IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Inter Partes Reexamination of U.S. Patent No. 8,057,825
`
`Entitled:
`
`Krill Extracts for Treatment of Cardiovascular Diseases
`
`Issued:
`
`15 November 2011 to Sampalis
`
`DECLARATION BY DR. NILS HOEM IN SUPPORT OF
`REQUEST FOR INTER P ARTES REEXAMINATION OF
`U.S. PATENT NO. 8,057,825
`
`EFS WEB Filed
`
`Mail Stop Inter Partes Reexam
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`I, Dr. Nils Hoem, state as follows:
`
`1.
`
`My present position is Chief Scientist of Aker Biomarine ASA. My Curriculum Vitae is
`
`attached hereto as Exhibit 1.
`
`2.
`
`I have reviewed the following references which are cited in this re-examination
`
`proceeding:
`
`• Makuta et al, Application ofEicosapentaenoic Acid to Health Food, Japan Fudo Saiensu
`
`(1986), 25:1, 29-35 (Makuta)
`
`• Gordeev et al., Chemistry ofNatural Compounds (1990) 26(2) 143-147 (Gordeev)
`
`• Kuroda et al., Comparison of Hypocholesterolemic Effect among Three Phospholipids
`
`Containing Different Fatty Acid and the Related Oils in Rats, Jap. J. Nutr. (1990),
`
`48(5):213-20 (Kuroda)
`
`• Canadian Application 2,251,265 (Beaudoin)
`
`• WO 00/23546 (Sherbrooke)
`
`•
`
`Japanese Laid Open Publication S63-23819 (Murata).
`
`RIMFROST EXHIBIT 1121 Page 0001
`
`

`

`In this Declaration, I also refer to Fricke et al., Lipid, Sterol and Fatty Acid Composition
`
`of Antarctic Krill (Euphausia superba Dana)(1984) Lipids 19(11):821-827 (attached as Exhibit
`
`2).
`
`3.
`
`Krill are rich in a variety of liposoluble compounds including phospholipids,
`
`carotenoids such as astaxanthin, and vitamin E (a-tocopherol). This fact is supported by
`
`Canadian Application 2,251,265 at p. 5 and WO 00/23546 at p. 9-11. Astaxanthin and a(cid:173)
`
`tocopherol are antioxidants. Id. The phospholipid fraction of krill contains phosphatidylcholine
`
`and phosphatidylethanolamine as well as other phospholipid species. See Fricke et al., p. 822,
`
`Table 1; See also WO 00/23546, p. 9-11 and Tables 14-18. A variety of fatty acids are attached
`
`to the phospholipids. These include docosahexaenoic acid, eicosahexaenoic acid, oleic acid, and
`
`linoleic acid among many others. WO 00/23546, p. 9-11 and Tables 14-18; Fricke et al., Tables
`
`2-6.
`
`4.
`
`Lipid extracts from krill have common characteristics. This is demonstrated by the fact
`
`that the different extraction protocols employed in WO 00/23546 (Tables 14-18), Fricke et al.
`
`(Tables 2-6), and Gordeev (Table 1) all produce lipid fractions containing phosphatidylcholine
`
`and phosphatidylethanolamine as well as other phospholipid species, docosahexaenoic acid,
`
`eicosahexaenoic acid, and oleic acid as well as many other fatty acids. The phospholipid
`
`fractions utilized by Kuroda (Tables 1 and 2) and described in Makuta (Tables 9 and 10) also
`
`contain these phospholipids and fatty acids. In each instance, liposoluble substances such as
`
`astaxanthin and a-tocopherol would be present in the various krill lipid extracts and phospholipid
`
`fractions as demonstrated in WO 00/23546 at p. 9-11 and Tables 14-18. This means that the
`
`phospholipid fractions and krill lipid extracts in each of the references listed in Paragraph 2
`
`above would contain phosphatidylcholine and phosphatidylethanolamine as well as other
`
`phospholipid species, docosahexaenoic acid, eicosahexaenoic acid, linoleic acid and oleic acid as
`
`well as many other fatty acids as listed in the various Tables, astaxanthin and a-tocopherol. The
`
`phospholipid fractions and krill lipid extracts would also contain triglycerides and free fatty
`
`acids.
`
`RIMFROST EXHIBIT 1121 Page 0002
`
`

`

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`
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`
`RIMFROST EXHIBIT 1121 Page 0003
`RIMFROST EXHIBIT 1121 Page 0003
`
`

`

`EXHIBIT 1
`
`RIMFROST EXHIBIT 1121 Page 0004
`RIMFROST EXHIBIT 1121 Page 0004
`
`

`

`Curriculum Vitae
`
`Nils Ove Hoem, M.Sc.(Pharm), Ph. D.
`
`PROFESSIONAL BACKGROUND
`
`Academic
`
`Appointments
`
`Non—Academic
`
`appointments
`
`1985—1989
`
`1989—1990
`
`1990—1998
`
`2000—2002
`
`Research Assistant, Department of Pharmacology, School
`of Pharmacy, University of Oslo.
`
`Assistant Professor, Department of Pharmacology, School
`of Pharmacy, University of Oslo.
`
`Associate Professor, Department of Pharmacology, School
`of Pharmacy, University of Oslo.
`
`Associate Professor, Department of Pharmacology, School
`of Pharmacy, University of Oslo
`
`2001 —present
`
`Associated member of Laboratory of Applied
`Pharmacokinetics, USC, Los Angeles
`
`1979—1980
`
`1984 — 2004
`
`1992—1996
`
`1999
`
`2003
`
`2003—2004
`
`2004—2007
`
`2007—2007
`
`2008—2010
`
`Teacher (Ellingsoy Junior High School)
`
`Several shorter periods (1 —4 weeks) as community
`Pharmacist in Norway
`
`Project manager: Development and implementation of a
`Post Graduate one—year continuing education program for
`Pharmacists.
`
`Senior Regulatory Advisor, Smerud Medical Research
`Group, Oslo, Norway.
`
`Senior Scientific Consultant, Smerud Medical Research
`
`Group, Oslo, Norway.
`
`Running own consultancy business. Hoem Pharma Consult
`in Oslo Norway. Consulting in Pharmacokinetics and in
`more general aspects of early drug development.
`
`Director PK/ PD (Europe) MDS Pharma Services,
`Hamburg, Germany and Belfast Northern—Ireland
`
`Director R&D Pronova Biocare AS, Lysaker, Norway
`
`Vice President Research and Development Aker
`BioMarine, Norway
`
`2011—present
`
`Chief Scientist Aker BioMarine, Norway
`
`LICENSURE
`
`1983 — present Certified to Dispense Drugs in Norway.
`
`RIMFROST EXHIBIT 1121 Page 0005
`RIMFROST EXHIBIT 1121 Page 0005
`
`

`

`HONOURS AND AWARDS
`
`1993—1997
`
`1993
`
`1997 —1998
`
`1996
`
`1999
`
`2000
`
`2000
`
`2000—2001
`
`2009
`
`2011
`
`Appointed Member of the Drug Approval Board,
`Norwegian Medicinal Authority, by Norwegian lVIinister
`of Health and Social Services.
`
`Member of Scientific Committee, European Workshop on
`Clinical Pharmacy, Oslo,]une 1993.
`
`Member of organizing Committee 3rd International
`Congress for Lifelong Learning in Pharmacy, Hillerod,
`Denmark, June 1998.
`
`Member of jury (2nd opponent) evaluation of Doctoral
`Thesis: Quy, N Diep; “Pivalic acid containing antibiotics
`induced carnitine deficiency”, University of Oslo.
`
`Member of jury (3rd opponent) evaluation of Doctoral
`Thesis: Anders Aasberg; “Effects of Cyclosporine A on
`microvascular function and endothelin—1 in renal
`
`transplant recipients.”, University of Oslo.
`
`Member of jury (3nd opponent) evaluation of Doctoral
`Thesis: Ole Andreas Loechen Oekstad; “Sequence analysis
`of Bacillus cereus genome fragments: A comparative
`genome analysis.” University of Oslo.
`
`Doctoral Thesis Advisory Committee; Siri Wang, "Aspects
`of ascorbic acid kinetics. In vivo and in vitro studies with
`
`focus on methodology.", University of Oslo.
`
`Sabbatical, September 2000—September 2001. Sponsor
`University of Oslo and Norwegian Research Council.
`Visiting Scientist with professor RogerJelliffe at the
`Laboratory of Applied Pharmacokinetics, Keck School of
`Medicine, University of Southern California, Los Angeles.
`
`External member of jury evaluation of Doctoral Thesis:
`“Optimisation de l’utilisation des techniques de
`modelisation dans le processus de développement d’un
`medicament: de l’étape pre—clinique a clinique.” University
`of Montreal, February 2009.
`
`EXternal expert during dissertation of Doctoral Thesis:
`“Development and Evaluation of Nonparametric lVIixed
`Effects Models”Uppsala University, March 2011.
`
`EDUCATION
`
`Undergraduate
`Studies
`
`1977 — 1982
`
`School of Pharmacy, University of Oslo, Norway
`
`Graduate studies
`
`1982—1983
`
`Department of Pharmacology, School of Pharmacy,
`University of Oslo and Nycomed A/S, Oslo,
`Norway.
`
`RIMFROST EXHIBIT 1121 Page 0006
`RIMFROST EXHIBIT 1121 Page 0006
`
`

`

`Post graduate studies
`
`1983
`
`MS (pharm): Thesis; “Measurement of arterial blood
`pressure and plasma level of prekallikrein, high molecular
`weight kininigen and plasminogen activator in rats after
`vascular administration of X—ray contrast media
`
`(Biligrafin® and Omnipaque®) N Hoem, S Ekelund.”
`
`Ph.D.— studies
`
`1983—1990
`
`Department of Pharmacology, School of Pharmacy,
`University of Oslo
`
`Doctorate
`
`Participation in
`workshops and
`shorter courses
`
`1985
`
`1984
`
`1992
`
`1992
`
`1993
`
`1993
`
`1996
`
`1998
`
`2000
`
`2000
`
`2005
`
`PBF 455 Clinical Pharmacology: Doctorate level course
`(4 credits).
`
`PBF 453 Toxicology: Doctorate level course (5 credits)
`
`Public Defense of Doctor Philosophiae. Thesis: “Studies
`on levels and interactions of contact activation factors in
`
`plasma: A basis for the elucidation of their function in
`anaphylactoid reactions to deXtran and to radiographic
`contrast media”
`
`Qualifying course for teaching responsibilities in higher
`education in Norway part 1
`
`Qualifying course for teaching responsibilities in higher
`education in Norway part 2
`
`Bayesian Individualization of Drug Dosage Regimens,
`Nonparametric EM population Pharmacokinetic EM
`Modeling, Modeling Drug Diffusion into Endocardial
`Vegetations and Bacterial Killing Curves, Satellite
`Workshop during 3rd World Congress on TDM,
`Philadelphia.
`
`SAAM II Kinetic Modeling Workshop, City University,
`London, UK
`
`Intermediate and Advanced population modeling, and
`application to model based, goal oriented individualized drug
`therapy, LAPK, USC, Los Angeles
`
`Workshop on Conducting Successful Clinical Trials, University
`of California, San Francisco.
`
`9th Workshop on Advanced Methods of PK/ PD Systems
`Analysis, University of Southern California, Biomedical
`Simulations Resource, Marina Del Rey, CA, USA,
`
`SMi's 8th Annual Conference Generics, Supergenerics &
`Patent Strategies, London; UK.
`
`RIMFROST EXHIBIT 1121 Page 0007
`RIMFROST EXHIBIT 1121 Page 0007
`
`

`

`SPECIFIC TEACHING RESPONSIBILITIES
`
`UnderGraduate LCVCI
`
`1985 — 1993
`
`Instructor in Experimental pharmacology , part of
`5 credit (full year=20 credits) subject PBF 250
`Pharmacodynamics, and PBF 150 Physiology with
`Anatomy (4 credits).
`
`1985—1993
`
`Course Coordinator PBF 250 Pharmacodynamics
`experimental course during 6 terms, School of Pharmacy,
`University of Oslo.
`
`1993—2003
`
`Lectures in PBF 251 Basic Pharmacology (5 credits) for
`3rd year Pharmacy students, University of Oslo.
`
`1993
`
`Master plan and description of main objectives for a new 4
`credit course (PBF 252) in Clinical Pharmacology at The
`School of Pharmacy, University of Oslo
`
`1993—2002
`
`Lectures in PBF151 Physiology (3 credits) for 2nd year
`Pharmacy students, University of Oslo
`
`2000—2001
`
`Course coordinator PBF 151 Physiology, School of
`Pharmacy, University of Oslo.
`
`Graduate Level
`
`1990 and 1992 Course coordinator for PBF 355Clinical
`
`Pharmacokinetics, School of Pharmacy, University of
`Oslo.
`
`POSt Graduate LCVCI
`
`1996— 1998
`
`Course Coordinator PBF 353 Advanced Pharmacology
`
`1992—1997
`
`Lectures in PVA330: “Advanced Topics in Pharmaceutical
`Sciences” (2/3 of 3 credits). Department of continuing
`and post graduate education, School of Pharmacy,
`University of Oslo
`
`1992—1995
`
`Course coordinator one—year course: Advanced Diploma
`in Community Pharmacy.
`
`1994, 1996
`
`Course coordinator PBF 455 Clinical Pharmacokinetics,
`
`Department of postgraduate and continuing education,
`School of Pharmacy, University of Oslo. In 1996 this
`course was classified as a National Research course
`
`2001
`
`PBF 455 Clinical Pharmacokinetics. Organized as one—year
`distance education Course using the VETTUS tool.
`Sole lecturer and Instructor at the same course (4 credits),
`University of Oslo.
`
`SUPCIViSOI
`
`1984—2005
`
`Supervisor for more than 15 individual one—year long
`master’s student research projects in the field of Contact
`Activation, Coagulation and Fibrinolytic Cascade System
`biology and pathophysiology, Department of
`
`RIMFROST EXHIBIT 1121 Page 0008
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`
`

`

`Pharmacology, School of Pharmacy, University of Oslo
`
`Ph.D project
`Supervisor
`
`1994—1997
`
`Supervisor of 2 student diploma projects, part of a one
`year long, advanced continuing education program for
`community Pharmacists, University of Oslo.
`
`1992—1997
`
`Ph. D student Siv Fossum.
`
`2000
`
`2000 — 2005
`
`Ph. D student Siri Wang.
`
`Ph D. Student: Kristin C. Carlsson, School of Pharmacy,
`University of Oslo.
`
`Co—supervisor
`
`1990 —present
`
`Co—supervisor for more than 30 one year long master’s
`student research projects in Pharmacology, University of
`Oslo.
`
`Continuing education
`Courses and
`
`Continuing education
`Workshops
`
`1996
`
`1998—
`
`1996
`
`Co—Supervisor one year long master’s student research
`project in Pharmacology at Thrombosis Research Center,
`Temple University, Philadelphia.
`
`Co—supervisor for 2 one year long master’s student
`research projects in Pharmacology, University of Tromso.
`
`Internet for Pharmacists, One day Workshop, Pharmakon,
`Hillerod, Denmark
`
`1996 — 1997
`
`Seven, one day hands on workshops on emerging net—
`
`based Information Technologies in the Pharmaceutical
`
`Sciences and Pharmaceutical Practice, Bodo, Tromso,
`
`Drammen, Forde, Aalesund, Brevik.
`
`Internet in the Pharmaceutical and Medical Fields. One
`
`day Hands on Workshop, Pharmakon, Hillerod, Denmark
`
`Net based Information technologies in the Helath
`Professions, Oslo
`
`Co—developer of VETTUS a Web based tool for
`Continuing and Post—Graduate Education, University of
`Oslo
`
`1998
`
`1999
`
`1999—2000
`
`2001 —present
`
`Several workshops in Population PK together with
`Professor Roger Jelliffe at LAPK, University of Southern
`California. Workshops held in the US, Spain, Italy, France
`and Switzerland.
`
`RIMFROST EXHIBIT 1121 Page 0009
`RIMFROST EXHIBIT 1121 Page 0009
`
`

`

`SPECIFIC ACADEMIC ADMINISTRATIVE RESPONSIBILITIES
`
`1981—1982
`
`1986,1987
`
`1986—1994
`
`1987—1997
`
`1989—1994
`
`1989—1995
`
`1990—1991
`
`1991—1992
`
`1991
`
`1991—1993
`
`1991—1994
`
`1997—1998
`
`1998
`
`1999 — 2000
`
`2000—2002
`
`Delegate to The students Parliament, University of Oslo
`
`Member of Senate, School of Pharmacy, representing
`Ph. D students and research assistants.
`
`Member of Technical Affair and Equipment Committee,
`School of Pharmacy, University of Oslo.
`
`Member of Computers and Information Technology
`Committee, School of Pharmacy, University of Oslo.
`
`Member of Clinical Pharmacy Committee of the
`Norwegian Pharmaceutical Society, representing
`University of Oslo.
`The Committee did during this period develop and
`implement a three—year specialization program in
`Clinical/ Hospital Pharmacy.
`
`Member of Board of the Continuing Education of
`Pharmacists Committee.
`
`Vice—President of Board of the Continuing Education of
`Pharmacists Committee.
`
`Appointed member of committee evaluating the
`establishment of a one year post—graduate educational
`specialization program for Community Pharmacists in
`Norway.
`
`Member of Working group for establishing an
`Independent Department of Continuing and Postgraduate
`Education at The School of Pharmacy, University of Oslo.
`
`Deputy member of Senate, School of Pharmacy,
`representing Scientific Faculty.
`
`Member; Reference group for establishing a School of
`Pharmacy, University of Tromsoe
`
`Member; Curriculum evaluation committee, School of
`Pharmacy, University of Oslo.
`
`Member, working group for evaluation of present, and
`propose new infrastructure of student oriented IT—
`technologies, Faculty of Mathematics and Natural
`Sciences, University of Oslo.
`
`Head of Department, Department of Pharmacology,
`School of Pharmacy, University of Oslo.
`
`Member; Curriculum revision working group, School of
`Pharmacy, University of Oslo.
`
`RIMFROST EXHIBIT 1121 Page 0010
`RIMFROST EXHIBIT 1121 Page 0010
`
`

`

`1993—2002
`
`Member of Senate, School of Pharmacy.
`
`PROFESSIONAL MEMBERSHIPS
`
`CONSULTANT
`
`Norwegian Society for Pharmacology and Toxicology
`
`1984—2000
`
`1993—1999
`
`1993—1998
`
`Norwegian Association of Pharmacists.
`
`European Society of Clinical Pharmacy
`
`New York Academy of Sciences
`
`1990—present
`
`Norwegian Association of Research Scientists
`
`1999
`
`1999—2001
`
`2000 — 2003
`
`2001 — 2003
`
`Norwegian Society for Regulatory Affairs Associates
`
`Norwegian Polytechnic Society
`
`International Association of Therapeutic Drug Monitoring
`and Clinical Toxicology
`
`American Society for Clinical Pharmacology and
`Therapeutics
`
`2008 — present
`
`Member of EUFEPS CIRR committee
`
`Scientific Reviewer, Pharmacology and Toxicology,
`
`Munksgaard, Copenhagen.
`
`1997—1999
`
`Scientific consultant: The KLOK project: Developing a
`
`computerized system for drug interaction warning, as
`
`integral part of General Practitioners Computerized
`
`Patient Record and Administration System. CPC
`
`Scandinavia, Subsidiary of MSD, Drammen, Norway
`
`Scientific project reviewer, NATO Advanced Study
`
`proposal.
`
`Consultant, Pharmacokinetic trial design and analysis,
`
`Drug development, Photocure ASA, Oslo Norway.
`
`Consultant, General Pharmacology and Pharmacokinetics,
`
`Drug development Project, Ernst & Young Consultants,
`
`Oslo Norway
`
`Scientific Consultant, Smerud Medical Research Group,
`
`Oslo Norway.
`
`Consultant, Pharmackinetic trial design and analysis, Drug
`
`1999
`
`1999
`
`2000
`
`2000—2003
`
`2003—2004
`
`RIMFROST EXHIBIT 1121 Page 0011
`RIMFROST EXHIBIT 1121 Page 0011
`
`

`

`development, Conjuchem Inc., Montreal, Canada.
`
`2001 —2007
`
`Consultant, Pharmackinetic trial design and analysis, Drug
`
`development, AleXion Pharmaceuticals Inc., Cheshire, CT,
`USA.
`
`2008—2010
`
`Member of Pain Management Advisory Board, Egalet
`APS, Denmark
`
`RESEARCHSUPPORT
`
`1984 — 1989
`
`Norwegian Pharmaceutical Society, Research support
`
`Fund, $ 5000
`
`1991—1994
`
`1991—1995
`
`1999—2000
`
`2000—2001
`
`Norwegian Association of Pharmacy Proprietors,
`
`Pharmaceutical Research Fund, $160000,—
`
`Norwegian Governmental Medicinal Products Whole—Sale
`
`organization: Pharmacological Research Fund, $12000
`
`Norwegian Research Council; New Equipment support:
`
`LC— MS MS; $ 175 000.
`
`Norwegian Research Council: Sabbatical Support, $ 32000.
`
`LANGUAGES
`
`Norwegian, English; fluently.
`
`German: Near fluent.
`
`Swedish and Danish; uninhibited oral and written understanding but
`restricted ability in writing and speaking.
`
`RIMFROST EXHIBIT 1121 Page 0012
`RIMFROST EXHIBIT 1121 Page 0012
`
`

`

`PUBLICATIONS
`
`Articles in Peer-
`'
`li
`'
`rev1ewed pub catlons
`
`.
`
`1.
`
`HOEM, N.-O and BRISEID, K. Reduced cofactor function of
`human high molecular weight kininogen induced by rat plasma
`kallikrein. A010 100077770001. 01 10961601. 57, 47—52, 1985.
`
`2.
`
`HOEM, N.—O. and BRISEID, K. Activation of factor XII in
`
`acetone—treated human plasma: Significance of the functional state
`
`of plasma kallikrein for the eXtent of activation. A010 100077770001. 01
`
`1090001. 59, 144—150, 1986.
`
`3.
`
`HOEM, N.—O., BRISEID, G., EKELUND, S. and SALVESEN,
`
`S. Effects of intravenous radiographic contrast media on the blood
`
`pressure and on factors of the contact activation system in the rat.
`
`A010 100077770001. 01 10961001. 59, 189—194, 1986.
`
`4.
`
`HOEM, N.—O. and BRISEID, G. Acetylcysteine in rats: Inhibition
`
`of activation of prekallikrein and factor XII — Protection against
`
`deXtran—induced blood pressure fall. 130017770001qu 2’?” T0X10010gy, 60,
`
`140—144,1987.
`
`5.
`
`JOHANSEN, H.T., HOEM, N.—O., VEGGELAND, T. and
`
`BRISEID, K. Assay kallikrein inhibitors and levels of acetone—
`
`activated kallikrein in plasma specimens from reactors to deXtran
`
`or to contrast media. 171111155. R000. 8, 185—192, 19
`
`6.
`
`HOEM, N.—O.,]OHANSEN, H. T.,]OHANNESEN, S. and
`
`BRISEID, K. Rock immunoassay of high and low molecular
`
`weight kininogens in human plasma. Adi/000w 2'0 Experimeflm/
`
`Medicz'fle 0710’B1010gy, 247A, Kim'm V. K. Abe, H.t S. Fujii (Eds),
`
`New York—London: Plenum Press, 1989, pp.337—343.
`
`7.
`
`HOEM N.—O.,]OHANNESEN, S. and BRISEID, K. Assay of
`
`factor XII in human plasma using prekallikrein or the chromogenic
`
`peptide 8—2222 as substrates. Significance of the functional state of
`
`plasma kallikrein. T070070. R05. 54, 197— 1989.
`
`8.
`
`BRISEID, K., HOEM, N.—O.,]OHANNESEN, S. and
`
`MARTINSEN, K. Functional correlation between kallikrein and
`
`factor XII activated in human plasma and the. T010070. Rex. 57, 945—
`
`956, 1990
`
`RIMFROST EXHIBIT 1121 Page 0013
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`
`

`

`9.
`
`STORMORKEN, H., BRISEID, K, HELLUM, B., HOEM,
`
`N.—O, JOHANSEN, H. T. and LY, B. A new case of total
`
`kininogen deficiency. Tbmmb. Rex. 60, 457A67, 1990.
`
`10
`
`BRISEID, K, HOEM, N.—O.,]OHANNESEN, S. and FOSSUM,
`
`S. Contact activation factors in plasma from pregnant women.
`Increased level of an association between factor X11 and kallikrein.
`
`T670676. Rex. 67, 123—133, 1991.
`
`11.
`
`HOEM, N.—O.,]OHANNESEN, S., HAUGE, G., RUD, A. C.,
`
`SANDEM, S. and BRISEID, K. Contact activation factors in
`
`plasma from women using oral contraceptives — Increased levels of
`
`factor XII, kinin—free high molecular weight kininogen and
`
`acetone—activated kallikrein. Tbmmb. Rex. 64, 427—434, 1991.
`
`12.
`
`HOEM, N.—O.,]OHANNESEN, S. and BRISEID, K. Formation
`of an association between factor X11 and kallikrein in human
`
`plasma — Significance of storage of plasma and the functional State
`
`of plasma kallikrein. Tbmmb. Rex. 66, 421 —434, 1992.
`
`13.
`
`HOEM, N.—O. Studies on levels and interactions of contact
`
`activation factors in plasma. A basis for the elucidation of their
`
`function in anaphylactoid reactions to deXtran and to radiographic
`
`contrast media. Tberirfir the degree ofDr. Phi/05., School of
`
`Pharmacy, University of Oslo, 1992, ISBN 82—91094—01—2.
`
`14.
`
`FOSSUM, S., HOEM, N.—O.,]OHANNESEN, S.,
`
`KORPBERGET, M., NYLUND, E SAND EM, S. and BRISEID,
`
`K. Contact factors in plasma from women on oral contraception —
`
`Significance of factor XI for the measured activity of factor XII.
`
`Tbmmb. Rex. 74, 477—485, 1994.
`
`15.
`
`BRISEID, K, HOEM, N.—O,]OHANNESEN, S. and HAUG, K.
`
`Amidolytic assay of factor X1 in human plasma — Significane of
`
`kallikrein for the activity measured. Tbmmb. Rex. 78, 239—250, 1995.
`
`16.
`
`BRISEID, K, HOEM, N.—O,]OHANNESEN, S., VANGEN,
`
`M., WESTGAARD, T.: Significance of IgG for the activity of
`
`factor XII measured in human plasma. Seemd C1271. Lab. lei/ext. 56,
`
`725—734, 1996.
`
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`

`17
`
`SATAS, S,]OHANNESSEN, S.I, HOEM, N.O, HAALAND, K.,
`
`SORENSEN, D.R., THORESEN, M. Lidocaine pharmacokinetics
`
`and toxicity in newborn pigs. A71m‘b./l7111{g. 85,306—312,1997
`
`18
`
`BRISEID K, HOEM N.O.,]OHANNESEN S. Part of
`
`prekallikrein removed from human plasma together with IgG —
`
`immunoblot experiments and functional tests. 5111ml. ]. C1171. Lab.
`
`[7112651. 59, 1—9, 1999.
`
`19
`
`POSSUM, S., HOEM, N.O., G]ONNAESS., H., BRISEID, K.
`
`Contact activation factors in plasma from women on estrogen
`
`replacement therapy after ovariohysterectomy. Tbmmb Rex, 93, 161—
`
`70, 1999.
`
`20
`
`SATAS, S., HOEM, N., MELBY, K., PORTER, H.,,
`
`WHITELAW, A., THORESEN, Influence of mild hypothermia
`
`after hypoxia—ischemia on the pharmacokinetics of gentamicin in
`
`newborn pigs. Biology oftbe 7160711116, 77, 50—57, 2000.
`
`21.
`
`WANG, S., BERGE, G.E., HOEM,N.O., SUND, R.B. Ascorbic
`
`Pharmacokinetics in dogs after oral administration of two different
`
`forms of ascorbic acid. Res Vet Sci. 2001 Aug;71(1):27—32.
`
`22
`
`CARLSSON, KC, HOEM, NO, MOBERG, ER, MATHIESEN,
`
`LC . Analgesic effect of deXtromethorphan in neuropathic pain.
`
`Acta Anaesthesiol Scand. 2004 Mar; 48(3):328—36.
`
`23
`
`CARLSSON, KC, HOEM, NO, GLAUSER,T, VINKS, AA.
`
`Development of a Population Pharmacokinetic Model for
`
`Carbamazepine Based on Sparse Therapeutic Monitoring Data
`
`from Pediatric Patients with Epilepsy Clin Ther 2005;27:618—26
`
`24
`
`BERINGER, P, NGUYEN, M, HOEM,N, LOUIE, S, GILL, M,
`
`GUREVITCH, M, BERINGER, AW: Absolute Bioavailability
`
`and Pharmacokinetics of Linezolid in Hospitalized Patients Given
`
`Enteral Feedings Antimicrob. Agents Chemother. 2005 49: 3676—
`3681.
`
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`

`

`25
`
`26
`
`27
`
`28
`
`29
`
`30
`
`31
`
`BERINGER, P, HUYNH KM, KRIENGKAUYKIAT J, BI L,
`
`HOEM N, LOUIE S, HAN E, NGUYEN T, HSU D, RAO PA,
`
`SHAPIRO B, GILL M. Absolute bioavailability and intracellular
`
`pharmacokinetics of azithrornycin in patients with cystic fibrosis.
`
`Antimicrob Agents Chemother. 2005 Dec; 49 (1 2):5013—7.
`
`CARLSSON, K.C., van de SCHOOTBRUGGE, HANSEN, H,.,
`
`MOBERG, E.R., HOEM, N.O. A Population Pharrnacokinetic
`
`Model of Gabapentin in Neuropatic Pain Patients. Ther Drug
`
`Monit. 2009 Feb; 31(1):86—94.
`
`WINTHER, B. , HOEM N., BERGE K, REUBSAET L.:
`
`Elucidation of phospholipid composition in krill oil extracted from
`
`Euphausia Superba. Lipids. 2011 Jan;46(1):25—36.
`
`KIRKHUS B, LAMGLAIT A, EILERTSEN KE, FALCH E,
`
`HAIDER T, VIK H, HOEM N, HAGVE TA, BASU S, OLSEN
`
`E, SELJEFLOT I, NYBERG L, ELIND E, ULVEN S. Effects of
`
`similar intakes of marine n—3 fatty acids from enriched food
`
`products and fish oil on cardiovascular risk markers in healthy
`
`humans. Submittedfirpub/z'mz‘z'ofl
`
`BURRI, L., HOEM N., BANNI S., BERGE K. Unique
`
`Nutritional Properties of Marine Omega—3 Phospholipids.
`
`Submittedfirpub/z'mz‘z'ofl
`
`HOEM, N., MELLE, F., MEYER, I CARLSSON, K.C., .
`
`Population Pharmacokinetics of EPA and DHA after intake in
`
`phospholipid and / or triglyceride bound forms from krill or fish
`
`oil. [71 prqbozmz‘z'ofl.
`
`HOEM, N., MELLE, E, MEYER I., Population pharmacokinetics
`
`of astaxanthin after intake of single doses of krill oil lipids. [71
`
`prqbozmz‘z'ofl.
`
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`

`

`Presentations 3901
`Posters at meet1ngs,
`conferences and
`
`1.
`
`HOEM, N. o., BRISEID, G., EKELUND, s., SALVESEN, 3.
`
`Effects of intravenous radiopgraphic contrast media on the blood
`
`congresses.
`
`pressure and on factors of the contact phase system in the rat.
`
`Prereflfotiofl, Wroter metiflg, Norb/egz'ofl Socz'eglfor Pborococo/ogy emo’
`
`Toxicology, Bez‘z‘o, Normal, Jclflfldfll 23—26 7986.
`
`2.
`
`HOEM, N.—O., BRISEID, G. Acetylcystein i rotte: Inhibisjon aV
`
`aktiveringe prekallikrein og faktor XII — beskyttelse mot dekstran—
`
`indusert blodtrykksfal Prereflfotiofl, Formoxio’ogefle, B/iflo’erfl, Norb/cm
`October 27. 7986.
`
`3.
`
`HOEM, N.—O.,]OHANSEN, H. T.,]OHANNESEN, S.,
`
`BRISEID, K. Rock immunoassay of high and low molecular
`
`weight kininogens in human plasma. Prerem‘oz‘z'oo, Kz'm'o V.
`
`Ioteroofiooo/ Coogrem or [671271, Nooeocber 29 — December 3, Tokyo, jopcm.
`
`4.
`
`JOHANSEN, H. T., ENG H, K. M., HOEM, N.—O.
`
`Hoymolekylaert kininogen. Effekten aV plasma kallikrein paa
`
`kofaktorfunksjonen. Prexeototioo, Formoxio’ogefle, B/ioo’ero, Nora/cal
`October 24. 7988.
`
`5.
`
`BRISEID, K. and HOEM, N.—O. Assay of factor XII in human
`
`plasma — Significance of the functional state of plasma kallikrein.
`
`Porter, Goro’oo Rereorcb Coflfz‘reflce or Kol/zkrez‘o emo’ Kz‘m'm, Oxmzro’,
`
`Cobform‘o, 22.— 77.jammy}, 7989.
`
`6.
`
`STORMORKEN, H., BRISEID, K., HELLUM, B., HOEM,
`
`N.O., JOHANSEN, and LY, B. A new case of kininogen
`
`deficiency. Prereototioo o’ccriflg XII. 15TH, jopcm 7989.
`
`7.
`
`HOEM, N.—O., EIDE, G., HORVEI, K., KEUSE—JENSEN, A.,
`
`I. WOLD. Postgraduate education in hospital pharmacy in
`
`Norway. Prexeototioo, sze/oflg [ear/1mg 2'71pborococem‘z‘co/rcz'eflceir emo’
`
`Jervicer, 751‘ ioterooz‘iooo/ coofereoce. Hillereo’, Deomor/é, 7990.
`
`8.
`
`BRISEID, K., HOEM, N.—O. and S. JOHANNESEN. Factor XII,
`
`kallikrein and high molecular weight kininogen are present in
`
`association in human plasma acetone—activated in the presence of
`
`benzamidine. Porter, Goro’oo Rereorcb Coofz‘reoce or Kol/zkrez‘o emo’
`
`Kz'm'm, Vem‘oro, Cobform'o, 78 — 22.ftbruar 7997.
`
`RIMFROST EXHIBIT 1121 Page 0017
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`

`

`9.
`
`HOEM, N. —O.,]OHANNESEN, S., HAUGE, G., RUD, A. C.,
`
`SANDEM, S., BRISEID, K. Contact activation factors in plasma
`
`from women using oral contraceptives. Porter, Ktm'b V, Ibtermztz'emz/
`
`Cebgrem or 1671271, September 8 —24, 799 7, Member, Germtmy.
`
`10
`
`ERIKSEN, I. L, FINSTAD, E., HOEM, N.—O. Advanced
`
`diploma in community pharmacy. A post—graduate program
`
`involving both traditional and long—distance educational methods.
`
`Porter PIP Ibtermztz‘omz/ Coflgrem, Tokyo, japom, September 7993
`
`11
`
`BRISEID K, HOEM, N.—O., POSSUM, S.,]OHANNESEN, S.
`
`Increased level factor XII, prekarnkrein and plasminogen
`
`proactivators in plasma from women on a low estrogen dose oral
`
`contraceptive. Significance of factor XI for activity levels of factor
`
`XHa and kallikrein. Porter, Ktm'b VI 93 Brazil, Ibtermztz'emz/ Cebgrem,
`
`Gamma, Brazil, October 27—22, 7993.
`
`12.
`
`HOEM, N.—O. Diplomstudieti apotekfarmasi. Et ettaarig ng
`
`universitetsstudium i apotekfarmasi. Status og erfaringer etter
`
`foerste studieaarr. Prexefltozttofl. 76tb. Nordte Coflgrem 071 Pbozr/mze ,
`
`Reykjabzk 22.—Iee/omd. jtme 7994.
`
`13.
`
`HOEM, N.—O, HUSEMOEN, R. Advanced diploma in
`
`community pharmacy Program involving both traditional and
`
`long—distance educational methods. Prerefltozttofl, porter 471dpractical
`
`dememtrtztz'eb. Tbe Seeeim’ Ibtermztz'emz/ Cebferebee 071 fife/071g Lear/mtg 2'71
`
`Pbozr/mze , Madtrofl, WI, US.14., Attgmt 22—26, 7994.
`
`14.
`
`BRISEID, K, HOEM, N.—O., S. JOHANNESEN, HAUG, K.
`
`Amidolytic assay of factor X1 in human plasma — Significance of
`
`kallikrein for the activity measured. Porter, Gordofl Rereozreb Cobfereflee
`
`or Kalli/weir 471d Ktm'm, Vefll‘tflfl, Ca/zferm'tz, Febrng/ 7995.
`
`15.
`
`HOEM, N. O. Internetbasert f]ernundervisning. (Internet as a tool
`
`for distance education). Ibrz'tedprexebtatz'eb 471d dememtratz'eb,
`
`Headquarterx, Apote/éozrmeietetefl, Stoe/ébolm, 7994.
`
`16.
`
`SATAS, S.,]OHANNESSEN, S., HOEM, N. 0., HAALAND, K,
`
`SORENSEN, D.R., WHITELAW, A., THORESEN, M. The
`
`convulsive plasma level and pharmacokinetics of lignocaine in the
`
`newborn piglet. Prereflttztz'ofl pttb/z'Jbed 2'71 Premtoz/ 471d Neomztoz/
`
`Medtcmeu 7996; 7 (Suppl. 7):724.
`
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`

`17.
`
`BRISEID, K., HOEM, N.O., JOHANNESEN S. A kallikrein
`
`fragment formed in human plasma in the absence of IgG shares
`
`immunological properties with factor XII. Porterprerem‘az‘z'oo, Goro’oo
`
`Coofereoee 071 Kalhkrez‘o aoo’ Karim, Barga, Bah! Meg! 7997.
`
`18.
`
`HOEM, N.O. Legemiddel, farmasi og helseinformasjon gjennom
`
`internett (Drug, pharmacy and health information by way of the
`
`Internet). Iooiz‘eo’prerem‘az‘z‘oo; I/an‘ra hrez‘reo , Loea/ hraoeh of
`
`Apoz‘eharroez'ez‘ez‘eo, Gotehharg, 7996.
`
`19.
`
`HOEM, N. O. Internettbaserte legemiddelinformasjonsressurser
`
`(Internet based drug info resources), Invited presentation,
`
`Lahemeo’e/Jhoogremeo, Stoehho/m, 7997
`
`20.
`
`CARLSSON, K.C.; HOEM, N.O.; MOBERG, E.R.; MATHISEN,
`
`LC. Analgesic effect of deXtromethorphan in neuropathic pain.
`
`IASP Niee, Frame. Septemher 2000.
`
`21.
`
`HOEM, N.O. Klinisk farmakokinetikk. Virkelighet eller fata
`
`morgana? (Clinical Pharmacokinetics — Reality or a distant Mirage?)
`
`InVited Presentation Popa/az‘z‘oo Im‘eren‘ Groap Meez‘z'og Copeohageo. Meg!
`2000.
`
`22.
`
`HOEM, N.O,]ELLIFFE, R. W.. Goal Oriented, Model Based
`
`Clinical Pharmacokinetics — InVited Presentation Popa/az‘z'oh
`
`Pharmaeo/éz'oez‘z'eJr aoo’ Sima/az‘ioo Im‘eren‘ Groap Meetz'og Copeohageo. Meg!
`2000.
`
`23.
`
`BOTNEN A, WANG X,]ELLIFFE R, THOMAS M, and
`
`HOEM N: Population Pharmacokinetic Modeling Via the World
`
`Wide Web. Poster presentation Ahhaa/Meez‘z'hg ofthe Popa/az‘z'oh
`
`Ahah/m Groap 2'71 Earope, Barel, Shaker/aha: jahe 7—8. 2007.
`
`24.
`
`HOEM N, and JELLIFFE R: An NPEM Populatin Analysis of
`
`Ciclosporine — Modelling Oral Drug Absorption as a Time—
`
`Dependent Function. Poster presentation: Ahhaa/Meez‘z'hg ofthe
`
`Popa/az‘z‘oo Ahah/m Groap 2'71 Earope, Barel, Shaker/aha, jaoe 7—8. 2007
`
`25.
`
`HOEM, N O. Modeling the oral absorption of drugs, an example
`
`with cyclosporine: Invited oral presentation: Tem‘h Worhxhop 2007
`
`071 Adapter/e Com‘ro/ ofDrag Therapy: Ioo’z‘oz‘o’aa/z‘zz‘og Drag Therapy 271
`
`2007— Neeerxifier, Dfiea/tier, aflo’ Opporz‘aoitiex’, Hoipz'z‘a/ Geriatriqae
`
`Am‘oz'he Charial, Fraaeheoz'l/e, Frame, 27—29 jaae, 2007.
`
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`

`

`26.
`
`27.
`
`28.
`
`29.
`
`HOEM, N 0. Modeling the oral absorption of drugs, an example
`
`with cyclosporine: Invited oral presentation: @mpwz'am 071 Papalaz‘z'ea
`
`Pdedffl/élflellfl' afla’ D0565 Aafimz‘mem‘ az‘ the 3rd Meez‘z'flg ofz‘be Federaz‘zefl
`
`ofz‘be Eampeafl Pharmacological Socieller, jag! 6—2200 7, Ljofl, Fraflce.
`
`BOTNEN A, JELLIFFE R, THOMAS M, and HOEM N:
`
`Population Pharmacokinetic / Dynamic Modeling via the World
`
`Wide Web. Oral Presentation: The 741‘” IEEE Sympwz‘am 071 Compaz‘er
`
`Barea’ Medical Sjln‘eim, jag! 26—27, 200 7, Bez‘bem’a MD. Pmceea’z'flgr, pp.
`7 63— 7 68.
`
`HOEM, NO. Optimising Tra