1005 Dunvegan Road
`West Chester, PA 19382
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`Lars J. S. Knutsen, Ph.D.
`Tel. 610.410.5810; cell 484.319.0117
`Lars.Knutsen@drexelmed.edu
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`
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`PROFILE
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`Results-driven Pharma R&D Consultant, Drug Discovery Director and Senior Medicinal Chemist. Expert in
`design and selection of Drug Candidates; broad neuroscience medicinal chemistry capability focused on
`treatments for epilepsy, sleep disorders, cognition and neurodegeneration. Motivated teams of scientists to
`achieve goals in 6 companies over a 30+ year Pharma/Biotech career. Superb analytical skills and deep pharma
`industry knowledge. Closely involved in 7 NCEs of which 5 progressed to clinical trials, including Vipadenant
`(Parkinson’s Disease) and Irdabisant (Cognition); anticonvulsant Gabitril™ marketed worldwide.
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`Adjunct Professor at Drexel University School of Medicine since 2009; regular major conference speaker
`with 45 peer-reviewed publications, 33 published PCT patents; 22 issued in US. Chaired Patent Committees at
`Ionix Pharma and Vernalis PLC; strong knowledge of Pharma patenting process in US and EU with its many
`issues. Member of NIMH/NCDDDG NIH Grant Review Panel, 2010 and 2011. Articulate and creative scientific
`leader with excellent interpersonal skills; methodical and focused. Peer recognized high-level heterocyclic,
`nucleoside and carbohydrate chemist with in depth knowledge of organic chemistry. Drug biology and PK/
`ADME knowledge, Fellow, Royal Society of Chemistry, ACS and SfN member; became a US Citizen in 2015.
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`PROFESSIONAL EXPERIENCE
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` Feb. 2009 - present
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`Discovery Pharma Consulting LLC. West Chester, PA USA
`President
`Founded as Lars’ 4th start-up in response to clients requesting expert Pharma R&D Consulting services.
`Specializing in IP Expert Witness work, Preclinical Drug Discovery; including Hit-to-Lead, Lead Optimization
`and Preclinical Development phases. Medicinal Chemistry input provided along with Strategic IP and R&D
`Portfolio reviews, see www.discoverypharm.com. Some assets have been transitioned into a new product-
`focused Biotech focused on drugs for sleep and CNS disorders, Requis Pharma Inc., where I am Acting CEO.
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`Drexel University College of Medicine Philadelphia, PA
`Adjunct Professor
`Appointed by Prof. James Barrett, Dept. of Pharmacology and Physiology, to advise and collaborate with faculty
`on drug R&D strategy, to teach Drug Discovery, and to drive entrepreneurism in the wider Drexel community.
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` May 2013 - present
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`Charcot-Marie Tooth Association
`Science Advisory Board and Therapy Expert Board Member, researching treatments for CMT disease, an
`inherited peripheral neuropathy, in the non-profit CMTA: http://www.cmtausa.org/research/star-advisory-board/
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`Cephalon, Inc. West Chester, PA USA
`Distinguished Scientist/ Project Leader
`Hired into this newly-created role, built new team; drove initiation of and managed new Schizophrenia project.
`Key input to strategic course of Cephalon R&D in Oncology and CNS in Project Management Group.
` Major contributor to Cognition program – invented Irdabisant (CEP-26401), my 5th career NCE and Cephalon’s
`most recent clinical drug: https://www.clinicaltrials.gov/ct2/show/NCT01903824?term=irdabisant&rank=1
` Synthesis lab. presence with high compound output; drove several projects with external chemistry CROs.
` Cephalon’s first Distinguished Scientist; consulted internally on the anticonvulsant Gabitril™, a Cephalon product
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`Ionix Pharmaceuticals Cambridge, UK
`Director of Chemistry
`Responsible for R & D Chemistry, including strategy/ budgeting, in this pain and ion-channel focused start-up
`company. Built outstanding team of 15+ medicinal chemists and computational chemist. Key member of Ionix
`Management Team, Product Management Group and Chair of Intellectual Property Strategy Meeting.
` Drove creative medicinal chemistry/parallel synthesis in calcium and sodium channel blocker projects. Project
`Leader of key Cav2.2 (N-type channel) program.
` Completed major drug design and synthesis projects with CROs such as Tripos and Evotec. Networked into
`European and worldwide CROs such as Penn, Onyx and SigmaAldrich, planning Preclinical and CMC phases.
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`November 2009 - present
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` 2005 - 2008
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`2001 – 2005
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`0001
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`MYLAN - EXHIBIT 1103
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`1997 – 2001
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`1993 – 1997
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`Vernalis (formerly Cerebrus), Wokingham, UK
`Associate Director, Medicinal Chemistry
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`Initiated Discovery project for new adenosine A2A antagonists for Parkinson’s Disease; Vipadenant (VR 2006) showed
`PoC, made it to Phase II in Biogen Idec, see: http://production.investis.com/ver/rdc/v2006/?t=print
` Leader of Sodium Channel program; Head of Pre-Project group; involved in Autism research.
` Started pre-project targeting novel CB1 antagonists in 2001; lead compound, V24343, entered clinical trials for obesity
`late in 2006, see: http://www.vernalis.com/media-centre/archive-releases/2006-releases/407
` Recruited and coached 5 medicinal chemists to join my team as direct reports.
` Member of Chemistry Management Team, devised company strategies for I.P. and Parallel Synthesis.
` Part of Integration Team following Vanguard merger with Cerebrus in late 1999.
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`Novo Nordisk, Pharmaceuticals Division, Måløv, Denmark
`Principal Scientist and Department Leader, Medicinal Chemistry
` Project Manager, Purine project group; initiated project on adenosine A1 receptor agonists for stroke. Led high-
`performing team of chemists. Promoted to Department Head in 1995.
` A1 agonist drug candidate NNC 21-0136, selected as pre-clinical compound 2¼ years from project start; back-up
`NNC 21-0149 also identified. Completed Novo management/ project manager training modules
` Gabitril launched as novel anticonvulsant in 1997; Invented back-up series to Gabitril, NNC-711 – authored
`1999 J. Med. Chem. article. NNC-711 reviewed in CNS Drug Reviews, 1999, 5, 317-330.
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`Novo Industri CNS Division, Copenhagen, Denmark
`Project Leader/ Senior Chemist
` Project Manager, GABA Uptake III project group. Promoted to Principal Scientist in 1993.
` Led project team driving discovery & selection of the marketed anticonvulsant Tiagabine (Gabitril).
` Principal author of 1993 J. Med. Chem. describing synthesis, SAR of Gabitril, as well as back-ups in 1999.
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`Glaxo Group Research, Ware, Herts. UK
`Research Chemist in Medicinal Chemistry
` Drove forward design and synthesis of novel nucleoside antiviral agents, acyclovir analogues and adenosine
`receptor ligands in this entry-level role; promoted to S2 chemist after 1 year.
` Completed Ph.D. studies externally through King’s College, London while at Glaxo.
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`1986 - 1993
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`1978 - 1986
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`AWARDS AND HONORS
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` Appointed to the Science Advisory Board of the Charcot Marie Tooth Association (2013)
` Awarded prize as top 10 reviewer for Bioorganic and Medicinal Chemistry Letters (2012)
` Appointed as an adjunct Professor at Drexel University College of Medicine (2009)
` Honored at dinner for the 2 Cephalon Distinguished Scientists; portrait placed in foyer of R&D HQ (2007)
` Awarded O-1 Outstanding Expert (“Rock Star”) Visa to the US (2005), became US Citizen (2015)
` Appointed as a Fellow of the Royal Society of Chemistry (1999)
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`EDUCATION
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`Ph.D. in Medicinal Chemistry (while employed at Glaxo, Ware, Herts, UK) in collaboration with Prof. C.B.
`Reese, Kings College, London & CNAA). Ph.D. thesis: "The Synthesis of Bridgehead Nitrogen C-Nucleosides"
`yielded 7 major peer-reviewed publications. Advisors: Prof. Roger F. Newton & Dr. David I.C. Scopes.
`B.A. (Hons.)/ M.A. in Chemistry 1978, Christ Church, University of Oxford
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`JOURNAL INVOLVEMENT & COLLABORATIONS
` Served on Editorial Advisory Board of Drug Development Research (1994 – 2010) and a regular reviewer
`for J. Med. Chem. and Bioorg. Med. Chem. Lett.
`Initiated collaborations with academic groups, with e.g. Dr. Ken Jacobson (NIH, USA), Prof. Joel Linden
`(Univ. of Virginia, Charlottesville, USA) and Prof. Stan Roberts, (Univ. of Liverpool, U.K.). When at Novo
`Nordisk, supervised 4 successive postgrad. students in Medicinal Chemistry with Prof. Roberts, 2 to
`successful Ph.D. and 2 to M.S. The students worked both in my lab. at Novo Nordisk and at Prof. Roberts’
`Dept. Funding provided by the Novo Nordisk Foundation:
`http://www.novonordisk.com/about_us/corporate_governance/foundation.asp
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`Lars J. S. Knutsen, Ph.D. ADDENDUM
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`Page 3 of 9
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`PUBLICATIONS
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`1. Knutsen, L.J.S.; Aimone, L.D.; Bacon, E.R.; Lyons, J.; Prouty, C.P.; Raddatz, R.; Sundar, B. and Hudkins,
`R.L. 3,6-Disubstituted Pyridazines as Novel Analogues of CEP-26401: CNS Penetrant Histamine H3
`Receptor Antagonists. Bioorg. Med. Chem. Lett., manuscript submitted.
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`2. Hudkins, R.L.; Raddatz, R.; Tao, M.; Mathiasen, J.R..; Aimone, L.D.; Becknell, N.C.; Prouty, C.P.;. Knutsen,
`L.J.S.; Yazdanian, M.; Moachon, G.; Ator, M.A.; Mallamo, J.P.; Marino, M.J.; Bacon, E.R. and Williams, M.
`Discovery
`and Characterization
`of
`6-{4-[3-(R)-2-Methylpyrrolidin-1-yl)prop-oxy]phenyl}-2H-
`pyridazin-3-one (CEP-26401, Irdabisant): A Potent, Selective Histamine H3 Receptor Inverse Agonist.
`J. Med. Chem., 2011, 54, 4781-4792.
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`3. Knutsen, L.J.S. Drug discovery management, small is still beautiful: Why a number of companies get it
`wrong. Drug Discovery Today, 2011, 16, 476-484.
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`4. Gillespie, R.J.; Adams, D.R.; Bebbington, D.; Benwell, K.; Cliffe, I.A.; Dawson, C.E.; Dourish, C.T.;
`Fletcher, A.; Gaur, S; Giles, P.R.; Jordan, A.M.; Knight, A.R.; Knutsen, L.J.S.; Lawrence, A.; Lerpiniere, J.;
`Misra, A.; Porter, R.H.P.; Pratt, R.M.; Shepherd, R. Upton, R.; Ward, S.E.; Weiss, S.M. and Williamson.
`D.S. Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-
`d]pyrimidine-4-methanone derivatives. Bioorg. Med. Chem. Lett., 2008, 18, 2916 - 2919.
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`5. Marino, M.J.: Knutsen, L.J.S and Williams M. Perspective: Emerging Opportunities for Antipsychotic
`Drug Discovery in the Postgenomic Era J. Med. Chem., 2008, 51, 1077 - 1107.
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`6. Knutsen, L.J.S., Hobbs, C.J.; Earnshaw, C.G., Fiumana, A., Gilbert, J., Mellor, S.L., Radford, F., Smith, N.J.,
`Birch, P.J., Burley, R., Thomas, D., Ward, S.D.C. and James, I.F. Synthesis and SAR of novel 2-
`arylthiazolidinones as selective analgesic N-type calcium channel blockers. Bioorg. Med. Chem. Lett.,
`2007, 17, 662 - 667.
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`7. Marino, M.J.: Davis, R.E.; Meltzer, H.E.; Knutsen, L.J.S and Williams M. Schizophrenia. In Comprehensive
`Medicinal Chemistry II (Taylor, J.B; Triggle, D. J., Editors-in-Chief) Vol. 6; Therapeutic Areas I (M.
`Williams, Volume Editor), 2006, pp. 17 - 44.
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`8. Knutsen, L.J.S and Williams M. Epilepsy. In Comprehensive Medicinal Chemistry II (Taylor, J.B; Triggle,
`D. J., Editors-in-Chief) Vol. 6; Therapeutic Areas I (M. Williams, Volume Editor), 2006, pp 279 - 296.
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`9. Bowdle, T. A., Knutsen, L.J.S and Williams M. Local and Adjunct Anesthesia. In Comprehensive
`Medicinal Chemistry II (Taylor, J.B; Triggle, D. J., Editors-in-Chief) Vol. 6; Therapeutic Areas I (M.
`Williams, Volume Editor), 2006, pp 351 - 368.
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`10. Haldeman, M.; Vieira, B.; Winer, F. and Knutsen, L.J.S. Exploration Tools for Drug Discovery and
`Beyond: Applying SciFinder® to Interdisciplinary Research. Current Drug Discovery Technologies,
`2005, 2, 69 - 74.
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`11. Knutsen, L.J.S.; Weiss, S.M; KW-6002, Kyowa Hakko Kogyo. Curr. Opin. Invest. Drugs (PharmaPress
`Ltd.), 2001, 2, 668 - 673.
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`12. Jacobson, K.A. and Knutsen, L.J.S.; P1 and P2 Purine and Pyrimidine Receptor Ligands. In Handbook of
`Experimental Pharmacology, Volume 151/I: Purinergic and Pyrimidinergic Signalling I; Abbracchio M.P.
`and Williams, M., Eds.; Springer-Verlag: Berlin, Germany; 2001, pp 129 - 175.
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`13. Bentley, J.M., Cliffe, I.A., Knutsen, L.J.S., Monck, N.J. Medicinal Chemistry – 16th International
`Symposium, I Drugs, 2000, 3, 1457 – 1486.
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`14. Dhanda, A.; Knutsen, L.J.S.; Nielsen, M-B; Roberts, S.M.; Varley, D.R. Facile conversion of 4-endo-
`hydroxy-2-oxabicyclo[3.3.0]oct-7-en-3-one into carbocyclic 2'-deoxyribonucleoside analogues. J. Chem.
`Soc., Perkin Trans. 1, 1999, 23, 3469 - 3475.
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`15. Cliffe, I.A., Bebbington, D., Gillespie, R.J. and Knutsen, L.J.S. RSC-SCI Tenth Medicinal Chemistry
`Symposium, I Drugs, 1999, Week 38, 25 - 29.
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`16. Andersen, K.E; Sorensen, J.L.; Huusfeldt, PO.; Knutsen, L.J.S.; Lau, J.; Lundt, B.F.; Petersen, H.; Suzdak,
`P.D.; Swedberg, M.D.B. Synthesis of Novel GABA Uptake Inhibitors. 4. Bioisosteric Transformation
`and Successive Optimization of Known GABA Uptake Inhibitors Leading to a Series of Potent
`Anticonvulsant Drug Candidates. J. Med. Chem., 1999, 42, 4281 - 4291.
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`17. Knutsen, L.J.S., Lau, J., Petersen, H., Thomsen, C., Weis, J.U., Shalmi, M., Judge, M.E., Hansen, A.J. and
`Sheardown, M.J.; N-Substituted Adenosines as Novel Neuroprotective A1 Agonists with Diminished
`Hypotensive Effects. J. Med. Chem., 1999, 42, 3463 - 3477.
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`18. Knutsen, L.J.S., Andersen, K.E., Lau, J., Lundt, B.F., Henry, R.F., Morton, H.E., Nærum, L., Petersen, H.,
`Stephensen, H., Suzdak, P.D., Swedberg, M.D.B., Thomsen, C. and Sørensen P.O. The Synthesis of Novel
`GABA Uptake Inhibitors. 3. Diaryloxime and Diarylvinylether Derivatives of Nipecotic acid and
`Guvacine as Anticonvulsant Agents. J. Med. Chem., 1999, 42, 3447 - 3462.
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`19. Knutsen L.J.S., Sheardown M.J., Roberts S.M., Mogensen J.P., Olsen U.B., Thomsen, C. and Bowler A.N.
`Adenosine A1 and A3 Selective N-Alkoxypurines as novel Cytokine Modulators and Neuroprotectants
`Drug Dev. Res. 1998, 45, 214 - 221.
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`20. Mogensen, J.P., Roberts, S.M., Bowler, A.N., Thomsen, C. and Knutsen, L.J.S.; The Synthesis of New
`Adenosine A3 Selective Ligands Containing Bioisosteric Isoxazoles. Bioorg. Med. Chem. Lett. 1998, 8,
`1767 - 1770.
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`21. Barkley, J.V., Dhanda, A., Knutsen, L.J.S., Nielsen, M-B., Roberts, S.M. and Varley, D.R. Stereoselective
`Conversion of 2',3'-Dideoxydidehydrocarbocyclic nucleosides into 2'-Deoxycarbocyclic nucleosides.
`Chem. Commun. 1998, 1117 - 1118.
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`[3H]-N-[R-(2-
`22. Thomsen, C., Valsborg, J.S., Foged, C. Knutsen, L.J.S. Characterization of
`benzothiazolyl)thio-2-propyl]-2-chloroadenosine ([3H]-NNC 21-0136) binding to rat brain: profile of
`novel selective agonist for adenosine A1 receptors. Drug Dev. Res. 1997, 42, 86 - 97.
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`23. Knutsen, L.J.S. and Murray, T.F. Adenosine and ATP in Epilepsy. Purinergic Approaches Exp. Ther.
`(1997), 423 - 447. Editors: Jacobson, Ken A.; Jarvis, Michael F. Publisher: Wiley-Liss, New York, N. Y.
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`24. Sheardown, M.J. and Knutsen, L.J.S.; Unexpected Neuroprotection Observed with the Adenosine A2A
`Receptor Agonist CGS 21680. Drug Dev. Res., 1996, 39, 108 - 114.
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`25. Valsborg, J.S., Knutsen, L.J.S., and Foged, C.; 14C-labelling of a Novel Antiischaemic Adenosine A1
`Agonist at purine C-8. J. Labelled Compounds Radiopharm., 1996, 38, 497 - 507.
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`26. Sheardown, M.J., Hansen A.J., Thomsen, C., Judge, M.E. and Knutsen, L.J.S.; Novel Adenosine Agonists:
`A Strategy for Stroke Therapy. In Ischemic Stroke: Recent Advances in Understanding and Therapy:
`Grotta, J., Miller, L., Buchan, A.M., Eds.; Published by International Business Communications, 1995, pp
`187 - 214.
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`27. Hibbs, D.E., Hursthouse, M.B., Knutsen, L.J.S., Abdul Malik, K.M., Olivio, H.F., Roberts, S.M., Sik, V.M.,
`Varley, D.R. and Xiong, H.; Preparation and Determination of the Absolute Configuration of Optically
`Active 9-Hydroxy-7-oxabicyclo[4.3.0]non-4-en-8-ones; Acta. Chem. Scand. 1995, 49, 122 - 127.
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`28. Valsborg, J.S., Knutsen, L.J.S., Lundt, I and Foged, C.; Synthesis of [8-14C-]-2,6-dichloro-9H-purine, a
`radiolabelled precursor for 14C-nucleosides; J. Labelled Compounds Radiopharm., 1995, 36, 454 - 464.
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`29. Knutsen, L.J.S., Lau, J., Eskesen, K., Sheardown, M.J., Thomsen, C., Weis, J.U., Judge, M.E. and Klitgaard,
`H.; Anticonvulsant Actions of Novel and Reference Adenosine Agonists. In Adenosine and Adenine
`Nucleotides: From Molecular Biology to Integrative Physiology; Belardinelli, L. and Pelleg, A., Eds.; Kluwer
`Academic Publishers: Norwell, MA USA; 1995, pp 479 - 487.
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`30. Knutsen, L.J.S., Lau, J., Sheardown, M.J., Thomsen, C.; The synthesis and biochemical evaluation of new
`A1 selective adenosine receptor agonists containing a 6-hydrazinopurine moiety; Bioorg. Med. Chem.
`Lett., 1993, 3, 2661 - 2666.
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`31. Klitgaard, H., Knutsen, L.J.S. and Thomsen, C.; Contrasting effects of adenosine A1 and A2 receptor
`ligands in different chemoconvulsive models; Eur. J. Pharmacol., 1993, 224, 221 - 228.
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`32. Andersen, K.E., Braestrup, C., Grønwald, F.C., Jørgensen, A.S., Nielsen, E.B., Sonnewald, U. Sørensen P.O.,
`Suzdak, P.D. and Knutsen, L.J.S.; The Synthesis of Novel GABA uptake inhibitors. 1. Elucidation of the
`structure activity studies leading to the choice of R-1-[4,4-bis (3-methyl-2-thienyl)-3-butenyl]-3-piper-
`idine carboxylic acid (Tiagabine) as an anticonvulsant drug candidate; J. Med. Chem., 1993, 36,
`1716 - 1725.
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`33. Suzdak, P.D.; Frederiksen, K.; Andersen, K.E.; Soerensen, P.O.; Knutsen, L..J.S.; Nielsen, E.B. NNC-711, a
`novel potent and selective -aminobutyric acid uptake inhibitor: pharmacological characterization.
`Eur. J. Pharmacol., 1992, 223, 189 - 198.
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`34. Suzdak, P.D., Swedberg, M.D.B., Andersen, K.E., Knutsen, L.J.S. and Braestrup, C.; In vivo labeling of the
`central GABA Uptake Carrier with 3H-Tiagabine; Life Sciences, 1992, 51, 1857 - 1868.
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`35. Knutsen, L.J.S.; The Chemistry of 2'-deoxyribo-C-nucleosides; Nucleosides Nucleotides, 1992, 11,
`961 - 983.
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`36. Nielsen, E.B., Suzdak, P.D., Andersen, K.E., Knutsen, L.J.S., Sonnewald, U. and Braestrup, C.;
`Characterisation of tiagabine (NO-328), a new potent and selective GABA-uptake inhibitor; Eur. J.
`Pharmacol., 1991, 196, 257 - 266.
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`37. Braestrup, C., Nielsen, E.B., Sonnewald, U., Knutsen, L.J.S., Andersen, K.E., Jansen, J.A., Frederiksen, K.,
`Andersen, P.H., Mortensen, A. and Suzdak, P.D.; (R)-N-[4,4-bis(3-methyl-2-thienyl)-but-3-en-1-yl]-
`nipecotic acid binds with high affinity to the brain -aminobutyric acid uptake carrier; J. Neurochem.,
`1990, 54, 639 - 647.
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`38. Braestrup, C., Nielsen, E.B., Wolffbrandt, K.H., Andersen, K.E., Knutsen, L.J.S. and Sonnewald, U.;
`Modulation of GABA receptor interaction with GABA uptake inhibitors; Int. Congr. Ser.-Exerpta Med.,
`1987, 750 (Pharmacology), 125 - 128.
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`39. Mitchell, W.L., Ravenscroft, P., Hill, M.L., Knutsen, L.J.S., Judkins, B.D., Newton, R.F. and Scopes, D.I.C.;
`Synthesis and antiviral properties of 5-(2-substituted-vinyl)-6-aza-2'-deoxyuridines; J. Med. Chem.,
`1986, 29, 809 - 816.
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`40. Knutsen, L.J.S., Judkins, B.D., Newton, R.F., Scopes, D.I.C. and Klinkert, G.; Synthesis of imidazo-fused
`bridgehead-nitrogen
`2'-deoxy-ribo-C-nucleosides:
`coupling
`elimination
`reactions
`of
`2,5-anhydro- 3,4,6-tri-O-benzoyl-D-allonic acid; J. Chem. Soc. Perkin Trans I, 1985, 621 - 630.
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`41. Mitchell, W.L., Ravenscroft, P., Hill, M.L., Knutsen, L.J.S., Newton, R.F. and Scopes, D.I.C.; Synthesis and
`antiviral activity of 5-halovinyl-6-aza-2'-deoxyuridines; Nucleosides Nucleotides, 1985, 4, 173 - 175.
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`Lars J. S. Knutsen, Ph.D.
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`Addendum, Page 6 of 9
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`42. Knutsen, L.J.S., Judkins, B.D., Mitchell, W.F., Newton, R.F. and Scopes, D.I.C.; Synthesis of imidazo-fused
`bridgehead-nitrogen C-nucleosides via dehydrative coupling reactions of 2,5-anhydro-3,4,6-tri-O-benz-
`oyl-D-allonic acid; J. Chem. Soc. Perkin Trans I, 1984, 229 - 238.
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`43. Knutsen, L.J.S., Newton, R.F., Scopes, D.I.C. and Klinkert, G.; Coupling-elimination reactions of
`2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid: synthesis of 2'-deoxyribo-C-nucleosides; Carbohydr.
`Res., 1982, 110, C5 - C8.
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`44. Knutsen, L.J.S., Judkins, B.D., Newton, R.F. and Scopes, D.I.C.; A novel elimination reaction of
`3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonic acid: ribose to 2'-deoxyribosyl conversion; Tetrahedron Lett.,
`1982, 23, 1013 - 1014.
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`45. Franks, D., Grossel, M.C., Hayward, R.C. and Knutsen, L.J.S.; Reduction of the carboxyl function in
`aromatic carboxylic acids by alkali metal liquid ammonia solutions; J. Chem. Soc. Chem. Commun.,
`1978, 941, 943.
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`PUBLISHED PATENT APPLICATIONS
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`1. Antihistamines in combination with a range of substance for improved health. Knutsen, L.J.S.; Knutsen, J.L.;
`Pimley, M.A. (Requis Pharmaceuticals Inc.). PCT Int. Appl. (2015), WO 2015/089489 A1, 18 June 2015.
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`2. Preparations for the treatment of sleep-related breathing disorders. Knutsen, L.J.S.; Hand, J.M. (Requis
`Pharmaceuticals Inc.). PCT Int. Appl. (2014), WO 2014/138162 A1, 12 September 2014.
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`3. Pyridazinone derivatives. Bacon, E.R.; Bailey, T.R.; Becknell, N.C.; Chatterjee, S.; Dunn, D.; Hostetler, G.A.;
`Hudkins, R.L.; Josef, K.A.; Knutsen, L.J.S.; Tao, M.; Zulli, A.L. (Cephalon, Inc.). U.S. Pat. Appl. Publ. (2014),
`US 20140142088 A1, 22 May 2014
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`4. Combination nutritional and nutraceutical products. Knutsen, J.L.; Knutsen, L.J.S. (Requis Pharmaceuticals
`Inc.). PCT Int. Appl. (2013), WO 2013/074531 A1, 23 May 2013.
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`5. Antihistamines combined with dietary supplements for improved health. Knutsen, L.J.S.; Knutsen, J.L.
`(Discovery Pharma Consulting LLC). U.S. Pat. Appl. Publ. (2012), 20120170883 A1, December 13, 2012.
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`6. Pyridazinone Derivatives. Bacon, E.R.; Bailey, T.R.; Becknell, N.C.; Chatterjee, S.; Dunn, D.; Hostetler, G.A.;
`Hudkins, R.L.; Josef, K.A.; Knutsen, L.J.S.; Tao, M.; Zulli, A.L. (Cephalon, Inc.). U.S. Pat. Appl. Publ. (2011),
`20110288075 A1, November 24, 2011.
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`7. Substituted pyridazine derivatives. Hudkins, R.L.; Knutsen, L.J.S.; Prouty, C.P.; Sundar, B.G.; Wells-Knecht,
`K.J. (Cephalon, Inc.). U.S. Pat. Appl. Publ. (2010), 20100311752 A1, December 9, 2010.
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`8. Pyridazinone Derivatives. Bacon, E.R.; Bailey, T.R.; Becknell, N.C.; Chatterjee, S.; Dunn, D.; Hostetler, G.A.;
`Hudkins, R.L.; Josef, K.A.; Knutsen, L.J.S.; Tao, M.; Zulli, A.L. (Cephalon, Inc.). U.S. Pat. Appl.
`Publ. (2010), US 20100280007 A1, 4 November, 2010.
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`9. Pyridazinone Derivatives. Bacon, E.R.; Bailey, T.R.; Becknell, N.C.; Chatterjee, S.; Dunn, D.; Hostetler, G.A.;
`Hudkins, R.L.; Josef, K.A.; Knutsen, L.J.S.; Tao, M.; Zulli, A.L. (Cephalon, Inc.). U.S. Pat. Appl.
`Publ. (2010), US 20100273779 A1, 28 October 2010.
`
`10. Substituted pyridazine derivatives which have histamine H3 antagonist activity. Hudkins, R.L.; Knutsen,
`L.J.S.; Prouty, C.P.; Sundar, B.G.; Wells-Knecht, K.J. (Cephalon, Inc.). PCT Int. Appl. (2009), WO 09/97306 A1,
`6 August 2009.
`
`11. Azacyclic compounds as inhibitors of sensory neuron specific channels (SNS). Hamlyn, R.; Huckstep, M.;
`Earnshaw, C.G.; Stokes, S.; Tickle, D.; Allart, B.; Boyd, J.W.; Knutsen, L.J.S.; Lynch, R.; Patient, L. (Ionix
`Pharmaceuticals Limited, UK). PCT Int. Appl. (2006), WO 06/082354 A1, 8 August 2006.
`
`12. Preparation of acyclic sulfonamides as N-type calcium channel antagonists. Hobbs, C.J.; Lynch, R.; Mellor,
`S.L.; Radford, F.; Gilbert, J.C.; Stokes, S.; Glen, A.; Fiumana, A.; Earnshaw, C.G.; Knutsen, L.J.S.; Dean, K.E.S.
`(Ionix Pharmaceuticals Limited, UK). PCT Int. Appl. (2006), WO 06/030211 A2 23 March 2006.
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`13. Sulfonamides, particularly N-(phenylsulfonyl)piperidines, as N-type calcium channels antagonists useful for
`treatment of pain and their preparation. Radford, F.; Lynch, R., Mellor, S. L.; Hobbs, C.J.; Gilbert, J.C.; Stokes,
`S.; Glen, A.; Fiumana, A.; Smith, N.J; Earnshaw, C.G.; Knutsen, L.J.S. (Ionix Pharmaceuticals Limited,
`UK). PCT Int. Appl. (2005), WO 05/068448 A1 28 July 2005.
`
`14. Preparation of benzene and phenol derivatives as inhibitors of sensory neuron specific (SNS) sodium
`channels. Jennings, N.S.; Stokes, S.; Hamlyn, R.J.; Tickle, D.C.; Huckstep, M. R.; Lynch, R.; Knutsen, L.J.S.
`(Ionix Pharmaceuticals Limited., UK). PCT Int. Appl. (2005), WO 05/00309 A2 06 January 2005.
`
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`15. 1,3-Thiazolin-4-ones as therapeutic compounds in the treatment of pain. Knutsen, L.J.S; Hobbs, C.J.;
`Radford, F.; Fiumana, A. (Ionix Pharmaceuticals Limited, UK). PCT Int. Appl. (2004) WO 04/17965 A1 04 March
`2004.
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`16. Five-membered heterocyclic compounds in the treatment of chronic and acute pain. Knutsen, L.J.S.; Hobbs,
`C.J.; Radford, F.; Fiumana, A.; Earnshaw, C.G.; Mellor, S.L.; Smith, N.J. (Ionix Pharmaceuticals Limited, UK).
`PCT Int. Appl. (2004), WO 04/17966 A1 04 March 2004.
`
`17. Preparation of 4-quinolinemethanol derivatives as purine receptor antagonists. (II). Gillespie, R. J.;
`Lerpiniere, J.; Giles, P.R.; Adams, D.R.; Knutsen, L..J.S.; Cliffe, I.A. (Cerebrus Ltd. UK) PCT Int. Appl. (2000),
`73 pp. WO 00/13682 A2, 16 March 2000.
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`18. Preparation of 4-quinolinemethanol derivatives as purine receptor antagonists. Gillespie, R.J.; Lerpiniere, J.;
`Gaur, S.; Adams, D.R.; Knutsen, L.J.S.; Ward, S.E. (Cerebrus Ltd. UK) PCT Int. Appl. (2000), 76 pp. WO
`00/13681 A2, 16 March 2000.
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`19. Novel pyridine and pyrimidine derivatives. Knutsen, L.J.S.; Lundemose, A.G.; Jeppesen, C.B.; Sorensen, A.R.;
`Danielsen, G.M. (Novo Nordisk A/S, Den.) WO 99/31098 A1, June 24, 1999.
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`20. (-)-Mefloquine to block purinergic receptors and to treat movement or neurodegenerative disorders.
`Shepherd, R.; Knutsen, L.J.S.; Porter, R.H.P.; Weiss, S.M. (Cerebrus Ltd. UK) WO 99/26627, 03 June 1999.
`
`21. Preparation of novel halo-N-[(heterocyclyl)thio-1-piperidinyl]adenosines as A1 receptor agonists. Knutsen,
`Lars. (Novo Nordisk A/S, Den.) WO 9816539 A1, 23 April 1998.
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`22. Prepn. of nucleosides for treating disorders related to cytokines in mammals. Knutsen, L.; Olsen, U.B.;
`Bowler, A.N. (Novo Nordisk A/S, Den.). PCT Int. Appl., 78 pp. WO97/33591A1 18 Sept 1997.
`
`23. Preparation of N-alkoxyadenosines as cytokine inhibitors. Knutsen, L.; Olsen, U.B.; Roberts, S.M.; Varley,
`D.R.; Bowler, A.N. (Novo Nordisk A/S, Den.). PCT Int. Appl., 70 pp. WO 98/01459 A1 15 January 1998.
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`24. Preparation of novel halo-N-[(heterocyclyl)thio-1-piperidinyl]adenosines as A1 receptor agonists. Knutsen,
`L. (Novo Nordisk A/S, Den.) WO 98/16539 A1, 23 April 1998.
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`25. Preparation of adenosine derivatives for treatment of central nervous system diseases. Lau, J.; Knutsen,
`L.J.S. (Novo Nordisk A/S, Den.). PCT Int. Appl., 62 pp. WO 95/07921 A1 23 March 1995.
`
`26. Preparation of N-(heterocyclylalkyl)purine derivatives as adenosine A1 agonists. Lau, J.; Knutsen, L.J.S.;
`Sheardown, M.; Hansen, A.J. (Novo Nordisk A/S, Den.). PCT Int. Appl., 68 pp. WO 94/14832 A1 7 July 1994.
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`27. Purine derivatives. Knutsen, L.J.S; Lau, J. (Novo Nordisk A/S, Den.). PCT Int. Appl., 49 pp. WO 93/23418 A1
`25 November 1993.
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`28. Adenosine derivatives. Knutsen, L.J.S.; Lau, J. (Novo Nordisk A/S, Den.). PCT Int. Appl., 39 pp. WO 93/23417
`A1 25 November 1993.
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`29. Preparation of 2,6-disubstituted purine nucleoside anticonvulsants. Knutsen, L.J.S; Lau, J. (Novo Nordisk
`A/S, Den.). PCT Int. Appl., 51 pp. WO 93/08206 A1 29 May 1993.
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`30. Novel heterocyclic carboxylic acids. Andersen, K.E; Knutsen, L.J.S; Soerensen, P.O; Lundt, B.F.; Lau, J.;
`Petersen, H. (Novo Nordisk A/S, Den.). PCT Int. Appl., 58 pp. WO 92/20658 A1 26 November 1992.
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`31. Preparation of N-[2-(3,3-diphenylpropoxy)ethyl]piperidine-3-carboxylates and analogs as GABA uptake
`inhibitors. Andersen, K.E; Knutsen, L.J.S; Sonnewald, U.; Soerensen, P.O. (Novo-Nordisk A/S, Den.). PCT Int.
`Appl., 63 pp. WO 9107389 A1 30 May 1991
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`32. Preparation of N-(aralkoxyalkyl)piperidinecarboxylates and analogs as GABA-uptake inhibitors. Knutsen,
`L.J.S; Jorgensen, A.S; Andersen, K.E; Sonnewald, U. (Novo-Nordisk A/S, Den.). Eur. Pat. Appl., 25 pp. EP
`374801 A2 27 June 1990.
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`33. Azacyclic carboxylic acid derivatives, their preparation and use as GABAergic agonist pharmaceuticals.
`Knutsen, L.J.S.; Andersen, K.E; Jorgensen, A.S; Sonnewald, U. (Novo Industri A/S, Den.). Eur. Pat. Appl., 26 pp.
`EP 342635 A1 23 November 1989.
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`
`Of these patents & patent applications, 22 have been issued in the USA:
`
`US 8,673,916 Methods of Treating Disorders Mediated by Histamine H3 receptors using Pyridazinone Derivatives
`US 8,586,588 Aryl Pyridazinone Derivatives and their use as H3 receptor ligands
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`0007
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`US 8,247,414 Pyridizinone derivatives and the use thereof as H3 inhibitors
`US 8,207,168 Pyridazinone derivatives
`US 8,076,331 Substituted Pyridazine derivatives
`US 6,608,085 4-Quinolinemethanol derivatives as purine receptor antagonists (II)
`US 6,583,156 4-Quinolinemethanol derivatives as purine receptor antagonists (I)
`US 6,197,788 (-)-Mefloquine to block puringergic receptors and to treat movement or neurodegenerative disorders
`US 5,683,989 Treatment of ischemias by administration of 2,N.sup.6 -substituted adenosines
`US 5,672,588 Purine derivatives
`US 5,589,467 2,5',N6-trisubstituted adenosine derivatives
`US 5,578,582 Methods of treating ischemia with C2, N6 -disubstituted adenosine derivatives
`US 5,484,774 2, N6 -disubstituted adenosines, tri-O-ester derivatives and their pharmaceutical compositions to treat ischemias
`US 5,432,164 C2,N6 -disubstituted adenosine derivatives
`US 5,430,027 2-Chloro-N6 -substituted adenosines, their pharmaceutical compositions, and activity in treating ischemias
`US 5,348,965 N-substituted azaheterocyclic carboxylic acids
`US 5,231,106 Azacyclic carboxylic acid derivatives and their preparation and use
`US 5,229,404 Azacyclic carboxylic acid derivatives and their preparation and use
`US 5,214,057 N-substituted azaheterocyclic carboxylic acids
`US 5,214,054 Azacyclic carboxylic acid derivatives and their preparation and use
`US 5,198,451 Heterocyclic carboxylic acids
`US 5,071,859 N-substituted azaheterocyclic carboxylic acids and pharmaceutical uses
`US 5,039,685 Azacyclic carboxylic acid derivatives, their preparation and use
`
`Selected Invited lectures (location/date/event/title):
`
`Philadelphia, USA, May 1994.
`5th. International Adenosine Symposium
`Anticonvulsant Actions of Adenosine Agonists and Antagonists
`
`Puerto Rico, December 1994.
`American College of Neuropsychopharmacology Meeting,
`CNS Effects of Novel Adenosine Agonists
`
`New Hampshire, USA, July/August 1995
`49th. Gordon Conference, Medicinal Chemistry
`Novel CNS Selective Adenosine Agonists as Antiischaemics
`
`Milan, Italy, July 1996, Purines '96. Molecular, Pharmacological and Therapeutic Advances
`Selective Agents for the Modulation of A1 Adenosine Receptors
`(Chairman of session “Purines and Inflammation”)
`
`Ferrara, Italy, May 1998
`Sixth International Purinergic Symposium
`New Adenosine A1 and A3 Selective N-Alkoxypurines
`
`New Hampshire, USA, August 1998
`51st Gordon Conference, Medicinal Chemistry
`Purinoceptors as Targets for Novel Therapeutics: Introduction and Overview
`
`Glaxo-Wellcome, Stevenage, Herts., November 2000
`SMR meeting “Trends in Medicinal Chemistry
`Novel Adenosine A1 and A3 agonists for the treatment of CNS disorders
`http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=3&p_RefId=210&p_IsPs=Y
`http://www.smr.org.uk/Archive/PastMeetings/Downloads/20001130.pdf
`
`National Institutes of Health, Washington D.C., USA, September 2009
`National Institute of Diabetes, Digestive and Kidney Disorders
`Seminar: Selective Adenosine Ligands as Innovative Drugs
`http://calendar.nih.gov/app/MCalInfoView.aspx?evtID=19988
`
`Boston, USA, October 2009
`Drug Discovery Partnership: Filling the Pipeline. Evolution of Drug Discovery Partnership Focus Day
`Workshop: Achieving Effective Alignment through Project Management, Contracts Negotiation, and Choosing the Right
`Partners
`http://www.opalevents.org/conferencehtml/2009/drug_discovery_partnership_2009/drug_discovery_partnership_agenda.php
`
`0008
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`Dubai, UAE, February 2010
`2nd International Conference on Drug Discovery and Therapy. Chairman of “Successful Drug Discovery from the Research Lab
`to the Marketplace” session
`Lecture: Tiagabine, a novel Anticonvulsant acting via Inhibition of GABA Uptake
`http://www.icddt.com/details/knutsen.htm
`
`UCSF, San Francisco, July 2013
`Lecture "The Importance of Enantiomers for The Antimalarial Mefloquine"
`http://qb3.org/content/special-seminar-lars-knutsen-discovery-pharma-consulting-importance-enantiomers-antimalarial
`
`Gilead Sciences, Foster City, CA, July 2013
`Seminar “Drug Discovery and its Management: the Secret to Pharma Growth”
`Delivered to 180 staff at