Claims for Patent: 8,546,548

Summary for Patent: 8,546,548

Title:	Method to produce a highly concentrated immunoglobulin preparation for subcutaneous use
Abstract:	The present invention relates to a new and improved method for preparing a highly concentrated immunoglobulin composition from pooled plasma for subcutaneous injection. A composition comprising 20% or more immunoglobulin suitable for subcutaneous use is also described.
Inventor(s):	Teschner; Wolfgang (Vienna, AT), Butterweck; Harald Arno (Vienna, AT), Pljevljakovic; Azra (Vienna, AT), Bauer; Theresa Friederike (Vienna, AT), Koelbl; Bernhard (Achau, AT), Schwarz; Hans-Peter (Vienna, AT), Nikolic; Nebojsa (Vienna, AT), Poelsler; Gerhard (Vienna, AT), Kindermann; Johanna (Maria Enzersdorf, AT)
Assignee:	Baxter International Inc. (Deerfield, IL) Baxter Healthcare S.A. (Glattpark (Opfikon), CH)
Application Number:	12/789,345
Patent Claims:	1. A method for preparing a concentrated immunoglobulin G (IgG) composition, comprising the steps: (A) concentrating a first solution comprising IgG to a protein concentration of from 2% to 10% (w/v) by ultrafiltration using a first ultra-/diafiltration system comprising a first ultrafiltration membrane, thereby forming a first IgG concentrate; (B) diafiltering the first IgG concentrate against a diafiltration buffer using the first ultra-diafiltration system comprising the first ultrafiltration membrane, thereby forming a first IgG diafiltrate; (C) concentrating the first IgG diafiltrate to a protein concentration of greater than 20% (w/v) by ultrafiltration using the first ultra-/diafiltration system comprising the first ultrafiltration membrane, thereby forming a second IgG concentrate; (D) collecting the second IgG concentrate from the first ultra-/diafiltration system; (E) washing the first ultrafiltration membrane by re-circulating a post-wash buffer through the first ultra-/diafiltration system wherein the first ultra-/diafiltration system is washed with a volume of post-wash buffer equal to at least two times the dead volume of the first ultra-/diafiltration system, thereby forming a first IgG post-wash solution; (F) transfering the first IgG post-wash solution from the first ultra-/diafiltration system into a second ultra-/diafiltration system comprising a second ultrafiltration membrane, wherein the surface area of the second ultrafiltration membrane is lower than the surface area of the first ultrafiltration membrane; (G) concentrating the first IgG post-wash solution to a protein concentration of greater than 20% (w/v) by ultrafiltration using the second ultra-/diafiltration system comprising a second ultra-/diafiltration membrane, thereby forming a third IgG concentrate; and (H) combining the third IgG concentrate from the second ultra-/diafiltration system with the second IgG concentrate, thereby forming a concentrated IgG composition. 2. The method of claim 1, wherein the first solution comprising IgG is concentrated in (A) to a protein concentration of 5.+-.1% (w/v). 3. The method of claim 1, wherein the first ultrafiltation membrane is an open-screen membrane. 4. The method of claim 1, wherein the first or second ultrafiltration membrane have a nominal molecular weight cut off (NMWCO) of 100 kDa or less. 5. The method of claim 1, wherein the first and second ultrafiltration membrane has a nominal molecular weight cut off (NMWCO) of 100 kDa or less. 6. The method of claim 1, wherein the first or second ultrafiltration membrane has a nominal molecular weight cut off (NMWCO) of 90 kDa or less. 7. The method of claim 1, wherein the first and second ultrafiltration membrane have a nominal molecular weight cut off (NMWCO) of 90 kDa or less. 8. The method of claim 1, wherein the first and second ultrafiltration membrane have a same nominal molecular weight cut off (NMWCO). 9. The method of claim 1, wherein the diafiltration buffer comprises from 0.2 M to 0.3 M glycine and a pH of 4.2.+-.0.1. 10. The method of claim 1, wherein the second IgG concentrate has a protein concentration of at least 22% (w/v). 11. The method of claim 1, wherein the surface area of the second ultrafiltration membrane is no more than a tenth of the surface area of the first ultrafiltration membrane. 12. The method of claim 1, wherein the protein concentration of the concentrated IgG composition formed in (H) is greater than 20% (w/v), and wherein the method further comprises adjusting the concentration of the concentrated IgG composition formed in (H) to about 20% (w/v). 13. The method of claim 1, wherein the pH of the concentrated IgG composition formed in (H) is from 4.0 to 6.0. 14. The method of claim 1, further comprising the steps of: (I) washing the second ultrafiltration membrane by re-circulating a post-wash buffer through the second ultra-/diafiltration system, thereby forming a second IgG post-wash solution; and (J) adjusting the protein concentration of the concentrated IgG composition formed in (H) by admixing at least a portion of the second IgG post-wash solution into the concentrated IgG composition formed in (H). 15. The method of claim 1, wherein the IgG is human IgG. 16. The method of claim 1, comprising the steps: (A) concentrating a first solution comprising IgG to a protein concentration of 5.+-.1% (w/v) by ultrafiltration using a first ultra-/diafiltration system comprising a first ultrafiltration membrane, thereby forming a first IgG concentrate, the first ultrafiltration membrane having a NMWCO of 60 kDa or less; (B) diafiltering the first IgG concentrate against a diafiltration buffer using the first ultra-/diafiltration system comprising the first ultrafiltration membrane, thereby forming a first IgG diafiltrate, the diafiltration buffer comprising glycine and a pH of 4.2.+-.0.1; (C) concentrating the first IgG diafiltrate to a protein concentration of greater than 20% (w/v) by ultrafiltration using the first ultra-/diafiltration system comprising the first ultrafiltration membrane, thereby forming a second IgG concentrate; (D) collecting the second IgG concentrate from the first ultra-/diafiltration system; (E) washing the first ultrafiltration membrane by re-circulating a post-wash buffer through the first ultra-/diafiltration system, thereby forming a first IgG post-wash solution, the post-wash buffer having a volume equal to at least two times the dead volume of the first ultra-/diafiltration system; (F) collecting the first IgG post-wash solution from the first ultra-/diafiltration system into a second ultra-/diafiltration system comprising a second ultrafiltration membrane, the second ultrafiltration membrane having a NMWCO of 60 kDa or less; (G) concentrating the first IgG post-wash solution to a protein concentration of greater than 20% (w/v) by ultrafiltration using the second ultra-/diafiltration system comprising a second ultra-/diafiltration membrane, wherein the surface area of the second ultrafiltration membrane is no more than a tenth of the surface area of the first ultrafiltration membrane, thereby forming a third IgG concentrate; (H) combining the third IgG concentrate from the second ultra-/diafiltration system with the second IgG concentrate, thereby forming a concentrated IgG composition; (I) washing the second ultrafiltration membrane by re-circulating a post-wash buffer through the second ultra-/diafiltration system, thereby forming a second IgG post-wash solution; and (J) adjusting the protein concentration of the concentrated IgG composition formed in (H) by admixing at least a portion of the second IgG post-wash solution into the concentrated IgG composition formed in (H).

Details for Patent 8,546,548

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Takeda Pharmaceuticals U.s.a., Inc.	GAMMAGARD LIQUID	immune globulin infusion (human)	Injection	125105	April 27, 2005	8,546,548	2030-05-27
Octapharma Pharmazeutika Produktionsges.m.b.h.	CUTAQUIG	immune globulin subcutaneous (human)-hipp	Solution	125668	December 12, 2018	8,546,548	2030-05-27

International Patent Family for US Patent 8,546,548

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2010138736
United States of America	9175068
United States of America	2022153823