Compositions and methods for treatment
AssigneeSarcode Bioscience Inc.
InventorsThomas Gadek, John Burnier, Min Zhong, Wang Shen, Johan D. Oslob, Kenneth Barr
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Abstract
The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
Claims97
A method of treating dry eye disease in a subject in need thereof comprising administering to said subject an effective amount of a lymphocyte function associated antigen-1 (LFA-1) antagonist or a pharmaceutically acceptable salt or ester thereof, wherein the LFA-1 antagonist is a peptide, a small organic molecule, or a combination thereof.
A method of treating dry eye disorder in a subject in need thereof comprising administering to an eye of said subject an effective amount of a pharmaceutical composition comprising a LFA-1 antagonist or a pharmaceutically acceptable salt or ester thereof;
- and a pharmaceutically acceptable vehicle;
- whereby said administration is effective in promoting tear secretion or mucin production in said eyes in said subject.
An ocular pharmaceutical formulation comprising an LFA-1 antagonist, a pharmaceutically acceptable carrier, and a pharmaceutically acceptable excipient.
The pharmaceutical formulation of claim 35 wherein said LFA-antagonist comprises a peptide or organic small molecule.
A method of identifying LFA-1 antagonists, said compounds being competitive inhibitors of the LFA-1:ICAM interaction, comprising:
- binding an antagonist candidate molecule at a known concentration to a ligand selected from group comprising ICAM-1, s-ICAM-1, and LFA-1 in a binding assay;
- adding a set of concentrations of a labeled compound, wherein said compound is known to be an inhibitor of a LFA-1 and ICAM interaction on the I domain of the alpha chain of LFA-1;
- obtaining a binding curve;
- determining EC50 values for each set of binding competitions;
- and
- determining the antagonistic properties of said candidate molecule based on said EC50 values.
A method of treating dry eye disease in a subject comprising performing a dry eye diagnostic test on said subject;
- determining whether said subject suffers from a dry eye disease based on the results of said diagnostic step;
- and upon diagnosis of said dry eye disease, administering to said subject an effective amount of a lymphocyte function associated antigen-1 (LFA-1) antagonist or a pharmaceutically acceptable salt or ester thereof.
A method of identifying compounds useful for treating human disease, comprising:
- obtaining siRNA cellular activity data in a preselected group of cell lines;
- comparing the pattern of modulation of growth in said cell lines treated with said siRNA with the pattern of modulation of growth in said cell lines when treated with potential therapeutic agents;
- and,
- identifying a therapeutic agent as active which displays a pattern of cellular activity substantially similar to that of the siRNA when said active therapeutic agent is administered to said cell lines.
A compound having the following formula:
- or a pharmaceutically acceptable salt thereof.
A compound having one of the following formulae:
- or a pharmaceutically acceptable salt thereof.
The method of claim 97 wherein the continuous or selective release device is an ocular insert or implant.
Dependencies are inferred from the claim text.