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US4727036A
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Antibodies for use in determining hemoglobin A1c
Assignee: MILES INC. A CORP. OF INDIANA
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Filing: 1985-09-27
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Granted: 1988-02-23
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Expires: 2005-09-27
Abstract
Abstract Monoclonal antibodies specific for the glucosylated N-terminal peptide residue in Hb A1c, a method for producing such antibodies, hybridoma cell lines secreting such antibodies and a method for their production, and immunoassay methods and reagent systems using such antibodies for the determination of Hb A1c in human blood samples. The monoclonal antibodies are secreted by hybridomas obtained from the fusion of a myeloma cell and a lymphocyte which has been taken from an animal, preferably a mouse, immunized with a synthetic peptide immunogen and which produces antibody specific for the glucosylated N-terminal peptide residue in Hb A1c. The synthetic peptide immunogen comprises an N-terminal plucosylated peptide residue having at least 2 amino acid units corresponding to the N-terminus of the beta-subunit of human hemoglobin and an immunogenic carrier to which the glucosylated peptide residue is linked. The immunoassay involves treatment of the blood sample to expose the glucosylated N-terminal peptide epitope and detection thereof by binding of the specific monoclonal antibody or a fragment thereof.
Inventors
- 👤 William J. Knowles
- 👤 Vincent T. Marchesi
- 👤 Wallace Haigh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 08:06
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/18; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/68; Y; Y10; Y10S; Y10S530/00; Y10S530/866
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
30 words
A monoclonal antibody or a fragment thereof comprising an antibody combining site, which binds specifically to the glucosylated form of the N-terminal peptide sequence in the beta-subunit of human hemoglobin.
Claim 2
Dependent Claim
30 words
A monoclonal antibody or a fragment thereof comprising an antibody combining site, which binds specifically to the glucosylated form of the N-terminal peptide sequence in the beta-subunit of human hemoglobin.
Claim 3
Dependent Claim
43 words
A monoclonal antibody or a fragment thereof of claim 1 which binds specifically to a glucosylated peptide residue of the formula: Glyco-(NH)Val-His-AA- wherein Glyco-(NH)Val represents a nonenzymatically glucosylated valine residue and AA is a bond or one or more additional amino acid residues.
Claim 4
Dependent Claim
32 words
A monoclonal antibody or a fragment thereof of claim 2, wherein AA is a sequence of from 1 to 12 amino acids corresponding to the N-terminus of the beta-subunit of human hemoglobin.
Claim 5
Dependent Claim
17 words
A monoclonal antibody or a fragment thereof of claim 1 which is secreted by a murine hybridoma.
Claim 6
Dependent Claim
46 words
A monoclonal antibody or a fragment of claim 1 which has been raised against an immunogen comprising a glucosylated peptide chemically linked to an immunogenic carrier material, the glucosylated peptide having at least 2 amino acid units corresponding to the N-terminus of the beta-subunit of hemoglobin.
Claim 7
Dependent Claim
66 words
A monoclonal antibody or a fragment thereof of claim 5, wherein the immunogen is of the formula: [Glyco-(NH)Val-His-AA-R].sub.n Carrier wherein Glyco-(NH)Val represents a nonenzymatic glucosylated valine residue, AA is a bond or one or more additional amino acid residues, R is a linking group, Carrier is an immunogenic carrier material, and n is on average from 1 to the number of available coupling sites on Carrier.
Claim 8
Dependent Claim
35 words
A monoclonal antibody or a fragment thereof of claim 6, wherein AA is selected from the group consisting of -Leu-, -Leu-Thr-, -Leu-Thr-Pro-, -Leu-Thr-Pro-Glu-, -Leu-Thr-Pro-Glu-Glu-, -Leu-Thr-Pro-Glu-Glu-Lys- and -Leu-Thr-Pro-Glu-Glu-Lys-Tyr-Tyr-Cys(SH), where -Cys(SH)-represents cysteine linked through its thiol group.
Claim 9
Dependent Claim
22 words
A monoclonal antibody or a fragment thereof of claim 6 wherein Carrier is an immunogenic protein or peptide other than human hemoglobin.
Claim 10
Dependent Claim
19 words
A murine monoclonal antibody or a fragment thereof of claim 1, which is secreted by hybridoma ATCC HB 8639.
Claim 11
Dependent Claim
19 words
A murine monoclonal antibody or a fragment thereof of claim 1, which is secreted by hybridoma ATCC HB 8869.
Claim 12
Dependent Claim
36 words
A monoclonal antibody or a fragment thereof of claim 1, which binds specifically to said glucosylated N-terminal peptide sequence in the beta-subunit of human hemoglobin A 1c upon being exposed sufficiently to provide steric access thereto.
Claim 13
Dependent Claim
29 words
A monoclonal antibody or a fragment thereof of claim 11, wherein said glucosylated peptide sequence is exposed to the antibody binding site by physical or chemical denaturation or digestion.
Claim 14
Dependent Claim
28 words
A monoclonal antibody or a fragment thereof of claim 11, wherein said glucosylated peptide sequence is exposed to the antibody binding site by denaturation with a chaotropic agent.
Claim 15
Dependent Claim
28 words
A monoclonal antibody or a fragment thereof of claim 13, wherein the chaotropic agent is selected from the group consisting of guanidine, sodium dodecylsulfate, potassium thiocyanate and urea.
Claim 16
Dependent Claim
15 words
A monoclonal antibody or a fragment thereof of claim 11 which is of murine origin.
Claim 17
Dependent Claim
14 words
A monoclonal antibody or a fragment thereof claim 12 which is of murine origin.
Claim 18
Dependent Claim
35 words
A monoclonal antibody or a fragment thereof of claim 1, which binds specifically to said glucosylated N-terminal peptide sequence in the beta-submit of human hemoglobin A1 c which has been adsorbed to a solid surface.
Claim 19
Dependent Claim
20 words
A monoclonal antibody or a fragment thereof of claim 17, wherein the solid surface is made of a carboxy-carrying material.
Claim 20
Dependent Claim
18 words
A monoclonal antibody or a fragment thereof of claim 17, wherein the solid surface is made of polystyrene.
Claim 21
Dependent Claim
18 words
A monoclonal antibody or a fragment thereof of claim 17, wherein the solid surface is made of cellulose.
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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) | 1991-02-22 | 1991-08-24 | 1992-02-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-02-22 | 1995-08-24 | 1996-02-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-02-22 | 1999-08-24 | 2000-02-23 | $7700.00 | Window Closed / Lapsed |