Anti-il-9 antibody formulations and uses thereof

Abstract

The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to an IL-9 polypeptide, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to an IL-9 polypeptide, which formulations are substantially free of surfactants, sugars, sugar alcohols, amino acids other than histidine (preferably with pKa values of less than 5 and above 7), and/or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating a disease or disorder associated with or characterized by aberrant expression and/or activity of an IL-9 polypeptide, a disease or disorder associated with or characterized by aberrant expression and/or activity of the IL-9R or one or more subunits thereof, an autoimmune disease, an inflammatory disease, a proliferative disease, or an infection (preferably, a respiratory infection), or one or more symptoms thereof, utilizing the liquid formulations of the present invention.

1 . An antibody formulation comprising an aqueous carrier, histidine, and 50 mg/ml or higher of an antibody or antibody fragment that immunospecifically binds to an IL-9 polypeptide. 
     
     
         2 . The formulation of  claim 1 , wherein the formulation is sterile. 
     
     
         3 . The formulation of  claim 1 , wherein the aqueous carrier is distilled water. 
     
     
         4 . The formulation of  claim 1 , wherein the formulation has a pH in the range between 5.0 and 7.0. 
     
     
         5 . The formulation of  claim 1 , wherein the antibody or antibody fragment is at a concentration of at least 95 mg/ml. 
     
     
         6 . The formulation of  claim 5 , wherein the antibody or antibody fragment is at a concentration of at least 100 mg/ml. 
     
     
         7 . (canceled) 
     
     
         8 . The formulation of  claim 1  further comprising glycine at a concentration in the range from about 1 to about 10 mM. 
     
     
         9 . The formulation of  claim 1 , wherein histidine is at concentration in the range from about 5 to about 25 mM. 
     
     
         10 .- 33 . (canceled) 
     
     
         34 . The formulation of  claim 1  further comprising an excipient. 
     
     
         35 . The formulation of  claim 34 , wherein the excipient is a saccharide. 
     
     
         36 . The formulation of  claim 34 , wherein the excipient is a polyol. 
     
     
         37 . The formulation of  claim 2 , wherein the antibody or antibody fragment is 4D4, 4D4 H2-1 D11, 4D4com-XF-9, 4D4com-2F9, 7F3, 71A10, 7F3 22D3, 7F3com-2H2, 7F3com-3H5, or 7F3com-3D4 or an antigen binding fragment thereof. 
     
     
         38 . (canceled) 
     
     
         39 . A pharmaceutical unit dosage form suitable for parenteral administration to a human which comprises an antibody formulation of  claim 37  in a suitable container. 
     
     
         40 . The pharmaceutical unit dosage form of  claim 39 , wherein the antibody formulation is administered intravenously, subcutaneously, or intramuscularly. 
     
     
         41 . A pharmaceutical unit dosage form suitable for aerosol administration to a human which comprises an antibody formulation of  claim 37  in a suitable container. 
     
     
         42 . The pharmaceutical unit dosage of  claim 41 , wherein the antibody formulation is administered intranasally. 
     
     
         43 . (canceled) 
     
     
         44 . A sealed container containing the formulation of  claim 37 . 
     
     
         55 . (canceled) 
     
     
         56 . A method of preventing, managing, treating or ameliorating an inflammatory disease, an autoimmune disease, a disorder associated with aberrant expression and/or activity of an IL-9 polypeptide, a disease or disorder associated with or characterized by aberrant expression and/or activity of an IL-9 polypeptide, a disease or disorder associated with or characterized by aberrant expression and/or activity of the IL-9R or one or more subunits thereof, an autoimmune disease, an inflammatory disease, a proliferative disease, or an infection (preferably, a respiratory infection), or one or more symptoms thereof, said method comprising administering to a subject in need thereof a prophylactically or therapeutically effective amount of an antibody formulation of  claim 2 . 
     
     
         57 . A method of preventing, managing, treating or ameliorating a disease or disorder associated with or characterized by aberrant expression and/or activity of an IL-9 polypeptide, a disease or disorder associated with or characterized by aberrant expression and/or activity of the IL-9R or one or more subunits thereof, an autoimmune disease, an inflammatory disease, a proliferative disease, or an infection (preferably, a respiratory infection), or one or more symptoms thereof, said method comprising administering to a subject in need thereof a prophylactically or therapeutically effective amount of an antibody formulation of  claim 37 . 
     
     
         58 .- 76 . (canceled) 
     
     
         77 . The method of  claim 57 , wherein the inflammatory disorder is asthma or an allergy. 
     
     
         78 .- 93 . (canceled) 
     
     
         94 . The formulation of  claim 37 , comprising NaCl. 
     
     
         95 . The formulation of  claim 94 , wherein the NaCl is at a concentration in the range from about 100 mM to about 200 mM. 
     
     
         96 . The formulation of  claim 95 , wherein the NaCl is at a concentration of 150 mM. 
     
     
         97 . The formulation of  claim 37 , wherein the histidine is at a concentration of 10 mM. 
     
     
         98 . The formulation of  claim 37 , wherein said formulation is substantially free of surfactants, sugars, sugar alcohols, and amino acids other than histidine. 
     
     
         99 . The formulation of  claim 98 , wherein said amino acids other than histidine have a pKa value of less than 5 or above 7. 
     
     
         100 .- 105 . (canceled)