US4886743A
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US
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Diagnostic reagents based on unique sequences within the variable region of the T cell receptor and uses thereof
Assignee: California Institute of Technology
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Filing: 1985-04-24
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Granted: 1989-12-12
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Expires: 2005-04-24
Abstract
Abstract This invention provides a reagent capable of binding to T cells and having specificity for a unique sequence within the variable region of the beta chain of the T cell receptor, the presence of increased number of T cells carrying the unique sequence relative to the number of T cells carrying the sequence present in a normal subject being associated with a specific disease. Specific diseases such as human cancers, e.g. lymphomas; autoimmune diseases, e.g. rheumatoid arthritis; Alzheimer's disease; infectious diseases, e.g. those caused by bacteria, yeast or parasite; or allergies, may be diagnosed as follows. A suitable sample containing T cells is obtained from a subject. The sample is contacted under appropriate conditions with such a reagent. If the subject's cells contain the unique sequence, a detectable complex is formed between the reagent and T cells which contain the sequence. By quantitatively determining the number of T cells containing the sequence present in the complex formed and comparing this number with the number of T cells carrying the sequence determined for a normal subject, the disease with which the unique sequence is associated may be diagnosed. Similar reagents and methods may also be used to detect organ transplant rejection.
Inventors
- 👤 Leroy E. Hood
- 👤 Irving L. Weissman
- 👤 Michael S. McGrath
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 10:27
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/18; C07K16/28; C07K16/2803; C07K16/2809; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5091; G01N33/53; G01N33/564; G01N33/569; G01N33/56966; G01N33/56972; G01N33/56983; G01N33/56988; G01N33/575; G01N33/57515; G01N33/576; A; A61; A61K; A61K38/00; G01N2800/00; G01N2800/10; G01N2800/101; G01N2800/102; G01N2800/24; G01N2800/245; Y; Y02; Y02A; Y02A50/00; Y02A50/30; Y10; Y10S; Y10S435/00; Y10S435/974; Y10S436/00; Y10S436/811; Y10S436/813; Y10T; Y10T436/00; Y10T436/11; Y10T436/117497
Claims Analysis
Total Claims: 62
Claim 1
Independent Claim
177 words
A method of diagnosing a specific disease in a subject which comprises: a. obtaining from the subject suspected of having the specific disease a suitable sample containing T cells; b. contacting the sample under appropriate conditions with a reagent (1) capable of binding to T cells and (2) indicative of the presence of, and having specificity for, a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of an increased number of cells carrying the unique sequence relative to the number of cells carrying the sequence present in a normal subject being associated with the specific disease, so as to form a detectable complex between the reagent and T cells which contain the unique sequence and are present in the sample; and c. quantitatively determining the number of the T cells carrying the sequence present in the complex, comparing the number so determined with the number of T cells carrying the sequence determined for a normal subject using the same procedure and thereby diagnosing the specific disease.
Claim 2
Independent Claim
177 words
A method of diagnosing a specific disease in a subject which comprises: a. obtaining from the subject suspected of having the specific disease a suitable sample containing T cells; b. contacting the sample under appropriate conditions with a reagent (1) capable of binding to T cells and (2) indicative of the presence of, and having specificity for, a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of an increased number of cells carrying the unique sequence relative to the number of cells carrying the sequence present in a normal subject being associated with the specific disease, so as to form a detectable complex between the reagent and T cells which contain the unique sequence and are present in the sample; and c. quantitatively determining the number of the T cells carrying the sequence present in the complex, comparing the number so determined with the number of T cells carrying the sequence determined for a normal subject using the same procedure and thereby diagnosing the specific disease.
Claim 3
Dependent Claim
12 words
A method of claim 1, wherein the specific disease is a cancer.
Claim 4
Dependent Claim
13 words
A method of claim 2, wherein the cancer is a human breast cancer.
Claim 5
Dependent Claim
13 words
A method of claim 2, wherein the cancer is a human colon cancer.
Claim 6
Dependent Claim
13 words
A method of claim 2, wherein the cancer is a human lung cancer.
Claim 7
Dependent Claim
12 words
A method of claim 2, wherein the cancer is a human lymphoma.
Claim 8
Dependent Claim
12 words
A method of claim 2, wherein the cancer is a human hepatoma.
Claim 9
Dependent Claim
12 words
A method of claim 2, wherein the cancer is a human leukemia.
Claim 10
Dependent Claim
13 words
A method of claim 1, wherein the specific disease is an autoimmune disease.
Claim 11
Dependent Claim
12 words
A method of claim 9, wherein the autoimmune disease is rheumatoid arthritis.
Claim 12
Dependent Claim
13 words
A method of claim 9, wherein the autoimmune disease is type 1 diabetes.
Claim 13
Dependent Claim
12 words
A method of claim 9, wherein the autoimmune disease is multiple sclerosis.
Claim 14
Dependent Claim
13 words
A method of claim 9, wherein the autoimmune disease is systemic lupus erythematosis.
Claim 15
Dependent Claim
15 words
A method of claim 9, wherein the autoimmune disease is myasthenia gravis or Graves disease.
Claim 16
Dependent Claim
17 words
A method of claim 1, wherein the specific disease is a degenerative disease of the nervous system.
Claim 17
Dependent Claim
13 words
A method of claim 1, wherein the specific disease is an infectious disease.
Claim 18
Dependent Claim
14 words
A method of claim 16, wherein the infectious disease is caused by a virus.
Claim 19
Dependent Claim
13 words
A method of claim 17, wherein the virus is HTLV-I or HTLV-III (LAV).
Claim 20
Dependent Claim
12 words
A method of claim 17, wherein the virus is HSV-I or HSV-II.
Claim 21
Dependent Claim
14 words
A method of claim 17, wherein the virus is hepatitis A or hepatitis B.
Claim 22
Dependent Claim
10 words
A method of claim 17, wherein the virus is cytomegalovirus.
Claim 23
Dependent Claim
14 words
A method of claim 16, wherein the infectious disease is caused by a yeast.
Claim 24
Dependent Claim
13 words
A method of claim 22, wherein the yeast is of the genus Candida.
Claim 25
Dependent Claim
14 words
A method of claim 16, wherein the infectious disease is caused by a parasite.
Claim 26
Dependent Claim
11 words
A method of claim 24, wherein the parasite is a schistosome.
Claim 27
Dependent Claim
12 words
A method of claim 24, wherein the parasite is filaria or mycobacterium.
Claim 28
Dependent Claim
11 words
A method of claim 24, wherein the parasite is Trichinella spiralis.
Claim 29
Dependent Claim
14 words
A method of claim 24, wherein the parasite is a protozoan which causes malaria.
Claim 30
Dependent Claim
15 words
A method of claim 24, wherein the parasite is a trypanosome which causes sleeping sickness.
Claim 31
Dependent Claim
14 words
A method of claim 15, wherein the infectious disease is caused by a bacterium.
Claim 32
Dependent Claim
11 words
A method of claim 30, wherein the bacterium produces tetanus toxoid.
Claim 33
Dependent Claim
12 words
A method of claim 1, wherein the specific disease is an allergy.
Claim 34
Dependent Claim
17 words
A method of claim 32, wherein the allergy is a delayed type hypersensitivity or a contact hypersensitivity.
Claim 35
Dependent Claim
11 words
A method of claim 1, wherein the subject is a human.
Claim 36
Dependent Claim
11 words
A method of claim 1, wherein the subject is an animal.
Claim 37
Dependent Claim
13 words
A method of claim 1, wherein the sample is derived from whole blood.
Claim 38
Dependent Claim
12 words
A method of claim 1, wherein the sample is derived from tissue.
Claim 39
Dependent Claim
43 words
A method of claim 1, wherein the unique sequence is at least 10 amino acids in length and is present within the first 30 amino acids located at the N-terminus of a variable region of the β chain of the T cell receptor.
Claim 40
Dependent Claim
11 words
A method of claim 38, wherein the unique sequence is Gly-Val-Ile-Gln-Ser-Pro-Arg-His-Glu-Val-Thr-Glu-Met-Gly-Gln-Glu-Val-Thr-Leu-Arg-Cys.
Claim 41
Dependent Claim
22 words
A method of claim 1, wherein the reagent is an antibody directed to an epitope corresponding to the unique amino acid sequence.
Claim 42
Dependent Claim
12 words
A method of claim 4, wherein the antibody is a monoclonal antibody.
Claim 43
Dependent Claim
33 words
A method of claim 1, wherein the reagent is a DNA hybridization probe of at least about 30 bases and is complementary to the DNA sequence which encodes the unique amino acid sequence.
Claim 44
Dependent Claim
33 words
A method of claim 1, wherein the reagent is a RNA hybridization probe of at least about 30 bases and is complementary to the DNA sequence which encodes the unique amino acid sequence.
Claim 45
Dependent Claim
15 words
A method of claim 40, wherein the monoclonal antibody is labeled with a detectable moiety.
Claim 46
Dependent Claim
13 words
A method of claim 44, wherein the detectable moiety is a fluorescent dye.
Claim 47
Dependent Claim
13 words
A method of claim 44, wherein the detectable moiety is a radioactive isotope.
Claim 48
Dependent Claim
20 words
A method of claim 44, wherein the detectable moiety is an enzyme which catalyzes a reaction producing a detectable product.
Claim 49
Dependent Claim
11 words
A method of claim 44, wherein the detectable moiety is biotin.
Claim 50
Dependent Claim
18 words
A method of claim 44, wherein the detectable moiety is a metal ion detectable by nuclear magnetic resonance.
Claim 51
Dependent Claim
16 words
A method of claim 42, wherein the DNA hybridization probe is labeled with a detectable moiety.
Claim 52
Dependent Claim
16 words
A method of claim 43, wherein the RNA hybridization probe is labeled with a detectable moiety.
Claim 53
Dependent Claim
28 words
A method of claim 45, wherein the quantitive determination of the number of T cells carrying the sequence present in the complex is by fluorescence activated cell sorting.
Claim 54
Dependent Claim
12 words
A method of claim 15, wherein the degenerative disease is Alzheimer's disease.
Claim 55
Dependent Claim
65 words
A monoclonal antibody capable of binding to T cells and having specificity for a unique amino acid sequence contained within the variable region of the β chain of the T cell receptor, the presence of increased number of T cells carrying the unique sequence relative to the number of T cells carrying the sequence present in a normal subject being associated with a specific disease.
Claim 56
Dependent Claim
65 words
A monoclonal antibody capable of binding to T cells and having specificity for a unique amino acid sequence contained within the variable region of the β chain of the T cell receptor, the presence of increased number of T cells carrying the unique sequence relative to the number of T cells carrying the sequence present in a normal subject being associated with a specific disease.
Claim 57
Dependent Claim
66 words
A monoclonal antibody capable of binding to T cells and having specificity for a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of increased numbers of T cells carrying the unique sequence relative to the number of T cells carrying the sequence present in a normal subject being associated with rejection of a transplanted organ.
Claim 58
Dependent Claim
66 words
A monoclonal antibody capable of binding to T cells and having specificity for a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of increased numbers of T cells carrying the unique sequence relative to the number of T cells carrying the sequence present in a normal subject being associated with rejection of a transplanted organ.
Claim 59
Dependent Claim
7 words
A purified polypeptide having the sequence: Gly-Val-Ile-Gln-Ser-Pro-Arg-His-Glu-Val-Thr-Glu-Met-Gly-Glu-Glu-Val-Thr-Leu-Arg-Cys.
Claim 60
Dependent Claim
7 words
A purified polypeptide having the sequence: Gly-Val-Ile-Gln-Ser-Pro-Arg-His-Glu-Val-Thr-Glu-Met-Gly-Glu-Glu-Val-Thr-Leu-Arg-Cys.
Claim 61
Independent Claim
192 words
A method for detecting organ transplant rejection in a subject into whom an organ from a different subject is transplanted which comprises: a. obtaining from the subject into whom the organ from a different subject has been transplanted a suitable sample containing T cells; b. contacting the sample under appropriate conditions with a reagent (1) capable of binding to T cells and (2) indicative of the presence of, and having specificity for, a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of an increased number of cells carrying the unique sequence relative to the number of cells carrying the sequence present in a normal subject being associated with organ transplant rejection, so as to form a detectable complex between the reagent and T cells which contain the unique sequence and are present in the sample; and c. quantitatively determining the number of the T cells carrying the sequence present in the complex, comparing the number so determined with the number of T cells carrying the sequence determined for a normal subject using the same procedure and thereby detecting organ transplant rejection.
Claim 62
Independent Claim
192 words
A method for detecting organ transplant rejection in a subject into whom an organ from a different subject is transplanted which comprises: a. obtaining from the subject into whom the organ from a different subject has been transplanted a suitable sample containing T cells; b. contacting the sample under appropriate conditions with a reagent (1) capable of binding to T cells and (2) indicative of the presence of, and having specificity for, a unique amino acid sequence within the variable region of the β chain of the T cell receptor, the presence of an increased number of cells carrying the unique sequence relative to the number of cells carrying the sequence present in a normal subject being associated with organ transplant rejection, so as to form a detectable complex between the reagent and T cells which contain the unique sequence and are present in the sample; and c. quantitatively determining the number of the T cells carrying the sequence present in the complex, comparing the number so determined with the number of T cells carrying the sequence determined for a normal subject using the same procedure and thereby detecting organ transplant rejection.
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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) | 1992-12-11 | 1993-06-12 | 1993-12-12 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-12-11 | 1997-06-12 | 1997-12-12 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-12-11 | 2001-06-12 | 2001-12-12 | $7700.00 | Window Closed / Lapsed |