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(12) United States Patent (10) Patent No.: US 8,716,300 B2 Piccariello Et Al USOO871 6300B2 (12) United States Patent (10) Patent No.: US 8,716,300 B2 Piccariello et al. (45) Date of Patent: *May 6, 2014 (54) FREQUENCY MODULATED DRUG FOREIGN PATENT DOCUMENTS DELIVERY (FMDD) EP O914826 A1 5, 1999 (75) Inventors: Thomas Piccariello, Blacksburg, VA WO WOO3,O74474 A2 9, 2003 (US); Scott B. Palmer, Wilmette, IL OTHER PUBLICATIONS (US); John D. Price, Blacksburg, VA (US); Robert Oberlender, Blacksburg, Ama et al., Bull. Chem. Soc. Jpn., vol. 62, pp. 3464-3468 (1989). VA (US); Mary C. Spencer, Blacksburg, International Preliminary Report on Patentability for International VA (US); Michaela E. Mulhare, Application No. PCT/US2009/067136, issued Jun. 14, 2011 (6 Christiansburg, VA (US) pages). International Search Report for International Application No. PCT/ (73) Assignee: Synthonics, Inc., Blacksburg, VA (US) US2009/067136, mailed Mar. 16, 2010 (2 pages). Islam, M. Saidullet al., “Antibacterial and antifungal activity of mixed (*) Notice: Subject to any disclaimer, the term of this ligand complexes of oxovanadium (IV), titanium (III) and cadmium patent is extended or adjusted under 35 (II) metal ions.” Oriental Journal of Chemistry, 19(3):547-554 U.S.C. 154(b) by 0 days. (2003). Jain, Sangeeta, et al., “Synthesis and biological evaluation of mixed This patent is Subject to a terminal dis ligand complexes of pyrazinamide and isoniazid.” Oriental Journal of claimer. Chemistry, 2002):409-410 (2004). Khan, F. “Study of mixed ligand complexes of Zn(ID with some (21) Appl. No.: 13/542,301 antibiotics and vitamin-B1 drugs, Kinetics of electrode reactions.” Journal of the Indian Chemical Society, 84(7):702-705 (Jul 2007). (22) Filed: Jul. 5, 2012 Khan, Farid, et al., “Study of thermodynamics in the mixed ligand complexes of Zn(II) with antibiotics and amplicillin.” Chemical & (65) Prior Publication Data Environmental Research, 10(1&2):37-40 (2001). US 2012/O277256A1 Nov. 1, 2012 Krymchantowski, A.V., et al., “The Future of Acute Care and Pre vention in Heachache.” Neurol. Sci., 2007, 28 Suppl 2, S166-S178. Lenz et al., Biochemistry, vol. 3, No. 6, pp. 750-753 (1964). Related U.S. Application Data Pool, J.L., “Direct Renin Inhibition: Focus on Aliskiren.” J. Manag. (63) Continuation of application No. 12/316,259, filed on Care Pharm., 2007, 13, S21-S33. Dec. 9, 2008, now Pat. No. 8,236,787. Siddiqui A et al., “Study of particle size and efficacy of transition metal complexes of mixed ligands, tolubutamide and gliclazide, the (51) Int. Cl. oral antidiabetic drugs. Biosciences Biotechnology Research Asia, A6 IK3I/522 (2006.01) 3(1):71-72 (Jun. 2005). CO7D 233/00 (2006.01) Singh, Rajender et al., “Solid, Solution, and antitumor activity stud CO7D 473/00 (2006.01) ies of mixed-ligand complexes with adenine-5-bromouracil base pair.” Synthesis and Reactivity in Inorganic and Metal-Organic (52) U.S. Cl. Chemistry, 32(5):853-872 (2002). USPC ........ 514/263.3: 514/400: 514/626; 54.4/264: Supplementary European Search Report for European Application 548/338.1564/194 No. 09836708.9, dated Aug. 17, 2012 (8 pages). (58) Field of Classification Search “Tekturna (aliskiren) Tablets 150mg-300mg.” MedScape from USPC ....................... 514/263.3, 400, 626; 54.4/265; WebMD. http://www.medscape.com/infosite?tekturnal article-phar 548/338.1564/194 macology, 3 pgs. (2008). See application file for complete search history. (Continued) (56) References Cited Primary Examiner — Porfirio Nazario Gonzalez U.S. PATENT DOCUMENTS (74) Attorney, Agent, or Firm — Brinks Gilson & Lione: Ryan L. Marshall 5,238,931 A 8, 1993 Yoshikawa et al. 5,373,093 A 12/1994 Vallarino et al. (57) ABSTRACT 6,071,545 A 6, 2000 Hendler et al. 2002fOO17305 A1 2/2002 Bagrov et al. Embodiments of the present disclosure include a coordina 2002/0120165 A1 8/2002 Zaworotko et al. tion complex, comprising a first biologically active moiety, a 2003,0224006 A1 12/2003 Zaworotko et al. 2004/O235.712 A1 11/2004 Lippard et al. second biologically active moiety, and a metal, wherein the 2007/0026O78 A1 2/2007 Almarsson et al. first biologically active moiety and second biologically active 2007/0059356 A1 3/2007 Almarsson et al. moiety are bound to the metal by covalent coordination 2009/0209046 A1 8, 2009 Moulton et al. bonds, and wherein the first biologically active moiety and 2009, 0227446 A1 9/2009 Chang et al. second biologically active moiety are different. These com 2010/0209354 A1 8/2010 Horcajada-Cortes et al. 2010, 0226991 A1 9/2010 Horcajada-Cortes et al. plexes may enhance the pharmacodynamic properties of bio 2010/0273642 A1 10/2010 Chang et al. logically active moieties. 2010.0311701 A1 12/2010 Almarsson et al. 2011/0052650 A1 3/2011 Morris et al. 15 Claims, 10 Drawing Sheets US 8,716,300 B2 Page 2 (56) References Cited de Ruijter, A.J.M.; van Gennip, A.H.; Caron, H.N.; Kemp, S.; van Kuilenburg, A.B.P. “Histone Deacetylases (HDACs): Characteriza OTHER PUBLICATIONS tion of the Classical HDAC Family.” Biochem. J., 2003, 370, 737 T49. Thompson, Katherine H., et al., “Metal complexes in medicinal DiNapoli. M.; Shah, I.M.; Stewart, D.A. “Molecular Pathways and chemistry: new vistas and challenges in drug design. Dalton Trans Genetic Aspects of Parkinson's Disease: From Bench to Bedside.” actions (Cambridge, England; 2003), 6:761-764 (Feb. 14, 2006). Expert Rev. Neurother, 2007, 7, 1693-1729. Acharya, M.R.: Sparreboom, A.; Venitz, J.; Figg, W.O. “Rational Diaz, M.; Patterson, S.G. "Management of Androgen-Independent Development of Histone Deacetylase Inhibitors as Anticancer Prostate Cancer Cancer Control, 2004, 11, 364-373. Agents: A Review.” Mol. Pharmacol., 2005, 68,917-932. Diem, R.; Sather, M.B.; Merkler, D.; Demmer, I., Maier, K.; Ananthan, S. "Opioid Ligands With Mixed u? delta Opioid Receptor Stadelmann, C.; Ehrenreich, H.; Bahr, M. "Combined Therapy With Interactions: An Emerging Approach to Novel Analgesics.” AAPS.J., Methylprednisolone and Erythropoietin in a Model of Multiple Scle 2006, 8, E118-E 125. rosis. Brain, 2005, 128,375-385. Anderson, S.; Komers, R. “Aliskiren Combined With Losartan in D'Souza, D.C.; Charney, D.; Krystal, J. "Glycine Site Agonists of the Diabetes and Nephropathy-To the Editors.” N. Engl. J. Med., 2008, NMDA Receptor: A Review.” CNS Drug Reviews, 1995, 1, 227-260. 359, 1068-1070. Encarnacion, E.V.; Hauser, R.A. “Considerations in Neuroprotection Ankarcrona, M.; Dypbukt, J.M.; Bonfoco, E.; Zhivotovsky, B.; in Parkinson's Disease.” Medscape Neurology and Neurosurgery, Orrenius, S.; Lipton, S.A.; Nicotera, P. “Glutamate-Induced 2007, www.medscape.com/viewarticle/563258. Neuronal Death: A Succession of Necrosis or Apoptosis Depending Fernandez, F.; Morishita, W.; Zuniga, E.; Ngyuen, J.; Blank. M.; on Mitochondrial Function Neuron. 1995, 15,961-973. Malenka, R.C.; Garner, C.C. “Pharmacotherapy for Cognitive Atkins, H. “Portfolio Optimization. Tying Down Gulliver: The Can Impairment in a Mouse Model of Down Syndrome.” Nat. Neurosci. nabinoid Therapy Market.” Specialty pharma, 2005. 1, 34-38. 2007, 10,411-413. Fischer, A.; Sananbenesi. F.; Wang, X.; Dobbin, M.; Tsai, L-H. Baran, E.J. "Metal Complexes of Carnosine.” Biochem. (Moscow), “Recovery of Learning and Memory is Associated With Chromatin 1999, 65,789-797. Remodeling.” Nature, 2007, 447, 178-183. Begon, S.; Pickering. G.; Eschalier, A.; Dubray, C. "Magesium Friderichs, E. “Introduction.” Analgesics. From Chemistry and Phar Increases Morphine Analgesic Effect in Different Experimental macology to Clinical Application, (Buschmann, H., Christoph, T.; Models of Pain.” Anesthesiology, 2002, 96,627-632. Friderichs, E.; Maul, C.; Sundermann, B. eds.) Wilev-VCH Verlag Berkley, K.J. “Chapter 21—Visceral Nociception and Pain.” Core GmbH & Co. KGaA. Federal Republic of Germany, 2002, 127-150. Topics in Pain, (Holdcroft, A.J., Jagger, S. eds.) Cambridge Univer Futaki, S.; Niwa, M.; Nakase, I., Tadokoro, A.; Zhang, Y.; Nagaoka, sity Press: United Kingdom, 2005, 145-150. M.; Wakako, N.; Sugiura, Y. "Arginine Carrier Peptide Bearing Ni(II) Bhalla, K.; List, A. “Histone Deacetylase Inhibitors in Chelator to Promote Cellular Uptake of Histidine-Tagged Proteins.” Myelodysplastic Syndrome.” Best Pract. Res. Clin. Haematol., 2004, Bioconjuq. Chem., 2004, 15, 475-481. 17, 595-611. Gonsette, R. E. "Combination Therapy for Multiple Sclerosis.” Int. Bhattacharya, P.K. Metal Ions in Biochemistry; Alpha Science Inter MS.J., 2004, 11, 10-21. national Ltd., 2005, Harrow. U.K., 16-65. Greenamyre, J.T.; Eller, R.V.; Zhang, Z. Ovadia, A.; Kurian, R.; Borman, S. "Drugs From Academia—Some Drug Discovery Efforts Gash. D.M. “Antiparkinsonian Effects of Remacemide Hydrochlo Are Anything But Academic’”Science & Technology, 2007, 85, ride, a Glutamate Antagonist, in Rodent and Primate Models of 42-47. Parkinson's Disease. Ann. Neurol., 1994, 35,655-661. Buvanendran, A.; McCarthy, R.J.; Kroin, J.S.: Leong, W.; Perry, P.; Hemby, S.E.; Co, C.; Dworkin, S.I.; Smith, J.E. "Synergistic Eleva Tuman, K.J. “Intrathecal Magnesium Prolongs Fentanyl Analgesia: tions in Nucleus Accumbens Extracellular Dopamine Concentrations A Prospective, Randomized, Controlled Trial.” Anesth. Analg., 2002, During Self-Administration of Cocaine/Heroin Combinations (Speedball) in Rats.” J. Pharmacol. Exp. Ther., 1999, 288,274-280. 95, 661-666. Isaacson, S. "Current Medical Treatment of Parkinson Disease.” Calabresi, P.; Marti, M.; Picconi, B.; Saulle, E.; Costa, C.: Centonze Evolving Concepts in Parkinson Disease, Pathophysiology, Diagno D.; Pisani. F.; Bernardi, G. "Lamotrigine and Remacemide Protect sis, and Treatment, 2007, 4-6. Striatal Neurons Against InVitro Ischemia: An Electrophysiological Jones, C.E.; Taylor, P.J.; McEwan, A.G.; Hanson, G.R. “Spectro Study.” Exp. Neurol., 2003, 182, 461–469. scopic Characterization of Copper(II) Binding to the Immunosup Campos, A.R.: Santos, F.A.; Rao, V.S. "Ketamine-Induced Potentia pressive Drug Mycophenolic Acid.” J. Am. chem ... Soc., 2006, 128, tion of Morphine Analgesia in Rat Tail-Flick Test: Role of Opioid-, 9378-9386.
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