High concentration antibody and protein formulations

Abstract

The present application relates to highly concentrated antibody and protein formulations with, reduced viscosity that are stable, relatively isotonic and are of low turbidity. The formulations are particularly suitable for subcutaneous administration. The application further describes articles of manufacture containing such formulations and method for using them to treat disorders treatable by the formulated antibody or protein.

1 . A stable, liquid formulation of low turbidity comprising (a) a protein or antibody in an amount of 100 to 260 mg/ml, (b) arginine-HCl in an amount of 50 to 200 mM, (c) histidine in an amount of 10 to 100 mM, (d) polysorbate in an amount of 0.01 to 0.1%, where the formulation further has a pH ranging from 5.5 to 7.0, a kinematic viscosity of about 50 cs or less and osmolarity ranging from 200 mOsm/kg to 450 mOsm/kg. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . A stable, liquid formulation of low turbidity comprising (a) an anti-IgE monoclonal antibody in an amount of 100 to 260 mg/ml, (b) arginine-HCl in an amount of 50 to 200 mM, (c) histidine in an amount of 10 to 100 mM, (d) polysorbate in an amount of 0.01 to 0.1%, where the formulation further has a pH ranging from 5.5 to 7.0, a kinematic viscosity of about 50 cs or less and osmolarity ranging from 200 mOsm/kg to 450 mOsm/kg. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . The formulation of  claim 9 , where the anti-IgE antibody is selected from the group consisting of rhuMAbE25, rhuMAbE26 and Hu-901. 
     
     
         17 . The formulation of  claim 9 , wherein the anti-lgE antibody is rhuMAbE25. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . A stable, liquid formulation of low turbidity comprising (a) an anti-IgE antibody in an amount of about 150 mg/ml, (b) arginine-HCl in an amount of 200 mM, (c) histidine in an amount of 20 mM, (d) polysorbate in an amount of 0.02%, where the formulation further has a pH of 6.0. 
     
     
         21 . The formulation of  claim 20 , wherein the anti-IgE antibody is E25. 
     
     
         22 . An article of manufacture comprising a container enclosing the formulation of  claim 1 . 
     
     
         23 - 27 . (canceled) 
     
     
         28 . A method of treating an IgE-mediated disorder comprising administrating to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20 . 
     
     
         29 . The method of  claim 28 , wherein the IgE-mediated disorder is selected from the group consisting of allergic rhinitis, asthma, allergic asthma, non-allergic asthma, atopic dermatitis and gastroenteropathy. 
     
     
         30 - 33 . (canceled) 
     
     
         34 . The method of  claim 28 , wherein the IgE-mediated disorder is selected from the group consisting of hypersensitivity, allergic bronchopulmonary aspergillosis, parasitic diseases, interstitial cystitis, hyper-IgE syndrome, ataxia-telangiectasia, Wiskott-Akdrich syndrome, thymic alymphoplasia, IgE myeloma and graft-versus-host reaction. 
     
     
         35 . The method of  claim 28  wherein the IgE-mediated disorder is hypersensitivity. 
     
     
         36 . The method of  claim 35 , wherein the hypersensitivity disorder is selected from the group consisting of anaphylaxis, urticaria and food allergy. 
     
     
         37 - 39 . (canceled) 
     
     
         40 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with an antihistamine. 
     
     
         41 . (canceled) 
     
     
         42 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with a bronchodialator. 
     
     
         43 . (canceled) 
     
     
         44 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with a glucocorticoid. 
     
     
         45 . (canceled) 
     
     
         46 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with a glucocorticoid. 
     
     
         47 . (canceled) 
     
     
         48 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with the administration of allergen desensitization. 
     
     
         49 . A method of treating an IgE-mediated disorder comprising administering to a patient in need thereof a therapeutically effective amount of the formulation of  claim 20  in combination with an NSAID. 
     
     
         50 . (canceled)