US2014105892A1PendingUtilityA1

High concentration antibody and protein formulations

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Assignee: BAYER HEALTHCARE LLCPriority: Aug 31, 2012Filed: Dec 16, 2013Published: Apr 17, 2014
Est. expiryAug 31, 2032(~6.1 yrs left)· nominal 20-yr term from priority
Inventors:Jun XiangXinghang Ma
C07K 16/38C07K 16/18A61K 2039/505A61K 39/39591A61P 7/04C07K 2317/94C07K 2317/41A61K 39/3955A61K 9/19A61K 47/22A61K 47/183A61K 9/0019A61K 47/20A61K 39/395A61K 47/26
66
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Claims

Abstract

Provided are salt-free antibody and other protein formulations that are substantially isosmotic and of low viscosity. Also provided are methods for the treatment of diseases using the disclosed formulations.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A salt-free antibody formulation, comprising:
 a. 10 mM to 30 mM histidine;   b. 50 ppm to 200 ppm of a non-ionic surfactant;   c. 88 mM to 292 mM of a sugar or sugar alcohol selected from mannitol, dextrose, glucose, trehalose, and sucrose;   d. 0 mM to 50 mM arginine;   e. 0 mM to 50 mM lysine;   f. 0 mM to 133 mM glycine or alanine;   g. 0 mM to 10 mM methionine; and   1 mg/ml to 150 mg/ml of a chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 4.0 to pH 6.0 and wherein said protein formulation contains substantially no inorganic salt.   
     
     
         2 . The salt-free antibody formulation of  claim 1  wherein said formulation has a viscosity ranging from 1 to 8 mPa-S at 22° C. 
     
     
         3 . The salt-free antibody formulation of  claim 1  wherein said formulation has an osmolality ranging from 240 to 380 mmol/kg. 
     
     
         4 . The salt-free antibody formulation of  claim 1  wherein said non-ionic surfactant is polysorbate 20 or polysorbate 80. 
     
     
         5 . The salt-free antibody formulation of  claim 1  wherein said sugar is sucrose. 
     
     
         6 . The salt-free antibody formulation of  claim 1  comprising between 10 mM and 50 mM arginine. 
     
     
         7 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 30 mM histidine,   b. 100 ppm polysorbate 80,   c. 292 mM sucrose, and   d. 20 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         8 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 234 mM sucrose,   d. 50 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         9 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 234 mM sucrose, and   d. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         10 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 88 mM sucrose,   d. 133 mM glycine, and   e. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         11 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 20,   c. 88 mM sucrose,   d. 133 mM glycine, and   e. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         12 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 200 ppm polysorbate 20,   c. 88 mM sucrose,   d. 133 mM glycine, and   e. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         13 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 88 mM sucrose, and   d. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         14 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 88 mM sucrose,   d. 10 mM arginine, and   e. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         15 . The salt-free antibody formulation of  claim 1 , comprising 5 mM to 10 mM methionine. 
     
     
         16 . The salt-free antibody formulation of  claim 1 , comprising:
 a. 10 mM histidine,   b. 75 ppm polysorbate 80,   c. 88 mM sucrose,   d. 30 mM lysine, and   e. 100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 5.0 to pH 6.0.   
     
     
         17 . The salt-free antibody formulation of  claim 1 , comprising:
 10 mM histidine,   75 ppm Tween 80,   234 mM sucrose,   30 mM arginine, and   10 mM methionine, and   100 mg/ml chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said anti-TFPI antibody formulation has a pH of 5.5.   
     
     
         18 . The salt-free antibody formulation of  claim 1  wherein said antibody is a human IgG 2  monoclonal antibody. 
     
     
         19 . The salt-free antibody formulation of  claim 18  wherein said human IgG 2  monoclonal antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         20 . A method for the treatment of a disorder in a patient, said method comprising administering to said patient a therapeutically effective amount of an antibody formulation comprising:
 10 mM to 30 mM histidine;   50 ppm to 200 ppm of a non-ionic surfactant;   88 mM to 292 mM of a sugar or sugar alcohol selected from mannitol, dextrose, glucose, trehalose, and sucrose;   0 mM to 50 mM arginine;   0 mM to 50 mM lysine;   0 mM to 133 mM glycine or alanine;   0 mM to 10 mM methionine; and   1 mg/ml to 150 mg/ml of a protein or an chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 4.0 to pH 6.0 and wherein-said protein formulation contains substantially no inorganic salt.   
     
     
         21 . The method of  claim 20  wherein said antibody formulation is administered intravenously, subcutaneously, or intramuscularly. 
     
     
         22 . A method for the treatment of hemophilia A or hemophilia B in a patient, said method comprising administering to said patient a therapeutically effective amount of an antibody formulation comprising:
 10 mM to 30 mM histidine;   50 ppm to 200 ppm of a non-ionic surfactant;   88 mM to 292 mM of a sugar or sugar alcohol selected from mannitol, dextrose, glucose, trehalose, and sucrose;   0 mM to 50 mM arginine;   0 mM to 50 mM lysine;   0 mM to 133 mM glycine or alanine;   0 mM to 10 mM methionine; and   1 mg/ml to 150 mg/ml of a protein or an chimeric, humanized, or human anti-TFPI IgG 2  monoclonal antibody;   wherein said antibody formulation has a pH ranging from pH 4.0 to pH 6.0 and wherein-said protein formulation contains substantially no inorganic salt.   
     
     
         23 . The method of  claim 22  wherein said antibody is a human IgG 2  monoclonal antibody. 
     
     
         24 . The method of  claim 23  wherein said human IgG 2  monoclonal antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         25 . The method of  claim 22 , wherein said antibody formulation is administered intravenously, intramuscularly, or subcutaneously.

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