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US6365352B1 Expired / Lapsed US ⏱️ 0.0 years remaining

Process to study changes in gene expression in granulocytic cells

Assignee: Yale University
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Filing: 2000-02-18
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Granted: 2002-04-02
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Expires: 2020-02-18
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Abstract

Abstract The present invention comprises a method to identify granulocytic cell genes that are differentially expressed upon exposure to a pathogen or in a sterile inflammatory disease by preparing a gene expression profile of a granulocytic cell population exposed to a pathogen or isolated from a subject having a sterile inflammatory disease and comparing that profile to a profile prepared from quiescent granulocytic cells. The present invention is particularly useful for identifying cytokine genes, genes encoding cell surface receptors and genes encoding intermediary signaling molecules. The invention also includes methods to identify a therapeutic agent that modulates the expression of at least one gene in a granulocytic population. Genes which are differentially expressed during neutrophil contact with a pathogen, such as a virulent bacteria, or that are differentially expressed in a subject having a sterile inflammatory disease are of particular importance.

Inventors

  • 👤 Subrahmanyam V. Yerramilli
  • 👤 Yatindra Prashar
  • 👤 Peter Newburger
  • 👤 Jon Goguen
  • 👤 Sherman M. Weissman

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-04 11:59
CPC Classifications
C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6876; C12Q1/6883; C12Q1/6809; C12Q2600/00; C12Q2600/142; C12Q2600/158

Claims Analysis

Total Claims: 27
Claim 1
Independent Claim 89 words
A method of diagnosing a sterile inflammatory disease in a patient comprising, (a) isolating a granulocyte population from the patient, (b) preparing a gene expression profile of said granulocyte population; (c) comparing the gene expression profile of step (b) to at least one gene expression profile of a granulocyte population from a subject known to have a sterile inflammatory disease or a gene expression profile of a granulocyte population from a subject that does not have a sterile inflammatory disease, to diagnose a sterile inflammatory disease in the patient.
Claim 2
Independent Claim 89 words
A method of diagnosing a sterile inflammatory disease in a patient comprising, (a) isolating a granulocyte population from the patient, (b) preparing a gene expression profile of said granulocyte population; (c) comparing the gene expression profile of step (b) to at least one gene expression profile of a granulocyte population from a subject known to have a sterile inflammatory disease or a gene expression profile of a granulocyte population from a subject that does not have a sterile inflammatory disease, to diagnose a sterile inflammatory disease in the patient.
Claim 3
Dependent Claim 39 words
The method of claim 1 , wherein the sterile inflammatory disease is selected from the group consisting of glomerulonephritis, psoriasis, rheumatoid arthritis, asthma, cardiac and renal reperfusion injury, thrombosis, adult respiratory distress syndrome, periodontal disease and inflammatory bowel disease.
Claim 4
Dependent Claim 13 words
The method of claim 1 , wherein the sterile inflammatory disease is glomerulonephritis.
Claim 5
Dependent Claim 28 words
The method of claim 1 , wherein the granulocyte population is a neutrophil population, an eosinophil population, a basophil population, or a combined population of different granulocytic cells.
Claim 6
Dependent Claim 14 words
The method of claim 1 , wherein the granulocyte population is a neutrophil population.
Claim 7
Dependent Claim 14 words
The method of claim 1 , wherein the granulocyte population is from peripheral blood.
Claim 8
Dependent Claim 17 words
The method of claim 2 , wherein the inflammatory bowel disease is Crohn's disease, of ulcerative colitis.
Claim 9
Independent Claim 88 words
A method of diagnosing a sterile inflammatory disease in a patient comprising, (a) preparing a gene expression profile from isolated polymorphonuclear white blood cells from the patient; (b) comparing the gene expression profile of step (a) to at least one gene expression profile of polymorphonuclear white blood cells from a subject known to have a sterile inflammatory disease or a gene expression profile of polymorphonuclear white blood cells from a subject that does not have a sterile inflammatory disease, to diagnose a sterile inflammatory disease in the patient.
Claim 10
Independent Claim 88 words
A method of diagnosing a sterile inflammatory disease in a patient comprising, (a) preparing a gene expression profile from isolated polymorphonuclear white blood cells from the patient; (b) comparing the gene expression profile of step (a) to at least one gene expression profile of polymorphonuclear white blood cells from a subject known to have a sterile inflammatory disease or a gene expression profile of polymorphonuclear white blood cells from a subject that does not have a sterile inflammatory disease, to diagnose a sterile inflammatory disease in the patient.
Claim 11
Dependent Claim 39 words
The method of claim 8 , wherein the sterile inflammatory disease is selected from the group consisting of glomerulonephritis, psoriasis, rheumatorid arthritis, asthma, cardiac and renal reperfusion injury, thrombosis, adult respiratory distress syndrome, periodontal disease and inflammatory bowel disease.
Claim 12
Dependent Claim 17 words
The method of claim 8 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
Claim 13
Dependent Claim 25 words
The method of claim 8 , wherein the polymorphonuclear white blood cells are neutrophils, eosinophils, basophils, or a combination of different polymorphonuclear white blood cells.
Claim 14
Dependent Claim 14 words
The method of claim 8 , wherein the polymorphonuclear white blood cells are neutrophils.
Claim 15
Dependent Claim 17 words
The method of claim 8 , wherein the polymorphonuclear white blood cells are isolated from peripheral blood.
Claim 16
Dependent Claim 13 words
The method of claim 9 , wherein the sterile inflammatory disease is glomerulonephritis.
Claim 17
Independent Claim 96 words
A method of diagnosing glomerulonephritis in a patient comprising, (a) isolating polymorphonuclear white blood cells from the patient; (b) isolating RNA from the isolated polymorphonuclear white blood cells; (c) preparing a gene expression profile from the isolated RNA; (d) comparing the gene expression profile of step (c) to at least one gene expression profile of polymorphonuclear white blood cells from a subject known to have a sterile inflammatory disease or a gene expression profile of polymorphonuclear white blood cells from a subject that does not have a sterile inflammatory disease, to diagnose glomerulonephritis in the patient.
Claim 18
Independent Claim 96 words
A method of diagnosing glomerulonephritis in a patient comprising, (a) isolating polymorphonuclear white blood cells from the patient; (b) isolating RNA from the isolated polymorphonuclear white blood cells; (c) preparing a gene expression profile from the isolated RNA; (d) comparing the gene expression profile of step (c) to at least one gene expression profile of polymorphonuclear white blood cells from a subject known to have a sterile inflammatory disease or a gene expression profile of polymorphonuclear white blood cells from a subject that does not have a sterile inflammatory disease, to diagnose glomerulonephritis in the patient.
Claim 19
Dependent Claim 22 words
The method of claim 15 , wherein the polymorphonuclear white blood cells are neutrophils, eosinophils, basophils, or a combination of different granulocytes.
Claim 20
Dependent Claim 14 words
The method of claim 15 , wherein the polymorphonuclear white blood cells are neutrophils.
Claim 21
Dependent Claim 20 words
The method of claim 15 , wherein the polymorphonuclear white blood cells are isolated from peripheral blood of the patient.
Claim 22
Independent Claim 28 words
A method of any one of claims 1 , 8 , or 15 , wherein the expression profile comprises the expression level of at least about 5 genes.
Claim 23
Dependent Claim 20 words
The method of claim 19 , wherein the expression profile comprises the expression level of at least about 10 genes.
Claim 24
Dependent Claim 20 words
The method of claim 19 , wherein the expression profile comprises the expression level of at least about 50 genes.
Claim 25
Dependent Claim 20 words
The method of claim 19 , wherein the expression profile comprises the expression level of at least about 100 genes.
Claim 26
Dependent Claim 25 words
The method of claim 19 , wherein the expression profile is prepared by hybridization of nucleic acids to nucleic acids immobilized on a solid substrate.
Claim 27
Dependent Claim 26 words
The method of claim 23 , wherein the solid substrate is selected from the group consisting of nitrocellulose membrane, nylon membrane, silicon wafer, and borosilicate slide.

References Cited (Backward Citations)

US5721351A Cited
WO1997005286A1 Cited

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3.5 Years (Year 4) 2005-04-01 2005-10-01 2006-04-02 $2000.00 Window Closed / Lapsed
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