Compositions and methods for the detection and treatment of ...

(54) COMPOSITIONS AND METHODS FOR THE DETECTION AND TREATMENT OF METHYLTHIOADENOSINE PHOSPHORYLASE DEFICIENT CANCERS

(75) Inventor: Lorenzo M. Leoni, San Diego, CA (US)

(73) Assignee: Cephalon, Inc., Frazer, PA (US)

( * ) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days.

(21) Appl. No.: 10/779,476

(22) Filed: Feb. 13, 2004

(65) Prior Publication Data

US 2004/0247600 Al Dec. 9, 2004

Related U.S. Application Data

(60) Provisional application No. 60/460,715, filed on Apr. 4, 2003, provisional application No. 60/447,888, filed on Feb. 14, 2003.

(51) Int. CI.

C07K16/00 (2006.01)
C07K16/18 (2006.01)

(52) U.S. CI 530/187.1; 530/388.1

(58) Field of Classification Search 530/387.1,

530/350, 388.1 See application file for complete search history.

(56) References Cited

U.S. PATENT DOCUMENTS

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OTHER PUBLICATIONS

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Nobori, T., et al., Absence of Methylthioadenosine Phosphorylase in Human Gliomas, Cancer Research, 51(6):3193-3197 (1991). Ragione, F.D., et al., Physicochemical and Immunological Studies on Mammalian 5'-Deoxy-5'-methylthioadenosine Phosphorylase, The Journal of Biological Chemistry, 265(ll):6241-4246 (1990). Tanimoto, T., et al., Evaluation of Antibodies Reactive with Porcine Lymphocytes and Lymphoma Cells in Formaliin-Fixed, ParaffinEmbedded, Antigen-Retrieved Tissue Sections, AJVR, 57(6):853859 (1996).

Cairns, P, et al., Frequency of homozygous deletion at pl6/CDKN2 in primary human tumours, Nature Genetics, 11:210-12 (1995). Carrera, C.J., et al., Toxicity of L-alanosine to MTAP-deficient cells: Selective treatment strategy for cancer with CDKN2 deletion, Proceedings of the American Association for Cancer Research, vol. 37, Abstract No. 2775 (1996).

Chen, Z.H., et al., Expression of methylthioadenosine phosphorylase cDNA in pl6, MTAP malignant cells: restoration of methylthioadenosine phosphorylase-dependent salvage pathways and alterations of sensitivity to inhibitors of purine de novo synthesis, Molecular Pharmacology, 52:903-911 (1997). Christopher, S.A., et al., Methylthioadenosine phosphorylase, a gene frequently codeleted with pl6cdkN2a/ARF, acts as a tumor supressor in a breast cancer cell line, Cancer Research, 62:66396644 (2002).

Efferth, T., et al., Methylthioadenosine phosphorylase as target to chemoselective treatment of T-cell acute lymphoblastic leukemic cells, Blood Cells, Molecules and Disease, 28(l):47-56 (2002). Fitchen, J.H., et al., Methylthioadenosine phosphorylase deficiency in human leukemias and solid tumors, Cancer Research, 46:54095412 (1986).

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(Continued)

Primary Examiner—Jeffrey Siew
Assistant Examiner—Lei Yao

(74) Attorney, Agent, or Firm—Pillsbury Winthrop Shaw Pittman LLP

OTHER PUBLICATIONS

Harasawa, H., et al., Chemotherapy targeting methylthioadenosine phosphorylase (MTAP) deficiency in adult T cell leukemia (ATL), Leukemia, 16:1799-1807 (2002).

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Handbook of Immunochemical Staining Methods, 3rd Edition, T. Boenisch, ed., DAKO Corporation, Carpinteria, California, 2001, 68 pages, available at: http://www.ihe.com/books/dako_handbook. pdf.

Kamatani, N., et al., Selective killing of human malignant cell lines deficient in methylthioadenosine phosphorylase, a purine metabolic enzyme, Proc. Natl. Acad. Sci. USA, 78(2): 1219-1223 (1981). Kamb, A., et al., A cell cycle regulator potentially involved in genesis of many tumor types, Science, 264(5157):436-440 (1994). Kohler, G., et al., Continuous cultures of fused cells secreting antibody of predefined specificity, Nature, 256:495-497 (1975). Kohler, G., et al., Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion, Eur. J. Immunol. 6:511-519 (1976).

Nobori, T., et al., Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers, Nature 368:753-756 (1994).

Nobori, T., et al., Methylthioadenosine phosphorylase deficiency in human non-small cell lung cancers, Cancer Research, 53:10981101 (1993).

Olopade, O.I., et al., Construction of a 2.8-megabase yeast artificial chromosome contig and cloning of the human methylthioadenosine phosphorylase gene from the tumor suppressor region on 9p21, Proc. Natl. Acad. Sci. USA, 92:6489-6493 (1995). Qiu, X., et al., Identification and characterization of a C(K/R)TC motif as a common epitope present in all subtypes of hepatis B surface antigen, /. Immunol., 156:3350-3356 (1996). Ragione, F.D., et al., Purification and characterization of recombinant human 5'-methylthioadenosine phosphorylase: Definite identification of coding cDNA, Biochemical and Biophysical Research Communications, 223:514-519 (1996).

Schofield, K., et al., The cell adhesion molecule, E-cadherin, distinguishes mesothelial cells from carcinoma cells in fluids, Cancer (Cancer Cythopathology) 81 (5):293-298 (1997). Toohey, J.I., et al., Methylthio group cleavage from methylthioadenosine. Description of an enzyme and its relationship to the methylthio requirement of certain cells in culture, Biochemical and Biophysical Research Communications, 78(4): 1273-1280 (1977).

* cited by examiner