Methods for monitoring drug activities in vivo

• US 7,643,943 B2
• Filed: 03/05/2004
• Issued: 01/05/2010
• Est. Priority Date: 02/11/2003
• Status: Expired due to Fees

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth LLC (Pfizer Inc.)
• Inventors: Stover, Jennifer, Twine, Natalie C., Boni, Joseph, Dorner, Andrew J., Trepicchio, William L., Fitzpatrick, Virginia, Burczynski, Michael E., Immermann, Fred
• Primary Examiner(s): Lin; Jerry
• Application Number:
  US10/793,032
• Publication Number:
  US 20040235020A1
• Time in Patent Office: 2,132 Days
• Field of Search: 702/19
• US Class Current: 702/19
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers

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

1. 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.

2. 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.

3. 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.

4. 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.