Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving transferase
Reexamination Certificate
2005-08-30
2005-08-30
Gitomer, Ralph (Department: 1651)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving transferase
C435S193000, C435S815000
Reexamination Certificate
active
06936431
ABSTRACT:
Disclosed are methods and compositions for the identification, characterization and inhibition of farnesyl protein transferases, enzymes involved in the farnesylation of various cellular proteins, including cancer related ras proteins such as p21ras. One farnesyl protein transferase which is disclosed herein exhibits a molecular weight of between about 70,000 and about 100,000 upon gel exclusion chromatography. The enzyme appears to comprise one or two subunits of approximately 50 kDa each. Methods are disclosed for assay and purification of the enzyme, as well as procedures for using the purified enzyme in screening protocols for the identification of possible anticancer agents which inhibit the enzyme and thereby prevent expression of proteins such as p21ras. Also disclosed is a families of compounds which act either as false substrates for the enzyme or as pure inhibitors and can therefore be employed for inhibition of the enzyme. The most potent inhibitors are ones in which phenylalanine occurs at the third position of a tetrapeptide whose amino terminus is cysteine.
REFERENCES:
patent: 5026554 (1991-06-01), Bartizal et al.
patent: 5043268 (1991-08-01), Stock
patent: 5055487 (1991-10-01), Bartizal et al.
patent: 5104975 (1992-04-01), McCormick et al.
patent: 5141851 (1992-08-01), Brown et al.
patent: 5185248 (1993-02-01), Barbacid et al.
patent: 5202456 (1993-04-01), Rando
patent: 5234839 (1993-08-01), McCormick et al.
patent: 5238922 (1993-08-01), Graham et al.
patent: 5245061 (1993-09-01), Singh
patent: 5420245 (1995-05-01), Brown et al.
patent: 5532359 (1996-07-01), Marsters et al.
patent: 5843941 (1998-12-01), Marsters, Jr. et al.
patent: 5962243 (1999-10-01), Brown et al.
patent: 5976851 (1999-11-01), Brown et al.
patent: 6083917 (2000-07-01), Brown et al.
patent: 0 456 180 (1991-11-01), None
patent: 0 461 869 (1991-12-01), None
patent: 0 520 823 (1992-12-01), None
patent: 0 523 873 (1993-01-01), None
patent: 0 528 486 (1993-02-01), None
patent: 0 535 730 (1993-04-01), None
patent: 0 535 731 (1993-04-01), None
patent: 2 261 373 (1993-05-01), None
patent: 2 261 374 (1993-05-01), None
patent: 2 261 375 (1993-05-01), None
patent: WO 91/16340 (1991-10-01), None
Reiss, Y. Inhibition of Purified p21ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides. Cell 62(1)81-88, Jul. 13, 1990.
Barbacis and Manne vs. Brown et al., “Final Decision on Remand from the Federal Circuit,” Interference No. 103,586, Paper No. 141, mailed Sep. 28, 2004.
Clarke et al., “Posttranslational modification of the Ha-ras oncogene protein: Evidence for a third class of protein carboxyl methyltransferases,”Proc. Natl. Acad. Sci. USA, 85:4643-4647, 1988.
Hancock et al., “All ras Proteins Are Polyisoprenylated but Only Some Are Palmitoylated,”Cell, 57:1167-77, 1989.
Schafer et al., “Genetic and Pharmacological Suppression of Oncogenic Mutations in RAS Genes of Yeast and Humans,”Science, 245:379-385, 1989.
Bos, “ras Oncogenes in Human Cancer: A Review,”Cancer Research, 49:4682-4689, 1989.
Lowy et al., “New Clue to Ras lipid glue,”Nature, 341:384-85, 1989.
Casey et al., “p21ras is modified by a farnesyl isoprenoid,”Proc. Natl. Acad. Sci. USA, 86:8323-8327, 1989.
Goldstein et al., “Regulation of the mevalonate pathway,”Nature, 343:425-430, 1990.
Schaber et al., “Polyisoprenylation of Ras in Vitro by a Farnesyl-Protein Transferase,”J.of Biol. Chem., 265:14701-14704, 1990.
Manne et al. “Identification and preliminary characterization of protein-cysteine farnesyltransferase,”Proc. Natl. Acad. Sci. USA, 87:7541-7545, 1990.
Reiss et al., “Inhibition of Purified p21ras Farnesyl:Protein Transferase by Cys-AAX Tetrapeptides,”Cell, 62:81-88, 1990.
Reiss et al., “Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase,”Proc. Natl. Acad. Sci. USA, 88:732-736, 1991.
Chen, et al., “cDNA Cloning and Expression of the Peptide-Binding βSubunit of Rat p21ras Farnesyltransferase, the Counterpart of Yeast DPR1/RAM1,”Cell, 66:327-334, 1991.
Goldstein, et al., “Nonfarnesylated Tetrapeptide Inhibitors of Protein Farnesyltransferase,”J. Biol. Chem., 266(24):15575-15578, 1991.
Goodman, et al., “Structure and Expression of Yeast DPR1, a Gene Essential for the Processing and Intracellular Localization of ras Proteins,”Yeast, 4:271-281, 1988.
Goodman, et al., “Mutants ofSaccharomyces cerevisiaedefective in the farnesylation of Ras proteins,”Proc. Natl. Acad. Sci. USA, 87:9665-9669, 1990.
Schaber, et al., “Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase,”Chem. Abstr., 114:302, Abstract # 38170r, 1991.
Kim, et al., “Prenylation of mammalian Ras protein in Xenopus oocytes,”Chem. Abstr., 114:373, Abstract # 3711r, 1991.
Kohl et al., “Structural Homology among Mammalian andSaccharomyces cerevisiaeIsoprenyl-protein Transferases,”J. Biol. Chem., 266(28):18884, 1991.
He et al., “RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins,”Proc. Natl. Acad. Sci. USA, 88:11373-11377, 1991.
Reiss, et al., “Divalent Cation and Prenyl Pyrophosphate Specificaties of the Protein Farnesyltransferase from Rat Brain, a Zinc Metalloenzyme,”J. Biol. Chem., 267:6403-6408, 1992.
Seabra, et al., “Protein Farnesyltransferase and Geranylgeranyl transferase Share a Common α Subunit,”Cell, 65:429-434, 1991.
Reiss, et al., “Purification of ras Farnesly:Protein Transferase,”Methods: A Companion to Methods in Enzymology, 1(3):241-245, 1990.
Brown Michael S.
Goldstein Joseph L.
Reiss Yuval
Board of Regents , The University of Texas System
Fulbright & Jaworski L.L.P.
Gitomer Ralph
LandOfFree
Methods and compositions for inhibiting farnesyl transferase... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and compositions for inhibiting farnesyl transferase..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for inhibiting farnesyl transferase... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3479105