US4629692A
Expired / Lapsed
US
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Immunoassay for nonenzymatically glucosylated proteins and protein fragments an index of glycemia
Assignee: Bayer Corp
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Filing: 1982-12-06
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Granted: 1986-12-16
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Expires: 2002-12-06
Abstract
Abstract An immunoassay method and reagent system for determining nonenzymatically glucosylated proteins and protein fragments in a biological fluid based on the specific binding of such proteins and fragments with anti(Amadori-rearranged glucose), e.g., antibodies which selectively recognize the rearranged deoxyfructose form of glucose resulting when proteins are nonenzymatically glucosylated. The antibodies are raised against an immunogen comprising an immunogenic carrier material bearing 1-deoxy-1-fructosyl residues or conformers of such residues. Measurement of nonenzymatically glucosylated proteins and fragments thereof provides a useful index of blood glucose levels.
Inventors
- 👤 Kenneth J. Dean
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 17:06
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/68; G01N33/6803; G01N33/6842; G01N33/66; G01N33/72; G01N33/721; G01N33/723; Y; Y10; Y10S; Y10S435/00; Y10S435/81; Y10S435/961; Y10S435/975; Y10S436/00; Y10S436/811; Y10S436/822; Y10S436/823
Claims Analysis
Total Claims: 52
Claim 1
Independent Claim
40 words
An antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR5## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group.
Claim 2
Dependent Claim
40 words
An antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR5## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group.
Claim 3
Dependent Claim
10 words
The antibody of claim 1 wherein R is a bond.
Claim 4
Dependent Claim
9 words
The antibody of claim 1 wherein R is --NH--.
Claim 5
Dependent Claim
11 words
The antibody of claim 1 wherein R is said lysyl residue.
Claim 6
Dependent Claim
29 words
The antibody of claim 1 prepared against an immunogen comprising one or more residues of the formula: ##STR6## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 7
Dependent Claim
20 words
The antibody of claim 5 wherein said residue or residues are covalently linked to amino groups in the carrier material.
Claim 8
Dependent Claim
27 words
The antibody of claim 6 wherein the amino groups in the carrier material to which said residue or residues are linked are ε-amino groups of lysyl residues.
Claim 9
Dependent Claim
40 words
An immunogen for preparing an antibody specific for binding to Amadori-rearranged glucose residues on nonenzymatically glucosylated proteins and fragments thereof, comprising one or more residues of the formula: ##STR7## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 10
Dependent Claim
40 words
An immunogen for preparing an antibody specific for binding to Amadori-rearranged glucose residues on nonenzymatically glucosylated proteins and fragments thereof, comprising one or more residues of the formula: ##STR7## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 11
Dependent Claim
20 words
The immunogen of claim 8 wherein said residue or residues are covalently linked to amino groups in the carrier material.
Claim 12
Dependent Claim
99 words
The immunogen of claim 9 of the formula: ##STR8## wherein Carrier is an immunogenic carrier material other than human hemoglobin, p is on the average from 1 to the number of available coupling sites on the carrier material, and R is (a) a bond to an ε-amino group on a lysyl residue in said carrier material, or (b) a linking group of the formula: ##STR9## wherein R' is hydroxyl and R" is a bond to a carboxyl group in said carrier material, or R" is hydrogen and R' is a bond to an amino group in said carrier material.
Claim 13
Dependent Claim
15 words
The immunogen of claim 10 wherein the carrier material is an immunogenic protein or polypeptide.
Claim 14
Dependent Claim
17 words
The immunogen of claim 10 wherein R is said bond and said crrier material is an albumin.
Claim 15
Dependent Claim
16 words
The immunogen of claim 10 wherein R is said bond and said carrier material is polylysine.
Claim 16
Dependent Claim
97 words
An immunoassay method for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising the steps of (a) contacting the fluid with an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR10## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (b) determining binding of proteins and fragments thereof in the fluid to said antibody as a function of the amount of total nonenzymatically glucosylated proteins and fragments thereof in the fluid.
Claim 17
Dependent Claim
97 words
An immunoassay method for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising the steps of (a) contacting the fluid with an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR10## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (b) determining binding of proteins and fragments thereof in the fluid to said antibody as a function of the amount of total nonenzymatically glucosylated proteins and fragments thereof in the fluid.
Claim 18
Dependent Claim
10 words
The method of claim 14 wherein R is a bond.
Claim 19
Dependent Claim
9 words
The method of claim 14 wherein R is --NH--.
Claim 20
Dependent Claim
11 words
The method of claim 14 wherein R is said lysyl residue.
Claim 21
Dependent Claim
33 words
The method of claim 14 wherein said antibody is prepared against an immunogen comprising one or more residues of the formula: ##STR11## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 22
Dependent Claim
20 words
The method of claim 18 wherein said residue or residues are covalently linked to amino groups in the carrier material.
Claim 23
Dependent Claim
27 words
The method of claim 19 wherein the amino groups in the carrier material to which said residue or residues are linked are ε-amino groups of lysyl residues.
Claim 24
Dependent Claim
68 words
The method of claim 14 wherein said fluid is also contacted with a labeled reagent which is capable of binding with said antibody and which comprises a detectable label, and wherein the amount of said label in either the resulting antibody-bound species or the free-species of the labeled reagent is measured as a function of the amount of total nonenzymatically glucosylated proteins and fragments thereof in the fluid.
Claim 25
Dependent Claim
37 words
The method of claim 21 of the homogeneous type wherein the label in the labeled reagent provides a detectable response that is different when the ragent is bound to said antibody compared to when not so bound.
Claim 26
Dependent Claim
15 words
The method of claim 22 wherein said label is a participant in an enzyme-catalyzed reaction.
Claim 27
Dependent Claim
24 words
The method of claim 23 wherein said label is an enzyme substrate, a coenzyme, an enzyme prosthetic group, an enzyme inhibitor, or an enzyme.
Claim 28
Dependent Claim
15 words
The method of claim 14 wherein said biological fluid is blood or a component thereof.
Claim 29
Dependent Claim
14 words
The method of claim 14 wherein said biological fluid is human serum or plasma.
Claim 30
Dependent Claim
74 words
A reagent composition for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising: (1) an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR12## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (2) a labeled reagent capable of binding with said antibody and comprising a detectable label.
Claim 31
Dependent Claim
74 words
A reagent composition for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising: (1) an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR12## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (2) a labeled reagent capable of binding with said antibody and comprising a detectable label.
Claim 32
Dependent Claim
10 words
The composition of claim 27 wherein R is a bond.
Claim 33
Dependent Claim
9 words
The composition of claim 27 wherein R is --NH--.
Claim 34
Dependent Claim
11 words
The composition of claim 27 wherein R is said lysyl residue.
Claim 35
Dependent Claim
33 words
The composition of claim 27 wherein said antibody is prepared against an immunogen comprising one or more residues of the formula: ##STR13## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 36
Dependent Claim
20 words
The composition of claim 31 wherein said residue or residues are covalently linked to amino groups in the carrier material.
Claim 37
Dependent Claim
27 words
The composition of claim 32 wherein the amino groups in the carrier material to which said residue or residues are linked are ε-amino groups of lysyl residues.
Claim 38
Dependent Claim
33 words
The composition of claim 27 wherein the label in the labeled reagent provides a detectable response that is different when the reagent is bound to said antibody compared to when not so bound.
Claim 39
Dependent Claim
15 words
The composition of claim 34 wherein said label is a participant in an enzyme-catalyzed reaction.
Claim 40
Dependent Claim
24 words
The composition of claim 35 wherein said label is an enzyme substrate, a coenzyme, an enzyme prosthetic group, an enzyme inhibitor, or an enzyme.
Claim 41
Dependent Claim
30 words
A test device for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising the reagent composition of claim 27 and a solid carrier member incorporated therewith.
Claim 42
Dependent Claim
80 words
A test kit for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising, in a packaged combination, containers holding: (1) an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR14## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (2) a labeled reagent capable of binding with said antibody and comprising a detectable label.
Claim 43
Dependent Claim
80 words
A test kit for determining total nonenzymatically glucosylated proteins and fragments thereof in a biological fluid, comprising, in a packaged combination, containers holding: (1) an antibody which binds specifically to a glucosylated peptide residue comprising Amadori-rearranged glucose and being of the formula: ##STR14## wherein R is a bond, --NH--, or a lysyl residue where the rearranged glucose moiety is coupled to its ε-amino group, and (2) a labeled reagent capable of binding with said antibody and comprising a detectable label.
Claim 44
Dependent Claim
11 words
The test kit of claim 38 wherein R is a bond.
Claim 45
Dependent Claim
10 words
The test kit of claim 38 wherein R is --NH'.
Claim 46
Dependent Claim
12 words
The test kit of claim 38 wherein R is said lysyl residue.
Claim 47
Dependent Claim
34 words
The test kit of claim 38 wherein said antibody is prepared against an immunogen comprising one or more residues of the formula: ##STR15## covalently linked to an immunogenic carrier material other than human hemoglobin.
Claim 48
Dependent Claim
21 words
The test kit of claim 42 wherein said residue or residues are covalently linked to amino groups in the carrier material.
Claim 49
Dependent Claim
28 words
The test kit of claim 43 wherein the amino groups in the carrier material to which said residue or residues are linked are ε-amino groups of lysyl residues.
Claim 50
Dependent Claim
38 words
The test kit of claim 38 of the homogeneous type wherein the label in the labeled reagent provides a detectable response that is different when the reagent is bound to said antibody compared to when not so bound.
Claim 51
Dependent Claim
16 words
The test kit of claim 45 wherein said label is a participant in an enzyme-catalyzed reaction.
Claim 52
Dependent Claim
25 words
The test kit of claim 46 wherein said label is an enzyme substrate, a coenzyme, an enzyme prosthetic group, an enzyme inhibitor, or an enzyme.
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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) | 1989-12-15 | 1990-06-16 | 1990-12-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-12-15 | 1994-06-16 | 1994-12-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-12-15 | 1998-06-16 | 1998-12-16 | $7700.00 | Window Closed / Lapsed |