Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2007-07-03
2007-07-03
Kifle, Bruck (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C540S461000
Reexamination Certificate
active
09937192
ABSTRACT:
Bifunctional molecules comprising two hsp-binding moieties which bind to hsp90 in the pocket to which ansamycin antibiotics bind connected via a linker are effective for inducing the degradation and/or inhibition of HER-family tyrosine kinases. For example, a compound of two geldanamycin moities joined by a four-carbon linker provides selective degradation of HER-family tyrosine kinases, without substantially affecting other kinases. These compounds can be used for treatment of HER-positive cancers with reduced toxicity, since these compounds potently kill cancer cells but affect fewer proteins than geldanamycin.
REFERENCES:
patent: 4261989 (1981-04-01), Sasaki et al.
patent: 5650430 (1997-07-01), Sugimura et al.
patent: 5932566 (1999-08-01), Schnur et al.
patent: 5968921 (1999-10-01), Gold
patent: 6239168 (2001-05-01), Ino et al.
Munster et al., “Inhibition of Heat Shock Protein 90 Function by Ansamycins Causes the Morphological and Functional Differentiation of Breast Cancer Cells”,Cancer Research. Apr. 1, 2001, vol. 61, pp. 2945-2952.
Schulte et al., “The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin”,Cancer Chemotherapy and Pharmacology, 1998, vol. 42, pp. 273-279.
Bohen, S.P., “Genetic and Biochemical Analysis of p23 and Ansamycin Antibiotics in the Function of HSP90-Dependent Signaling Proteins”,Molecular and Cellular Biology, Jun. 1998, vol. 18, No. 6, pp. 3330-3339.
Pratt, W.B., “The hsp90-based Chaperone System: Involvement in Signal Transduction from a Variety of Hormone and Growth Factor Receptors”, Proceedings of the Society for Experimental Biology and Medicine, Apr. 1998, vol. 217, No. 4, pp. 420-434.
Scheibel, et al., “Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence”, Proceedings of the National Academy of Sciences of the USA, Feb. 17, 1998, vol. 95, No. 4, pp. 1495-1499.
Chen, et al., “The Ah Receptor is a Sensitive Target of Geldanamycin-Induced Protein Turnover”,Archives of Biochemistry and Biophysics, Dec. 1, 1997, vol. 348, No. 1, pp. 190-198.
Landel, et al., “Estrogen Receptor Accessory Proteins Augment Receptor-DNA Interaction and DNA Bending”,The Journal of Steroid Biochemistry&Molecular Biology, vol. 63, No. 1-3, pp. 59-73.
Bamberger, et al., “Inhibition of Mineralocorticoid and Glucocorticoid receptor function by the heat shock protein 90-binding agent geldanamycin”,Molecular and Cellular Endocrinology, Aug. 8, 1997, vol. 131, No. 2, pp. 233-240.
Segnitz, et al., “The Function of Steroid Hormone Receptors s Inhibited by the hsp90-specific Compound Geldanamycin”,The Journal of Biological Chemistry, Jul. 25, 1997, vol. 272, No. 30, pp. 18694-18701.
Hurst, S. et al., “HSP90 inhibitors block the mitotic checkpoint and are synergistically toxic with spindle poisons”,Clinical Cancer Res., Nov. 1999, vol. 8, p. 3788s, #293.
Kherfellah, d. et al, “Effect of the combination of topoisomerase I and topoisomerase II inhibitors on rat glioblastoma cells and drug-resistant variants”,Pharmacol. Experimental Therapeutics, Mar. 1999, vol. 40, p. 109, #724.
Stebbins, c. E. et al, “Crystal structure of the Hsp90-Geldanamycin complex: targeting of a protein chaperone by an antitumor agent”,Cell, Apr. 1997, vol. 89, pp. 239-240 and 246-248.
Rosenhagen, M. C. et al, “Synergistic inhibition of the Glucocorticoid receptor by radicicol and benzoquinone ansamycins”,Biol. Chem., Mar. 2001, vol. 382, pp. 499-504.
Chavany et al. “p185crbB2Binds to GRP94 in Vivo”, Journal of Biological Chemistry, vol. 271, No. 9 Mar. 1, 1996, pp. 4974-4977.
Neckers, “Effects of Geldanamycin and Other Naturally Occurring Small Molecule Antagonists of Heat Shock Protein 90 on HER2 Protein Expression”, Breast Disease 11 (2000) 49-59. pp. 49-59.
Schnur, et al. “erbB-2 Oncogene Inhibition by Geldanamycin Derivatives: Synthesis, Mechanism of Action, and Structure—Activity Relationships”, J. Med. Chem. 1995, 38, 3813-3820.
Glonek,31P NMR of Mg-ATP in Dilute Solutions: Complexation and Exchange, Int. J. Biochem, 1992, pp. 1533-1559, vol. 24, No. 10.
Haystead et. al., γ-Phosphate-linked ATP-Sepharose for the affinity purification of pretein kinases, Eur. J. Biochem., 1993, pp. 459-467, vol. 214.
Prodromou et. al., Identification and Structural Characterization of the ATP/ADP-Binding Site in the Hsp90 Molecular Chaperone, Cell, Jul. 11, 1997, pp. 65-75, vol. 90.
Danishefsky Samuel J.
Kuduk Scott D.
Ouerfelli Ouatek
Rosen Neal
Sepp-Lorenzino Laura
Kifle Bruck
Marina Larson & Associates LLC
Sloan-Kettering Institute for Cancer Research
LandOfFree
Methods and compositions for degradation and/or inhibition... 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 degradation and/or inhibition..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and compositions for degradation and/or inhibition... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3799581