Formulations of single domain antigen binding molecules

Abstract

The invention relates to formulations of single domain antigen binding molecules, e.g., nanobody molecules, in particular formulations of TNF-binding nanobody molecules. The single domain antigen binding molecules can include one or more single binding domains that interact with, e.g., bind to, one or more target proteins. The formulations are useful, e.g., as pharmaceutical formulations. Method of preparing, and using the formulations described herein, to treat, e.g., TNF-associated disorders, are also disclosed.

1 .- 23 . (canceled) 
     
     
         24 . A method of treating or preventing a disorder, comprising administering to a subject a pharmaceutical composition that comprises: (a) a therapeutic agent at a concentration of 0.1 mg/mL to about 350 mg/mL; (b) a lyoprotectant; and (c) a buffer at a concentration of about 5 to about 50 mM, such that the pH of the pharmaceutical composition is about 5.0 to 7.5. 
     
     
         25 . The method of  claim 24 , wherein the disorder is an inflammatory or an autoimmune disorder. 
     
     
         26 . The method of  claim 24 , wherein the disorder is chosen from rheumatoid arthritis (RA), arthritic conditions (e.g., psoriatic arthritis, polyarticular juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), psoriasis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, and multiple sclerosis. 
     
     
         27 . A method of analyzing a manufacturing process, comprising:
 providing a sample formulation; assessing a parameter of the sample formulation chosen from color, clarity, viscosity, or an amount of one or more HMW, LMW, acidic or basic species; and   determining whether the parameter meets a preselected criteria, thereby analyzing the process;   wherein the sample formulation comprises: (a) a therapeutic agent at a concentration of 0.1 mg/mL to about 350 mg/mL; (b) a lyoprotectant; and (c) a buffer at a concentration of about 5 to about 50 mM, such that the pH of the formulation is about 5.0 to 7.5.   
     
     
         28 . The method of  claim 27 , further comprising comparing two or more sample formulations in a method of monitoring or controlling batch-to-batch variation or to compare the sample to a reference standard. 
     
     
         29 . The method of  claim 28 , further comprising classifying, selecting, accepting or discarding, releasing or withholding, processing into a drug product, shipping, moving to a different location, formulating, labeling, packaging the formulation, based upon the comparison. 
     
     
         30 . The method of  claim 29 , further comprising providing a record which includes data relating to the assessed parameter of the formulation and optionally includes an identifier for a batch of the formulation; submitting said record to a decision-maker; optionally, receiving a communication from said decision maker; optionally, deciding whether to release or market the batch of formulation based on the communication from the decision maker. 
     
     
         31 . A formulation comprising: (a) a therapeutic agent at a concentration of about 0.1 mg/mL to about 350 mg/mL; (b) a lyoprotectant; and (c) a buffer at a concentration of about 5 to about 50 mM, such that the pH of the formulation is about 5.0 to 7.5. 
     
     
         32 . The formulation of  claim 31 , wherein said lyoprotectant is selected from the group consisting of sugars, optionally sucrose, sorbitol, and trehalose; amino acids; methylamines, optionally betaine; lyotrophic salts, optionally magnesium sulfate; polyols, optionally trihydric sugar alcohols and higher sugar alcohols, including glycerin, erythritol, glycerol, arabitol, xylitol, and mannitol; propylene glycol; polyethylene glycol; pluronics; and combinations thereof. 
     
     
         33 . A method or process of preparing the formulation of  claim 31 , the method comprising: purifying a therapeutic agent by passing the therapeutic agent through a chromatography purification step and/or an ultrafiltration/diafiltration step; adjusting the concentration of the therapeutic agent to about 0.1 to about 350 mg/mL in the presence of a lyoprotectant at a concentration of about 5% to about 10% and a buffer at a concentration about 5 to about 50 mM, such that the pH of the formulation is about 5 to 7.5. 
     
     
         34 . A method of preparing the formulation of  claim 31 , the method comprising: lyophilizing a mixture comprising a therapeutic agent, a lyoprotectant, and a buffer, thereby forming a lyophilized mixture; and reconstituting the lyophilized mixture in a diluent, thereby preparing the formulation, wherein the reconstituted formulation comprises: (a) the therapeutic agent at a concentration of about 0.1 mg/mL to about 350 mg/mL; (b) a lyoprotectant at a concentration of about 5% to about 10%; and (c) a buffer at a concentration about 5 to about 50 mM, such that the pH of the formulation is about 5.0 to 7.5. 
     
     
         35 . A kit or an article of manufacture, comprising a container containing the formulation of  claim 31 , and instructions for use. 
     
     
         36 . The kit or article of manufacture of  claim 35 , wherein the formulation is present in a vial or an injectable syringe.