ErbB surface receptor complexes as biomarkers

Abstract

The invention is directed to a new class of biomarker in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more dimers of ErbB cell surface membrane receptors measured directly in a patient sample, in particular a fixed tissue sample. In another aspect, the invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more dimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.

Description

[0001] This is a continuation-in-part of U.S. patent application Ser. No. 10 / 623,057 filed 17 Jul. 2003; priority is further claimed under U.S. provisional applications Ser. No. 60 / 459,888 filed 1 Apr. 2003; Ser. No. 60 / 494,482 filed 11 Aug. 2003; Ser. No. 60 / 508,034 filed 1 Oct. 2003; Ser. No. 60 / 512,941 filed 20 Oct. 2003; and Ser. No. 60 / 523,258 filed 18 Nov. 2003, all of the above of which are incorporated in their entirety by reference.FIELD OF THE INVENTION [0002] The present invention relates generally to biomarkers, and more particularly, to the use of ErbB cell surface receptor complexes, such as dimers and oligomers, as biomarkers. BACKGROUND OF THE INVENTION [0003] A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention, Atkinson et al, Clin. Pharmacol. Ther., 69: 89-95 (2001). Biomarkers vary widely in nature, ease of measure...

AI Technical Summary

Benefits of technology

"The invention is about a method for determining the status of a disease or healthful condition in a patient by measuring the amounts of specific receptors in cell surface membranes. This can be done by measuring the amounts of these receptors in a patient sample and comparing them to the amounts in a reference sample. The method can also predict the effectiveness of drugs that target these receptors. The invention provides a way to better understand the disease status of a patient and to improve the effectiveness of treatments for cancer and other diseases."

Problems solved by technology

However, individual receptor expression level alone is not always a reliable indicator of a disease status or condition, e.g. Chow et al, Clin.

Despite the important role that receptor dimerization plays in cellular and disease processes, receptor dimer expression has not been employed as a biomarker, in part due to the inconvenience and lack of sensitivity of current measurement technologies and the inability or impracticality of using such technologies to carry out measurements on patient samples, which may be formalin fixed and / or in too small a quantity for analysis, e.g. Price et al, Methods in Molecular Biology, 218: 255-267 (2003); Stagljar, Science STKE 2003, pe56 (2003); Koll et al, International patent publication WO 2004 / 008099; Golemis, editor, Protein-Protein Interactions (Cold Spring Harbor Laboratory Press, New York, 2002); Sorkin et al, Curr. Biol., 10: 1395-1398 (2000); McVey et al, J. Biol. Chem., 17: 14092-14099 (2001); Salim et al, J. Biol. Chem., 277: 15482-15485 (2002); Angers et al, Annu. Rev. Pharmacol. Toxicol., 42: 409435 (2002); Szollosi et al, Reviews in Molecular Biotechnology, 82: 251-266 (2002); Matko et al, Meth. in Enzymol., 278: 444462 (1997); Reed-Gitomer, U.S. Pat. No. 5,192,660.

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