US4391746A
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US
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Blood-coagulation-promoting products and methods of preparing them
Assignee: Oesterreichisches Institut fuer Haemoderivate
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Filing: 1982-05-05
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Granted: 1983-07-05
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Expires: 2002-05-05
Abstract
Abstract Blood-coagulation-promoting products substantially free of thrombin are prepared from human blood plasma by contacting a human blood plasma fraction containing coagulation Factors II, VII, IX and X with an anion exchanger to adsorb the coagulation Factors, which are subsequently eluted from the anion exchanger. The eluate is treated to generate a substance having Factor VIII Inhibitor Bypassing Activity and being substantially free of thrombin, and activated Factor X.
Inventors
- 👤 Gautam Mitra
- 👤 Michael H. Coan
- 👤 Shohachi Wada
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 13:42
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/644; C12N9/647; C12Y; C12Y304/00; C12Y304/21; C12Y304/21022; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/827; Y10S530/829; Y10S530/83; Y10S530/831
Claims Analysis
Total Claims: 41
Claim 1
Independent Claim
90 words
A method of producing a blood-coagulation-promoting preparation substantially free of thrombin from human blood plasma, which comprises (a) contacting a human blood plasma fraction containing coagulation Factors II, VII, IX, and X with an anion exchanger to adsorb the coagulation Factors on the anion exchanger, (b) eluting the adsorbed coagulation Factors from the anion exchanger, (c) treating the eluate containing the coagulation Factors to generate a Factor VIII Inhibitor Bypassing Activity (FEIBA) substance substantially free of thrombin, and (d) treating the eluate to stop the generation of a FEIBA substance.
Claim 2
Independent Claim
90 words
A method of producing a blood-coagulation-promoting preparation substantially free of thrombin from human blood plasma, which comprises (a) contacting a human blood plasma fraction containing coagulation Factors II, VII, IX, and X with an anion exchanger to adsorb the coagulation Factors on the anion exchanger, (b) eluting the adsorbed coagulation Factors from the anion exchanger, (c) treating the eluate containing the coagulation Factors to generate a Factor VIII Inhibitor Bypassing Activity (FEIBA) substance substantially free of thrombin, and (d) treating the eluate to stop the generation of a FEIBA substance.
Claim 3
Dependent Claim
15 words
The method of claim 1 wherein the fraction of Step (a) is Cohn Effluent I.
Claim 4
Dependent Claim
15 words
The method of claim 1 wherein the anion exchanger of Step (a) is DEAE Sephadex®.
Claim 5
Dependent Claim
35 words
The method of claim 1 which further includes the step of selectively washing the anion exchanger of Step (a) to remove inhibitors to the generation of a FEIBA sustance without eluting the adsorbed coagulation Factors.
Claim 6
Dependent Claim
31 words
The method of claim 4 wherein the anion exchanger is washed selectively with aqueous ammonium bicarbonate at a concentration sufficient to remove said inhibitors but insufficient to elute said coagulation Factors.
Claim 7
Dependent Claim
33 words
The method of claim 5 wherein the anion exchanger further is washed selectively with an aqueous solution having an ionic strength sufficient to remove said inhibitors but insufficient to elute said coagulation Factors.
Claim 8
Dependent Claim
18 words
The method of claim 6 wherein the ionic strength of the aqueous solution is less than about 0.3.
Claim 9
Dependent Claim
13 words
The method of claim 6 wherein the aqueous solution is aqueous sodium chloride.
Claim 10
Dependent Claim
55 words
The method of claim 1 wherein the eluate is treated in Step (c) with a source of calcium ions in an amount sufficient to generate substantial amounts of FEIBA substance but insufficient to generate substantial amounts of thrombin at a temperature and pH and for a period of time sufficient to generate a FEIBA substance.
Claim 11
Dependent Claim
15 words
The method of claim 9 wherein the temperature in Step (c) is about 0°-30° C.
Claim 12
Dependent Claim
15 words
The method of claim 9 wherein the temperature in Step (c) is about 5°-20° C.
Claim 13
Dependent Claim
15 words
The method of claim 9 wherein the temperature in Step (c) is about 8°-14° C.
Claim 14
Dependent Claim
15 words
The method of claim 9 wherein the temperature in Step (c) is about 10° C.
Claim 15
Dependent Claim
16 words
The method of claim 9 wherein the pH in Step (c) is about 6 to 9.
Claim 16
Dependent Claim
16 words
The method of claim 9 wherein the pH in Step (c) is about 7 to 8.
Claim 17
Dependent Claim
20 words
The method of claim 9 wherein the concentration of free calcium ions is about 0.000025-0.0008 mole per liter of solution.
Claim 18
Dependent Claim
9 words
A pharmaceutical composition comprising the product of claim 9.
Claim 19
Dependent Claim
26 words
The method of claim 1 wherein the adsorbed coagulation Factors are selectively eluted with aqueous ammonium bicarbonate in an amount sufficient to elute the coagulation Factors.
Claim 20
Dependent Claim
38 words
The method of claim 18 wherein the eluate is (a) treated to remove ammonium bicarbonate, and (b) treated with free calcium ions in a concentration of about 0.0005-0.0008 mole per liter of solution to generate a FEIBA substance.
Claim 21
Dependent Claim
14 words
The method of claim 19 wherein the eluate is lyophilized to remove ammonium bicarbonate.
Claim 22
Dependent Claim
9 words
A pharmaceutical composition comprising the product of claim 19.
Claim 23
Dependent Claim
27 words
The method of claim 1 wherein the adsorbed coagulation Factors are selectively eluted with an aqueous solution having an ionic strength sufficient to elute the coagulation Factors.
Claim 24
Dependent Claim
12 words
The method of claim 22 wherein the ionic strength is about 0.35-2.0.
Claim 25
Dependent Claim
13 words
The method of claim 22 wherein the aqueous solution is aqueous sodium chloride.
Claim 26
Dependent Claim
25 words
The method of claim 22 wherein the eluate is held at a temperature and pH and for a time sufficient to generate a FEIBA substance.
Claim 27
Dependent Claim
9 words
A pharmaceutical composition comprising the product of claim 25.
Claim 28
Dependent Claim
48 words
The method of claim 22 wherein the eluate is treated with a source of calcium ions in an amount sufficient to generate a FEIBA substance but insufficient to generate substantial amounts of thrombin at a temperature and pH and for a time sufficient to generate a FEIBA substance.
Claim 29
Dependent Claim
18 words
The method of claim 27 wherein the amount of free calcium ions is about 0.000025-0.0005 mole per liter.
Claim 30
Dependent Claim
9 words
A pharmaceutical composition comprising the product of claim 27.
Claim 31
Dependent Claim
97 words
A lyophilized blood-coagulation-promoting composition substantially free of thrombin comprising a product prepared by a process which includes the steps of (a) contacting a human blood plasma fraction containing coagulation Factors II, VII, IX, and X with an anion exchanger to adsorb said coagulation Factors on the anion exchanger, (b) eluting the adsorbed coagulation Factors from the anion exchanger, (c) treating the eluate containing the coagulation Factors to generate a Factor VIII Inhibitor Bypassing Activity (FEIBA) substance substantially free of thrombin, (d) treating the eluate to stop the generation of a FEIBA substance, and (e) lyophilizing the eluate.
Claim 32
Dependent Claim
97 words
A lyophilized blood-coagulation-promoting composition substantially free of thrombin comprising a product prepared by a process which includes the steps of (a) contacting a human blood plasma fraction containing coagulation Factors II, VII, IX, and X with an anion exchanger to adsorb said coagulation Factors on the anion exchanger, (b) eluting the adsorbed coagulation Factors from the anion exchanger, (c) treating the eluate containing the coagulation Factors to generate a Factor VIII Inhibitor Bypassing Activity (FEIBA) substance substantially free of thrombin, (d) treating the eluate to stop the generation of a FEIBA substance, and (e) lyophilizing the eluate.
Claim 33
Dependent Claim
9 words
A pharmaceutical preparation comprising the composition of claim 30.
Claim 34
Dependent Claim
22 words
The composition of claim 30 wherein the process further includes the step of subjecting the eluate of Step (d) to sterile filtration.
Claim 35
Dependent Claim
9 words
A pharmaceutical preparation comprising the composition of claim 32.
Claim 36
Dependent Claim
17 words
The composition of claim 30 wherein the FEIBA concentration is at least about 60 Units per milliliter.
Claim 37
Dependent Claim
14 words
The preparation of claim 30 wherein the FEIBA:thrombin ratio is at least about 1000:1.
Claim 38
Dependent Claim
14 words
The preparation of claim 30 wherein the FEIBA:thrombin ratio is at least about 50:1.
Claim 39
Dependent Claim
11 words
The preparation of claim 30 which is essentially free of thrombin.
Claim 40
Dependent Claim
15 words
The preparation of claim 30 wherein the FEIBA:Factor Xa ratio is at least about 45:1.
Claim 41
Dependent Claim
29 words
The preparation of claim 30 wherein the FEIBA:Factor II ratio, the FEIBA:Factor VII ratio, the FEIBA:Factor IX ratio, and the FEIBA:Factor X ratio are about 10:1 to 0.1:., respectively.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-07-04 | 1987-01-03 | 1987-07-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-07-04 | 1991-01-03 | 1991-07-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-07-04 | 1995-01-03 | 1995-07-05 | $7700.00 | Window Closed / Lapsed |