Claims for Patent: 9,352,035

Summary for Patent: 9,352,035

Title:	High concentration antibody formulations
Abstract:	The present disclosure relates to, inter alia, stable aqueous solutions comprising a high concentration of an antibody that binds to human complement component C5 and methods for preparing the solutions. The disclosure also provides methods for treating or preventing complement-associated disorders (for example, age-related macular degeneration or rheumatoid arthritis) using the solutions. Also featured are therapeutic kits containing one or more of the solutions and a means for administering the solutions to a patient in need such a treatment.
Inventor(s):	Zhou; Xiao-Hong (Madison, CT), Wang; Yi (Woodbridge, CT)
Assignee:	Alexion Pharmaceuticals, Inc. (New Haven, CT)
Application Number:	14/072,476
Patent Claims:	1. A method for producing a stable concentrated antibody solution comprising eculizumab at a concentration of 100 mg/mL to 150 mg/mL, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, the method comprising: i) providing a first aqueous solution comprising eculizumab, the first aqueous solution having a first formulation and comprising no more than 50 mg/mL of eculizumab; ii) subjecting the first aqueous solution to diafiltration into a formulation comprising 20 mkt histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, at pH 7.0 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration; and iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution comprising 100 mg/mL to 150 mg/mL of eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol. 2. The method of claim 1, wherein eculizumab is not lyophilized prior to or following the diafiltration or concentrating. 3. The method of claim 1, wherein the concentrating comprises tangential flow filtration. 4. The method of claim 1, wherein eculizumab remains at least 97% monomeric during storage at 2.degree. C. to 8.degree. C. for at least six months as determined by SEC-HPLC. 5. The method of claim 1, wherein the stable concentrated antibody solution comprises 105 mg/mL of eculizumab. 6. The method of claim 1, wherein the pH of the stable concentrated antibody solution is 7.0. 7. A method for producing a stable concentrated antibody solution consisting of eculizumab at a concentration of 100 mg/mL to 150 mg/mL, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, the method comprising: i) providing a first aqueous solution comprising eculizumab, the first aqueous solution having a first formulation and comprising no more than 50 mg/mL of eculizumab; ii) subjecting the first aqueous solution to diafiltration into a formulation comprising 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, at pH 7.0 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration, and iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution consisting of 100 mg/mL to 150 mg/mL of eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol. 8. The method of claim 7, wherein eculizumab is not lyophilized prior to or following the diafiltration or concentrating. 9. The method of claim 7, wherein the concentrating comprises tangential flow filtration. 10. The method of claim 7, wherein eculizumab remains at least 97% monomeric during storage at 2.degree. C. to 8.degree. C. for at least six months as determined by SEC-HPLC. 11. The method of claim 7, wherein the pH of the stable concentrated antibody solution is 7.0. 12. A method for producing a stable concentrated antibody solution comprising 105 mg/mL eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, the method comprising: i) providing a first aqueous solution comprising eculizumab, the first aqueous solution having a first formulation and comprising no more than 50 mg/mL of eculizumab; ii) subjecting the first aqueous solution to diafiltration into a formulation comprising 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, at pH 7.0 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration; and iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution comprising 105 mg/mL of eculizumab. 13. The method of claim 12, wherein eculizumab is not lyophilized prior to or following the diafiltration or concentrating. 14. The method of claim 12, wherein the concentrating comprises tangential flow filtration. 15. The method of claim 12, wherein eculizumab remains at least 97% monomeric during storage at 2.degree. C. to 8.degree. C. for at least six months as determined by SEC-HPLC. 16. The method of claim 12, wherein the pH of the stable concentrated antibody solution is 7.0. 17. A method for producing a stable concentrated antibody solution consisting of 105 mg/mL eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, the method comprising: i) providing a first aqueous solution comprising eculizumab, the first aqueous solution having a first formulation and comprising no more than 50 mg/mL of eculizumab; ii) subjecting the first aqueous solution to diafiltration into a formulation consisting of 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, at pH 7.0 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration; and iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution consisting of 105 mg/mL eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol. 18. The method of claim 17, wherein eculizumab is not lyophilized prior to or following the diafiltration or concentrating. 19. The method of claim 17, wherein the concentrating comprises tangential flow filtration. 20. The method of claim 17, wherein eculizumab remains at least 97% monomeric during storage at 2.degree. C. to 8.degree. C. for at least six months as determined by SEC-HPLC. 21. The method of claim 17, wherein the pH of the stable concentrated antibody solution is 7.0. 22. A method for producing a stable concentrated antibody solution consisting of 105 mg/mL eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, wherein eculizumab remains at least 97% monomeric during storage at 2.degree. C. to 8.degree. C. for at least six months as determined by SEC-HPLC, and wherein the pH of the stable concentrated antibody solution is 7.0, the method comprising: i) providing a first aqueous solution comprising eculizumab, the first aqueous solution having a first formulation and comprising no more than 50 mg/mL of eculizumab; ii) subjecting the first aqueous solution to diafiltration into a formulation consisting of 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol, at pH 7.0 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration; and iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution consisting of 105 mg/mL eculizumab, 20 mM histidine, 50 mM serine, 3% sorbitol, and 1.5% mannitol.

Details for Patent 9,352,035

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Alexion Pharmaceuticals, Inc.	SOLIRIS	eculizumab	Injection	125166	03/16/2007		2031-03-08