Claims for Patent: 10,585,086

Summary for Patent: 10,585,086

Title:	Unmasking endotoxins in solution
Abstract:	The invention relates to unmasking endotoxins in compositions so that previously present, but undetectable endotoxins are rendered detectable.
Inventor(s):	Buchberger; Bernd (Zeitlarn/Laub, DE)
Assignee:	HYGLOS INVEST GMBH (Bernried, DE)
Application Number:	15/316,884
Patent Claims:	1. An aqueous composition comprising a protein, an aliphatic compound with C8-C16 as the main chain, and lipopolysaccharide (LPS), wherein the aliphatic compound is an alkanol, and wherein the protein is a pharmaceutically active ingredient (API). 2. The aqueous composition according to claim 1, wherein the alkanol is an unbranched 1-alkanol. 3. The aqueous composition according to claim 1, wherein the alkanol is a branched compound with at least one substitution in the main chain selected from a methyl, ethyl, propyl and butyl group. 4. The aqueous composition according to claim 1, further comprising a detergent selected from an anionic detergent, a cationic detergent, a nonionic detergent, an amphoteric detergent and any combination thereof. 5. The aqueous composition according to claim 4, wherein said detergent is an anionic detergent chosen from the group consisting of: alkyl sulfates; alkyl-ether sulfates; cholesterol sulfate; sulfonates; alkyl sulfo succinates; sulfoxides; phosphates; and carboxylates. 6. The aqueous composition according to claim 4, wherein said detergent is a cationic detergent chosen from the group consisting of: primary amines; secondary amines; tertiary amines; and quaternary ammonium cations; or cetyl trimethylammonium chloride (CTAC)); cetylpyridinium chloride (CPC); quaternary ammonium detergents; and hydroxyethylcellulose ethoxylate, quaternized Polyquaternium-10. 7. The aqueous composition according to claim 4, wherein said detergent is a nonionic detergent chosen from the group consisting of: polyoxyethylene glycol sorbitan alkyl esters (polysorbates); polyoxyethylene glycol alkyl ethers; polyoxypropylene glycol alkyl ethers; glucoside alkyl ethers; polyoxyethylene glycol octylphenol ethers; polyoxyethylene glycol alkylphenol ethers; glycerol alkyl esters; sorbitan alkyl esters; block copolymers of polyethylene glycol and polypropylene glycol; cocamide MEA; sterols; cyclodextrins; poloxamers; and cocamide DEA. 8. The aqueous composition according to claim 4, wherein said detergent is an amphoteric detergent chosen from the group consisting of: CHAPS (3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate); sultaines; betaines; amino oxides; and lecithin. 9. The aqueous composition according to claim 4, wherein the detergent is selected from polysorbate 20, Polysorbate 80, Poloxamer 188, Octoxynol 9, Laurylamineoxid, tris[2-(2-hydroxyethoxy)ethyl]-octadecyl-ammonium phosphate, trilaureth-4 phosphate and sodium stearate. 10. The aqueous composition according to claim 1, wherein the protein is chosen from an antibody, an antibody fragment, a hormone, an enzyme, a fusion protein, a protein conjugate and any combination thereof. 11. The aqueous composition according to claim 10, wherein the protein is an antibody fragment selected from a Fab, a Fab', a F(ab')2 and an Fv, a single chain antibody and any combination thereof. 12. The aqueous composition according to claim 1, containing a further protein which is an albumin. 13. The aqueous composition according to claim 1, further comprising a chaotropic agent, a cation or a combination thereof. 14. The aqueous composition according to claim 13, wherein the composition comprises a chaotropic agent selected from urea, guanidinium chloride, butanol, ethanol, lithium perchlorate, lithium acetate, magnesium chloride, phenol, propanol and thiourea. 15. The aqueous composition according to claim 13, wherein the composition comprises a cation that is a divalent cation. 16. The aqueous composition according to claim 15, wherein the divalent cation is selected from Ca2+, Mg2+, Sr2+ and Zn2+. 17. The aqueous composition according to claim 12, wherein the further protein is present in a concentration from 0.1-20 mg/ml; the aliphatic compound is present in the concentration from 0.01-100 mM; the detergent is present in a concentration from 0.001-1.0 wt %; and the divalent cation is present in the concentration from 1-400 mM. 18. The aqueous composition according to claim 17, further comprising a chaotropic agent in a concentration from 1 mM-1 M. 19. The aqueous composition according to claim 1, wherein the pH is in the range from pH 2-12. 20. The aqueous composition according to claim 1, further containing Factor C protein. 21. The aqueous composition of claim 2, wherein the unbranched 1-alkanol is 1-dodecanol. 22. The aqueous composition of claim 5, wherein the alkyl sulfo succinate is disodium lauryl sulfosuccinate. 23. The aqueous composition of claim 5, wherein the sulfoxide is dodecyl methyl sulfoxide. 24. The aqueous composition of claim 5, wherein the phosphate is trilaureth-4 phosphate. 25. The aqueous composition of claim 5, wherein the carboxylate is sodium stearate or sodium lauroyl sarcosinate. 26. The aqueous composition of claim 5, wherein the alkyl-ether sulfate is sodium laureth sulfate or sodium myreth sulfate. 27. The aqueous composition of claim 5, wherein the sulfonate is dodecylbenzensulfonate, sodiumlauryl sulfoacetate or xylene sulfonate. 28. The aqueous composition of claim 5, wherein the alkyl sulfate is ammonium lauryl sulfate or sodium lauryl sulfate (SDS). 29. The aqueous composition of claim 6, wherein the quaternary ammonium cation is a alkyltrimethylammonium salt. 30. The aqueous composition of claim 29, wherein said alkyltrimethylammonium salt is cetyl trimethylammonium bromide (CTAB). 31. The aqueous composition of claim 6, wherein the quaternary ammonium detergent is tris[2-(2-hydroxyethoxy)ethyl]-octadecyl-ammonium phosphate. 32. The aqueous composition of claim 7, wherein the polyoxyethylene glycol sorbitan alkyl esters (polysorbates) is polysorbate 20, polysorbate 40, polysorbate 60 or polysorbate 80. 33. The aqueous composition of claim 7, wherein the poloxamer is a pluronic block polymer. 34. The aqueous composition of claim 7 wherein the sterol is cholesterol. 35. The aqueous composition according to claim 8, wherein said sultaine is cocamidopropyl hydroxysultaine. 36. The aqueous composition of claim 8, wherein the amino oxides is palmitamine oxide, laurylamine oxide or amine oxide of general formula R.sup.3N.sup.+O.sup.-, wherein R.sup.3 is C.sub.8-C.sub.18 alkyl, C.sub.8-C.sub.18 alkenyl, or C.sub.8-C.sub.18 alkynyl. 37. The aqueous composition of claim 12, wherein the albumin is human serum albumin, bovine serum albumin and/or ovalbumin. 38. The aqueous composition according to claim 17, wherein the further protein is present in a concentration from 1-10 mg/ml; the aliphatic compound is present in the concentration from 0.01-100 mM; the detergent is present in a concentration from 0.001-1.0 wt %; and the divalent cation is present in the concentration from 1-400 mM. 39. The aqueous composition according to claim 38, wherein the further protein is present in a concentration from 1-10 mg/ml; the aliphatic compound is present in the concentration from 0.1-10 mM; the detergent is present in a concentration from 0.05-0.5 wt % or 0.02-0.2 wt %; and the divalent cation is present in the concentration from 10-200 mM. 40. The aqueous composition according to claim 18, wherein the further protein is present in a concentration from 1-10 mg/ml; the aliphatic compound is present in the concentration from 0.1-10 mM; the detergent is present in a concentration from 0.05-0.5 wt %, preferably from 0.02-0.2 wt %; and the divalent cation is present in the concentration 10-200 mM. 41. The aqueous composition according to claim 19, wherein the pH is in the range from pH 5-10. 42. The aqueous composition according to claim 20, wherein the Factor C protein is recombinant Factor C protein. 43. The aqueous composition of claim 18, wherein the chaotropic agent is in a concentration of from 10 mM-200 mM. 44. The aqueous composition of claim 8, wherein the betaine is cocamidopropyl betaine.

Details for Patent 10,585,086

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	October 21, 1942	10,585,086	2035-06-12
Takeda Pharmaceuticals U.s.a., Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	March 03, 1954	10,585,086	2035-06-12
Central Laboratory Of The Netherlands Red Cross Blood Transfusion Service	N/A	albumin (human)	Injection	101993	September 07, 1979	10,585,086	2035-06-12
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	July 23, 1976	10,585,086	2035-06-12
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	August 15, 1978	10,585,086	2035-06-12
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	November 29, 2022	10,585,086	2035-06-12
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	February 17, 1995	10,585,086	2035-06-12