Processing of SLPI by chymase
AssigneeOrtho-McNeil Pharmaceutical, Inc.
InventorsStanley Belkowski, Michael D'Andrea
Life of this patent
Estimating the term…
Abstract
It is now discovered that human chymase cleaves human SLPI at a specific site and that this cleavage can be used as an indicator of chymase activity. The present invention provides methods of diagnosing a chymase-associated disease or evaluating the efficiency of a treatment of a chymase-associated disease in a human subject by measuring SLPI processing, as well as other related methods and compositions.
Claims37
A method of detecting a chymase-associated disease in a human subject, comprising the steps of:
- a. obtaining a biological sample from the human subject;
- b. measuring the level of human SLPI cleavage by human chymase in the biological sample;
- and
- c. comparing the level measured from step b) to a control of the level of human SLPI cleavage by human chymase in a healthy human subject, wherein an elevated level of human SLPI cleavage by human chymase compared to said control indicates that the human subject has a chymase-associated disease or has increased risk of a chymase-associated disease.
A method of evaluating the effectiveness of a treatment to a chymase-associated disease in a human patient, comprising the steps of:
- a. obtaining a biological sample from the human patient;
- b. measuring the level of human SLPI cleavage by human chymase in the biological sample;
- and
- c. comparing the level measured from step b) to a control of the level of human SLPI cleavage by human chymase in the human patient prior to the treatment, wherein a decreased level of human SLPI cleavage by human chymase compared to said control indicates that the treatment to a chymase-associated disease in said patient is effective.
A method of measuring the biological activity of a human chymase, comprising the steps of:
- a. contacting the human chymase with a human SLPI in an assay mixture;
- b. incubating the assay mixture under a condition wherein the human chymase cleaves the human SLPI;
- and
- c. measuring the level of human SLPI cleavage by human chymase in the assay mixture.
A method of identifying a compound that decreases the biological activity of a human chymase comprising the steps of:
- a. contacting a test compound with a human chymase and a human SLPI in an assay mixture;
- b. incubating the assay mixture under a condition wherein the human chymase cleaves the human SLPI;
- c. measuring the level of human SLPI cleavage by human chymase in the assay mixture;
- and
- d. comparing the level detected from step c) to that detected from a control, wherein the test compound is omitted from the assay mixture.
A kit comprising
- a. an antibody that binds specifically to a SLPI fragment consisting essentially of the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:4;
- and
- b. an instruction for correlating the measured level of said SLPI fragment with the biological activity of a human chymase.
A method of classifying a patient who has a better chance to respond to a treatment involving a chymase inhibitor, comprising the steps of:
- a. obtaining a biological sample from a patient;
- b. measuring the level of human SLPI cleavage by human chymase in the biological sample;
- and
- c. comparing the level measured from step b) to a control of the level of human SLPI cleavage by human chymase in a healthy human subject, wherein an elevated level of human SLPI cleavage by human chymase compared to said control indicates that the patient has a better chance to respond to a treatment involving a chymase inhibitor.
Dependencies are inferred from the claim text.