Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2007-07-25
2010-11-23
Prouty, Rebecca E. (Department: 1657)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C435S015000, C514S312000, C514S617000, C514S316000, C514S399000, C424S009200
Reexamination Certificate
active
07838531
ABSTRACT:
Although it can be farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.
REFERENCES:
patent: 6060038 (2000-05-01), Burns et al.
patent: 6342487 (2002-01-01), Riou et al.
patent: 6737410 (2004-05-01), Doherty et al.
patent: 2002/0044941 (2002-04-01), Rosen et al.
patent: 2002/0098495 (2002-07-01), Burmer et al.
patent: 2003/0119864 (2003-06-01), Gordon et al.
patent: 2003/0125326 (2003-07-01), Rybak
patent: 2004/0110769 (2004-06-01), End
patent: WO 97/30053 (1997-08-01), None
patent: WO 01/64218 (2001-09-01), None
patent: WO 02/04662 (2002-01-01), None
patent: WO 2004/035753 (2004-04-01), None
patent: WO 2006/081444 (2006-08-01), None
patent: WO 2006/128180 (2006-11-01), None
Mounkes et al. The A-Type Lamins: Nuclear Structural Proteins As a Focus for Muscular Dystrophy and Cardiovascular Disease; Trends in Cardiovascular Medicine, vol. 11, No. 7 (2001) pp. 280-285.
Parnaik et al. Laminopathies: Multiple Disorders Arising From Defects in Nuclear Architecture; Journal of Bioscience, vol. 31, No. 3 (2006) pp. 405-421.
Cohen et al. Inhibitors of Prenylation of Ras and Other G-Proteins and Their Application As Therapeutics; Biochemical Pharmacology, vol. 60 (2000) pp. 1061-1068.
Adjei et al., “Comparison of Potential Markers of Farnesyltransferase Inhibition,”Clinical Cancer Res., 6:2318-2325, Jun. 2000.
Adjei et al. “A phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity,”Cancer Research60 (7): 1871-1877, 2000.
Adjei et al. “Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer,”J Clinical Oncology21 (9): 1760-1766, 2003.
Alsina et al. “Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma,”Blood103(9): 3271-3277, May 2004.
Ayral-Kaloustian and Salaski, “Protein Farnesyltransferase Inhibitors,”Current Medical Chemistry9 (10): 1003-1032, 2002.
Basso et al. “Farnesyl transferase inhibitors,”Journal of Lipid Research47: 15-31, 2006.
Beck et al. “Isprenylation is Required for the Processing of the Lamin A Precursor,”Journal of Cell Biology110: 1489-1499, May 1990.
Bonne et al., “Clinical and Molecular Genetic Spectrum of Autosomal Dominant Emery-Dreifuss Muscular Dystrophy due to Mutations of the Lamin A/C Gene,”Annals of Neurology48(2):170-180, Aug. 2000.
Bonne et al., “Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy,”Nature Genetics21(3): 285-288, Mar. 1999.
Burke and Stewart, “Life at the Edge: The Nuclear Envelope and Human Disease,”Molecular Cell Biology—Nature Reviews3:575-585, Aug. 2002.
Capell et al., “Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome,”PNAS102(36): 12879-12884, Sep. 2005.
Cao et al. “A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells,”PNAS104(12): 4949-4954, Mar. 2007.
Cao and Hegele, “LMNAis mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090),”J. Hum. Genet. 48:271-274, 2003.
Chen et al. “LMNA mutations in atypical Werner's syndrome,”Lancet362 (9382): 440-445, 2003.
Cohen et al., “Inhibitors of Prenylation of Ras and Other G-proteins and Their Application as Therapeutics,”Biochem. Pharm., 60:1061-1068, 2000.
Cox and Der, “Farnesyltransferase inhibitors: promises and realities,”Curr. Opin. Pharm. 2:388-393, 2002.
Delahunt et al., “Progeria kidney has abnormal mesangial collagen distribution,”Pediatr. Nephrol. 15:279-285, 2000.
De Sandre-Giovannoli et al., “Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder Type 2) and Mouse,”Am. J. Hum. Genet. 70(3): 726-736, 2002.
De Sandre-Giovannoli, et al., “Lamin A Truncation in Hutchinson-Gilford Progeria,”Science300(4):2055, Jun. 27, 2003.
Eriksson et al., “Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford Progeria Syndrome,”Nature423:293-298, May 15, 2003.
Faivre et al., “Can Hutchinson-Gilford Progeria Syndrome be a Neonatal Condition?”Letter to the Editor—Am. J. Med. Genet. 87:450-452, 1999.
Fisher et al., “cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins,”Proc. Natl. Acad. Sci. USA83:6450-6454, Sep. 1986.
Fong et al., “Heterozygosity forLmnadeficiency eliminates the progeria-like phenotypes inZmpste24-deficient mice,”Proc. Natl. Sci. Acad. USA101(52)18111-18116, Dec. 28, 2004.
Fong et al. “A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria,”Science311(5767); 1621-1623, Published Online Feb. 2006.
Fong et al. “Prelamin A and lamin A appear to be dispensable in the nuclear lamina,”J. Clin. Invest. 116(3): 743-752, Mar. 2006.
Garcia et al., “Peptidomimetic Inhibitors of Ras Farnesylation and Function in Whole Cells,”J. Biol. Chem., 268(25):18415-18418, 1993.
Genschel et al., “Mutations in the LMNA Gene Encoding Lamin A/C,”Human Mutation16(6): 451-459, 2000.
Glynn et al. “Incomplete processing of mutant lamin A in Hutchinson-Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition,”Human Molecular Genetics14(20): 2959-2969, 2005.
Goldman et al., “Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome,” 101(24):8963-8968, Jun. 15, 2004.
Ha et al., “Cardiovascular Findings of Hutchinson-Gilford Syndrome—A Doppler and two-dimensional Echocardiographic study--,”Yonset Med. J. 34(4):352-355, 1993.
Hegele, “Premature Atherosclerosis Associated with Monogenic Insulin Resistance,”Circulation103(18): 2225-2229, 2001.
Hegele et al., “Common Genomic Variation in LMNA Modulates Indexes of Obesity in Inuit,”J Clinical Endocrinology and Metabolism86(6): 2747-2751, 2001.
Henig, “Racing with Sam,”The New York Times Magazine, 46-51, Jan. 30, 2005.
Hoeffel et al., “Mandibulo-acral dysplasia,”Skeletal Radiol. 29:668-671, 2000.
Hoover et al., “Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336,”Blood, 100(3):1068-1071, Aug. 1, 2002.
Huang et al. “Correction of cellular phenotypes of Hutchinson-Gilfor
Capell Brian C.
Collins Francis S.
Cox Adrienne D.
Der Channing J.
Glover Thomas
Klarquist Sparkman LLP.
Martin Paul C
Progeria Research Foundation, Inc.
Prouty Rebecca E.
The Regents of the University of Michiga
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