USOO766277OB2 (12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb. 16, 2010 (54) LOW MOLECULARWEIGHT PROTEIN WO WOO1? 12172 A1 2, 2001 TYROSINE PHOSPHATASE (LMW-PTP) ASA WO WO 01/12840 A2 2, 2001 DAGNOSTIC AND THERAPEUTIC TARGET WO WOO3,O94859 A2 11/2003 WO WOO3,O993 13 A1 12/2003 75 WO WO 2004/O14292 A2 2, 2004 (75) Inventor: Michael S. Kinch, Laytonville, MD WO WO 2004/O14292 A3 2, 2004 WO WO 2005/051307 A2 6, 2005 (73) Assignee: Purdue Research Foundation, West W W SE A. 3. LaFayette, IN (US) WO WO 2005/055948 A3 6, 2005 - WO WO 2005/056766 A2 6, 2005 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 350 days. Carles-Kinchet al., “Antibody targeting of the EphA2tyrosine kinase inhibits malignant cell behavior.” May 15, 2002 Cancer Research (21) Appl. No.: 10/515,358 62(10):2840-2847. 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US 2006/0093608A1 May 4, 2006 2001 Cancer Epidemiology, Biomarkers & Prevention 10:687-696. National Center for Biotechnology Information, National Library of Related U.S. Application Data Medicine, National Institutes of Health. GenBank Locus NM 007099, Accession No. NM 007099, Version NM 007099.1 (60) Provisional application No. 60/382.988, filed on May GI:6005987, "Homo sapiens acid phophatase 1, soluble (ACP1), 23, 2002. transport variant b, mRNA. online). Bethesda, MD retrieved on Mar. 26, 2008). Retrieved from the Internet: <http://www.ncbi.nlm. (51) Int. Cl. nih.gov/entrez/viewer.fcgi?6005987:OLD12:5701672; 3 pgs. A6 IK 38/00 (2006.01) National Center for Biotechnology Information, National Library of (52) U.S. Cl. .......................................................... 5142 Medicine, National Institutes of Health, GenPept Locus P24666, Accession No. P24666, Version P24666 GI: 1709543, “Red cell acid (58) Field of Classification Search ............... ... 514/2 phosphatase 1, isoenzyme F (ACP1) (Low molecular weight See application file for complete search history. phosphotyrosine phosphatase) (Adipocyte acid phosphatase, isoenzyme alpha).” online). Bethesda. MD retrieved on Mar. 25. (56) References Cited 2008. Retrieved from the Internet: <http://www.ncbi.nlm.nih.gov/ U.S. PATENT DOCUMENTS entrez/viewer.fcgi? 1709543:OLD11:669086>; 4pgs. Akerud et al., “Intramolecular Dynamics of Low Molecular Weight 5,876,949 A 3/1999 Dreyfuss et al. Protein Tyrosine Phosphatase in Monomer-Dimer Equilibrium Stud 5,958,957 A 9, 1999 Andersen et al. ied by NMR: A Model for Changes in Dynamics Upon Target Bind 6,927,203 B1 8, 2005 Kinch et al. ing.” J. Mol. Biol. Sep. 6, 2002; 322(1):137-152. 7,101,976 B1 9/2006 Kilpatricket al. 7,192,698 B1 3/2007 Kinch et al. (Continued) 7,479,368 B2 1/2009 Brown et al. 7,485.420 B2 2/2009 Markowitz Primary Examiner Christopher HYaen 7,507,418 B2 3/2009 Atkinson et al. (74) Attorney, Agent, or Firm Mueting Raasch & Gebhardt, 2004/0028685 A1 2/2004 Kinch et al. P.A. 2004/009 1486 A1 5, 2004 Kinch et al. (57) ABSTRACT 2005, 0147593 A1 7, 2005 Kinch 2005. O152899 A1 7, 2005 Kinch et al. Low molecular weight protein tyrosine phosphatase (LMW 2005. O153923 A1 7, 2005 Kinch PTP) is identified as a novel diagnostic and therapeutic target 2005, 0169931 A1 8, 2005 Kinch et al. in cancer diagnosis, prognosis and treatment. The invention 2006, OO88541 A1 4/2006 Kinch et al. 2006/0093608 A1 5, 2006 Kinch provides diagnostic and treatment methods useful in connec 2007, OO86943 A1 4/2007 Kinch et al. tion with cancers expressing LMW-PTP and, optionally, 2008.00899.31 A1 4, 2008 Kinch EphA2 receptor. Also provided is a screening method that utilizes changes in the amount and/or activity of LMW-PTP FOREIGN PATENT DOCUMENTS to identify candidate cancer therapeutic agents that effec tively target the oncoprotein EphA2. EP 1242060 B1 5, 2006 EP 16957 O2 A2 8, 2006 15 Claims, 22 Drawing Sheets US 7,662,770 B2 Page 2 OTHER PUBLICATIONS Gilardi-Hebenstreitet al., “An Eph-related Receptor Protein Tyrosine Kinase Gene Segmentally Expressed in the Developing Mouse Andres et al., “Expression of Two Novel eph-related Receptor Pro Hindbrain.” Oncogene, Dec. 1992;7(12):2499-2506. tein Tyrosine Kinases in Mammary Gland Development and Gustafson et al., “Solution Structure of the Low Molecular Weight Carcinogenesis.” Oncogene, May 1994:9: 1461-1467. Protein Tyrosine Phosphatase From Tritrichomonas foetus Reveals a Arakawa et al., “Genomic Organization of the Klebsiella Flexible Phosphate Binding Loop.” Protein Sci., Oct. 2005; pneumoniae cps Region Responsible for Serotype K2 Capsular 14(10):2515-2525. Polysaccharide Synthesis in the Virulent Strain Chedid.” J. Heinrikson, "Purification and Characterization of a Low Molecular Bacteriol. Apr. 1995; 177(7):1788-1796. 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Chernoff et al., “A Major Phosphotyrosyl-Protein Phosphatase from Kinch, Michael, “EphA2—A Marker of Breast Cancer Progression.” Bovine Heart is Associated with a Low-Molecular-Weight Acid Grant Abstract, Grant No. 5R21CA85615-02 online. National Can Phosphatase.” Arch. Biochem. Biophy's. Jul. 1985:240(1):135-145. cer Institute, project dates Apr. 1, 2000 to Mar. 31, 2002 retrieved Chiaraugi et al., “The Src and Signal Transducers and Activators of Sep. 22, 2006). Retrieved from the Internet:<URL:http://crisp.cit. Transcription Pathways. As Specific Targets for Low Molecular nih.gov/>; 2 pgs. Weight Phosphotyrosine-protein Phosphatase in Platelet-derived Kinch et al., “Overexpression and Functional Alterations of the Growth Factor Signaling.” J. Biol. Chem. Mar. 20. EphA2 Tyrosine Kinase in Cancer.” Clin. Exp. Metastasis, 1998:273(12):6776-6785. 2003:20(1):59-68. 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