Claims for Patent: 10,215,761

Summary for Patent: 10,215,761

Title:	Bcl-2-like protein 11 SRM/MRM assay
Abstract:	Specific peptides, and derived ionization characteristics of those peptides, from the Bcl-2-like protein 11 (BIM) are provided that are particularly advantageous for quantifying the BIM protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM). Such biological samples are chemically preserved and fixed where the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue.TM. reagents and protocol, and the BIM protein is quantitated in the Liquid Tissue.TM. sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a BIM peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.
Inventor(s):	Krizman; David (Gaithersburg, MD), Hembrough; Todd (Gaithersburg, MD), Thyparambil; Sheeno (Frederick, MD), Liao; Wei-Li (Herndon, VA)
Assignee:	Expression Pathology, Inc. (Rockville, MD)
Application Number:	15/262,736
Patent Claims:	1. A method for diagnosing cancer in a subject, comprising detecting and quantifying the amount of a human Bcl-2-like protein 11 (BIM) fragment peptide in a protein digest prepared from a human biological sample of formalin-fixed tissue from said subject using mass spectrometry; and calculating the amount of BIM protein in said sample; wherein the BIM fragment peptide consists of the peptide of SEQ ID NO:2, wherein said level is a relative level or an absolute level, and, wherein detecting and quantifying the level of said BIM fragment peptide in the protein digest indicates the presence of BIM protein and an association with cancer in the subject. 2. The method of claim 1, further comprising correlating the results of detecting and quantifying the level of said BIM fragment peptide, or the level of the BIM protein to the diagnostic stage/grade/status of the cancer. 3. The method of claim 1, further comprising administering to the subject, from which the biological sample is obtained, a therapeutically effective amount of a therapeutic agent, wherein the therapeutic agent and/or amount of the therapeutic agent administered is based upon the level of said BIM fragment peptide or the level of BIM protein, and wherein said therapeutic agent is a kinase receptor inhibitor. 4. The method of claim 3, wherein the therapeutic agent is directed to cancer cells expressing BIM protein. 5. The method of claim 3, wherein said kinase receptor inhibitor is an antibody. 6. The method of claim 3 wherein said kinase receptor inhibitor is trastuzumab, cetuximab, or panitumumab. 7. The method of claim 3 wherein said kinase receptor inhibitor is selected from the group consisting of Lapatinib, Erlotinib, Gefitinib, Vandetanib, Pelitinib, Canertinib, Foretinib, Crizotinib, Afatinib, Cabozantinib, Axitinib, Vatalanib, BMS-536924, OSI-906, Saracatinib, and Ponatinib.

Details for Patent 10,215,761

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2031-01-13
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2031-01-13
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2031-01-13
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2031-01-13
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2031-01-13
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2031-01-13