US2006275834A1PendingUtilityA1
Methods and compositions related to joint inflammation diseases
Individually held — no corporate assignee on recordPriority: Mar 14, 2003Filed: Mar 15, 2004Published: Dec 7, 2006
Est. expiryMar 14, 2023(expired)· nominal 20-yr term from priority
Y10S436/811G01N 33/6887Y10T436/13G01N 33/5055G01N 2800/102Y10T436/101666Y10S435/973G01N 33/56966
28
PatentIndex Score
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Cited by
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Claims
Abstract
Disclosed are compositions and methods related to joint inflammation diseases. Disclosed is the relationship between osteoclasts and inflammatory joint diseases and osteoclast cells.
Claims
exact text as granted — not AI-modified1 . A method of diagnosing a subject with an inflammatory joint disease comprising measuring how many osteoclast precursor cells (OCP) are in the blood of the subject.
2 . The method of claim 1 , further comprising collecting the subject's PBMCs.
3 . The method of claim 2 , wherein the step of measuring comprises counting the number of cells comprising at least one marker selected from the group consisting of CD14, CD11a, CD11b, CD51/CD61, RANK, CCR1, CCR4, VCAM (CD106), VLA-4 (CD49d), CD16, MHC Class II, B7.1, B7.2, CD40, and c-fms.
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11 . The method of claim 1 wherein the step of measuring comprises counting the number of cells that are CD 16− (negative).
12 . The method of claim 1 , wherein the number of cells in the subject is compared to the number of cells obtained in a healthy control.
13 . The method of claim 1 , wherein the amount of OCP is determined by staining the PBMC sample with fluorescently labeled antibodies for at least one marker selected from the group consisting of CD14, CD11b, CD51/CD61, RANK, CCR1, CCR4, VCAM (CD106), VLA-4 (CD49d), CD16, CD11a, MHC Class II, B7.1, B7.2, CD40, and c-fms and visualizing the cells with labeled antibody bound to at least one of CD14+, CD11b+, CD51/CD61+, RANK+, CCR1+, CCR4+, VCAM+(CD106), VLA-4+(CD49d), CD11a, MHC Class II, B7.1, B7.2, CD40, c-fms or CD16− (negative) using Fluorescence Activated Cell Sorting (FACS).
14 . The method of claim 1 , wherein the number of OCP is determined by removing a tissue sample from the subject and visualizing the sample using immunohistochemistry for at least one marker selected from the group consisting of CD14, CD11b, CD51/CD61, RANK, CCR1, CCR4, VCAM (CD106), VLA-4 (CD49d), CD11a, MHC Class II, B7.1, B7.2, CD40, c-fms and CD16.
15 . The method of claim 1 , wherein the amount of OCP is measured by removing a tissue sample from the subject and staining the tissue section with TRAP, counting how many multinucleated cells there are producing a number of multinucleated cells in the sample from the subject, and comparing the number of multinucleated cells in the sample from the subject to a number of multinucleated cells in a sample from a healthy control, wherein more multinucleated cells in the sample from the subject than in the sample from the healthy control indicates an inflammatory joint disease in the subject.
16 . The method of claim 15 , wherein the sample is a blood sample.
17 . The method of claim 15 , wherein the sample is from the synovium of the subject.
18 . The method of claim 15 , wherein the sample comprises perivascular mononuclear cells or bone marrow.
19 . The method of claim 1 , wherein the amount of OCP in the subject's blood is measured using a colorimetric assay, and comparing the amount of OCP in the subject's blood to a standard curve.
20 . The method of claim 1 , wherein the amount of OCP in the subject's blood is measured using a colorimetric assay, and comparing the amount of OCP in the subject's blood to the amount of OCP in a control's blood.
21 . The method of claim 1 ,wherein the amount of OCP in the subject's blood is measured using FACS methods, Immunohistochemistry methods, Western methods, Southern methods, hybridization methods, RT-PCR methods, ELISA methods, ELISPOT methods, labeling methods, microarray methods, bone wafer resorption methods or Immunoprecipitation methods.
22 . The method of claim 1 , wherein the disease is psoriatic arthritis (PsA) or Rheumatoid arthritis (RA).
23 . The method of claim 1 , wherein measuring the number of OCP comprises identifying RANK, CD11b and CD14 positive cells in the blood sample.
24 . The method of claim 1 , wherein the subject shows bone erosion on a radiograph.
25 . The method of claim 1 , wherein the disease is psoriatic arthritis (PsA) or Rheumatoid arthritis (RA), aseptic joint loosening of orthopedic implants, non-nion of a fracture, spondyloarthropathies, psoriasis and Crohns disease.
26 . A method of diagnosing an inflammatory joint disease comprising culturing peripheral blood mononuclear cells from a subject (PBMC) and assaying the number of osteoclasts formed.
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32 . A method of diagnosing an inflammatory joint disease comprising culturing peripheral blood mononuclear cells (PBMC) from a subject and measuring the amount of TNF-α secreted.
33 . A method of determining the presence of an inflammatory joint disease in a subject comprising, obtaining a PBMC sample from the subject, and measuring how many OCP are in the PBMC of the subject, wherein more OCP in the PBMC of the subject than in a sample from a control subject indicates the presence of disease in the subject.
34 . A method of determining whether a subject has an inflammatory joint disease comprising, collecting PBMCs from the subject, allowing the PBMC to settle, fixing the cells, staining with anti-TRAP or TRAP activity, and examining the stained cells under a microscope, wherein the presence of TRAP indicates the subject has an inflammatory joint disease.
35 . A method of determining whether a subject has an inflammatory joint disease comprising isolating PBMC from the subject, and probing for a surface marker of mononuclear OCP.
36 . The method of claim 35 , wherein the surface marker comprises a marker selected from the group consisting of CD14, CD11b, CD51/CD61, RANK, CCR1, CCR4, VCAM (CD106), VLA-4 (CD49d), CD11a, MHC Class II, B7.1, B7.2, CD40, c-fms and or CD16.
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46 . A method of determining whether a subject has an inflammatory joint disease, comprising obtaining PBMC from the subject, culturing the PBMC on cortical bone wafers, and assaying the amount of eroded bone material in the cortical bone wafer.
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49 . A method of determining whether a subject has an inflammatory joint disease comprising assaying whether the osteoclasts of the subject express RANK.
50 . A method of monitoring the treatment for an inflammatory joint disease in a subject comprising, administering an anti-inflammatory disease agent to the subject, and measuring the number of osteoclast precursor cells (OCP) in the blood of the subject.
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52 . A method of treating a subject with an inflammatory joint disease comprising measuring how many OCP are in the PMBC of the subject producing a number of OCP in the subject and administering an anti-inflammatory disease agent if the number of OCP in the PMBC of the subject is greater than a number of OCP in PBMC of a control subject.
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71 . A method of treating a subject with an inflammatory joint disease comprising administering an anti-inflammatory disease agent to the subject, after administering the anti-inflammatory disease agent measuring how many OCP are in the PMBC of the subject, and adjusting the administration of the anti-inflammatory disease agent based on the number of OCP in the PBMC.
72 . A method of screening the efficacy of a pharmaceutical agent for the ability to treat an inflammatory joint disease comprising measuring the number of OCP in the PBMC of a subject, wherein the pharmaceutical agent was administered to the subject, wherein a decrease in the number of OCP in the subject after treatment indicates efficacy of the pharmaceutical agent.
73 . A method of identifying a pharmaceutical agent having the ability to treat an inflammatory joint disease comprising measuring the number of OCP in a sample, assaying the number of OCP in sample from a non-treated control, and comparing the number of OCP in the subject and the non-treated control.
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76 . A kit for diagnosing an inflammatory joint disease comprising reagents for identifying an OCP, and a standard sample of a control subject without an inflammatory joint disease.
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80 . A method of determining whether to continue administering an anti-inflammatory disease agent in a subject with an inflammatory joint disease comprising determining the number of OCP present in the subject after administration of the anti-inflammatory disease agent a first time, determining the number of OCP present in the subject after administration of the anti-inflammatory disease agent at a second time, comparing the number of OCP in the subject at the first time and at the second time, and if the number of OCP is less at the second time than at the first time, continuing administration of the anti-inflammatory disease agent.
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