Conjugates activated by cell surface proteases and therapeutic uses thereof
AssigneeCorvas International, Inc.
InventorsEdwin L. Madison, Joseph Edward Semple, George P. Vlasuk, Scott Jeffrey Kemp, Mallareddy Komandla, Daniel Vanna Siev
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Abstract
Conjugates, compositions and methods for treatment, prevention, or amelioration of one or more symptoms of cell surface protease-related diseases, including MTSP-related, urokinase-type plasminogen activator (uPA) or endotheliase-related diseases, are provided. The conjugates for use in the compositions and methods are peptidic conjugates that contain therapeutic, including cytotoxic, agents.
Claims136
A conjugate, comprising a therapeutic agent and a peptidic substrate linked thereto optionally via a linker, wherein the peptidic substrate is proteolytically cleaved by a cell surface protease or a soluble, released or shed form thereof, to liberate the therapeutic agent, wherein the conjugate is not substantially cleaved by plasmin or prostate specific antigen (PSA).
A conjugate selected from among those set forth in FIGS. 1-5, wherein the therapeutic agent doxorubicin (Dox) or taxol (Tax) optionally is replaced with any therapeutic agent.
A conjugate, comprising a therapeutic agent and a nucleic acid substrate linked thereto via a peptidic linker, wherein the peptidic linker is proteolytically cleaved by a cell surface protease or a soluble, released or shed form thereof, to liberate the therapeutic agent, wherein the conjugate is not substantially cleaved by plasmin or prostate specific antigen (PSA).
A method of treatment of a cell-surface protease-associated disease, comprising administering a conjugate, comprising a therapeutic agent and a peptidic substrate linked thereto optionally via a linker, wherein the peptidic substrate is proteolytically cleaved by a cell surface protease or a soluble, released or shed form thereof to liberate the therapeutic agent, to a subject exhibiting symptoms of a cell-surface protease-associated disorder.
A method, comprising:
- a) selecting a disease;
- b) identifying a cell involved in the disease process or a cell in the vicinity of the cell involved in the disease process;
- and
- c) identifying a cell surface protease on the cell, thereby identifying proteases to target conjugates for treatment of diseases.
Dependencies are inferred from the claim text.