US5089602A
Expired / Lapsed
US
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Process for the manufacture of apolipoproteins from human blood plasma or serum
Assignee: CSL Behring AG
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Filing: 1991-03-11
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Granted: 1992-02-18
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Expires: 2011-03-11
Abstract
Abstract Apolipoproteins are isolated from human blood plasma fractions which contain apolipoproteins by suspending these fractions in buffer solutions. The suspensions are subsequently incubated with a lower aliphatic alcohol, either with or without an organic solvent. The phase which contains the lipoproteins is separated and concentrated. The products obtained according to the procedure may be used primarily for the treatment of cardiovascular diseases, in particular hypercholesterolemia.
Inventors
- 👤 Henri Isliker
- 👤 Manuel C. Peitsch
- 👤 Hans J. Heiniger
- 👤 Peter G. Lerch
- 👤 Jean J. Morgenthaler
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 09:50
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/775; A; A61; A61P; A61P3/00; A61P3/06; A61P9/00; A61K; A61K38/00
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
100 words
A process of preparing apolipoproteins, which comprises the following steps: providing an apolipoprotein-containing fraction resulting from subjecting human blood plasma or serum to an ethanol precipitation process; suspending said fraction in an aqueous buffer solution having a pH of 3 to 9 to obtain a suspension; adding a lower aliphatic alcohol to said suspension and incubating the resulting mixture to precipitate undesirable contaminants from said mixture and form an apolipoprotein-containing phase; separating said apolipoprotein-containing phase from the precipitated contaminants; and concentrating the separated apolipoprotein-containing phase to a higher concentration of apolipoproteins to obtain a product which contains mostly apolipoprotein A-I.
Claim 2
Dependent Claim
100 words
A process of preparing apolipoproteins, which comprises the following steps: providing an apolipoprotein-containing fraction resulting from subjecting human blood plasma or serum to an ethanol precipitation process; suspending said fraction in an aqueous buffer solution having a pH of 3 to 9 to obtain a suspension; adding a lower aliphatic alcohol to said suspension and incubating the resulting mixture to precipitate undesirable contaminants from said mixture and form an apolipoprotein-containing phase; separating said apolipoprotein-containing phase from the precipitated contaminants; and concentrating the separated apolipoprotein-containing phase to a higher concentration of apolipoproteins to obtain a product which contains mostly apolipoprotein A-I.
Claim 3
Dependent Claim
19 words
The process according to claim 1, wherein the pH of the aqueous buffer solution is from 3 to 5.
Claim 4
Dependent Claim
19 words
The process according to claim 1, wherein the pH of the aqueous buffer solution is from 6 to 9.
Claim 5
Dependent Claim
27 words
The process according to claim 1, wherein the aqueous buffer solution contains a member selected from the group consisting of chaotropic substances, surface-active substances and water-soluble salts.
Claim 6
Dependent Claim
26 words
The process according to claim 1, wherein the separation of the apolipoprotein-containing phase from the precipitated contaminants is conducted by means of filtration, centrifugation or decantation.
Claim 7
Dependent Claim
23 words
The process according to claim 1, wherein the apolipoprotein is obtained as a precipitate, and the process further comprises dissolving the apolipoprotein precipitate.
Claim 8
Dependent Claim
32 words
The process according to claim 1, wherein the suspension in the aqueous buffer solution is first filtered, centrifuged or decanted, before the filtrate or supernatant is incubated with the lower aliphatic alcohol.
Claim 9
Dependent Claim
20 words
The process according to claim 1, wherein the incubation with the lower aliphatic alcohol is carried out in the cold.
Claim 10
Dependent Claim
55 words
The process according to claim 1, wherein the apolipoprotein containing phase is brought to a higher concentration of apolipoproteins by membrane filtration, lyophilization, precipitation at pH 5 to 6, or by addition of a lower aliphatic alcohol, a water-soluble salt or a polymeric substance, or by adsorption to and elution from a solid carrier material.
Claim 11
Dependent Claim
40 words
The process according to claim 6, wherein the apolipoprotein precipitate is dissolved by moderate heating or by adding chaotropic substances, surface-active substances, or a slightly basic buffer solution, said substances then being removed by dialysis, diafiltration, adsorption or gel filtration.
Claim 12
Dependent Claim
54 words
The process according to any one of claims 1, 7, 8, 9 or 10, wherein the separated, apolipoprotein-containing phase for further purification is dialyzed against an aqueous buffer solution of pH range 3 to 5 or 6 to 9 before the apolipoproteins are brought to a higher concentration, and the dialyzed solution is recovered.
Claim 13
Dependent Claim
54 words
The process according to any one of claims 1, 7, 8, 9 or 10, wherein the separated, apolipoprotein-containing phase for further purification is treated with an aqueous buffer solution of pH about 8 before the apolipoproteins are brought to a higher concentration, the thus formed precipitate is discarded and the liquid phase is recovered.
Claim 14
Dependent Claim
59 words
The process according to any one of claims 1, 7, 8, 9 or 10, wherein the suspension in the aqueous buffer solution is incubated with the lower aliphatic alcohol in admixture with a non-polar organic solvent, thereby causing the formation of a multi-phase system from which the aqueous phase is separated and incubated again with the lower aliphatic alcohol.
Claim 15
Dependent Claim
32 words
The process according to any one of claims 1, 7, 8, 9 or 10, wherein the product, in addition, is treated at any stage with an organic solvent for removal of lipids.
Claim 16
Independent Claim
46 words
A method for prophylactic or therapeutic treatment of cardiovascular diseases, and after heart surgery, which comprises administering to a patient in need thereof an effective amount of the apolipoproteins as prepared by the process according to any one of claims 1, 7, 8, 9 or 10.
Claim 17
Dependent Claim
12 words
The method according to claim 15, wherein the cardiovascular disease is hypercholesterolemia.
References Cited (Backward Citations)
JPS6153222A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1995-02-17 | 1995-08-19 | 1996-02-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-02-17 | 1999-08-19 | 2000-02-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-02-17 | 2003-08-19 | 2004-02-18 | $7700.00 | Window Closed / Lapsed |