` Professor, Center for Drug Design, The University of Minnesota
`7-216 PWB • 516 Delaware St SE • Minneapolis, MN • patte219@umn.edu • O: 612-625-7962 • Fax: 612-625-8154
`EDUCATION
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`• UNIVERSITY OF NOTRE DAME
`
`Bayer Postdoctoral Research Associate
` GEORGIA STATE UNIVERSITY
` Received Dissertation Grant Award 1992
`Dissertation Title: Synthesis and Computational Studies of
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`Ph.D., Chemistry, 1995
`Heterocyclic Systems that Bind to Nucleic Acids
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` GEORGIA STATE UNIVERSITY
` B.S., Chemistry, 1991
`RESEARCH EXPERIENCE
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`1996-1998
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`AUG 2004-PRESENT
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`CENTER FOR DRUG DESIGN, THE UNIVERSITY OF MINNESOTA
` • Professor
`Research concerns efficient preparation of novel nucleosides, nucleotide analogs and heterocyclics as
`anti-infectives, antiprotozoals, antiviral, anti-cancer agents and cyanide antidotes. Responsible for care
`and operation of the departmental LCMS system. Discovered new class of antiprotozoal agents that
`are 10 times as potent as metronidazole. Currently investigating novel HIV combination therapy that
`induces error catastrophe what was discovered in my group. Developing the cyanide antidote
`sulfanegen. Funded by the NSF, NIH-NINDS and NIH-NIAID.
`
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` Feb 2000-Jul 2004
`
`PHARMASSET, INC.
`
`• Senior Scientist – Discovery-Analytical Dr. Kyoichi Watanabe and Dr. Kris Pankiewicz
`Head of analytical chemistry group. Research concerns efficient preparation of novel nucleoside
`analogs as anti-infectives, nucleotide anti-cancer agents and mycophenolic acid analogues. The focus
`is on antivirals, specifically HBV, HCV, and HIV as well as anti-leukemia agents and
`immunosuppressants. Extensive experience with NMR, HPLC and preparative LC. Familiar with
`LCMS, GC, GCMS, FTNMR, FTIR and computational chemistry. Hired with job title Lead Scientist.
`Promoted to Senior Scientist July 2002.
` May 1998-Jan 2000
`GEORGIA COMBICHEM CENTER
` Prof. David W. Boykin
` • Visiting Research Scholar
`Research concerned solid phase parallel synthesis of novel heterocyclic molecules using automated
`combinatorial methodology. The research was focused on efficient preparation of small molecule
`organic libraries as potential therapeutic agents. Research experience includes preparation of libraries
`on the ACT 496Ω and 384HTS synthesizers. Familiar with HPLC, LCMS, GC, GCMS, FTNMR,
`FTIR and computational chemistry.
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`February 1996-April 1998
`
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`UNIVERSITY OF NOTRE DAME
`
`
`Prof. Richard E. Taylor
` • Bayer Postdoctoral Research Associate
`
`Research concerned two aspects of developing selective receptors for carbohydrates and carbohydrate
`derivatives such as sialic acid and UTP. The first was combinatorial libraries of fluorescent peptide
`based sensors on solid support. The second involved libraries of water soluble fluorescent sensors for
`carbohydrates.
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`GEORGIA STATE UNIVERSITY
`• Graduate Research Assistant
`
`September 1991-January 1996
`Prof. Lucjan Strekowski
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 1
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`Research concerned efficient synthesis and rational design of non-nucleoside anti-HIV agents that bind
`to DNA and RNA. Extensive application of molecular mechanics and semi-empirical methods to
`design potential anti-HIV agents, explain the interaction of intercalators with nucleic acid and
`understand the reactivity of heterocyclic systems. Extensive experience with FTNMR.
`GEORGIA STATE UNIVERSITY
`
`
`November 1989 - September 1991
`• Research Assistant
`
`
`
`Prof. Lucjan Strekowski
`Research concerned efficient synthesis of novel potential anti-cancer agents and bleomycin amplifiers
`that bind to DNA via intercalation and efficient synthesis of potential anti-HIV agents.
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` Strekowski, L; Wydra, R L.; Cegla, M T.; Czarny, A; Harden, D B.; Patterson, S E.; Battiste, M A.;
`Coxon, J M. "An unusual base-mediated cyclization of ketimines derived from 2-(trifluoromethyl)aniline
`that involves the trifluoromethyl group: an expedient route to 2-arylquinolines" J Org Chem. 1990 55,
`4777-9.
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` •
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` Wydra, RL.; Patterson, S E.; Strekowski, L;" An activated trifluoromethyl group as a new synthon for
`4,5-dihydro-1H-imidazole and 1,4,5,6-tetrahydropyrimidine systems" J.Heterocycl Chem. 1990 27, 803-5.
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` •
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` Strekowski, L; Harden, D; Grubb, WB; III; Patterson, S E.; Czarny, A; Mokrosz, M J.; Cegla, M T.;
`Wydra, R L." Synthesis of 2-chloro-4,6-di(heteroaryl)pyrimidines" J.Heterocycl Chem. 1990 27, 1393-
`400.
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` •
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` Strekowski, L; Mokrosz, J L.; Honkan, V A.; Czarny, A; Cegla, M T.; Wydra, R L.; Patterson, SE.;
`Schinazi, RF. "Synthesis and quantitative structure-activity relationship analysis of 2-(aryl or heteroaryl)
`quinolin-4-amines, a new class of anti-HIV-1 agents" J Med Chem 1991 34, 1739-46.
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` •
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`Janda, L; Nguyen, J; Patterson, S.E.; Strekowski, L. "Synthesis of fluoro and trifluoromethyl
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`derivatives of 2-phenylquinolin-4-ol" J.Heterocycl Chem. 1992 29, 1753-6.
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` •
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` L. Strekowski, S.E. Patterson, L. Janda, R.L. Wydra, D.B. Harden, M. Lipowska, and M.T. Cegla,
`"Further Studies on the Cyclization of Aromatic Azomethines ortho-Substituted with a Trifluoromethyl
`Group: Synthesis of 2,4-Di or 2,3,4-Trisubstituted Quinolines," J.Org.Chem. 1992 57, 196-201.
`
` •
`
` S.E. Patterson, L. Janda, and L. Strekowski " A new synthesis of N-substituted-2-alkyl(or aryl)
`quinazolin-4-amines by amide base-mediated cyclization of carboximidamides derived from 2-
`(trifluoromethyl)benzenamine" J. Heterocyclic Chem. 1992 29, 703-6.
`
` •
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` W.D. Wilson, M. Zhao, S.E. Patterson, R.L. Wydra, L. Janda, and L. Strekowski, "Design of RNA
`Interactive Anti-HIV-1 Agents: Unfused Aromatic Intercalators," Med Chem Res 1992, 2, 102-10.
`
` •
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` M. Lipowska, S.E. Patterson, G. Patonay, and L. Strekowski "A Highly Selective Hydrogen
`Deuterium Exchange in Indolinium Cyanines" J Heterocyclic Chem. 1993, 30, 1977-80.
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`AWARDS
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`DISSERTATION GRANT AWARD, GEORGIA STATE UNIVERSITY, 1992
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`BAYER FELLOWSHIP, THE UNIVERSITY OF NOTRE DAME, 1996-1998
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`PUBLICATIONS
`• Strekowski, L; Patterson, S; Cegla, M T.; Wydra, R L.; Czarny, A; Harden, D B. "Addition and
`lithiation reactions of N-(1-phenylalkylidene)anilines with lithium dialkylamides" Tetrahedron Letters
`1989 30, 5197-200.
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 2
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` L. Strekowski, M. Hojaat, S.E. Patterson and A.S. Kiselyov "Experimental and Computational
`Studies of Trifluoromethylation of Aromatic Amines by the System Trifluoroiodomethane-Zinc-Sulfur
`Dioxide," J.Heterocyclic Chem. 1994 31, 1413-16.
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` •
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` L. Strekowski, L. Janda, S.E. Patterson and J. Nguyen "Amination by Lithium Alkylamide Reagents
`of Ketimines Derived from 2-(Trifluoromethylanilines and Methyl Halophenyl Ketones and their
`Cyclization Products 2-(Halophenyl)quinolin-4-amines," Tetrahedron 1996 52, 3273-82.
`
` •
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` L. Strekowski, S.-Y. Lin, K. Van Aken and S.E. Patterson “Three Heterocyclic Rings Fused (6:6:6)”
`in Comperhensive Heterocyclic Chemistry II vol. 8; A.R. Katritzky, C.W. Rees and E.F.V. Scriven, Eds.;
`Elsevier Science: Tarrytown, 1996; pp 1109-1134.
`
`• S. Patterson, J.M. Coxon, W.D. Wilson, and L. Strekowski "Intercalation of Ethidium and Analogues
`with Nucleic Acids: A Molecular Orbital Study," Bioorg.Med.Chem. 1997, 5, 277-81.
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` •
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` Patterson, S.E; Smith, B.D. and Taylor, R.E. “Fluorescence Sensing of a Ribonucleoside 5’-
`Triphosphate,” Tetrahedron Letters 1997 38, 6323.
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` •
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` Patterson, S; Smith, B.D; and Taylor, R.E. “Tuning the Affinity of a Synthetic Sialic Acid
`Receptor Using Combinatorial Chemistry,” Tetrahedron Lett, 1998, 37, 3111.
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` •
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` Strekowski, L; Abdou, I.M; Attia A.M.E. and S.E. Patterson, “The First Direct Ammonolysis of 2-
`Thiouracil Nucleosides to 2-Thiosytosine Nucleosides,” Tetrahedron Letters 2000 41, 4757-61.
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` Pankiewicz, K.W; Lesiak-Watanabe, K.B; Watanabe, K.A; Patterson, S; Jayaram, H.N; Yalowitz, J;
`Miller, M.D; Seidman, M; Majumdar, A; Prehna, G and B.M. Goldstein, “Novel Mycophenolic Adenine
`Bis(phosphonate) Analogues as Potential Differentiation Agents Human Leukemia,” J.Med.Chem. 2002,
`45, 703-12.
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` Yalowitz, J; Pankiewicz, K; Patterson, S.E. and H.N. Jayaram M.D. “Cytotoxicity and Cellular
`Differentiation Activity of Methylenebis(phosphonate) Analogs of Tiazofurin and Mycophenolic Acid
`Adenine Dinucleotide in Human Cell Lines,” Cancer Lett. 2002 181, 31-38.
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` Clark, J.L; Patterson, S.E; Mason, J.C; Otto, M.J; Schinazi, R.F; Watanabe, K.A; Risal, K.A;
`Goldstein B.M.
`
`and K. Pankiewicz.
`“Novel
`Inhibitors
`of
`Inosine Monophosphate
`Dehydrogenase,”Coll.Czech.Chem. Comm.Symp.Ser. 2002, 5, 256-60.
`
`Stuyver, L.J.; Lostia, S.; Patterson, S.E; Watanabe, K.A.; Otto M.J. and K.W. Pankiewicz.
`•
`“Inhibitors of the IMPDH enzyme as potential anti-bovine viral diarrhoea virus agents,” Antiviral
`Chemistry and Chemotherapy 2002, 13, 345-352.
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` Pankiewicz, K. W.; Patterson, S. E.; Black, P. L.; Jayaram, H. N.; Risal, D. et al. Cofactor mimics as
`selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major
`therapeutic target. Curr Med Chem 2004, 11, 887-900
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` •
`
` Hollecker L, Du J, Hassan A, Shi J, Wang P, Patterson SE, Khan N, Hobs A, Clark J, Rachakonda S,
`Chun BK, Pinar I, Lostia S, McBrayer T, Stuyver LJ, Otto MJ, Pankiewicz KW. “Synthesis and antiviral
`activity of a mutagenic N4-hydoxycytidine and its analogues.” Developments in Nucleic Acids, Schinazi
`RF, Liotta D. eds. . IHL Press, 2004
`
`• Patterson SE, Clark JL, Mason JC, Pankiewicz KW “The reaction of alcohols and nucleosides with
`methylenebis(phosphonic acid dichloride):
` Facile synthesis of methylenebis-(phosphonic acid)
`monoesters.” Frontiers in Nucleosides and Nucleic Acids, Schinazi RF, Liotta D. eds. IHL Press, 2004
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 3
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`• Patterson SE, Black PL, Clark JL, Risal D, Goldstein BM, Jayaram HN, Schinazi, RF, Pankiewicz
`KW. “The mechanism of action and antileukemic activity of bis(phosphonate) analogue of mycophenolic
`adenine dinucleotide (C2-MAD); An alternative for tiazofurin.” Frontiers in Nucleosides and Nucleic
`Acids, Schinazi RF, Liotta D. eds. IHL Press, 2004
`
` Pankiewicz KW, Patterson SE, Black PL, Jayaram HN, Risal D, Goldstein BM, Stuyver LJ, Schinazi
`RF., Cofactor Mimics as Selective Inhibitors of NAD-dependent Inosine Monophosphate Dehydrogenase
`(IMPDH) Curr. Med. Chem., 2004, 11, 887-900.
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`• Du J, Patterson S, Shi J, Chun BK, Stuyver LJ, Watanabe KA., “Synthesis of 5'-C-methyl-1',3'-
`dioxolan-4'-yl nucleosides” Bioorg Med Chem Lett. 2004, 14,1243-5
`
`• L. Strekowski, A.N. Parker, M. Hojjat, M. Say, O. Zegrocka-Stendel, S.E. Patterson, F.A. Tanious
`and W.D. Wilson,
`“Triple-Helix DNA Selective
`2-(2-Naphthyl)Quinoline
`Intercalators”
`Acta.Pol.Pharm.2004, 61 Suppl, 70-2.
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` Wang, P.; Hollecker, L.; Pankiewicz, K. W.; Patterson, S. E.; Whitaker, T. et al. “Synthesis of N3,5'-
`Cyclo-4-(beta-D-ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one, a Novel Compound with Anti-Hepatitis
`C Virus Activity.” J Med Chem 2004, 47, 6100-6103
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` Chun, B.-K.; Clark, J. L.; Du, J.; Furman, P. A.; Hassan, A. E.; Hollecker, L.; McBrayer, T.; Otto, M.
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`E.; Pankiewicz, K. W.; Patterson, S. E.; et al “5',9-Anhydro-3-(β-D-ribofuranosyl) purine nucleoside
`analogues as potential anti-HCV agents.” Collection Symposium Series 2005, 7(Chemistry of Nucleic Acid
`Components), 319-327.
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` •
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`• Clark, J.L.; Hollecker, L.; Mason, J.C.; Stuyver, L.J.; Tharnish, P.M.; Lostia, S.; McBrayer, T.R.;
`Schinazi, R.F.; Watanabe, K.A.; Otto, M.J.; Furman, P.A.; Stec, W.J.; Patterson, S.E.; Pankiewicz, K.W.
`“Design, Synthesis, and Antiviral Activity of 2'-Deoxy-2'-fluoro-2'-C-methyl-cytidine, a Potent Inhibitor
`of Hepatitis C Virus Replication.” J Med Chem 2005, 48, 5504-5508.
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` Shi, J.; Du, J.; Ma, T.; Pankiewicz, K. W.; Patterson, S. E. et al. Synthesis and anti-viral activity of a
`series of D- and L-2'-deoxy-2'-fluororibonucleosides in the subgenomic HCV replicon system. Bioorg
`Med Chem 2005, 13, 1641-1652.
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` Wang, P.; Hollecker, L.; Pankiewicz, K. W.; Patterson, S. E.; Whitaker, T.; McBrayer, T R.;
`Tharnish, P M.; Stuyver, L J.; Schinazi, R F.; Otto, M J “Synthesis of N3,5'-cyclo-4-(beta-D-
`ribofuranosyl)-vic-triazolo[4,5-b]pyridin-5-one and its 3'-deoxysugar analogue as potential anti-hepatitis
`C virus agents.” Nucleosides Nucleotides Nucleic Acids 2005, 24, 957-960.
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`• Shi, J.; Du, J.; Ma, T.; Pankiewicz, K. W.; Patterson, S. E. Hassan, Abdalla E. A.; Tharnish, Phillip
`M.; McBrayer, Tamara R.; Lostia, Stefania; Stuyver, Lieven J.; et al “Synthesis and in vitro anti-HCV
`activity of beta-D- and 1-2'-deoxy-2'-fluororibonucleosides.” Nucleosides Nucleotides Nucleic Acids 2005,
`24, 875-879.
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`• Shi, J.; Du, J.; Ma, T.; Pankiewicz, K. W.; Patterson, S. E. ; Phillip PM.; McBrayer, TR.; Stuyver,
`LJ.; Otto, MJ.; Chu, CK.; et al “Synthesis and anti-viral activity of a series of d- and l-2'-deoxy-2'-
`fluororibonucleosides in the subgenomic HCV replicon system.” Bioorg Med Chem 2005, 13, 1641-1652.
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`• Rejman D, Olesiak M Chen L Patterson SE, Wilson D, Jayaram HN, Hedstrom L, Pankiewicz KW.
`“Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide Inhibition of
`Inosine Monophosphate Dehydrogenase.” J. Med. Chem., 2006, 49, 5018-22
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`• Pankiewicz KW; Gao G; Patterson S E “Synthesis of methylenebis(phosphonate) analogs of
`dinucleotide pyrophosphates” Curr Protocol Nuc Acid., 2006, DOI: 10.1002/0471142700.NC1305S24
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 4
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`• Chen L; Rejman D; Bonnac L; Pankiewicz K W; Patterson S E “Nucleoside-5'-phosphoimidazolides:
`reagents for facile synthesis of dinucleoside pyrophosphates” Curr Protocol Nuc Acid., 2006, DOI:
`10.1002/0471142700.NC1304S23
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` Paliakov, E; Henary, M; Say, M. Patterson SE; Parker, A, Manzel, L; Macfarlane, DE; Bojarski, AJ
`and Strekowski, L. “Fujita-Ban QSAR analysis and CoMFA study of quinoline antagonists of
`immunostimulatory CpG-oligonucleotides” Bioorg Med Chem 2007, 324-332
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`• Bonnac, L; Chen, L; Pathak, R; Gao, G; Ming, Q; Bennett, E; Felczak, F; Kullberg, M; Patterson SE,
`Magni, G and Pankiewicz, KW. “Probing binding requirements of NAD kinase with modified substrate
`(NAD) analogues.” Bioorg Med Chem Lett 2007, 17, 1512-1515.
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`• Suk, D-H; Bonnac, L; Dykstra, CC; Pankiewicz, KW and Steven E. Patterson “Rational Design and
`Synthesis of Novel Nucleotide Anti-Giardia Agents” Bioorg Med Chem Lett 2007, 2064-2067.
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`• Suk, D-H; Rejman, D; Dykstra, CC; Pankiewicz, KW and Patterson, SE “Phosphonoxins: Rational
`Design and Discovery of a Potent Nucleoside anti-Giardia Agent”. Bioorg Med Chem Lett 2007, 17, 2811-
`2816.
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`• Crankshaw, D. L.; Goon, D. J. W.; Briggs, J. E.; DeLong, D.; Kuskowski, M.; Patterson, S. E.;
`Nagasawa, H. T. A Novel Paradigm for Assessing Efficacies of Potential Antidotes against Neurotoxins in
`Mice. Toxicol Lett 2007, 174, 111-117.
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`• Nagasawa, H. T.; Goon, D. J. W.; L.Crankshaw, D.; Vince, R.; Patterson, S. E. “Novel, Orally
`Effective Cyanide Antidotes.” J Med Chem 2007, 50, 6462-4
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`• Zhou, D.; Staake, M.; and Patterson, S.E. “Phosphonoxins II: Diastereoselective synthesis of
`phosphonic acid analogs of polyoxins”Org Lett 2008, 10, 2179.
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`• Michael J. Dapp, Christine L. Clouser, Steven Patterson, and Louis M. Mansky “5-Azacytidine Can
`Induce Human Immunodificiency Virus Type 1 Lethal Mutagenesis” J. Virol. 2009, 83, 11950
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`• Wattenberg LW, Patterson S, Antonides JD. “Chitin or chitin-like glycans as targets for late-term
`cancer chemoprevention.” Cancer Prev Res (Phila). 2010, 3,1519-22.
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`• M. Brenner, S. B. Mahon, J. G. Kim, J. Lee, D. Mukai, K.A Kreuter, W Blackledge, S. Patterson, H.
`Singh, and G. Boss “Intramuscular Cobinamide Sulfite in a Rabbit Model of Sublethal Cyanide Toxicity”
`Ann Emg Med 2010, 55, 352-63.
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` Brenner, M; Kim, JG; Lee, J; Mahon, SB; Lemor, D; Ahdout, R; Boss, GR; Nagasawa, H; and
`Patterson SE. “Sulfanegen Sodium Treatment in a Rabbit Model of Sub-Lethal Cyanide Toxicity” J
`Pharmacol Toxicol 2010, 248, 269-76.
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`• Christine L. Clouser, Steven E. Patterson, Irene J. Dorweiler and Louis M. Mansky “Exploiting Drug
`Repositioning for the Discovery of a Novel Combination Therapy That Inhibits Human
`Immunodeficiency Virus Type 1 Replication” J Virol 2010, 84, 9301-9.
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`• Michael Staake, Ding Zhou, Aaron Shanker, Atasi De Chatterjee, Siddhartha Das, and Steven E.
`Patterson “Phosphonoxins III: Synthesis of α-Aminophosphonate Analogs of Antifungal Polyoxins,”
`Org Lett. 2010, 12, 4596-9.
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`• Jay Chauhan, Alexandre R. Monteil, Steven E. Patterson “Synthesis of novel benzo[b]furans and
`benzo[b]thiophenes: analogs of combretastatin and resveratrol.” Heterocyclic Communications 2010, 16,
`241–244.
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 5
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`• Chan A, Crankshaw DL, Monteil A, Patterson SE, Nagasawa HT, Briggs JE, Kozocas JA, Mahon SB,
`Brenner M, Pilz RB, Bigby TD, Boss GR. “The combination of cobinamide and sulfanegen is highly
`effective in mouse models of cyanide poisoning.” Clin Toxicol (Phila). 2011, 49, 366-73.
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` Greggs WM 3rd, Clouser CL, Patterson SE, Mansky LM. “Broadening the use of antiretroviral
`therapy: the case for feline leukemia virus.” Ther Clin Risk Manag 2011 7, 115-22.
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`• Clouser CL, Holtz CM, Mullett M, Crankshaw DL, Briggs JE, Chauhan J, VanHoutan IM, Patterson
`SE, Mansky LM. “Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine.” PLoS One.
`2011, 6, e15840.
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`• Belani KG, Singh H, Beebe DS, George P, Patterson SE, Nagasawa HT, Vince R. “Cyanide toxicity
`in juvenile pigs and its reversal by a new prodrug, sulfanegen sodium” Anesth Analg 2012, 114, 956-61.
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`Singh, H.; Beebe, D.; Patterson, SE.; Nagasawa, H. T.; Vince, R.; Belani, K., “Reversal of
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`Sodium Nitroprusside Induced Cyanide Toxicity by a New Prodrug, Sulfanegen Sodium, in Juvenile
`Pigs.” Anesthes Analg 2012, 114, 956-61.
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`Kim, J. G.; Lee, J.; Mahon, S. B.; Mukai, D.; Patterson, SE.; Boss, G. R.; Tromberg, B. J.;
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`Brenner, M., “Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals
`differences in brain and muscle metabolism.” J Biomed Opt 2012, 17, 105005.
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`Greggs, W. M., 3rd; Clouser, C. L.; Patterson, SE.; Mansky, L. M., “Discovery of drugs that
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`possess activity against feline leukemia virus.” J Gen Virol 2012, 93, 900-5.
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`Clouser, C. L.; Holtz, C. M.; Mullett, M.; Crankshaw, D. L.; Briggs, J. E.; O'Sullivan, M. G.;
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`Patterson, S. E.; Mansky, L. M., “Activity of a novel combined antiretroviral therapy of gemcitabine and
`decitabine in a mouse model for HIV-1.” Antimicrob Agents Chemother 2012, 56, 1942-8.
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`Clouser, C. L.; Chauhan, J.; Bess, M. A.; van Oploo, J. L.; Zhou, D.; Dimick-Gray, S.; Mansky, L.
`•
`M.; Patterson, S. E., “Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by
`the combination of resveratrol and decitabine.” Bioorg Med Chem Lett 2012, 22 (21), 6642-6.
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`Smith, S. E.; Bida, A. T.; Davis, T. R.; Sicotte, H.; Patterson, S. E.; Gil, D.; Schrum, A. G.,” IP-
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`FCM measures physiologic protein-protein interactions modulated by signal transduction and small-
`molecule drug inhibition.” PloS one 2012, 7, e45722.
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`Dapp, M. J.; Patterson, S. E.; Mansky, L. M., “Back to the future: revisiting HIV-1 lethal
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`mutagenesis.” Trends Microbiol 2013, 21, 56-62.
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`Patterson, S. E.; Monteil, A. R.; Cohen, J. F.; Crankshaw, D. L.; Vince, R.; Nagasawa, H. T.,
`•
`“Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-
`Mercaptopyruvate for Intramuscular Administration.” J Med Chem 2013, 56, 1346–1349.
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`Bonnac, L; Mansky, L.M. and Patterson, S.E., “Structure-Activity Relationship, Design of Viral
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`Mutagens and Application to Lethal Mutagenesis” J Med Chem 2013, 56, 9403-14.
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`Valberg, S.J.; Sponseller, B.T.; Hegeman, A.D.; Earing, J; Bender, J.B.; Martinson, K.L.;
`•
`Patterson, S.E.; Sweetman, L. “Seasonal pasture myopathy/atypical myopathy in North America
`associated with ingestion of hypoglycin A within seeds of the box elder tree” Equine vet J 2013, 45, 419-
`26.
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`Clouser, CL; Bonnac, L; Mansky, LM; and Patterson, SE “Characterization of Permeability,
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`Stability, and Anti-HIV-1 Activity of Decitabine and Gemcitabine Divalerate Prodrugs” Antivir Chem
`Chemother 2013, doi: 10.3851/IMP2682
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`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 6
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`Rawson, J.M.; Heineman, R.H.; Beach, L.B.; Martin, J.L.; Schnettler, E.K.; Dapp, M.J.;
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`Patterson, S.E. and Mansky, L.M. Bioorg Med Chem 2013, 21, 7222-8.
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`
`
`Jackson, KE, Pogula, PK and Patterson, SE “Polyoxin and nikkomycin analogs: recent design
`•
`and synthesis of novel peptidyl nucleosides” Heterocycl Lett. 2013, 19, 375-86.
`
`Dapp MJ, Bonnac L, Patterson SE, Mansky LM. “Discovery of novel ribonucleoside analogues
`•
`with activity against human immunodeficiency virus type-1” J. Virol 2014, 88, 356-63.
`
` •
`
`Stuttleberg, MW; Vinnakota, CV; Mitchell, BL; Monteil, AR; Patterson, SE and Logue BA.
`
`“Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography
`tandem mass spectrometry” J Chromatog B, 2014, 949-950, 94-8.
`
`Beach LB, Rawson JM, Kim B, Patterson SE, Mansky LM. “Novel inhibitors of human
`•
`immunodeficiency virus type 2 infectivity” J Gen Virol, 2014, 2778-83, doi: 10.1099/vir.0.069864-0.
`
` •
`
`Lee J, Kim JG, Mahon SB, Mukai D, Yoon D, Boss GR, Patterson SE, Rockwood G, Isom G,
`
`Brenner M. “Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical
`spectroscopy” J biomed Opt, 2014, 19, 055001, doi: 10.1117/1.JBO.19.5.055001.
`
` •
`
`Rawson JM, Landman SR, Reilly CS, Bonnac L, Patterson SE, Mansky LM. “Lack of mutational
`
`hotspots during decitabine-mediated HIV-1 mutagenesis” Antimicrob Agents Chemother 2015, 59, 6834-
`43 doi:10.1128/AAC.01644-15
`
` •
`
`Guest editorial special edition Heterocyclic Communications 2015, 5 special issue in memory of
`
`Kyoichi A. Watanabe (in press).
`
` •
`
`Stutelberg MW, Dzisam JK, Monteil AR, Petrikovics I, Boss GR, Patterson SE, Rockwood GA,
`
`Logue BA. Simultaneous determination of 3-mercaptopyruvate and cobinamide in plasma by liquid
`chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 (in
`press) doi: 10.1016/j.jchromb.2015.11.027
`
`
`
`
`
`
` RESEARCH SUPPORT
`Current:
`
`1R01 GM105876
`
`9/15/13-5/31/17
`
`NIH-NIAID
`HIV Therapy and Mutagenesis
`
`
`Salary support 20%
`PI: Mansky and Patterson
`$112,755 direct costs
`
`
`
`
`
`
`2U01 NS058087
`09/01/2011-08/31/2016
`NIH-NINDS
` Countermeasures Against Chemical Threats: Countermeasures Against Cyanide
`Salary Support: 20%
`PI: Patterson
`$502,908 direct costs
`
`
`
`
`Completed
`
`
`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 7
`
`
`
`
`
`
`
`
`
`W81XWH-12-2-0098
`09/26/2012 – 09/25/2014
`University of California Irvine (US DOD Army)
`Collaborative Studies for Acceleration of Advanced CN
`Salary Support: 5%
`PI: Patterson
`$18,853 direct costs
`
`S9000080, No 34305767
`09/26/2012 – 09/25/2014
`University of California San Diego (US DOD Army)
`Cyanide Antidotes for Mass Casualties Comparison
`Salary Support: 5%
`PI: Patterson
`$18,853 direct costs
`
` Minnesota Discovery and Translational Grant – (intramural)
`
`Investigation of HIV-1 Lethal Mutagenesis in a Humanized HIV Mouse Model
`Salary Support: 0%
`PI: Patterson
`$50,000 total costs
`
`
`
`
`
`
`
`
`3R01 GM056615
`09/01/2009-08/31/2011
`NIH
`Mechanisms of HIV-1 Variation.
`Salary Support: 20%
`PI: Mansky – CoPI: Patterson
`$127,111 direct costs
`
`
`U54 NS063718
`06/01/10-11/30/11
`NIH-NINDS
`Combined Use of Cobinamide and a 3-Mercaptopyruvate Prodrug
`Salary Support: 20%
`PI: Patterson
`$205,748 direct costs (does not include funds for subawards)
`
`
`FRD# 10.26 (intramural)
`01/01/2011-12/31/2012
`AHC Faculty Research Development Grant
`Use of Percaptopyruvate Prodrugs for Prevention of Post-Transplant Obliterative Bronchiolitis in a
`Murine Model
`Salary Support: 0%
`PI: Panoskaltsis – CoPI: Patterson
`$11,200 direct costs
`
`
`
`“Multiplex assay of T cell protein complexes for high-throughput drug screening” R01. Co-investigator
`Agency: NIH-NIAID
`The goal of this project is to develop high throughput methods for multiplex protein screening in discovery
`of novel cancer chemotherapeutics.
`
`
`“Novel combination therapy for HIV”
`Co-Principal Investigator
`
`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 8
`
`
`
`Grant Period: August 1, 2007-July 31, 2009
`Agency: Academic Health Center, University of Minnesota
`Type: Intramural Translational Research
`The goal of this project was the synthesis and testing of compounds for antiretroviral activity.
`
`
`
`
`
`Novel Selective Inhibitors of IMPDH Type II Against CML
`Coinvestigator
`Period: 12/01/2004 – 11/30/2007
`Agency: DOD
`
`The major goal of this project is to develop a highly selective inhibitor of IMPDH type II that is
`effective against chronic myelogenous leukemia.
`
`
`Combinatorial Based Chemistry and High Throughput Screening Methods to Identify Rac GTPase Inhibitors
`
`PI
`
`Period: 5/01/2006 – 4/30/2008
`
`Agency: Minnesota Partnership for Biotechnology and Medical Genomics
`
`The major goals of this project are to develop combinatorial chemistry and high throughput
`screening methods to identify Rac GTPase inhibitors with clinical potential as anti-proliferative agents for
`treatment of pancreatic cancer.
`
`
`Novel Agents Against West Nile Virus Infections
`Coinvestigator
`
`Application # 1 R43 AE056869
`
`Agency: NIAID
`
`TYPE: SBIR
`
`Period: 07/01/03 – 06/30/04
`
`The goal of this project was to discover and develop effective agents against West Nile virus for
`potential clinical development.
`
`
`Novel Class of Compounds for Treatment of HCV Infections
`Coinvestigator
`
`Application # 1R43 AI056720
`
`Agency: NIAID
`
`Period: 07/01/03 – 06/30/04
`
`Type: SBIR
`
`The goal of this project was to discover and develop new active compounds against HCV based on
`the lead compound containing the bicyclo[4.2.1]nonane ring system.
`
`
`Novel Cofactor Analogs as Immunosuppressants
`Coinvestigator
`
`Agency: NIAID
`
`Period: 08/15/00 – 08/31/01
`
`Type: SBIR
`
`The goal of this project was to discover and develop NAD analogs that specifically inhibit activity
`of IMPDH in activated lymphocytes.
`
`
`Novel Benzamide Analogs as Anticancer Agents
`Coinvestigator
`
`Application # 1R43 CA88578
`
`Agency: NIH
`
`Period: 05/10/01 – 04/30/04
`
`Type: SBIR
`
`The major goal of this project was to develop benzamide riboside analogs as anti-cancer agents
`
`
`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 9
`
`
`
`PATENTS
`
` •
`
` L. Strekowski, R.L. Wydra, S.E. Patterson, and R.F. Schinazi, "Novel 4-(Alkylamino or Dialkylamino)
`Quinoline and Their Method of Preparation," U.S. Serial No. 5304554; Apr. 27, 1990.
`
`• L.J. Stuyver, K. Pankiewcz, S. Patterson, K. Watanabe, and M.J. Otto, "Antiviral Agents For Treatment
`of Flaviviridae Infections," PCT WO 2002048165 A2 20020620
`
`• K. Pankiewcz, L. Bonnac and S. Patterson "Method for Synthesis of Benzamide Riboside and
`Analogues" abandoned.
`
`
`
`
`
`
`
`
`
`• S. Patterson, D.-H. Suk, D Rejman and C Dykstra "Agents for Treatment of Protozoal Infections"
`abandoned.
`
` •
`
` S. Patterson, R. Vince, H Nagasawa "Preparation of Amino Salts of Sulfanegen as Cyanide Antidotes"
`PCT Int. Appl. (2011), WO 2011133893 A2 20111027.
`
`
`
`
`
`
`
`PROFESSIONAL AFFILIATIONS
`American Chemical Society; Organic Division, Medicinal Chemistry Division
`International Society for Nucleosides, Nucleotides and Nucleic Acids
`Society of Toxicology (full member)
`
`SERVICE AND MENTORING
`Graduate student dissertation committees
`
`Michael Dapp
`
`Wil Greggs
`Lauren Beach
`Bryant Moeller (Advisor)
`Christopher Richard
`Erik Carlson
`
`
`NSF Workshop in Medicinal Chemistry (Director)
`Summer 2012.
`Summer 2013
`Summer 2014
`Summer 2016 (scheduled)
`
`
`Study section: special emphasis panel for CounterACT/NIH.
`
`Invited Lectures
`
`St Cloud State University
`
`NIH CounterACT Symposium
`
`The Breck School
`
`Cyanide Industry Users Safety Conference
`
`American Thoracic Society Workshop on Chemical Inhalation
`
`Hamline University
`
`Technicians
`
`Mary Mullet
`
`Jacquie Briggs
`
`Postdoctoral Research Associates
`
`Dae-Hwan Suk
`
`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 10
`
`
`
`
`
`
`Michael Staake
`Claire LeMenach
`Ding Zhou
`Praveen Pogula
`Kristal Jackson
`Marzena Baran
`
`
`Research Associates
`
`Jonathan Cohen
`
`Daune Crankshaw
`
`Alexandre Monteil
`Laurent Bonnac
`
`Petitioner Torrent Pharmaceuticals Limited - Exhibit 1004 - Page 11
`
`