JPWO2020205716A5 - - Google Patents

Claims (27)

An antibody formulation comprising an antibody and at least one cholate surfactant having a critical micelle concentration (CMC ) value of 2.0 mM or greater or 0.2% (w/v) or greater in water at 25°C, ,
The formulation is for injection or infusion by subcutaneous, intravenous, intraperitoneal, intramuscular, intraarterial, intralesional or intraarticular route. 2. The formulation of claim 1 , wherein said antibody is a monoclonal antibody. The cholate surfactant is zwitterionic, nonionic, anionic, or CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), SGH ( sodium glycocholate hydrate), sodium taurocholate hydrate (STH), sodium cholate hydrate (SCH), SdTH, SdCH, ScdCH and BigCHAP (N,N'-bis-(3-D-gluconate Amidopropyl) cholamide ). 4. The formulation of claim 3 , comprising CHAPS at a concentration (w/v) of 0.5% or less . 4. The formulation of claim 3 , comprising BigCHAP at a concentration (w/v) of 0.5% or less . 4. The formulation of claim 3 , comprising SGH, STH, or SCH at a concentration (w/v) of 0.5% or less . a zwitterionic or non-ionic cholate detergent and containing less than 50 mM salts, less than 40 mM salts, less than 30 mM salts, or less than 25 mM salts, such as sodium, arginine, or histidine salts; 6. The formulation of any one of claims 1-5 , which is a low ionic strength formulation. A high ionic strength formulation comprising an anionic cholate surfactant and containing at least 175 mM salt, at least 200 mM salt, at least 225 mM salt, or at least 250 mM salt, such as sodium, arginine, or histidine salts. , a formulation according to any one of claims 1 to 3 and 6 . 9. The formulation of any one of claims 1-8 , which has not been subjected to lyophilization. 9. The formulation of any one of claims 1-8 , which is a reconstituted lyophilized formulation. 11. The formulation of any one of claims 1-10 , which does not contain any non-cholate surfactants. at least one cholate surfactant, at least one antibody species, at least one buffer species, and at least one non-surfactant stabilizer such as a sugar, sugar alcohol, amino acid, peptide, salt, or other 12. A formulation according to claim 10 or 11 , consisting essentially of protein). 11. The formulation of any one of claims 1-10 , further comprising at least one polysorbate or poloxamer. 14. The formulation of claim 13 , further comprising polysorbate 20 or polysorbate 80. 15. The formulation of claim 14 , comprising no more than 0.05% or no more than 0.01% polysorbate 20 or 80. 16. The formulation of claim 15 , which does not contain any surfactant other than said cholate surfactant and said polysorbate 20 or 80. 2. The antibody formulation of claim 1 for therapeutic use, comprising at least one therapeutic antibody species and a surfactant consisting essentially of CHAPS at a concentration (w/v) of 0.5% or less , ,
may further comprise one or more buffers, salts, lyoprotectants, or stabilizers, including one or more of sugars, sugar alcohols, amino acids, or other protein species;
a. the formulation may be of low ionic strength; and/or
b . A formulation, wherein the formulation may be a liquid formulation that is not lyophilized prior to use. 18. The formulation of claim 17 , wherein said surfactant consists essentially of 0.01% to 0.05% or 0.025% to 0.05% (w/v) CHAPS. 2. The antibody formulation of claim 1 for therapeutic use , comprising at least one therapeutic antibody species and a surfactant consisting essentially of BigCHAP at a concentration (w/v) of 0.5% or less ,
may further comprise one or more buffers , salts, lyoprotectants, or stabilizers, including one or more of sugars, sugar alcohols, amino acids, or other protein species;
a. the formulation may be of low ionic strength; and/or
b . A formulation, wherein the formulation may be a liquid formulation that is not lyophilized prior to use. 20. The formulation of claim 19 , wherein said surfactant consists essentially of 0.01-0.05% or 0.025%-0.05% (w/v) BigCHAP. 2. The antibody of claim 1 , for therapeutic use, comprising at least one therapeutic antibody species and a surfactant consisting essentially of STH, SGH, or SCH at a concentration (w/v) of 0.5% or less. A formulation,
The formulation is a high ionic strength formulation and contains one or more buffers , salts, lyoprotectants, or stabilizers, including one or more of sugars, sugar alcohols, amino acids, or other antibody species. may further include
A formulation, wherein the formulation may be a liquid formulation that is not lyophilized prior to use. 22. The formulation of claim 21 , wherein said surfactant consists essentially of 0.01-0.05%, or 0.025%-0.05% (w/v) of STH, SGH, or SCH. . 23. A method of making an antibody formulation of any one of claims 1-22 , comprising mixing the antibody with the at least one cholate surfactant to form a cholate-containing aqueous solution. A method, including A method of inhibiting aggregation of antibodies present in an aqueous solution, comprising at least one cholic acid having a critical micelle concentration (CMC) value of about 2 mM or greater or 0.2% (w/v) in water at 25°C. adding a salt surfactant to said aqueous solution at a concentration below its CMC value in water at 25° C. to form a cholate-containing aqueous solution. 25. The method of claim 24 , wherein said antibody is a monoclonal antibody. 26. The method of any one of claims 23-25 , further comprising lyophilizing the cholate-containing aqueous solution. 26. The method of any one of claims 23-25 , which does not comprise lyophilizing the cholate-containing aqueous solution.