ErbB surface receptor complexes as biomarkers

Abstract

The present invention relates to a new class of biomarkers in patient samples comprising dimers of ErbB cell surface membrane receptors. In one aspect, the invention includes a method of determining a disease state or a health condition, wherein such condition is correlated with one or more ErbB cell surface membrane receptors measured directly in a patient sample, particularly a fixed tissue sample. associated with the number of aggregates. In another aspect, the invention includes a method of determining the status of cancer in a sample from an individual, wherein a measure of the amount of one or more ErbB cell surface receptor dimers in the cells of the sample is correlated with the status, comprising Presence or absence of a precancerous state, presence or absence of a cancerous state, cancer prognosis, or responsiveness to therapy. Preferably, the methods of the invention are carried out by employing panels of binding compounds with releasable molecular tags specific for various components of one or more types of receptor dimers. After binding, the molecular tags are released and isolated from the assay mixture for analysis.

Description

[0001] This application is a continuation-in-part of U.S. Patent Application Serial No. 10 / 623057, filed July 17, 2003; it also claims priority from the following U.S. Provisional Application: Ser. No. 1, filed April 1, 2003. .60 / 459888; Ser. No. 60 / 494482 filed August 11, 2003; Ser. No. 60 / 508034 filed October 1, 2003; Ser. No. 60 filed October 20, 2003 Ser. No. 60 / 523258, filed November 18, 2003, all of which are incorporated by reference in their entirety. field of invention [0002] The present invention generally relates to biomarkers, and in particular, to the use of ErbB cell surface receptor complexes, such as dimers or oligomers, as biomarkers. Background of the invention [0003] A biomarker is a characteristic that can be objectively measured and calculated as an indicator of a normal biological process, a pathogenic process, or a pharmacological response to a therapeutic intervention, Atkinson et al., Clin.P...

AI Technical Summary

Problems solved by technology

Although receptor dimerization plays an important role in cellular and disease processes, expression of receptor dimers has not been adopted as a biomarker, in part due to the inconvenience and lack of sensitivity of current measurement techniques, and the inability to or cannot practically use this technique to measure formalin-fixed and / or patient samples that are too small 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, NewYork, 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: 409-435 (2002); Szollosi et al., Reviews in Molecular Biotechnology, 82: 251-266 (2002); Matko et al., Meth. in Enzymol., 278: 444-462 (1997); US Patent 5,192,660 to Reed-Gitomer

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