(12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb

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(12) United States Patent (10) Patent No.: US 7,662,770 B2 Kinch (45) Date of Patent: Feb 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. Parket al., “Low-molecular-weight protein tyrosine phosphatase is a (22) PCT Filed: May 22, 2003 positive component of the fibroblast growth factor receptor signaling pathway.” May 15, 2002 Molecular and Cellular Biology (86). PCT No.: PCT/USO3A16269 22(10):3404-3414. Souza et al., “From immune response to cancer: a spot on the low S371 (c)(1), molecular weight protein tyrosine phosphatase.” Apr. 2009 Cellular (2), (4) Date: Aug. 11, 2005 and Molecular Life Sciences 66(6):1140-1153. Available online on Nov. 11, 2008. (87) PCT Pub. No.: WO03/0993 13 Supplementary European Search Report mailed Jun. 8, 2009, for EP Application No. 03734142.7 (3 pgs). PCT Pub. Date: Dec. 4, 2003 Cann, "Genetic clues to dispersal in human populations: retracting the past from the present.” Mar. 2, 2001 Science 291: 1742-1748. O O Garcia-Closas et al., “Collection of genomic DNA from adults in (65) Prior Publication Data epidemiological studies by buccal cytobrush and mouthwash.” Jun. 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. Available online at Journal Weight Acid Phosphatase from Bovine Liver.” J. Biol. Chem. of Bacteriology retrieved Oct. 25, 2006). Retrieved from the 1969:244(2):299-307. Available online at JBC Online retrieved Oct. Internet:<URL:http://b.asm.org/cgi/reprint/177/7/1788>; 9 pgs. 25, 2006). Retrieved from the Internet:<URL:http://www.jbc.org/ Boivin et al., “The Human Red Cell Acid Phosphatase Is a cgi/reprint/244/2/299>; 9 pgs. Phosphotyrosine Protein Phosphatase Which Dephosphorylates the Hesset al., “Molecular Regulation of Tumor Cell Vasculogenic Mim Membrane ProteinBand 3.” Biochem. Biophys. Res. Commmun., Jan. icry by Tyrosine Phosphorylation: Role of Epithelial Cell Kinase 29, 1986; 134(2):557-564. (Eck/EphA2).” Cancer Res, Apr. 15, 2001:61(8):3250-3255. Bugert et al., “Characterization of the aims 1 Gene Product as a Low Hirai et al., “A Novel Putative Tyrosine Kinase Receptor Encoded by Molecular Weight Acid Phosphatase Controlling Exopolysaccharide the eph Gene.” Science, Dec. 18, 1987:238(4834): 1717-1720. Synthesis of Erwinia amylovora,” FEBS Lett., Jan. 1997:400(2):252 Huang et al., “HCPTPA, a Protein Tyrosine Phosphatase That Regu 256. lates Vascular Endothelial Growth Factor Receptor-Mediated Signal Brackenbury, “Control of Carcinoma Cell Motility by E-Cadherin.” Transduction and Biological Activity.” J. Biol. Chem. Dec. 31. Abstract and Final Report, Grant No. DAMD 17-98-1-8292; United 1999:274(53):38183-38188. States Army Medical Research and Material Command Grant, Jacob et al., “A Receptor Tyrosine Kinase, UFO/Axl, and Other project dates Aug. 1, 1998 to Jul. 31, 2002 retrieved on Jun. 7, 2007). Genes Isolated by a Modified Differential Display PCR Are Retrieved from the Internet:<URL:http://stinet.dtic.mil/oai?oai? Overexpressed in Metastatic Prostatic Carcinoma Cell Line DU145.” &verb-getRecord&metadataPrefix=html Cancer Detect Prev., 1999:23(4):325-332. &identifier=ADA409404; 31 pgs. Kikawa et al., “Regulation of the EphA2 Kinase by the Low Molecu Caselli et al., “The Inactivation Mechanism of Low Molecular lar Weight Tyrosine Phosphatase Induces Transformation.” J. Biol. Weight Phosphotyrosine-protein Phosphatase by H.O.” J. Biol. Chem. Oct. 18, 2002:277(42):39274-39279; electronically pub Chem. Dec. 4, 1998; 273(49): 32554-32560. Available online at JBC lished Aug. 6, 2002. Online retrieved Oct. 25, 2006. Retrieved from the Kinch et al., “Tyrosine Phosphorylation Regulates the Adhesions of Internet:<URL:http://www.jbc.org/cgi/reprint/273/49/325542; 7 Ras-Transformed Breast Epithelia.” J. Cell Biol. Jul. pg.S. 1995; 130(2):461-471. 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. Clarket al., “Overexpression of the Ras-related TC21/R-Ras2 Pro Kinch et al., “Predictive Value of the EphA2 Receptor Tyrosine tein May Contribute to the Development of Human Breast Cancers.” Kinase in Lung Cancer Recurrence and Survival.” Clin. Cancer Res., Oncogene, 1996 12(1): 169-176. Feb. 2003:9(2):613-618. Corden et al. “Low Molecular Weight Phosphatase.” Abstract, p. 20 Lindberg et al., “cDNA Cloning and Characterization of eck, an of Project Detail, General Basic Research in the Walther Cancer Epithelial Cell Receptor Protein-Tyrosine Kinase in the eph/elk Fam Center of Excellence online).
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