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US6492126B2 Expired / Lapsed US ⏱️ 0.0 years remaining

Compositions and methods for the treatment and diagnosis of cardiovascular disease

Assignee: Millennium Pharmaceuticals Inc
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Filing: 1999-08-11
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Granted: 2002-12-10
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Expires: 2019-08-11
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Abstract

Abstract The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease. Moreover, the present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of cardiovascular disease, and for monitoring the efficacy of compounds in clinical trials. Additionally, the present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions.

Inventors

  • 👤 Dean A. Falb
  • 👤 Michael A. Gimbrone, Jr.

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 09:18
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/113; A; A61; A61P; A61P9/00; A61P9/10; A61P9/12; C07; C07K; C07K14/00; C07K14/435; C07K14/46; C07K14/47; A01; A01K; A01K2217/00; A01K2217/05; A61K; A61K38/00; C12N2310/00; C12N2310/10; C12N2310/12; C12N2310/121; C12N2310/15

Claims Analysis

Total Claims: 27
Claim 1
Independent Claim 115 words
A method for identifying a substance that modulates the TGF-β signaling response comprising: (a) contacting a genetically engineered cell with TGF-β and a test substance, said cell comprising 1) a reporter gene in operative association with an inducible TGF-β regulatory element; and 2) a recombinant construct comprising a gene encoding the fchd540 protein; and (b) detecting expression of said gene in operative association with the TGF-β regulatory element, in which ability of the test substance to modulate the TGF-β signaling response is indicated by a change in expression of the reporter gene in operative association with the inducible TGF-β regulatory element as compared to the amount of expression in the absence of the test substance.
Claim 2
Independent Claim 115 words
A method for identifying a substance that modulates the TGF-β signaling response comprising: (a) contacting a genetically engineered cell with TGF-β and a test substance, said cell comprising 1) a reporter gene in operative association with an inducible TGF-β regulatory element; and 2) a recombinant construct comprising a gene encoding the fchd540 protein; and (b) detecting expression of said gene in operative association with the TGF-β regulatory element, in which ability of the test substance to modulate the TGF-β signaling response is indicated by a change in expression of the reporter gene in operative association with the inducible TGF-β regulatory element as compared to the amount of expression in the absence of the test substance.
Claim 3
Dependent Claim 22 words
The method of claim 1 , wherein expression of the gene in operative association with the inducible TGF-β regulatory element is increased.
Claim 4
Dependent Claim 22 words
The method of claim 1 , wherein expression of the gene in operative association with the inducible TGF-β regulatory element is decreased.
Claim 5
Dependent Claim 27 words
The method of claim 1 , wherein the cell is further genetically engineered to express at least one member of the TGF-β signaling pathway other than fchd540.
Claim 6
Dependent Claim 17 words
The method of claim 4 , wherein the other member of the TGF-β signaling pathway is MADR1.
Claim 7
Dependent Claim 24 words
The method of claim 4 , wherein the other member of the TGF-β signaling pathway is MADR2, DPC4, TβR1, ALK6, TSR1, ALK3, or ActR1β.
Claim 8
Dependent Claim 23 words
The method of claim 1 , wherein the gene in operative association with an inducible TGFP-β regulatory element is endogenous to the cell.
Claim 9
Dependent Claim 24 words
The method of claim 1 , wherein the gene in operative association with an inducible TGF-β regulatory element has been introduced into the cell.
Claim 10
Dependent Claim 17 words
The method of claim 1 , wherein the inducible TGF-β regulatory element is endogenous to the cell.
Claim 11
Dependent Claim 18 words
The method of claim 1 , wherein the inducible TGF-β regulatory element has been introduced into the cell.
Claim 12
Dependent Claim 24 words
The method of claim 1 , wherein the gene in operative association with the inducible TGF-β regulatory element is heterologous to the regulatory element.
Claim 13
Dependent Claim 15 words
The method of claim 1 , wherein the fchd540 gene is endogenous to the cell.
Claim 14
Dependent Claim 16 words
The method of claim 1 , wherein the fchd540 gene has been introduced into the cell.
Claim 15
Dependent Claim 34 words
The method of claim 1 , wherein expression of the gene in operative association with the inducible TGF-β regulatory element is detected by assaying the enzymatic activity of a protein encoded by said gene.
Claim 16
Dependent Claim 24 words
The method of claim 1 , wherein expression of the gene in operative association with the inducible TGF-β regulatory element is detected by immunoassay.
Claim 17
Dependent Claim 22 words
The method of claim 1 , wherein mRNA of the gene in operative association with the inducible TGF-β regulatory element is detected.
Claim 18
Dependent Claim 13 words
The method of claim 16 , wherein the mRNA is detected using PCR.
Claim 19
Dependent Claim 14 words
The method of claim 16 , wherein the mRNA is detected using Northern analysis.
Claim 20
Dependent Claim 12 words
The method of claim 1 , wherein the substance is a peptide.
Claim 21
Dependent Claim 14 words
The method of claim 1 , wherein the substance is a small organic compound.
Claim 22
Dependent Claim 14 words
The method of claim 1 , wherein the substance is a small inorganic compound.
Claim 23
Dependent Claim 15 words
The method of claim 1 , wherein the substance is an antibody or antibody fragment.
Claim 24
Dependent Claim 12 words
The method of claim 1 , wherein the substance is an oligonucleotide.
Claim 25
Dependent Claim 13 words
The method of claim 23 , wherein the oligonucleotide is an antisense molecule.
Claim 26
Dependent Claim 13 words
The method of claim 23 , wherein the oligonucleotide is a ribozyme molecule.
Claim 27
Dependent Claim 14 words
The method of claim 23 , wherein the oligonucleotide is a triple helix molecule.

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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) 2005-12-09 2006-06-10 2006-12-10 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2009-12-09 2010-06-10 2010-12-10 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2013-12-09 2014-06-10 2014-12-10 $7700.00 Window Closed / Lapsed

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