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(12) United States Patent (10) Patent No.: US 6,599,912 B1 Au Et Al

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(12) United States Patent (10) Patent No.: US 6,599,912 B1 Au Et Al USOO65999 12B1 (12) United States Patent (10) Patent No.: US 6,599,912 B1 Au et al. (45) Date of Patent: Jul. 29, 2003 (54) METHODS AND COMPOSITIONS FOR Rubio, Eur, J Cancer 31:244-251, 1995. MODULATING CELL PROLIFERATION AND Small, et al., J. Clin Onc., 18:1440–1450, 2000. CELL DEATH Soliven, et al., Muscle & Nerve, 20:83-91, 1997. (76) Inventors: Jessie L. -S. Au, 2287 Palmleaf Ct., Sturla, et al., Clin. Cancer Res. (Supp), 5:43, 1999. Columbus, OH (US) 43235; Guillaume Swain, et al., Invest. New Drugs 13:55-62, 1995. Wientjes, 2287 Palmleaf Ct., Tu, et al., Clin. Cancer Res., 4:1193–1201, 1998. Columbus, OH (US) 43235 Wang, et al., Cancer Res., 57:1750–1757, 1997. Wang, et al., Exper. Cell Res., 238:177-187. 1998. (*) Notice: Subject to any disclaimer, the term of this Westermann, et al., Cancer Chemother. Pharmacol., patent is extended or adjusted under 35 46:57–62, 2000. U.S.C. 154(b) by 0 days. Wellstein, et al., J. Natl. Cancer Inst., 83:716–720, 1991. Wild, et al., Microvasc. Res., 59:368-376, 2000. (21) Appl. No.: 09/587,559 Motzer, et al., Cancer Res., 2:5775–5779, 1992. (22) Filed: Jun. 5, 2000 Motzer, et al., Cancer, 72:33.13–3317, 1993. Myers, et al., J. Clin. Onc., 10:881–889, 1992. Related U.S. Application Data Nguyen, et al., Anticancer Res., 13:2143-2148, 1993. (60) Provisional application No. 60/187,445, filed on Mar. 7, PDQ Clinical Trial Database (http://www.nci.nih.gov). 2000, provisional application No. 60/172,031, filed on Dec. 23, 1999, provisional application No. 60/165.983, filed on Ramirez, et al., Invest. New Drugs, 13:51–53, 1995. Nov. 17, 1999, and provisional application No. 60/137,345, Rapoport, et al., Ann. Onc., 4:567-573, 1993. filed on Jun. 3, 1999. Reed, et al., Eur. J. Cancer, 28A:864-866, 1992. (51) Int. Cl." ................................................ A61K 31/44 Robbins, et al., Arch. Otolaryngol. Head Neck Surg., (52) U.S. Cl. ....................... 514/283; 514/553; 514/597; 120:288–292, 1994. 514/119, 514/171; 424/130.1 Rosen, et al., Cancer Surv., 23:231-234, 1995. (58) Field of Search ............................. 514/4, 119, 171, Rosen, et al., J. Clin. Onc., 14:1626-1636, 1996. 514/553,597, 283; 530/388.22,387.9, 395; Laohavini, et al, Lung Cancer, 26:175-185, 1999. 424/130.1, 185.1 Larocca, et al., Ann. Onc., 3:571-573, 1992. (56) References Cited (List continued on next page.) U.S. PATENT DOCUMENTS Primary Examiner Mary E. Mosher ASSistant Examiner Misook Yu 5,102,870 A 4/1992 Florine et al. ................ 514/12 5,252,718 A * 10/1993 Baird et al. (74) Attorney, Agent, or Firm Mueller and Smith, LPA 5,486,509 A 1/1996 Jimenez et al. ............. 514/167 (57) ABSTRACT 5,574,026 A 11/1996 Backer et al. .............. 514/152 5,597.830 A 1/1997 Kilohs Methods and compositions for modulating the FGF effect on 5,716,981 A 2/1998 Hunter et al. ............... 514/449 the Sensitivity of malignant and normal cells to anticancer 5,767,110 A 6/1998 Klohs et al. ......... ... 514/119 agents are provided. In particular, methods and composi 5,783,568 A 7/1998 Schlessinger et al.......... 514/53 tions for inhibiting FGF-induced resistance to a broad Spec 6,013.477 A 1/2000 Greene et al. ............. 435/69.1 trum of anticancer agents in Solid and Soft-tissue tumors, FOREIGN PATENT DOCUMENTS metastatic lesions, leukemia and lymphoma are provided. Preferably, the compositions include at least one FGF inhibi EP O 455 422 A2 6/1991 tor in combination with a cytotoxic agents, e.g., antimicro WO WO9934796 7/1999 tubule agents, topoisomerase I inhibitors, topoisomerase II WO WO9960O23 11/1999 inhibitors, antimetabolites, mitotic inhibitors, alkylating WO WO9965515 12/1999 agents, intercalating agents, agents capable of interfering OTHER PUBLICATIONS with a signal transduction pathway (e.g., g., a protein kinase Kiefer et al., 1990, Biochemistry, 87:6985–6989.* C inhibitor, e.g., an anti-hormone, e.g., an antibody against Kato, et al., Cancer Research, 54:5143-5147.* growth factor receptors), an agent that promotes apoptosis Kano, et al., Biotherapy, 10:530-532.* and/or necrosis, and interferon, an interleukin, a tumor Falcone, et al., Tumori, 84.666-668.* necrosis factor, and radiation. Pesenti, et al., Br. J. Cancer, 66:367-372.* In other embodiments, methods and composition for pro Fujimoto, et al., 1997, Cancer Letters, 113:187-194.* tecting a cell in a Subject, from one or more of killing, Stein, et al., 1989, J. Clin Oncol, 7(4):499-508.* inhibition of growth or division or other damage caused, Takano, et al., Cancer Research, 54.2654-2660.* e.g., by a cytotoxic agent, are provided. Preferably, the Woll, et al., Ann. Onc., 5:597–600, 1994. method includes: administering, to the Subject, an effective Yamaoka, et al., Cancer Res., 53:5233–5236, 1993. amount of at least one FGF agonist, thereby treating the cell, Zhang, et al., J. Pharmacol. Exp. Therap., 299:426-433, e.g., protecting or reducing the damage to the dividing cell 2001. from Said cytotoxic agent. Zhou and Sorrero, Growth Factors, 9:123-131, 1993. Zugmaier, et al., Ann. NY Acad. Sciences, 886:243-248, 1999. 40 Claims, 7 Drawing Sheets US 6,599.912 B1 Page 2 OTHER PUBLICATIONS Danilenko DM, et al. Keratinocyte growth factor is an important endogenous mediator of hair follicle growth, Lawrence, et al., Clin. Cancer Res., 3:1713–1720, 1997. development, and differentiation. Normalization of the Lopez, et al., Eur. J. Cancer, 30:1549, 1994. nu/nu follicular differentiation defect and amelioration of Lush, et al., Ann. Onc., 7:939–944, 1996. chemotherapy-induced alopecia. Am J Pathol. Jul. Ma, et al., Cancer Res., 61:5491-5498, 2001. 1995;147(1):145–54. Matsuzaki, et al., Proc Natl. Acad. Sci. USA, 86:9911-9915, Davol PA, et al. Combining Suramin and a chimeric toxin 1989. directed to basic fibroblast growth factor receptors increases Mcleskey, et al., Br. J. Cancer 73:1053-1062, 1996. therapeutic efficacy against human melanoma in an animal Miglietta, et al., J. Cancer Res. Clin. Onc., 23:407-410, model. Cancer. Nov. 1, 1999;86(9): 1733–41. 1997. Ding I, et al. Acidic fibroblast growth factor (FGF1) Mirza, et al., Acta Oncologica, 36:171-174, 1997. increases Survival and haematopoietic recovery in total body Mitchen, et al., Prostate, 22:75-89, 1993. irradiated C3H/HeNCr mice. Cytokine. Jan. Hussain, et al., J. Clin. Onc., 18:1043–1049, 2000. 1997;9(1):59-65. Hutson, et al., Clin. Cancer Res., 4:1429-1436, 1998. Ding I, et al. Radioprotection of hematopoietic tissue by Kehinde, et al., Cancer Surv., 23:217-229, 1995. fibroblast growth factors in fractionated radiation experi Kelly, et al., J. Clin. Onc., 13:2208–2213, 1995. ments. Acta Oncol. 1997;36(3):337–40. Kerbel, Carcinogenesis, 21:505-515, 2000. Ding I, et al. Tumor growth and tumor radioSensitivity in Kobayashi, et al., J. Clin. Onc., 13:2196-2207, 1995. mice given myeloprotective doses of fibroblast growth fac Konig, et al., Leukemia, 11:258-265, 1997. tors. J Natl Cancer Inst. Oct. 2, 1996;88(19): 1399–404. Kubota, et al., Clin. Cancer Res., 1:1537-1543, 1995. Daoud, et al. Potentiation of camptothecin-induced cyto Kuratsu, et al., Anticancer Res., 15:1263-1268, 1995. toxicity by a monoclonal antibody against bFGB receptor in Langer, et al., J. Clin. Onc., 13:1860–1870, 1995. human breast cancer and endothelial cells. Proceedings of Langer, et al., Eur. J. Cancer, 36:183-193, 2000. the American ASSociation for Cancer Research Annual Falcone, et al, Cancer 75:440-443, 1995. Meeting 1995; 36: 427. Falcone, et al., Tumori 84:666–668, 1998. Falcone A, et al. Suramin in combination with weekly Falcone, et al., Cancer, 85:470-476, 1999. epirubicin for patients with advanced hormone-refractory Fenig, et al., Clin. Cancer Res., 3:135-142, 1997. prostate carcinoma. Cancer. Aug. 1, 1999;86(3):470-6. Fenig, et al., J. Cancer Res. Clin. Oncol, 125:556-562, 1999. Falcone A, et al. Synergistic antiproliferative activity of Folkman, In: Cancer: Principles and Practice of Oncology. Suramin and alpha 2A-interferon against human colorectal Fifth Edition, Eds. Devita, Hellman and Rosenberg, 1997, adenocarcinoma cell lines: in vitro Studies. Eur J Cancer. pp. 3075-3085. 1994:30A(4):516–20. Furukawa, et al., Clin. Cancer Res., 1:305-311, 1995. Falcone A, et al. Suramin in patients with metastatic col Garcia-Schurmann, et al., Urology, 53:535-541, 1999. orectal cancer pretreated with fluoropyrimidine-based che Gradishar, et al., Oncology, 58:324-333, 2000. motherapy. A phase II Study. Cancer. Jan. 15, Grossman, et al., J. Clin. Onc., 19:3260-3266, 2001. 1995;75(2):440-3. Helsing, et al., Lung Cancer, 24:107-113, 1999. Falcone A, et al. Suramin in combination with 5-fluorouracil Abdiu, et al, Cancer Letters, 146:189-194, 1999. (5-FU) and leucovorin (LV) in metastatic colorectal cancer Bhargava, et al., Clin. Cancer Res., 5:1989–1995, 1999. patients resistant to 5-FU--LV-based chemotherapy. Bowden, et al., Cancer Chemother. Pharmacol., 39:1-8, Tumori. Nov.-Dec. 1998;84(6):666-8. 1996. Fenig E, et al. Basic fibroblast growth factor potentiates Cardinali, et al., J. Clin Invest., 89:1242–1247, 1992. cisplatinum-induced cytotoxicity in MCF-7 human breast Dawson, et al., Cancer, 76:453-462, 1995. cancer cells. J Cancer Res Clin Oncol. Oct. Dawson, et al., Clin.
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