Claims for Patent: 6,150,504

Summary for Patent: 6,150,504

Title:	Process for the purification of serum albumin
Abstract:	Recombinantly produced serum albumin is purified in a series of steps, optionally by incubation with an anion-exchange adsorbent, followed by affinity chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase. The immobile phase comprises a carrier coupled to a 2-mercapto or 2-hydroxy alkanoic acid.
Inventor(s):	Van Der Laken; Cornelis Jacobus (Leiden, NL), Piet; Marcellinus Petrus Johannes (Haarlem, NL)
Assignee:	DSM Patents & Trademarks (Delft, NL)
Application Number:	08/810,813
Patent Claims:	1. A lipophilic immobile phase for affinity chromatography comprising (a) a carrier activated with an epoxy compound that forms a spacer, that has up to about 10 C, and is linked to the carrier; and (b) a ligand, immobilized to the carrier through coupling with the spacer, wherein the ligand comprises a 2-mercapto C4-C14 alkanoic acid or a 2-hydroxy C4-C14 alkanoic acid, which immobile ligand selectively binds 40-50 kD fragments having Domains I and II of the mature serum albumin compared to intact recombinant serum albumin that has Domains I, II and III. 2. A method for producing purified recombinant serum albumin substantially free of albumin degradation products and substantially free of cellular components of microorganisms or cell lines from which said albumin is produced, which method comprises isolating said purified recombinant serum albumin from an affinity purified eluate of step (d), below, said eluate having been prepared by the steps of: (a) adding an anion-exchange agent at about physiologic pH to a clarified fermentation broth or clarified cell lysate of microorganisms or cell lines producing said recombinant serum albumin; (b) after incubation, eluting the anion-exchange agent with an acidic buffer solution and collecting a series of first eluate fractions which contain said recombinant serum albumin; (c) contacting said first eluate fractions at about physiologic pH with an affinity chromatography system comprising i. the lipophilic immobile phase of claim 1, wherein said alkanoic acid compounds were in the form of an acid or a salt or an ester thereof, and ii. an aqueous mobile phase; and (d) eluting said recombinant serum albumin from said immobile phase by adding to said aqueous mobile phase a water-soluble lipid anion desorbent and collecting an affinity purified eluate which contains said recombinant serum albumin, thereby producing said purified recombinant serum albumin substantially free of albumin degradation products and cellular components of said microorganisms or cell lines. 3. The method according to claim 2, wherein said epoxy compound is an epoxyether. 4. The method according to claim 3, wherein said epoxyether is a diglycidylether. 5. A method according to claim 3 or 4, further comprising a step of dialyzing said purified recombinant serum albumin. 6. A method according to claim 2, 3, or 4, wherein said recombinant albumin is human albumin. 7. A composition comprising isolated recombinantly produced serum albumin which is 99.9% to 100% pure monomeric, mature serum albumin, free of 40-50 kD serum albumin fragments having Domains I and II of mature serum albumin and is produced by the method of claim 2. 8. The composition according to claim 7 which is 99.95% to 100% pure monomeric, mature serum albumin. 9. A composition comprising isolated recombinantly produced serum albumin which is 99.9% to 100% pure monomeric, mature serum albumin, wherein the composition is free of 40-50 kD serum albumin fragments having Domains I and II of mature serum albumin.

Details for Patent 6,150,504

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2011-07-12
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2011-07-12
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2011-07-12
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2011-07-12
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2011-07-12