Abstract
Methods, systems and equipment useful for monitoring in vivo activities of CCI-779 or other drugs. Numerous drug activity genes can be identified by the present invention. The expression profiles of these genes in peripheral blood mononuclear cells are modulatable by CCI-779 or other drugs. Therefore, these genes can be used as surrogate markers for detecting or monitoring drug activities in vivo.
Claims
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A method for monitoring CCI-779 activity in a patient having a non-blood disease, the method comprising:
(a) generating an expression profile of an ubiquitin specific protease 11 (USP11) gene in a peripheral blood sample obtained from the patient having the non-blood disease and at a stage of treatment with CCI-779, wherein the expression profile is generated by isolating a plurality of ribonucleic acid (RNA) molecules from the peripheral blood sample, labeling said plurality of RNA molecules with a labeling moiety, and probing said plurality of RNA molecules for the presence of a USP11 RNA;
(b) comparing the expression profile of said USP11 gene generated from step (a) to a reference expression profile of said USP11 gene; and
(c) making a determination of CCI-779 activity in the patient based on the comparison result from step (b), wherein
(i) the determination is provided to a user,
(ii) said USP11 gene is differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients who have the non-blood disease during the treatment with CCI-779 as compared to PBMCs of said patients before the treatment, and
(iii) the non-blood disease is a solid tumor.
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A method for monitoring CCI-779 activity in a patient having a non-blood disease, the method comprising:
(a) generating an expression profile of at least one CCI-779 activity gene in a peripheral blood sample obtained from the patient having the non-blood disease and at a stage of treatment with CCI-779, wherein the expression profile is generated by isolating a plurality of ribonucleic acid (RNA) molecules from the peripheral blood sample, labeling said plurality of RNA molecules with a labeling moiety, and probing said plurality of RNA molecules for the presence of one or more CCI-779 activity RNAs set forth in Table 1;
(b) comparing the expression profile of said at least one CCI-779 activity gene generated from step (a) to a reference expression profile of said at least one CCI-779 activity gene; and
(c) making a determination of CCI-779 activity in the patient based on the comparison result from step (b),
wherein,(i) the determination is provided to a user,
(ii) said at least one CCI-779 activity gene is a gene that is differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients who have the non-blood disease during the treatment with CCI-779 as compared to PBMCs of said patients before the treatment,
(iii) the non-blood disease is a solid tumor,
(iv) the expression profile of said at least one CCI-779 activity gene comprises an expression level of said at least one CCI-779 activity gene,
(v) the expression level is an absolute level, a normalized level, or a relative level of said at least one CCI-779 activity gene,
(vi) the determination of the CCI-779 activity is based on an increase or decrease of the expression level of said at least one CCI-779 activity gene by at least 2-fold compared to the reference expression level, and
(vii) the at least one CCI-779 activity gene is selected from the group of genes set forth in Table 1.
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A method for monitoring CCI-779 activity in a patient having a non-blood disease, the method comprising:
(a) generating an expression profile of an ubiquitin specific protease 11 (USP11) gene in a peripheral blood sample obtained from the patient having the non-blood disease and at a stage of treatment with CCI-779, wherein the expression profile is generated by isolating ribonucleic acid (RNA) molecules from the peripheral blood sample, and hybridizing said RNA molecules to a plurality of nucleic acid probes, wherein the plurality of nucleic acid probes comprises a ubiquitin protease 11 (USP11) nucleic acid probe;
(b) comparing the expression profile of said USP11 gene generated from step (a) to a reference expression profile of said USP11 gene; and
(c) making a determination of CCI-779 activity in the patient based on the comparison result from step (b), wherein (i) the determination is provided to a user, (ii) said USP11 gene is differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients who have the non-blood disease during the treatment with CCI-779 as compared to PBMCs of said patients before the treatment, and (iii) the non-blood disease is a solid tumor.
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A method for monitoring CCI-779 activity in a patient having a non-blood disease, the method comprising:
(a) generating an expression profile of at least one CCI-779 activity gene in a peripheral blood sample obtained from the patient having the non-blood disease and at a stage of treatment with CCI-779, wherein the expression profile is generated by isolating ribonucleic acid (RNA) molecules from the peripheral blood sample, and hybridizing said RNA molecules to a plurality of nucleic acid probes, wherein the plurality of nucleic acid probes comprises one or more CCI-779 activity gene probes;
(b) comparing the expression profile of said at least one CCI-779 activity gene generated from step (a) to a reference expression profile of said at least one CCI-779 activity gene; and
(c) making a determination of CCI-779 activity in the patient based on the comparison result from step (b), wherein, (i) the determination is provided to a user, (ii) said at least one CCI-779 activity gene is a gene that is differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients who have the non-blood disease during the treatment with CCI-779 as compared to PBMCs of said patients before the treatment, (iii) the non-blood disease is a solid tumor, (iv) the expression profile of said at least one CCI-779 activity gene comprises an expression level of said at least one CCI-779 activity gene, (v) the expression level is an absolute level, a normalized level, or a relative level of said at least one CCI-779 activity gene, (vi) the determination of the CCI-779 activity is based on an increase or decrease of the expression level of said at least one CCI-779 activity gene by at least 2-fold compared to the reference expression level, and (vii) the at least one CCI-779 activity gene is selected from the group of genes set forth in Table 1.
Owners (US)
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Wyeth
(Jun 06 2005)
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Applicants
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Wyeth Llc
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Inventors
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Burczynski Michael E
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Boni Joseph
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Dorner Andrew J
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Twine Natalie C
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Stover Jennifer
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Trepicchio William L
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Fitzpatrick Virginia
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Immermann Fred
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CPC Classifications
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C12Q1/6886
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C12Q2600/106
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C12Q2600/158
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IPC Classifications
US Classifications
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702/19
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Document History
- Publication: Jan 5, 2010
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Application:
Mar 5, 2004
US 79303204 A
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Priority:
Mar 5, 2004
US 79303204 A
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Priority:
Feb 11, 2004
US 77516904 A
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Priority:
Jan 23, 2004
US 53824604 P
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Priority:
Apr 3, 2003
US 45978203 P
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Priority:
Feb 11, 2003
US 44613303 P