US4292296A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Diagnostic method
Assignee: Baxter Healthcare Corp
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Filing: 1978-09-12
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Granted: 1981-09-29
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Expires: 1998-09-12
Abstract
Abstract Free analytes in samples containing free analytes and receptorbound analytes are determined by absorbing at least a portion of free analyte from the sample with insolubilized receptor or receptor which is then made insoluble, washing the insoluble receptor, adding labelled sample analyte or labelled sample analyte receptor, incubating, washing the insoluble phase free of the soluble phase and determining the label in either phase. The method solves a long standing need in the assay of free thyroid hormones.
Inventors
- 👤 George H. Parsons, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:28
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/74; G01N33/78; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10S436/815; Y10S436/817
Claims Analysis
Total Claims: 53
Claim 1
Independent Claim
117 words
A method for directly determining free, unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind the free analyte in the sample; (b) removing the sample from contact with the unlabelled receptor; (c) contacting the unlabelled receptor with a labelled reagent selected from the group of (i) a labelled analyte analogue, or (ii) a labelled, soluble analyte receptor; (d) separating the receptor of step c from unbound labelled reagent; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 2
Independent Claim
117 words
A method for directly determining free, unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind the free analyte in the sample; (b) removing the sample from contact with the unlabelled receptor; (c) contacting the unlabelled receptor with a labelled reagent selected from the group of (i) a labelled analyte analogue, or (ii) a labelled, soluble analyte receptor; (d) separating the receptor of step c from unbound labelled reagent; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 3
Dependent Claim
11 words
The method of claim 1 wherein the label is a radioisotope.
Claim 4
Dependent Claim
12 words
The method of claim 1 wherein said analyte receptor is an antibody.
Claim 5
Dependent Claim
22 words
The method of claim 3 wherein the antibody is coated onto at least a portion of the inner surface of a container.
Claim 6
Dependent Claim
20 words
The method of claim 1 wherein at least substantially all of the free sample analyte is absorbed from the sample.
Claim 7
Dependent Claim
27 words
The method of claim 1 wherein the unlabelled analyte receptor is washed after it is contacted with sample analyte but before it is contacted with labelled reagent.
Claim 8
Dependent Claim
12 words
The method of claim 1 wherein the sample analyte is a drug.
Claim 9
Dependent Claim
18 words
The method of claim 4 wherein the sample is diluted before or during contact with the unlabelled receptor.
Claim 10
Dependent Claim
15 words
The method of claim 1 wherein the sample analyte is thyroxine, triiodothyronine, testosterone or diphenylhydantion.
Claim 11
Dependent Claim
13 words
The method of claim 1 wherein the labelled reagent is labelled analyte analogue.
Claim 12
Dependent Claim
32 words
The method of claim 10 wherein the quantity of receptor is such that the number of its binding sites is less than the combined amount of sample analyte and sample analyte analogue.
Claim 13
Dependent Claim
37 words
The method of claim 11 wherein said receptor is contacted with the labelled analyte analogue until the sample analyte analogue and sample analyte associate with and dissociate from the receptor, respectively, to a point of stable equilibrium.
Claim 14
Dependent Claim
13 words
The method of claim 1 wherein said labelled reagent is labelled analyte receptor.
Claim 15
Dependent Claim
29 words
The method of claim 13 wherein the quantity of receptor is such that the number of its binding sites is at least equal to the amount of sample analyte.
Claim 16
Independent Claim
85 words
A method for determining free thyroid hormone in a fluid also containing endogenously bound thyroid hormone, comprising: (a) contacting said fluid with a receptor for said hormone whereby free hormone is absorbed from the fluid; (b) separating the receptor from the fluid; (c) contacting the receptor with labelled hormone; (d) separating the receptor from unbound, labelled hormone; (e) determining the amount of unbound or receptor-bound labelled hormone; and (f) correlating the measured amount in step e with the amount of free hormone in the fluid.
Claim 17
Independent Claim
85 words
A method for determining free thyroid hormone in a fluid also containing endogenously bound thyroid hormone, comprising: (a) contacting said fluid with a receptor for said hormone whereby free hormone is absorbed from the fluid; (b) separating the receptor from the fluid; (c) contacting the receptor with labelled hormone; (d) separating the receptor from unbound, labelled hormone; (e) determining the amount of unbound or receptor-bound labelled hormone; and (f) correlating the measured amount in step e with the amount of free hormone in the fluid.
Claim 18
Dependent Claim
11 words
The method of claim 15 wherein the thyroid hormone is thyroxine.
Claim 19
Dependent Claim
32 words
The method of claim 15 wherein the receptor is a thyroxine antibody coated onto at least a portion of the inner surface of a container and the fluid is a diluted sample.
Claim 20
Dependent Claim
19 words
The method of claim 16 wherein at least substantially all of the free thyroxine is absorbed from the fluid.
Claim 21
Dependent Claim
18 words
The method of claim 16 wherein the fluid is blood serum diluted about from 1 to 15 times.
Claim 22
Dependent Claim
34 words
The method of claim 16 wherein the receptor is contacted with labelled hormone until free receptor binding sites are occupied with labelled hormone but before essentially any dissociation of sample hormone from the receptor.
Claim 23
Dependent Claim
25 words
The method of claim 20 wherein the receptor is contacted with labelled hormone until the receptor reaches equilibrium with the labelled and sample thyroid hormone.
Claim 24
Dependent Claim
17 words
The method of claim 15 wherein the receptor is washed after it is separated from the fluid.
Claim 25
Dependent Claim
22 words
The method of claim 17 wherein the thyroxine antibody is reacted with glutaraldehyde before the thyroxine antibody is coated onto the surface.
Claim 26
Dependent Claim
14 words
The method of claim 15 wherein the amount of receptor-bound labelled hormone is determined.
Claim 27
Dependent Claim
11 words
The method of claim 15 wherein the label is a radioisotope.
Claim 28
Dependent Claim
10 words
The method of claim 25 wherein the radioisotope is radioiodine.
Claim 29
Dependent Claim
27 words
The method of claim 15 wherein the fluid is undiluted blood serum and a diluent is added to the serum before separating the receptor from the serum.
Claim 30
Dependent Claim
23 words
The method of claim 27 wherein a sufficient amount of diluent is added to dilute the serum about from 1 to 15 times.
Claim 31
Independent Claim
139 words
A method for directly determining free unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind the free analyte in the sample, the affinity and capacity of the unlabelled receptor being selected so that the receptor will not adsorb analyte bound to sample receptor; (b) removing the sample from contact with the unlabelled receptor; (c) contacting the unlabelled receptor with a labelled reagent selected from the group of (i) a labelled analyte analogue, or (ii) a labelled, soluble analyte receptor; (d) separating the receptor of step (c) from unbound labelled reagent; (e) measuring the amount of receptor-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 32
Independent Claim
139 words
A method for directly determining free unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind the free analyte in the sample, the affinity and capacity of the unlabelled receptor being selected so that the receptor will not adsorb analyte bound to sample receptor; (b) removing the sample from contact with the unlabelled receptor; (c) contacting the unlabelled receptor with a labelled reagent selected from the group of (i) a labelled analyte analogue, or (ii) a labelled, soluble analyte receptor; (d) separating the receptor of step (c) from unbound labelled reagent; (e) measuring the amount of receptor-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 33
Independent Claim
106 words
A method for directly determining free, unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, wherein the analyte has a molecular weight up to about 3000, comprising (a) contacting the sample with an analyte antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the analyte antibody; (c) contacting the antibody with a labelled analyte analogue; (d) separating the antibody from unbound labelled analyte analogue; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 34
Independent Claim
106 words
A method for directly determining free, unbound analyte in a sample containing a proportion of analyte bound to a receptor in the sample, wherein the analyte has a molecular weight up to about 3000, comprising (a) contacting the sample with an analyte antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the analyte antibody; (c) contacting the antibody with a labelled analyte analogue; (d) separating the antibody from unbound labelled analyte analogue; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free analyte in the sample.
Claim 35
Independent Claim
94 words
A method of directly determining free, unbound aldosterone in a sample containing a proportion of aldosterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a aldosterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the aldosterone antibody; (c) contacting the antibody with labelled aldosterone; (d) separating the antibody from unbound labelled aldosterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free aldosterone in the sample.
Claim 36
Independent Claim
94 words
A method of directly determining free, unbound aldosterone in a sample containing a proportion of aldosterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a aldosterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the aldosterone antibody; (c) contacting the antibody with labelled aldosterone; (d) separating the antibody from unbound labelled aldosterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free aldosterone in the sample.
Claim 37
Independent Claim
94 words
A method for directly determining free, unbound progesterone in a sample containing a proportion of progesterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a progesterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the progesterone antibody; (c) contacting the antibody with labelled progesterone; (d) separating the antibody from unbound labelled progesterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free progesterone in the sample.
Claim 38
Independent Claim
94 words
A method for directly determining free, unbound progesterone in a sample containing a proportion of progesterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a progesterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the progesterone antibody; (c) contacting the antibody with labelled progesterone; (d) separating the antibody from unbound labelled progesterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free progesterone in the sample.
Claim 39
Independent Claim
94 words
A method for directly determining free, unbound testosterone in a sample containing a proportion of testosterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a testosterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the testosterone antibody; (c) contacting the antibody with labelled testosterone; (d) separating the antibody from unbound labelled testosterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free testosterone in the sample.
Claim 40
Independent Claim
94 words
A method for directly determining free, unbound testosterone in a sample containing a proportion of testosterone bound to sex hormone binding globulin in the sample, comprising (a) contacting the sample with a testosterone antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the testosterone antibody; (c) contacting the antibody with labelled testosterone; (d) separating the antibody from unbound labelled testosterone; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free testosterone in the sample.
Claim 41
Independent Claim
91 words
A method for directly determining free, unbound diphenylhydantoin in a sample containing a proportion of diphenylhydantoin bound to albumin in the sample, comprising (a) contacting the sample with a diphenylhydantoin antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the diphenylhydantoin antibody; (c) contacting the antibody with labelled diphenylhydantoin; (d) separating the antibody from unbound labelled diphenylhydantoin; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free diphenylhydantoin in the sample.
Claim 42
Independent Claim
91 words
A method for directly determining free, unbound diphenylhydantoin in a sample containing a proportion of diphenylhydantoin bound to albumin in the sample, comprising (a) contacting the sample with a diphenylhydantoin antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the diphenylhydantoin antibody; (c) contacting the antibody with labelled diphenylhydantoin; (d) separating the antibody from unbound labelled diphenylhydantoin; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free diphenylhydantoin in the sample.
Claim 43
Independent Claim
93 words
A method for directly determining free, unbound cortisol in a sample containing a proportion of cortisol bound to cortisol binding protein in the sample, comprising (a) contacting the sample with a cortisol antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the cortisol antibody; (c) contacting the antibody with labelled cortisol; (d) separating the antibody from unbound labelled cortisol; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free cortisol in the sample.
Claim 44
Independent Claim
93 words
A method for directly determining free, unbound cortisol in a sample containing a proportion of cortisol bound to cortisol binding protein in the sample, comprising (a) contacting the sample with a cortisol antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the cortisol antibody; (c) contacting the antibody with labelled cortisol; (d) separating the antibody from unbound labelled cortisol; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free cortisol in the sample.
Claim 45
Independent Claim
95 words
A method for directly determining free, unbound insulin in a sample containing a proportion of insulin bound to insulin antibody in the sample, comprising (a) contacting the sample with an insulin antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the insulin antibody; (c) contacting the antibody with labelled insulin antibody; (d) separating the container-absorbed antibody from unbound labelled insulin antibody; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free insulin in the sample.
Claim 46
Independent Claim
95 words
A method for directly determining free, unbound insulin in a sample containing a proportion of insulin bound to insulin antibody in the sample, comprising (a) contacting the sample with an insulin antibody adsorbed to the inner surface of a container; (b) removing the sample from contact with the insulin antibody; (c) contacting the antibody with labelled insulin antibody; (d) separating the container-absorbed antibody from unbound labelled insulin antibody; (e) measuring the amount of antibody-bound or unbound label; and (f) correlating the measured amount in step (e) with the amount of free insulin in the sample.
Claim 47
Independent Claim
108 words
A method for directly determining free, unbound analyte in a native or diluted native sample containing a proportion of the analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind free analyte present in the sample; (b) removing the sample from contact with the unlabelled receptor; (c) then contacting the unlabelled receptor with a labelled analyte analogue; (d) separating the receptor of step c from unbound labelled analyte analogue; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step e with the amount of free analyte in the sample.
Claim 48
Independent Claim
108 words
A method for directly determining free, unbound analyte in a native or diluted native sample containing a proportion of the analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind free analyte present in the sample; (b) removing the sample from contact with the unlabelled receptor; (c) then contacting the unlabelled receptor with a labelled analyte analogue; (d) separating the receptor of step c from unbound labelled analyte analogue; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step e with the amount of free analyte in the sample.
Claim 49
Independent Claim
112 words
A method for directly determining free, unbound analyte in a sample containing a proportion of the analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind free analyte present in the sample; (b) washing the unlabelled receptor until it is substantially free of sample receptor or sample receptor-bound analyte; (c) then contacting the washed unlabelled receptor with a labelled analyte analogue; (d) separating the receptor of step c from unbound labelled analyte analogue; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step e with the amount of free analyte in the sample.
Claim 50
Independent Claim
112 words
A method for directly determining free, unbound analyte in a sample containing a proportion of the analyte bound to a receptor in the sample, comprising (a) contacting the sample with an unlabelled receptor for the analyte to bind free analyte present in the sample; (b) washing the unlabelled receptor until it is substantially free of sample receptor or sample receptor-bound analyte; (c) then contacting the washed unlabelled receptor with a labelled analyte analogue; (d) separating the receptor of step c from unbound labelled analyte analogue; (e) measuring the amount of bound or unbound label; and (f) correlating the measured amount in step e with the amount of free analyte in the sample.
Claim 51
Independent Claim
21 words
The method of claims 1, 29 or 38 wherein the sample is diluted before contact with unlabelled receptor for the analyte.
Claim 52
Independent Claim
16 words
The method of claims 1, 29, 30, 37 or 38 wherein the analyte is a hormone.
Claim 53
Independent Claim
26 words
The method of claims 1, 30, 37 or 38 in which at least a significant portion of the free analyte is bound by the unlabelled receptor.
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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) | 1984-09-28 | 1985-03-30 | 1985-09-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-09-28 | 1989-03-30 | 1989-09-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-09-28 | 1993-03-30 | 1993-09-29 | $7700.00 | Window Closed / Lapsed |