer is 10 mM histidine, the surfactant is 0-0.05% (w/v) of polysorbate 80, and the tonicity adjustment agent is 7% (w/v) sucrose. 
     
     
         8 . The solution formulation of  claim 1 , wherein the anti-IL-23p19 antibody hum13B8-b retains about 100% of the potency of the antibody prior to storage for about 24 months at about 5° C. 
     
     
         9 . The solution formulation of  claim 1 , wherein the anti-IL-23p19 antibody hum13B8-b predominantly sediments as one species with a sedimentation coefficient (so) of 70S as measured by Sedimentation Velocity Analytical Ultracentrifugation. 
     
     
         10 . The solution formulation of  claim 1 , wherein the solution is in a pre-filled syringe or autoinjector. 
     
     
         11 . The solution formulation of  claim 1 , wherein the solution is for subcutaneous administration. 
     
     
         12 . A low acidic variant formulation comprising an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1, wherein the formulation comprises less than 25% total acidic variant of the anti-IL-23p19 antibody hum13B8-b. 
     
     
         13 . The formulation of  claim 12 , wherein the acidic variants of the anti-IL-23p19 antibody hum13B8-b are quantified based on the relative area percent of peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of the anti-IL-23p19 antibody hum13B8-b. 
     
     
         14 . A solution formulation comprising an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1, wherein the formulation has a viscosity of about 4 centipoises to about 6 centipoises at about 25° C. 
     
     
         15 . A solution formulation comprising an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1, wherein following storage at about 5° Celsius for about 24 months the solution formulation comprises less than 2% high molecular weight species (HMWS) as measured by high-performance size exclusion chromatography (HP-SEC). 
     
     
         16 . A stable solution formulation comprising an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1, wherein the formulation has no more than 6000 sub-visible particles per mL having size greater than 10 micron. 
     
     
         17 . A method of treating an autoimmune disease, inflammatory disease, or proliferative disorder in a subject in need thereof, comprising administering to the subject the solution formulation of  claim 1 . 
     
     
         18 . A method of treating psoriasis or psoriatic arthritis in a subject in need thereof, comprising administering to the subject the solution formulation of  claim 1 . 
     
     
         19 . A method of treating moderate-to-severe plaque psoriasis in a subject in need thereof comprising administering to the subject a solution formulation comprising 100 mg/mL of an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1;
 wherein a first dose of the solution formulation is administered subcutaneously to the subject at week 0 and a second dose of the solution formulation is administered subcutaneously to the subject at week 4 and subsequent doses of the solution formulation are administered subcutaneously to the subject every twelve weeks thereafter; and   wherein the subject is eligible for systemic therapy or phototherapy.   
     
     
         20 . A pre-filled syringe comprising 1 mL of a solution formulation comprising 100 mg/mL of an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1. 
     
     
         21 . An autoinjector comprising a syringe comprising 1 mL of a solution formulation comprising 100 mg/mL of an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1. 
     
     
         22 . A vial comprising a solution formulation comprising 100 mg/mL of an anti-IL-23p19 antibody hum13B8-b comprising a light chain polypeptide having the amino acid sequence of SEQ ID NO: 2 and a heavy chain polypeptide having the amino acid sequence of SEQ ID NO: 1.