Curriculum vitae
`
`
`
`
` ALEXANDER M. KLIBANOV
`
`
`
`July 15, 1949, in Moscow (Russia)
`
`Naturalized U.S. Citizen (1983)
`
`
`
`
`
`Date and Place of Birth:
`
`Nationality:
`
`Education:
` 1974
`1971
`
`
`
`
`
`
`
`Ph.D. in Chemical Enzymology, Moscow University
`M.S. in Chemistry, Moscow University
`
`
`Honors:
` 2015 Tau Beta Pi's Leonardo Da Vinci Lecturer, MIT
` 2007-11 and 2014- Novartis Chair Endowed Professorship, MIT
` 2012-13 Roger and Georges Firmenich Endowed Professorship, MIT
` 2011 MIT Biological Engineering Senior Class Faculty Award
` 2006 Distinguished GRUM Lecturer in Drug Discovery & Development,
`
`
`
`
` University of Montreal (Canada)
` 2004 UNAM Distinguished Lecturer, National University of Mexico (Mexico City)
`
`2001
`
`
`Walter Enz Lecturer in Pharmaceutical Chemistry, University of Kansas
`
`2001
`
`
`Elected a Corresponding Fellow of the Royal Society of Edinburgh
`
`(Scotland's National Academy of Science and Letters)
`Merck Distinguished Lecturer, Rutgers University
`
`
`2000
`Top 20 Biotechnology & Bioengineering Papers of the Last Forty Years
`
`
`2000
`Robert Lutz Lecturer, University of Virginia
`
`
`1998
`Perkin-Elmer Distinguished Lecturer, University of Pittsburgh
`
`
`1996
`Elected to the National Academy of Sciences of the U.S.A.
`
`
`1995
`Nathan O. Kaplan Memorial Lecturer in Biological Chemistry, University of
`
`
`1995
` California at San Diego
`1994
`
`
`R.W. Johnson PRI Lecturer, Pharmaceutical Research Institute
`1994
`
`
`Warren McCabe Lecturer, North Carolina State University
`1993
`
`
`Elected to the National Academy of Engineering of the U.S.A.
`1993
`
`
`Arthur C. Cope Scholar Award of the American Chemical Society
`1993
`
`
`Biotechnology Divisional Lectureship Award of the Institute of Food
`Technologists
`Charles Sabat Lecturer, Rutgers University
`Elected a Founding Fellow of the American Institute for Medical and
`Biological Engineering
`Louis C. Jordy Research Scholar Lecturer, Drew University
`International Enzyme Engineering Award
`Marvin J. Johnson Award of the American Chemical Society
`Monsanto Lecturer, Ohio State University
`NRC Distinguished Lecturer, Academia Sinica (Taiwan)
`Ipatieff Prize of the American Chemical Society
`Backer Lecturer, Groningen University (Holland)
`Dow Lecturer, University of Ottawa (Canada)
`Distinguished Scholar Lecturer, Hope College
`Leo Friend Award of the American Chemical Society
`Who's Who in Frontier Science and Technology
`
`
`
`
`
`
`
`
`
`
`
`1992
`1992
`
`1992
`1991
`1991
`1990
`1990
`1989
`1989
`1988
`1987
`1986
`1984
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 1 of 41
`
`

`
`
`1984
`
`1982
`1981-1983
`1975
`
`
`
`
`
`
`
`
`
`
`Sohio Lecturer, Case Western Reserve University
`American Men and Women of Science
`Henry L. Doherty Career Development Professorship, MIT
`U.S.S.R. Ministry of Higher Education Prize
`
`Roger and Georges Firmenich Professor of Natural Products Chemistry
`Department of Chemistry, MIT
`
`
`Professional Experience:
` 2007-11 and 2014- Novartis Chair Endowed Professor of Chemistry and Bioengineering, MIT
`
`2012-2013
`
`
`
`
`
`
`
`
`
`
`
`
`
`2000-present
`
`
`
`1988-present
`
`
`
`1987-1988
`
`1983-1987
`
`1979-1983
`
`1977-1979
`
`1974-1977
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Professor of Bioengineering
`Department of Biological Engineering, MIT
`
`Professor of Chemistry
`Department of Chemistry, MIT
`
`Professor of Applied Biochemistry
`Department of Applied Biological Sciences, MIT
`
`Associate Professor of Applied Biochemistry
`Department of Applied Biological Sciences (formerly
`Department of Nutrition and Food Science), MIT
`
`Assistant Professor of Applied Biochemistry
`Department of Nutrition and Food Science, MIT
`
`Postdoctoral Associate, Department of Chemistry
`University of California at San Diego
`
`Research Chemist
`Department of Chemistry, Moscow University
`
`
`Current Journal Editorial/Advisory Boards:
`"Biocatalysis and Biotransformation”, "Applied Biochemistry and Biotechnology", “Central
`European Journal of Chemistry”, "Biotechnology Progress", “Biotechnology & Bioengineering”,
`“Microbial Biotechnology”, “Open Journal of Pharmacology”, “Nanocarriers”, “Journal of Antivirals
`and Antiretrovirals”, “Open Access Academic Books in Chemistry”, “Journal of Biological
`Chemistry and Molecular Pharmacology”, “Recent Patents in Biotechnology”, “Current
`Pharmaceutical Biotechnology”
`
`
`Professional Societies:
`U.S. National Academy of Sciences, U.S. National Academy of Engineering, American Chemical
`Society, Society for Applied Microbiology
`
`
`Current Research Interests:
`Enzyme chemistry and biotechnology Medicinal and formulation chemistry
`Protein drug delivery Antimicrobial polymers
`Enzymes as stereoselective catalysts in organic syntheses
`Stabilization and formulation of macromolecular pharmaceuticals
`
`
`
`2
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 2 of 41
`
`

`
`
`
`
`
` 2.
`
`
`
` 3.
`
`
`
` 4.
`
`
`
` 5.
`
`
`
` 6.
`
`
`
` 7.
`
`
`
` 8.
`
`
`
` 9.
`
`Publications:
` 1.
`Varfolomeyev, S.D., Klibanov, A.M., Berezin, I.V. 1971. Light-initiated enzymic activity
` caused by photostereoisomerization of cis-4-nitrocinnamoyl-α-chymotrypsin. FEBS Lett. 15:
` 118 -120.
`
`Varfolomeyev, S.D., Klibanov, A.M., Martinek, K., Berezin, I.V. 1972. Light-sensitive catalysts.
`4-Nitrocinnamoyl residue as a chromophoric reporter group in the α-chymotrypsin active center.
`Dokl. Acad. Nauk SSSR 203: 616-619.
`
`Klibanov, A.M., Samokhin, G.P., Martinek, K., Berezin, I.V. 1974. Mechanochemistry of
`catalytic systems. Regulation by a mechanical action of the enzymatic properties of
`α-chymotrypsin covalently attached to a nylon fiber. Dokl. Acad. Nauk SSSR 218: 715-718.
`
`Berezin, I.V., Varfolomeyev, S.D., Klibanov, A.M., Martinek, K. 1974. Light and ultrasonic
`regulation of α-chymotrypsin catalytic activity. Proflavin as a light- and sound- sensitive
`competitive inhibitor. FEBS Lett. 39: 329-331.
`
`Berezin, I.V., Klibanov, A.M., Martinek, K. 1974. The mechanochemistry of immobilized
`enzymes. How to steer a chemical process at the molecular level by a mechanical device.
`Biochim. Biophys. Acta 364: 193-199.
`
`Berezin, I.V., Klibanov, A.M., Goldmacher, V.S., Martinek, K. 1974. Mechanochemistry of
`catalytic systems. Regulation by a mechanical action of the enzymatic activity of trypsin
`entrapped in polyacrylamide gel. Dokl. Acad. Nauk SSSR 218: 367-370.
`
`Klibanov, A.M., Martinek, K., Berezin, I.V. 1974. The effect of ultrasound on α-chymotrypsin.
`A novel approach to studying conformational transitions in active centers of enzymes.
`Biochemistry SSSR 39: 878-887.
`
`Berezin, I.V., Klibanov, A.M., Klyosov, A.A., Martinek, K., Svedas, V.K. 1975. The effect of
`ultrasound as a new method of studying conformational transitions in enzyme active centers.
`pH- and temperature-induced conformational transitions in the active center of penicillin
`amidase. FEBS Lett. 49: 325-328.
`
`Berezin, I.V., Klibanov, A.M., Martinek, K. 1975. Kinetic and thermodynamic aspects of
`catalysis by immobilized enzymes. Russ. Chem. Revs. 44: 17-47.
`
`
` 10. Martinek, K., Goldmacher, V.S., Klibanov, A.M., Berezin, I.V. 1975. Denaturing agents (urea,
`acrylamide) protect enzymes against irreversible thermoinactivation: a study with native and
`immobilized α-chymotrypsin and trypsin. FEBS Lett. 51: 152-155.
`
`
` 11. Martinek, K., Klibanov, A.M., Tchernysheva, A.V., Berezin, I.V. 1975. The stabilization of
`α-chymotrypsin by entrapment in polymethacrylate gels. Dokl. Acad. Nauk SSSR 223: 233-236.
`
`Tchernysheva, A.V., Goldmacher, V.S., Klibanov, A.M., Martinek, K., Berezin, I.V. 1975. The
`catalytic activity and thermostability of α-chymotrypsin oligomers entrapped in cross-linked
`polymeric gels. Bull. Moscow Univ. 19: 428-431.
`
`3
`
`
` 12.
`
`
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 3 of 41
`
`

`
` 13.
`
`
` 14.
`
`
` 15.
`
`
` 16.
`
`
` 17.
`
`
` 19.
`
`
` 20.
`
`
` 21.
`
`
` 23.
`
`
` 18. Martinek, K., Goldmacher, V.S., Klibanov, A.M., Torchilin, V.P., Smirnov, V.N., Chazov, E.I.,
`Berezin, I.V. 1976. Thermal stabilization of α-chymotrypsin by covalent attachment to a
`complementary surface of a polymeric matrix. Dokl. Acad. Nauk SSSR 228: 1468-1471.
`
`Poglazov, B.F., Samokhin, G.P., Klibanov, A.M., Levitsky, D.I., Martinek, K., Berezin, I.V. 1977.
`Mechanochemistry of the myosin molecule. Dokl. Acad. Nauk SSSR 234: 482-485.
`
`Berezin, I.V., Klibanov, A.M., Samokhin, G.P., Goldmacher, V.S., Martinek, K. 1977.
`Mechanosensitive and sound-sensitive systems as chemical amplifiers of weak signals. In:
`Biomedical Applications of Immobilized Enzymes and Proteins (T.M.S. Chang, ed.), vol. 2, pp.
`237-251, Plenum Press, New York.
`
`Klibanov, A.M., Samokhin, G.P., Martinek, K., Berezin, I.V. 1977. A new mechanochemical
`method of enzyme immobilization. Biotechnol. Bioeng. 19: 211-218.
`
`
` 22. Martinek, K., Klibanov, A.M., Samokhin, G.P., Semenov, A.M., Berezin, I.V. 1977. Preparative
`enzymatic synthesis in biphasic water-organic systems. J. Bioorg. Chem. (Russ.) 3: 696-702.
`
`Tchernysheva, A.V., Martinek, K., Klibanov, A.M., Mevkh, A.T., Berezin, I.V. 1975. The catalytic
`properties and thermostability of α-chymotrypsin in different polymethacrylate gels. Izvestia
`Acad. Nauk SSSR, Ser. Khim. No.8: 1764-1768.
`
`Klibanov, A.M., Samokhin, G.P., Martinek, K., Berezin, I.V. 1976. Enzymatic mechano-
`chemistry: a new approach to studying the mechanism of enzyme action. Biochim. Biophys.
`Acta 438: 1-12.
`
`Berezin, I.V., Klibanov, A.M., Samokhin, G.P., Martinek, K. 1976. Mechanochemistry of
`immobilized enzymes: a new approach to studies in fundamental enzymology. Regulation by a
`mechanical device of the catalytic properties of enzymes covalently attached to elastic polymeric
`supports. Meth. Enzymol. 44: 558-571.
`
`Berezin, I.V., Klibanov, A.M., Goldmacher, V.S., Martinek, K. 1976. Mechanochemistry of
`immobilized enzymes: a new approach to studies in fundamental enzymology. Regulation by a
`mechanical device of the catalytic activity of enzymes trapped in polyacrylamide gel. Meth.
`Enzymol. 44: 571-576.
`
`Klibanov, A.M., Kazanskaya, N.F., Larionova, N.I., Martinek, K., Berezin, I.V. 1976. A
`comparative study of the dynamic structures of the active centers of proteolytic enzymes by the
`ultrasonic method. The effect of ultrasound on α-trypsin, ß-trypsin, and trypsinogen. J. Bioorg.
`Chem. (Russ.) 2: 828-836.
`
`Klibanov, A.M., Samokhin, G.P., Martinek, K., Berezin, I.V. 1977. A new approach to
`preparative enzymatic synthesis. Biotechnol. Bioeng. 19: 1351-1361.
`
`
` 24. Martinek, K., Klibanov, A.M., Goldmacher, V.S., Berezin, I.V. 1977. The principles of enzyme
`stabilization. I. Increase in thermostability of enzymes covalently bound to a complementary
`surface of a polymeric support in a multipoint fashion. Biochim. Biophys. Acta 485: 1-12.
`
`
`
`4
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 4 of 41
`
`

`
` 25. Martinek, K., Klibanov, A.M., Goldmacher, V.S., Tchernysheva, A.V., Mozhaev, V.V., Berezin,
`I.V., Glotov, B.O. 1977. The principles of enzyme stabilization. II. Increase in thermostability of
`enzymes as a result of multipoint non-covalent interactions with a polymeric support. Biochim.
`Biophys. Acta 485: 13-28.
`
`Torchilin, V.P., Maksimenko, A.V., Smirnov, V.N., Martinek, K., Klibanov, A.M., Berezin, I.V.
`1978. The principles of enzymes stabilization. III. The effect of the length of intramolecular
`cross-linking agents on the thermostability of enzymes. Biochim. Biophys. Acta 522: 277-283.
`
`Samokhin, G.P., Klibanov, A.M., Martinek, K. 1978. Photochemical immobilization of enzymes.
` Bull. Moscow Univ. 19: 433-436.
`
`Poglazov, B.F., Samokhin, G.P., Klibanov, A.M., Levitsky, D.I., Martinek, K., Berezin, I.V. 1978.
`The effect of mechanical stretching of myosin rod part (fragment LMM + HMM S-2) on the
`ATPase activity of myosin. Biochim. Biophys. Acta 524: 245-253.
`
`Klibanov, A.M., Semenov, A.N., Samokhin, G.P., Martinek, K. 1978. Enzymatic reactions in
`water-organic solutions. The criterion for selecting optimal organic co-solvents. J. Bioorg.
`Chem. (Russ.) 4: 236-242.
`
`Sinitsyn, A.P., Klibanov, A.M., Klesov, A.A., Martinek, K. 1978. The dependence of stability of
`immobilized glycoamylase on the method of immobilization. Appl. Biochem. Microbiol. (Russ.)
`14: 236-242.
`
`Klibanov, A.M., Mozhaev, V.V. 1978. On the mechanism of irreversible thermoinactivation of
`enzymes and possibilities for reactivation of "irreversibly" inactivated enzymes. Biochem.
`Biophys. Res. Commun. 83: 1012-1017.
`
`Klibanov, A.M., Kaplan, N.O., Kamen, M.D. 1978. A rationale for stabilization of oxygen-labile
`enzymes: application to a clostridial hydrogenase. Proc. Natl. Acad. Sci. USA 75: 3640-3643.
`
`Torchilin, V.P., Maksimenko, A.V., Smirnov, V.N., Berezin, I.V., Klibanov, A.M., Martinek, K.
`1979. The principles of enzyme stabilization. IV. Modification of "key" functional groups in the
`tertiary structure of proteins. Biochim. Biophys. Acta 567: 1-11.
`
`Klibanov, A.M., Kaplan, N.O., Kamen, M.D. 1979. Chelating agents protect hydrogenase
`against oxygen inactivation. Biochim. Biophys. Acta 547: 411-416.
`
`Klibanov, A.M. 1979. Stabilization of enzymes by immobilization. Anal. Biochem. 93: 1-25.
`
`Klibanov, A.M., Kaplan, N.O., Kamen, M.D. 1980. Thermal stabilities of membrane-bound,
`solubilized and artificially immobilized hydrogenase from Chromatium vinosum. Arch. Biochem.
`Biophys. 199: 545-549.
`
`Klibanov, A.M., Puglisi, A.V. 1980. The regeneration of coenzymes using immobilized
`hydrogenase. Biotechnol. Lett. 2: 445-450.
`
`Klibanov, A.M., Kaplan, N.O., Kamen, M.D. 1980. Approaches to stabilization of hydrogenase
`and nitrogenase against oxygen inactivation. In: Enzyme Engineering V (H.H. Weetall and G.P.
`Royer, eds.), pp.135-142, Plenum Press, New York.
`
`5
`
`
` 26.
`
`
` 27.
`
`
` 28.
`
`
` 29.
`
`
` 30.
`
`
` 31.
`
`
` 32.
`
`
` 33.
`
`
` 34.
`
`
` 35.
`
` 36.
`
`
` 37.
`
`
` 38.
`
`
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 5 of 41
`
`

`
` 39.
`
`
` 40.
`
`
` 41.
`
`
` 42.
`
`
` 43.
`
`
` 44.
`
`
` 45.
`
`
` 46.
`
`
` 48.
`
`
` 49.
`
`
` 50.
`
`
` 51.
`
`
` 52.
`
`
` 53.
`
`
` 54.
`
`
`
`
`
`
` 47. Maneepun, S., Klibanov, A.M. 1982. Stabilization of microbial proteases against autolysis using
`acylation with dicarboxylic acid anhydrides. Biotechnol. Bioeng. 24: 483-486.
`
`Klibanov, A.M., Alberti, B.N., Morris, E.D., Felshin, L.M. 1980. Enzymatic removal of toxic
`phenols and anilines from waste waters. J. Appl. Biochem. 2: 414-421.
`
`Khan, S.M., Klibanov, A.M., Kaplan, N.O., Kamen, M.D. 1981. The effect of electron carriers
`and other ligands on oxygen stability of clostridial hydrogenase. Biochim. Biophys. Acta 659:
`457-465.
`
`Klibanov, A.M., Morris, E.D. 1981. Horseradish peroxidase for the removal of carcinogenic
`aromatic amines from water. Enzyme Microb. Technol. 3: 119-122.
`
`Klibanov, A.M., Huber, J. 1981. Application of immobilized hydrogenase for the de-tritiation of
`water. Biotechnol. Bioeng. 23: 1537-1551.
`
`Klibanov, A.M., Barta, T.E. 1981. Protection of immobilized sulfhydryl groups against auto-
`oxidation by alterations in their microenvironment. Appl. Biochem. Biotechnol. 6: 201-207.
`
`Alberti, B.N., Klibanov, A.M. 1981. Enzymatic removal of dissolved aromatics from industrial
`aqueous effluents. Biotechnol. Bioeng. Symp. 11: 373-379.
`
`Klibanov, A.M., Berman, Z., Alberti, B.N. 1981. Preparative hydroxylation of aromatic
`compounds catalyzed by peroxidase. J. Am. Chem. Soc. 103: 6263-6264.
`
`Klibanov, A.M., Alberti, B.N., Zale, S.E. 1982. Enzymatic synthesis of formic acid from H2 and
`CO2 and production of hydrogen from formic acid. Biotechnol. Bioeng. 24: 25-36.
`
`Klibanov, A.M., Giannousis, P.P. 1982. Geometrically specific oxidation of ß-arylacroleins
`catalyzed by xanthine oxidase: the preparative potential. Biotechnol. Lett. 4: 57-60.
`
`Alberti, B.N., Klibanov, A.M. 1982. Preparative production of hydroquinone from benzoquinone
`catalyzed by immobilized glucose oxidase. Enzyme Microb. Technol. 4: 47-49.
`
`Klibanov, A.M., Siegel, E.H. 1982. Geometric specificity of porcine liver carboxyl esterase and
`its application for the production of cis arylacrylic esters. Enzyme Microb. Technol. 4: 172-174.
`
`Klibanov, A.M., Giannousis, P.P. 1982. Geometric specificity of alcohol dehydrogenases and its
`potential for separation of trans and cis isomers of unsaturated aldehydes. Proc. Natl. Acad.
`Sci. USA 79: 3462-3465.
`
`Klibanov, A.M., Weare, N.M. 1982. Oxygen inactivation and stabilization of Azotobacter
`nitrogenase. In: From Cyclotrones to Cytochromes (N.O. Kaplan and A.B. Robinson, eds.),
`pp. 509-516, Academic Press, New York.
`
`Zale, S.E., Klibanov, A.M. 1982. Application of immobilized hydrogenase to H2 storage in
`concentrated solutions of methyl viologen. Appl. Biochem. Biotechnol. 7: 317-323.
`
`Klibanov, A.M., Alberti, B.N., Marletta, M.A. 1982. Stereospecific oxidation of aliphatic alcohols
`catalyzed by galactose oxidase. Biochem. Biophys. Res. Commun. 108: 804-808.
`
`6
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 6 of 41
`
`

`
`Pungor, E., Klibanov, A.M., Cooney, C.L., Weaver, J.C. 1982. Continuous 2HHO determination
`in H2O solutions by a computer-controlled mass spectrometer. Biomed. Mass Spectrom. 9: 181-
`-185.
`
`Klibanov, A.M. 1983. Unconventional catalytic properties of conventional enzymes: applications
`in organic chemistry. In: The Biological Basis of New Developments in Biotechnology (A.
`Hollaender, A.I. Laskin, and P. Rogers, eds.), pp. 497-518, Plenum Press, New York.
`
`Klibanov, A.M. 1983. Biotechnological potential of the enzyme hydrogenase. Process
`Biochem. 18: 13-16.
`
`Pelsy, G., Klibanov, A.M. 1983. Remarkable positional (regio-) specificity of xanthine oxidase
`and some dehydrogenases in the reactions with substituted benzaldehydes. Biochim. Biophys.
`Acta 742: 352-357.
`
` 55.
`
`
` 56.
`
`
` 57.
`
`
`58.
`
`
`
`
` 60.
`
`
` 61.
`
`
` 62.
`
`
` 63.
`
`
` 64.
`
`
` 65.
`
` 59. Klibanov, A.M. 1983. Stabilization of enzymes against thermal inactivation. Adv. Appl.
`Microbiol. 29: 1-28.
`
`Klibanov, A.M., Chendrasekhar, A., Alberti, B.N. 1983. Enzymatic separation of cis and trans
`isomers of alicyclic alcohols. Enzyme Microb. Technol. 5: 265-268.
`
`Klibanov, A.M. 1983. Immobilized enzymes and cells as practical catalysts. Science 219:
`722-727.
`
`Pelsy, G., Klibanov, A.M. 1983. Preparative separation of α- and ß- naphthols catalyzed by
`immobilized sulfatase. Biotechnol. Bioeng. 25: 919-928.
`
`Zale, S.E., Klibanov, A.M. 1983. On the role of reversible denaturation (unfolding) in the
`irreversible thermal inactivation of enzymes. Biotechnol. Bioeng. 25: 2221-2230.
`
`Klibanov, A.M., Tu, T.-M., Scott, K.P. 1983. Peroxidase-catalyzed removal of phenols from coal
`conversion wastewaters. Science 221: 259-261.
`
`Atlow, S.C., Bonadonna-Aparo, L., Klibanov, A.M. 1984. Dephenolization of industrial
`wastewaters catalyzed by polyphenol oxidase. Biotechnol. Bioeng. 26: 599-603.
`
`
` 66. Cambou, B., Klibanov, A.M. 1984. Preparative production of optically active esters and alcohols
`using esterase-catalyzed stereospecific transesterifications in organic media. J. Am. Chem.
`Soc. 106: 2687-2692.
`
`
` 67. Dropsy, E.P., Klibanov, A.M. 1984. Cholinesterase-catalyzed resolution of D,L-carnitine.
`Biotechnol. Bioeng. 26: 911-915.
`
`
` 68. Cambou, B., Klibanov, A.M. 1984. Lipase-catalyzed production of optically active acids via
`asymmetric hydrolysis of esters: effect of the alcohol moiety. Appl. Biochem. Biotechnol. 9:
`255-260.
`
`Zaks, A., Klibanov, A.M. 1984. Enzymatic catalysis in organic media at 100oC. Science 224:
`1249-1251.
`
`7
`
`
` 69.
`
`
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 7 of 41
`
`

`
` 70. Cambou, B., Klibanov, A.M. 1985. Comparison of different strategies for the lipase- catalyzed
`preparative resolution of racemic acids and alcohols: asymmetric hydrolysis, esterification, and
`transesterification. Biotechnol. Bioeng. 26: 1449-1454.
`
`Scollar, M.P., Sigal, G., Klibanov, A.M. 1985. Preparative resolution of D,L-threonine catalyzed
`by immobilized phosphatase. Biotechnol. Bioeng. 27: 247-252.
`
`Ahern, T.J., Klibanov, A.M. 1985. The mechanism of irreversible enzyme inactivation at 100°C.
`Science 228: 1280-1284.
`
`
` 73. Cesti, P., Zaks, A., Klibanov, A.M. 1985. Preparative regioselective acylation of glycols by
`enzymatic transesterification in organic solvents. Appl. Biochem. Biotechnol. 11: 401-407.
`
`
` 71.
`
`
` 72.
`
`
` 74.
`
`
` 75.
`
`
` 76.
`
`
` 77.
`
`Zaks, A., Klibanov, A.M. 1985. Enzyme-catalyzed processes in organic solvents. Proc. Natl.
`Acad. Sci. USA 82: 3192-3196.
`
`Kazandjian, R.Z., Klibanov, A.M. 1985. Regioselective oxidation of phenols catalyzed by
`polyphenol oxidase in chloroform. J. Am. Chem. Soc. 107: 5448-5450.
`
`Kirchner, G., Scollar, M.P., Klibanov, A.M. 1985. Resolution of racemic mixtures via lipase
`catalysis in organic solvents. J. Am. Chem. Soc. 107: 7072-7076.
`
`Lavin, A., Sung, C., Klibanov, A.M., Langer, R.S. 1985. Enzymatic removal of bilirubin from the
`blood: a potential treatment of neonatal jaundice. Science 230: 543-545.
`
`
` 78. Hammond, D.A., Karel, M., Klibanov, A.M., Krukonis, V.J. 1985. Enzymatic reactions in
`supercritical gases. Appl. Biochem. Biotechnol. 11: 393-400.
`
`
` 79. Sung, C., Lavin, A., Klibanov, A.M., Langer, R. 1986. An immobilized enzyme reactor for the
`treatment of severe jaundice. Trans. Am. Soc. Artif. Intern. Organs. 31: 264-269.
`
`
` 80.
`
`Kazandjian, R.Z., Dordick, J.S., Klibanov, A.M. 1986. Enzymatic analyses in organic solvents.
`Biotechnol. Bioeng. 28: 417-421.
`
`Klibanov, A.M. 1986. Enzymes that work in organic solvents. CHEMTECH 16: 354-359.
`
`
` 81.
`
` 82. Dordick, J.S., Klibanov, A.M., Marletta, M.A. 1986. Horseradish peroxidase-catalyzed
`hydroxylations: mechanistic studies. Biochemistry. 25: 2946-2951.
`
`
` 83.
`
`
` 84.
`
`Sung, C., Lavin, A., Klibanov, A.M., Langer, R. 1986. An immobilized enzyme reactor for the
`detoxification of bilirubin. Biotechnol. Bioeng. 28: 1531-1539.
`
`Zaks, A., Klibanov, A.M. 1986. Substrate specificity of enzymes in organic solvents vs. water is
`reversed. J. Am. Chem. Soc. 108: 2767-2768.
`
`
` 85. Dordick, J.S., Marletta, M.A., Klibanov, A.M. 1986. Peroxidases depolymerize lignin in organic
`media but not in water. Proc. Natl. Acad. Sci. USA 83: 6255-6257.
`
`Zale, S.E., Klibanov, A.M. 1986. Why does ribonuclease irreversibly inactivate at high
`temperatures? Biochemistry 25: 5432-5444.
`
`8
`
`
` 86.
`
`
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 8 of 41
`
`

`
` 87. Grunwald, J., Wirz, B., Scollar, M.P., Klibanov, A.M. 1986. Asymmetric oxidoreductions
`catalyzed by alcohol dehydrogenase in organic solvents. J. Am. Chem. Soc. 108: 6732-6734.
`
`
` 88.
`
`
` 89.
`
`
` 90.
`
`
` 91.
`
`
` 92.
`
`Therisod, M., Klibanov, A.M. 1986. Facile enzymatic preparation of monoacylated sugars in
`pyridine. J. Am. Chem. Soc. 108: 5638-5640.
`
`Boeriu, C.G., Dordick, J.S., Klibanov, A.M. 1986. Enzymatic reactions in liquid and solid
`paraffins: application for enzyme-based temperature abuse sensors. Bio/Technol. 4: 997-999.
`
`Klibanov, A.M., Cambou, B. 1987. Enzymatic production of optically active compounds in
`biphasic aqueous-organic systems. Meth. Enzymol. 136C: 117-137.
`
`Ahern, T.J., Casal, J.I., Petsko, G.A., Klibanov, A.M. 1987. Control of oligomeric enzyme
`thermostability by protein engineering. Proc. Natl. Acad. Sci. USA 84: 675-679.
`
`Shaw, J.F., Klibanov, A.M. 1987. Preparation of various glucose esters via lipase-catalyzed
`hydrolysis of glucose pentaacetate. Biotechnol. Bioeng. 29: 648-651.
`
`
` 93. Casal, J.I., Ahern, T.J., Davenport, R.C., Petsko, G.A., Klibanov, A.M. 1987. Subunit interface
`of triosephosphate isomerase: site-directed mutagenesis and characterization of the altered
`enzyme. Biochemistry 26: 1258-1264.
`
`
` 94. Dordick, J.S., Marletta, M.A., Klibanov, A.M. 1987. Polymerization of phenols catalyzed by
`peroxidase in non-aqueous media. Biotechnol. Bioeng. 30: 31-36.
`
`
` 95.
`
`
` 97.
`
`
` 98.
`
`
` 99.
`
`Visuri, K., Klibanov, A.M. 1987. Enzymatic production of high fructose corn syrup (HFCS)
`containing 55% fructose in aqueous ethanol. Biotechnol. Bioeng. 30: 917-920.
`
`
` 96. Margolin, A.L., Crenne, J.-Y., Klibanov, A.M. 1987. Stereoselective oligomerizations catalyzed
`by lipase in organic solvents. Tetrahedron Lett. 28: 1607-1610.
`
`Volkin, D.B., Klibanov, A.M. 1987. Thermal destruction processes in proteins involving cystine
`residues. J. Biol. Chem. 262: 2945-2950.
`
`Therisod, M., Klibanov, A.M. 1987. Regioselective acylation of secondary hydroxyl groups in
`sugars catalyzed by lipases in organic solvents. J. Am. Chem. Soc. 109: 3977-3981.
`
`Ahern, T.J., Klibanov, A.M. 1987. Analysis of processes causing thermal inactivation of
`enzymes. Meth. Biochem. Analysis 33: 91-127.
`
`
`100. Margolin, A.L., Klibanov, A.M. 1987. Peptide synthesis catalyzed by lipases in anhydrous
`organic solvents. J. Am. Chem. Soc. 109: 3802-3804.
`
`
`101. Barzana, E., Klibanov, A.M., Karel, M. 1987. Enzyme-catalyzed gas phase reactions. Appl.
`Biochem. Biotechnol. 15: 25-34.
`
`
`102. Margolin, A.L., Tai, D.-F., Klibanov, A.M. 1987. Incorporation of D-amino acids into peptides via
`enzymatic condensation in organic solvents. J. Am. Chem. Soc. 109: 7885-7887.
`
`
`
`9
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 9 of 41
`
`

`
`103. Chopineau, J., McCafferty, F.D., Therisod, M., Klibanov, A.M. 1988. Production of
`biosurfactants from sugar alcohols and vegetable oils catalyzed by lipases in a non-aqueous
`medium. Biotechnol. Bioeng. 31: 208-214.
`
`
`104. Mullon, C.J.P., Klibanov, A.M., Langer, R. 1988. Kinetics of soluble bilirubin oxidase and
`modelling of an immobilized bilirubin oxidase reactor for bilirubin detoxification. Biotechnol.
`Bioeng. 31: 536-546.
`
`
`105. Riva, S., Chopineau, J., Kieboom, A.P.G., Klibanov, A.M. 1988. Protease-catalyzed
`regioselective esterification of sugars and related compounds in anhydrous dimethylformamide.
`J. Am. Chem. Soc. 110: 584-589.
`
`
`106. Tomazic, S.J., Klibanov, A.M. 1988. Mechanisms of irreversible thermal inactivation of Bacillus
`α-amylases. J. Biol. Chem. 263: 3086-3091.
`
`
`107. Tomazic, S.J., Klibanov, A.M. 1988. Why is one Bacillus α-amylase more resistant against
`irreversible thermoinactivation than another? J. Biol. Chem. 263: 3092-3096.
`
`
`108. Zaks, A., Klibanov, A.M. 1988. Enzymatic catalysis in non-aqueous solvents. J. Biol. Chem.
`263: 3194-3201.
`
`
`109. Riva, S., Klibanov, A.M. 1988. Enzymo-chemical regioselective oxidation of steroids without
`oxidoreductases. J. Am. Chem. Soc. 110: 3291-3295.
`
`
`110. Zaks, A., Klibanov, A.M. 1988. The effect of water on enzyme action in organic media. J. Biol.
`Chem. 263: 8017-8021.
`
`
`111. Russell, A.J., Klibanov, A.M. 1988. Inhibitor-induced enzyme activation in organic solvents.
`J. Biol. Chem. 263: 11624-11626.
`
`
`112. Weaver, J.C., Williams, G.B., Klibanov, A.M., Demain, A.L. 1988. Gel microdroplets: rapid
`detection and enumeration of individual microorganisms by their metabolic activity.
`Bio/Technology 6: 1084-1089.
`
`
`113. Kitaguchi, H., Tai, D.-F., Klibanov, A.M. 1988. Enzymatic formation of an isopeptide bond
`involving the ε-amino group of lysine. Tetrahedron Lett. 29: 5487-5488.
`
`
`114. Sakurai, T., Margolin, A.L., Russell, A.J., Klibanov, A.M. 1988. Control of enzyme enantio-
`selectivity by the reaction medium. J. Am. Chem. Soc. 110: 7236-7237.
`
`
`115. Volkin, D.B., Klibanov, A.M. 1989. Mechanism of thermoinactivation of immobilized glucose
`isomerase. Biotechnol. Bioeng. 33: 1104-1111.
`
`
`116. Chinsky, N., Margolin, A.L., Klibanov, A.M. 1989. Chemoselective enzymatic monoacylation of
`bifunctional compounds. J. Am. Chem. Soc. 111: 386-388.
`
`
`117. Russell, A.J., Trudel, L.J., Skipper, P.L., Groopman, J.D., Tannenbaum, S.R., Klibanov, A.M.
`1989. Antibody-antigen binding in organic solvents. Biochem. Biophys. Res. Commun. 158:
`80-85.
`
`
`
`10
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 10 of 41
`
`

`
`118. Barzana, E., Karel, M., Klibanov, A.M. 1989. Enzymatic oxidation of ethanol in the gaseous
`phase. Biotechnol. Bioeng. 34: 1178-1185.
`
`
`119. Kitaguchi, H., Fitzpatrick, P.A., Huber, J.E., Klibanov, A.M. 1989. Enzymatic resolution of
`racemic amines: crucial role of the solvent. J. Am. Chem. Soc. 111: 3094-3095.
`
`
`120. Dorval, B.L., Chow, M., Klibanov, A.M. 1989. Stabilization of poliovirus against heat
`inactivation. Biochem. Biophys. Res. Commun. 159: 1177-1183.
`
`
`121. Barzana, E., Klibanov, A.M., Karel, M. 1989. A colorimetric method for the enzymatic analysis of
`gases: the determination of ethanol and formaldehyde vapors using solid alcohol oxidase. Anal.
`Biochem. 182: 109-115.
`
`
`122. Volkin, D.B., Klibanov, A.M. 1989. Minimizing protein inactivation. In: Protein Function - A
`Practical Approach (T.E. Creighton, ed.), pp. 1-24, IRL Press, Oxford.
`
`
`123. Klibanov, A.M. 1989. Enzymatic catalysis in anhydrous organic solvents. Trends Biochem.
`Sci. 14: 141-144.
`
`
`124. Kanerva, L.T., Klibanov, A.M. 1989. Hammett analysis of enzyme action in organic solvents.
`J. Am. Chem. Soc. 111: 6864-6865.
`
`
`125. Burke, P.A., Smith, S.O., Bachovchin, W.W., Klibanov, A.M. 1989. Demonstration of structural
`integrity of an enzyme in organic solvents by solid-state NMR. J. Am. Chem. Soc. 111: 8290-
`8291.
`
`
`126. Kitaguchi, H., Klibanov, A.M. 1989. Enzymatic peptide synthesis via segment condensation in
`the presence of water mimics. J. Am. Chem. Soc. 111: 9272-9273.
`
`
`127. Braco, L., Dabulis, K., Klibanov, A.M. 1990. Design of novel receptors by molecular imprinting
`of proteins. Proc. Natl. Acad. Sci. USA 87: 274-277.
`
`
`128. Margolin, A.L., Klibanov, A.M. 1990. Enzymatic synthesis of peptides in anhydrous organic
`solvents. In: Peptides. Chemistry, Structure and Biology (J.E. Rivier and G.R. Marshall, eds.),
`pp. 355-359, ESCOM Science Publishers, Leiden.
`
`
`129. Dorval, B.L., Chow, M., Klibanov, A.M. 1990. Lysine and other diamines dramatically stabilize
`poliovirus against thermoinactivation. Biotechnol. Bioeng. 35: 1051-1054.
`
`
`130. Klibanov, A.M. 1990. Asymmetric transformations catalyzed by enzymes in organic solvents.
`Acc. Chem. Res. 23: 114-120.
`
`
`131. Adams, K.A.H., Chung, S.-H., Klibanov, A.M. 1990. Kinetic isotope effect investigation of
`enzyme mechanism in organic solvents. J. Am. Chem. Soc. 112: 9418-9419.
`
`
`132. Liu, W.R., Langer, R., Klibanov, A.M. 1991. Moisture-induced aggregation of lyophilized
`proteins in the solid state. Biotechnol. Bioeng. 37: 177-184.
`
`
`133. Rubio, E., Fernandez-Mayorales, A., Klibanov, A.M. 1991. Effect of the solvent on enzyme
`regioselectivity. J. Am. Chem. Soc. 113: 695-696.
`
`
`
`11
`
`
`
`NOVARTIS EXHIBIT 2402
`Par v Novartis, IPR 2016-00084
`Page 11 of 41
`
`

`
`134. Chang, N., Hen, S.J., Klibanov, A.M. 1991. Protein separation and purification in neat dimethyl
`sulfoxide (DMSO). Biochem. Biophys. Res. Commun. 176: 1462-1468.
`
`
`135. Volkin, D.B., Staubli, A., Langer, R., Klibanov, A.M. 1991. Enzyme thermoinactivation in
`anhydrous organic solvents. Biotechnol. Bioeng. 37: 843-853.
`
`
`136. Schulze, B., Klibanov, A.M. 1991. Inactivation and stabilization of subtilisins in neat organic
`solvents. Biotech. Bioeng. 38: 1001-1006.
`
`
`137. Fitzpatrick, P.A., Klibanov, A.M. 1991. How can the solvent affect enzyme enantioselectivity?
`J. Am. Chem. Soc. 113: 3166-3171.
`
`
`138. Margolin, A.L., Fitzpatrick, P.A., Dubin, P.L., Klibanov, A.M. 1991. Chemo-enzymatic synthesis
`of optically active (meth)acrylic polymers. J. Am. Chem. Soc. 113: 4693-4694.
`
`
`139. Sluzky, V., Tamada, J.A., Klibanov, A.M., Langer, R. 1991. Kinetics of insulin aggregation in
`aqueous solutions upon agitation in the presence of hydrophobic surfaces. Proc. Natl. Aca