US008O39240B2 (12) United States Patent (10) Patent No.: US 8,039,240 B2 Roiz et al. (45) Date of Patent: Oct. 18, 2011 (54) RECOMBINANT HUMAN T2 RNASE AND 5,281.521 A 1/1994 Trojanowski et al. USES THEREOF 5,786.457 A 7, 1998 Nett et al. 6,590,075 B2 7/2003 Ruben et al. 7,101,839 B1 9, 2006 Roiz et al. (75) Inventors: Levava Roiz, Givat-Shmuel (IL); Betty 2005/O113327 A1 5/2005 Roiz et al. Schwartz, Rechovot (IL); Patricia 2008, OO13419 A1 1/2008 Lee et al. Smirnoff, Rehovot (IL); Oded Shoseyov, Karme Yossef (IL) FOREIGN PATENT DOCUMENTS AU T69011 3, 2001 EP 1207 755 5, 2002 (73) Assignee: Yissum Reseach Development WO WO99,33981 7, 1999 Company of the Hebrew University of WO WOO1/15531 8, 2001 Jerusalem, Jerusalem (IL) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this Smirnoff et al., Cancer 107(12):2760-2769; 2006.* patent is extended or adjusted under 35 Garret et al., European Journal of Cancer 35(14): 2010-2030, 1999.* U.S.C. 154(b) by 834 days. 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CI2O I/44 (2006.01) Bradford "A Rapid and Sensitive Method for the Quantitation of CI2N 9/16 (2006.01) Microgram Quantities of Protein Utilizing the Principle of Protein CI 2N 9/22 (2006.01) Dye Binding”. Analytical Biochemistry, 72: 248-254, 1976. CO7K (4/OO (2006.01) Yokota et al. “Isolation and Characterization of Plant Myosin From Pollen Tubes of Lily”. Protoplasma, 177: 153-162, 1994. (52) U.S. C. ......... 435/196; 424/94.6:435/199: 435/19; Lin et al. “Characterization of the Mechanism of Cellular and Cell 530/350 Free Protein Synthesis Inhibition by an Anti-Tumor Ribonuclease'. (58) Field of Classification Search .................. 435/196, Biochemical and Biophysical Research Communications, 204(1): 435/199, 19; 424/94.6; 530/350 156-162, 1994. See application file for complete search history. (Continued) (56) References Cited Primary Examiner — Delia Ramirez U.S. PATENT DOCUMENTS (57) ABSTRACT 3,791932 A 2f1974 Schuurs et al. 3,839,153 A 10, 1974 Schuurs et al. The cloning and heterologous expression of human T2 3,850,578 A 11/1974 McConnell RNase6PL are disclosed. Further disclosed are methods for 3,850,752 A 11/1974 Schuurs et al. preventing, inhibiting and/or reversing cell motility, actin 3,853.987 A 12/1974 Dreyer 3,867,517 A 2/1975 Ling filament assembly or disassembly, proliferation, coloniza 3,879,262 A 4, 1975 Schuurs et al. tion, differentiation, accumulation and/or development of 3,901,654 A 8, 1975 Gross abnormal cells in a subject is disclosed. The methods are 3,935,074 A 1/1976 Rubenstein et al. effected by administering to the subject a therapeutically 3,984,533 A 10/1976 Uzgiris effective amount of a RNase6PL ribonuclease or close homo 3.996,345 A 12/1976 Ullman et al. 4,034,074 A T. 1977 Miles logues thereof. 4,098,876 A 7, 1978 Piasio et al. 4,879,219 A 11, 1989 Wands et al. 5 Claims, 49 Drawing Sheets 5,011,771 A 4, 1991 Bellet et al. 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