US4885207A
Expired / Lapsed
US
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Biocompatible protein or ligand immobilization system
Assignee: Honeywell UOP LLC
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Filing: 1987-07-13
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Granted: 1989-12-05
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Expires: 2007-07-13
Abstract
Abstract A support matrix generally useful for the immobilization of biologically active proteins is made by coating with a polymeric alcohol a core support of titania or a carbonaceous pyropolymer deposited on a high surface area refractory inorganic oxide, cross-linking the alcohol, and converting a portion of the hydroxyl moieties to sulfonate esters. Such supports covalently bind enzymes and antibodies via a strong carbon-nitrogen single bond to give, for example, an immobilized antibody system extremely resistant to leaching of the antibody, the cross-linked alcohol, or of metals from the core support.
Inventors
- 👤 Susan S. Johnson
- 👤 James R. Goodman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 02:44
CPC Classifications
A; A61; A61M; A61M1/00; A61M1/36; A61M1/3687; C; C07; C07K; C07K17/00; C07K17/02; C07K17/06; C12; C12N; C12N11/00; C12N11/14; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/54393; G01N33/551; G01N33/552; G01N33/553; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/812; Y10S530/815; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2991; Y10T428/2998; Y10T428/30
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
97 words
A method of making a support matrix for immobilization of biologically active proteins comprising coating with a polymeric alcohol a core support which is titania, titanated alumina, or a carbonaceous pyropolymer possessing recurring units containing at least carbon and hydrogen atoms deposited on a high surface area inorganic oxide, cross-linking the polymeric alcohol by reacting it with an hydroxyl-reactive cross-linking agent which is in a molar excess relative to the molar proportion of said polymeric alcohol, converting a portion of the hydroxyl groups of the cross-linked alcohol to a sulfonate ester and recovering the resulting support matrix.
Claim 2
Independent Claim
97 words
A method of making a support matrix for immobilization of biologically active proteins comprising coating with a polymeric alcohol a core support which is titania, titanated alumina, or a carbonaceous pyropolymer possessing recurring units containing at least carbon and hydrogen atoms deposited on a high surface area inorganic oxide, cross-linking the polymeric alcohol by reacting it with an hydroxyl-reactive cross-linking agent which is in a molar excess relative to the molar proportion of said polymeric alcohol, converting a portion of the hydroxyl groups of the cross-linked alcohol to a sulfonate ester and recovering the resulting support matrix.
Claim 3
Dependent Claim
11 words
The method of claim 1 where the core support is titania.
Claim 4
Dependent Claim
35 words
The method of claim 1 where the core support is a carbonaceous pyropolymer deposited on an inorganic oxide selected from the group consisting of alumina, silica-alumina, silica-zirconia, silica, controlled pore glass, hydroxyapatite, zirconia-titania, and alumina-zirconia.
Claim 5
Dependent Claim
11 words
The method of claim 3 where the inorganic oxide is alumina.
Claim 6
Dependent Claim
26 words
The method of claim 1 where the polymeric alcohol is selected from the group consisting of polyvinyl alcohol, agarose, and cellulose esters containing free hydroxyl groups.
Claim 7
Dependent Claim
11 words
The method of claim 5 where the alcohol is polyvinyl alcohol.
Claim 8
Dependent Claim
22 words
The method of claim 5 where the polyvinyl alcohol has a molecular weight in the range between about 2,000 and about 25,000.
Claim 9
Dependent Claim
20 words
The method of claim 1 where the core support is coated with at least 3% by weight of polyvinyl alcohol.
Claim 10
Dependent Claim
22 words
The method of claim 8 where the core support is coated with from about 7 to about 15 weight percent polyvinyl alcohol.
Claim 11
Dependent Claim
55 words
The method of claim 1 where the cross-linking agent is selected from: a diglycidyl ether of formula ##STR3## where x is an integer from 1 to about 10; epichlorohydrin; aliphatic diisocyanates of the formula OCN(CH 2 ) y NCO where y is an integer from 2 to about 10; benzene diisocyanate; toluene diisocyanate; and divinylsulfone.
Claim 12
Dependent Claim
21 words
The method of claim 10 where the cross-linking agent is a diglycidyl ether and x is from 2 through about 6.
Claim 13
Dependent Claim
21 words
The method of claim 10 where the cross-linking agent is an aliphatic diisocyanate where y is from 4 through about 8.
Claim 14
Dependent Claim
23 words
The method of claim 1 where the sulfonate ester is selected from the group consisting of trifluoroethanesulfonate, trifluoromethanesulfonate, para-toluenesulfonate, para-bromobenzenesulfonate, para-nitrobenzenesulfonate, and 2,4-dinitrobenzenesulfonate.
Claim 15
Dependent Claim
46 words
The method of claim 1 further characterized in that the sulfonate ester is formed by the reaction with from about 0.1 to about 5.0 molar proportions, based on the hydroxyl moieties in the polymeric alcohol coating, of an activated sulfonic acid with the cross-linked polymeric alcohol.
Claim 16
Dependent Claim
10 words
A support matrix resulting from the method of claim 1.
Claim 17
Dependent Claim
37 words
An immobilized biologically active protein system having covalently bound biologically active protein resulting from nucleophilic displacement of sulfonate ester groups of the support matrix of claim 15 by a primary amino or sulfhydryl moiety of said protein.
Claim 18
Dependent Claim
20 words
The immobilized biologically active protein system of claim 16 where the protein is an enzyme, an antibody, or an antigen.
Claim 19
Dependent Claim
83 words
The immobilized biologically active protein system of claim 17 where the protein is an enzyme selected from the group consisting of glucose isomerase, glucoamylase, lactase, cellulase, glucose oxidase, peroxidase, ribonuclease, urease, histidase, trypsin, papain, hexakinase, chymotrypsin, acylase, invertase, ficin, lysozyme, protease, pepsin, rennin, xylanase, beta amylase, gamma amylase, asparaginase, cholesterol oxidase, alcohol dehydrogenase, amino acid oxidase, collagenase, arginase, catalase, deoxyribonuclease, heparinase, uricase, glutaminase, bilirubin oxidase, B-glucuronidase, phenylalanine ammonia lyase, arginase, UDP glucurolnyl transferase, streptokinase, tyrosinase, alpha-galactosidase, urokinase, superoxide dismutase, fibrinolysin and carboxypeptidase G-1.
Claim 20
Dependent Claim
42 words
The immobilized biologically active protein system of claim 17 where the protein is an antibody selected from the group consisting of I g A, I g E, I g M, I g D and I g G immunoglobulins and F ab fragments.
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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) | 1992-12-04 | 1993-06-05 | 1993-12-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-12-04 | 1997-06-05 | 1997-12-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-12-04 | 2001-06-05 | 2001-12-05 | $7700.00 | Window Closed / Lapsed |