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.
`
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`
`

`

`i further decisre that all statement nade herein of my won knowledgearetrue and that all
`3
`Statements made on dvfarmation and belief are believed ts be true, andRurther that these
`
`statements weremade with the knowledge that willfd false statements and the likese made are
`
`punishable by fine ar imprisonment, or both, under sechton [O01 af ile TS of the Uiited States
`Code, sud that such willful false siatements may jeopardize the validity of the application or any
`
`patent issuedthereon.
`
`Respectiully submitted,
`
`
`
`Br Ntis Hoenn
`
`Pate
`
`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
`
`Teacher (Ellingsoy Junior High School)
`
`1984 - 2004
`
`1992-1996
`
`1999
`
`2003
`
`2003-2004
`
`2004-2007
`
`2007-2007
`
`2008-2010
`
`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 PharmaServices,
`Hamburg, Germany and Belfast Northern-Ireland
`
`Director R&D Pronova Biocate 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 Minister
`of Health and Social Services.
`
`Member of Scientific Committee, European Workshop on
`Clinical Pharmacy, Oslo, June 1993.
`
`Memberof organizing Committee 34 International
`Congress for Lifelong Learning in Pharmacy, Hillerod,
`Denmark, June 1998.
`
`Member of jury (2°4 opponent) evaluation of Doctoral
`Thesis: Quy, N Diep; “Pivalic acid containing antibiotics
`induced carnitine deficiency’, University of Oslo.
`
`Member of jury 3" 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 (3"4 opponent) evaluation of Doctoral
`Thesis: Ole Andreas Loechen Oekstad; “Sequence analysis
`of Bacillus cereus genome fragments: A comparative
`genomeanalysis.” 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 Roger Jelliffe 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 Putilisation des techniques de
`modeélisation dans le processus de développement d’un
`médicament: de l’étape pré-clinique 4 clinique.” University
`of Montreal, February 2009.
`
`External expert during dissertation of Doctoral Thesis:
`“Development and Evaluation of Nonparametric Mixed
`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
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`
`

`

`Post graduate studies
`
`1983
`
`MS (pharm): Thesis; “Measurement of arterial blood
`pressure and plasmalevel of prekallikrein, high molecular
`weight kininigen and plasminogen activatorin 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 Norwaypart 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 31 World Congress on TDM,
`Philadelphia.
`
`SAAM IIT 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.
`
`9% 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 Level
`
`1985 — 1993
`
`1985-1993
`
`1993-2003
`
`1993
`
`1993-2002
`
`2000-2001
`
`Graduate Level
`
`1990 and 1992
`
`Instructor in Experimental pharmacology, part of
`5 credit (full year=20 credits) subject PBF 250
`Pharmacodynamics, and PBF 150 Physiology with
`Anatomy (4 credits).
`
`Course Coordinator PBF 250 Pharmacodynamics
`experimental course during 6 terms, School of Pharmacy,
`University of Oslo.
`
`Lectures in PBF 251 Basic Pharmacology (5 credits) for
`3rd year Pharmacy students, University of Oslo,
`
`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
`
`Lectures in PBF151 Physiology (3 credits) for 274 year
`Pharmacy students, University of Oslo
`
`Course coordinator PBF 151 Physiology, School of
`Pharmacy, University of Oslo.
`
`Course coordinator for PBF 355Clinical
`Pharmacokinetics, School of Pharmacy, University of
`Oslo.
`
`Post Graduate Level
`
`1996— 1998
`
`Course Coordinator PBF 353 Advanced Pharmacology
`
`1992-1997
`
`1992-1995
`
`1994, 1996
`
`2001
`
`Supervisor
`
`1984-2005
`
`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
`
`Course coordinator one-year course: Advanced Diploma
`in Community Pharmacy.
`
`Course coordinator PBF 455 Clinical Pharmacokinetics,
`Department of postgraduate and continuing education,
`School of Pharmacy, University of Oslo. In 1996 this
`course wasclassified as a National Research course
`
`PBF 455 Clinical Pharmacokinetics. Organized as one-year
`distance education Course using the VETTUStool.
`Sole lecturer and Instructor at the same course (4 credits),
`University of Oslo.
`
`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
`yeat long, advanced continuing education program for
`community Pharmacists, University of Oslo.
`
`1992-1997
`
`Ph. D student Siv Fossum.
`
`2000
`
`Ph. D student Siri Wang.
`
`2000 - 2005
`
`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.
`
`1996
`
`1998-
`
`1996
`
`Continuing education
`Courses and
`Continuing education
`Workshops
`
`1996 - 1997
`
`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
`
`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.
`
`1998
`
`1999
`
`Internet in the Pharmaceutical and Medical Fields. One
`day Hands on Workshop, Pharmakon, Hillerod, Denmark
`
`Net based Information technologies in the Helath
`Professions, Oslo
`
`1999-2000
`
`Co-developer of VETTUS a Web basedtoolfor
`Continuing and Post-Graduate Education, University of
`Oslo
`
`2001 -present
`
`Several workshops in Population PK together with
`Professor RogerJelliffe at LAPK, University of Southern
`California. Workshopsheld in the US, Spain, Italy, France
`and Switzerland.
`
`RIMFROST EXHIBIT 1121 Page 0009
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`
`

`

`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.
`
`Memberof 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
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`
`

`

`1993-2002
`
`Memberof 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
`
`1997-1999
`
`1999
`
`1999
`
`2000
`
`Scientific Reviewer, Pharmacology and Toxicology,
`Munksgaard, Copenhagen.
`
`Scientific consultant: The KLOKproject: 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
`
`2000-2003
`
`Scientific Consultant, Smerud Medical Research Group,
`Oslo Norway.
`
`2003-2004
`
`Consultant, Pharmackinetic trial design and analysis, Drug
`
`RIMFROST EXHIBIT 1121 Page 0011
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`
`

`

`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
`
`RESEARCH SUPPORT
`
`1984 - 1989
`
`Norwegian Pharmaceutical Society, Research support
`Fund, $ 5000
`
`1991-1994
`
`1991-1995
`
`1999-2000
`
`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.
`
`2000-2001
`
`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
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`
`

`

`PUBLICATIONS
`
`Articles in peer-
`reviewed publications.
`
`HOEM,N.-O and BRISEID, K. Reduced cofactor function of
`human high molecular weight kininogen induced by rat plasma
`kallikrein. Actapharmacol. et toxicol, 57, 47-52, 1985.
`
`HOEM,N.-O. and BRISEID, K. Activation of factor XII in
`
`acetone-treated human plasma: Significance of the functional state
`of plasmakallikrein for the extent of activation. Actapharmacol. et
`toxtcol. 59, 144-150, 1986.
`
`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 therat.
`Adapharmacol. et toxicol. 59, 189-194, 1986.
`
`HOEM,N.-O. and BRISEID, G.Acetylcysteine in rats: Inhibition
`of activation of prekallikrein and factor XII - Protection against
`dextran-induced blood pressure fall. Pharmacology ¢» Toxicology, 60,
`140-144,1987,
`
`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. Int J. Tiss. Reac. 8, 185-192, 19
`
`HOEM,N.-O., JOHANSEN,H.T., JOHANNESEN,S. and
`BRISEID, K. Rock immunoassay of high and low molecular
`weight kininogens in human plasma. Advances in Experimental
`Medicine and Biology, 247A, Kinins V. IX. Abe, H.t S. Fujii (Eds.),
`New York-London: Plenum Press, 1989, pp.337-343.
`
`HOEM N.-O., JOHANNESEN,S. and BRISEID, K. Assay of
`factor XII in human plasma using prekallikrein or the chromogenic
`peptide $-2222 as substrates. Significance of the functional state of
`plasmakallikrein. Thromb. Res. 54, 197- 1989.
`
`BRISEID, K., HOEM, N.-O., JOHANNESEN,S. and
`MARTINSEN,K. Functional correlation between kallikrein and
`
`factor XII activated in human plasma and the. Thromb. Res. 57, 945-
`956, 1990
`
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`
`

`

`10
`
`11.
`
`12.
`
`13.
`
`14.
`
`15.
`
`16.
`
`STORMORKEN,H., BRISEID, K., HELLUM, B., HOEM,
`N.-O, JOHANSEN,H. T. and LY, B. A new caseoftotal
`kininogen deficiency. Thromb. Res. 60, 457A67, 1990.
`
`BRISEID, K., HOEM, N.-O., JOHANNESEN,S. and FOSSUM,
`S. Contact activation factors in plasma from pregnant women,
`Increased level of an association between factor XII and kallikrein.
`
`Thromb. Res. 61, 123-133, 1991.
`
`HOEM,N.-O., JOHANNESEN,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 XI, kinin-free high molecular weight kininogen and
`acetone-activated kallikrein. Thromb. Res. 64, 427-434, 1991,
`
`HOEM,N.-O., JOHANNESEN,5. and BRISEID, K. Formation
`of an association between factor XII and kallikrein in human
`
`plasma- Significance of storage of plasma and the functional State
`of plasma kallikrein. Thromb. Res. 66, 421-434, 1992.
`
`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. Thesisfor the degree ofDr. Philos., School of
`Pharmacy, University of Oslo, 1992, ISBN 82-91094-01-2.
`
`FOSSUM,S., HOEM,N.-O., JOHANNESEN,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 measuredactivity of factor XII.
`Thromb. Res. 74, 477-485, 1994.
`
`BRISEID, K., HOEM, N.-O, JOHANNESEN,S. and HAUG,K.
`Amidolytic assay of factor XI in human plasma- Significane of
`kallikrein for the activity measured. Thromb. Res. 78, 239-250, 1995.
`
`BRISEID, K., HOEM, N.-O, JOHANNESEN,S., VANGEN,
`M., WESTGAARD,T:: Significance of IgG for the activity of
`factor XII measured in human plasma. Scand Chin. Lab. Invest. 56,
`725-734, 1996.
`
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`

`

`17
`
`18
`
`19
`
`SATAS, S, JOHANNESSEN,S.I, HOEM, N.O, HAALAND,K.,
`SORENSEN,D.R., THORESEN,M.Lidocaine pharmacokinetics
`and toxicity in newborn pigs. Anesth. Analg. 85,306-312,1997
`
`BRISEID kK, HOEM N.O., JOHANNESENS. Part of
`prekallikrein removed from human plasma together with IgG -
`immunoblot experiments and functional tests. Scand. J. Clin, Lab.
`Invest. 59, 1-9, 1999,
`
`FOSSUM,S., HOEM, N.O., GIONNAESS., H., BRISEID, K.
`Contact activation factors in plasma from women on estrogen
`replacement therapy after ovariohysterectomy. Thromb Res, 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. Bzology ofthe neonate, 77, 50-57, 2000.
`
`21,
`
`22
`
`23
`
`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.
`
`CARLSSON, KC, HOEM, NO, MOBERG, ER, MATHIESEN,
`
`LC. Analgesic effect of dextromethorphan in neuropathic pain.
`Acta Anaesthesiol Scand. 2004 Mar; 48(3):328-36.
`
`CARLSSON, KC, HOEM, NO, GLAUSER,T, VINKS, AA.
`
`Developmentof 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
`
`BERINGER, P, HUYNH KM, KRIENGKAUYKIATJ, BIL,
`HOEM N, LOUIE S, HAN E, NGUYEN T, HSU D, RAO PA,
`
`SHAPIROB, GILL M.Absolute bioavailability and intracellular
`pharmacokinetics of azithromycin in patients with cystic fibrosis.
`Antimicrob Agents Chemother. 2005 Dec; 49(12):5013-7.
`
`26
`
`CARLSSON,K.C., van de SCHOOTBRUGGE, HANSEN,H,.,
`
`MOBERG,E.R., HOEM, N.O. A Population Pharmacokinetic
`Model of Gabapentin in Neuropatic Pain Patients. Ther Drug
`Monit. 2009 Feb; 31(1):86-94.
`
`27
`
`28
`
`29
`
`30
`
`31
`
`WINTHER, B. , HOEM N., BERGE K., REUBSAETL.:
`
`Elucidation of phospholipid composition in krill oil extracted from
`Euphausia Superba. Lipids. 2011 Jan;46(1):25-36.
`
`KIRKHUS B, LAMGLAIT A, ETLERTSEN KE, FALCH E,
`
`HAIDERT, VIK H, HOEM N, HAGVE TA, BASU S, OLSEN
`E, SELJEFLOT I, NYBERG L, ELIND E, ULVENS. Effects of
`similar intakes of marine n-3 fatty acids from enriched food
`products and fish oil on cardiovascular risk markers in healthy
`humans. Submittedforpublication
`
`BURRI, L., HOEM N., BANNI S., BERGE K. Unique
`Nutritional Properties of Marine Omega-3 Phospholipids.
`Submittedforpublication
`
`HOEM,N., MELLE, F., MEYER, I CARLSSON, K.C., .
`
`Population Pharmacokinetics of EPA and DHAafter intake in
`phospholipid and/ortriglyceride bound forms ftom krill or fish
`oil. In preparation.
`
`HOEM, N., MELLE, F., MEYERI., Population pharmacokinetics
`of astaxanthin after intake of single doses of krill oil lipids. I”
`preparation.
`
`RIMFROST EXHIBIT 1121 Page 0016
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`
`

`

`Presentations and
`Posters at meetings,
`conferences and
`
`congresses.
`
`HOEM,N.O., BRISEID, G., EKELUND, S., SALVESEN,S.
`
`Effects of intravenous radiopgraphic contrast media on the blood
`pressure and on factors of the contact phase system in the rat.
`Presentation, Winter meting, Norwegian Societyfor Pharmacology and
`Toxicology, Betto, Norway, January 23-26 1986.
`
`HOEM,N.-O., BRISEID,G. Acetylcystein i rotte: Inhibisjon av
`aktiveringe prekallikrein og faktor XII - beskyttelse mot dekstran-
`indusert blodtrykksfal Presentation, Farmasidagene, Blindern, Norway,
`October 27. 1986.
`
`HOEM,N.-O., JOHANSEN,H. T., JOHANNESEN,S.,
`BRISEID,K. Rock immunoassay of high and low molecular
`weight kininogens in human plasma. Presentation, Kinin V.
`International Congress on Kinin, November 29 - December 3, Tokyo, Japan.
`
`JOHANSEN,H.T., ENG H, Kk. M., HOEM, N.-O.
`Hoymolekylaert kininogen. Effekten av plasma kallikrein paa
`kofaktorfunksjonen. Presentation, Parmasidagene, Blndern, Norway
`October 24, 1988.
`
`BRISEID, K. and HOEM,N.-O. Assay of factor XII in human
`plasma — Significance of the functional state of plasma kallikrein.
`Poster, Gordon Research Confirence on Kalhkrein and Kinins, Oxnard,
`Cahiformia, 22.- 17January, 1989.
`
`STORMORKEN,H., BRISEID, K., HELLUM, B., HOEM,
`
`N.O., JOHANSEN,and LY, B. A new case of kininogen
`deficiency. Presentation during XIL ISTH, Japan 1989.
`
`HOEM,N.-O., EIDE, G., HORVELK.,KEUSE-JENSEN,A.,
`I. WOLD. Postgraduate education in hospital pharmacy in
`Norway. Presentation, Lifelong learning in pharmaceutical sciences and
`services, 1st international conference. Hillered, Denmark, 1990.
`
`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. Poster, Gordon Research Confirence on Kallikrein and
`Kinins, Ventura, Cahiforma, 18 - 22.ftbruar 1997,
`
`RIMFROST EXHIBIT 1121 Page 0017
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`
`

`

`HOEM,N.-O., JOHANNESEN,S., HAUGE, G., RUD, A.C,
`SANDEM,S., BRISEID, K. Contact activation factors in plasma
`from women using oral contraceptives. Poster, Kinin VV, International
`Congress on Kinin, September 8 -24, 1991, Munchen, Germany.
`
`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.
`Poster PIP International Congress, Tokyo, Japan, September 1993
`
`11
`
`12.
`
`13.
`
`14.
`
`15.
`
`16.
`
`BRISEID K., HOEM,N.-O., FOSSUM,S., JOHANNESEN,S.
`Increased level factor XT, prekarnkrein and plasminogen
`proactivators in plasma from women ona low estrogen dose oral
`contraceptive. Significance of factor XI for activity levels of factor
`XIIa and kallikrein. Poster, Kinin VI 93 Brazil, International Congress,
`Guaruja, Brazil, October 27-22, 1993.
`
`HOEM,N.-O. Diplomstudiet i apotekfarmasi. Et ettaarig ng
`universitetsstudium 1 apotekfarmasi. Status og erfaringer etter
`foerste studicaarr. Presentation. 16th. Nordic Congress on Pharmacy,
`Reykjavik, 22.-Iceland. June 1994.
`
`HOEM,N.-O, HUSEMOEN,R. Advanced diplomain
`community pharmacy Program involving both traditional and
`long-distance educational methods. Presentation, poster andpractical
`demonstration. The Second International Conference on Lafelong Learning in
`Pharmacy, Madison, WI, U.S_A., August 22-26, 1994.
`
`BRISEID, K., HOEM, N.-O., S. JOHANNESEN, HAUG,K.
`Amidolytic assay of factor XI in human plasma- Significance of
`kallikrein for the activity measured. Poster, Gordon Research Conference
`on Kallikrein and Kinins, Ventura, California, Pebruary 1995.
`HOEM,N.O. Internetbasert ffernundervisning. (Internet as a tool
`for distance education). Invitedpresentation and demonstration,
`Headquarters, Apotekarsocieteten, Stockholm, 1994.
`
`SATAS, S.,JOHANNESSEN,S., HOEM, N. O., HAALAND,K.,
`SORENSEN,D.R., WHITELAW, A., THORESEN,M. The
`
`convulsive plasma level and pharmacokinetics of lignocaine in the
`newborn piglet. Presentation published in Prenatal and Neonatal
`Medicine., 1996, 1 (Suppl. 1):124.
`
`RIMFROST EXHIBIT 1121 Page 0018
`RIMFROST EXHIBIT 1121 Page 0018
`
`

`

`17.
`
`18.
`
`19.
`
`20.
`
`21,
`
`22,
`
`23.
`
`24.
`
`25,
`
`BRISEID, K., HOEM, N.O.,JOHANNESENS. A kallikrein
`fraement formed in human plasmain the absence of IgG shares
`immunological properties with factor XII. Posterpresentation, Gordon
`Conference on Kallikrein and Kinins, Barga, Italy May 1997.
`
`HOEM,N.O. Legemiddel, farmasi og helseinformasjon ejennom
`internett (Drug, pharmacy and health information by way of the
`Internet). Invitedpresentation, Vastra kretsen , Local branch of
`Apotekarsocieteten, Gotenburg, 1996.
`HOEM,N.O. Internettbaserte legemiddelinformasjonsressurser
`(Internet based drug info resources), Invited presentation,
`Lakemedelskongressen, Stockholn, 1997
`
`CARLSSON,K.C.; HOEM, N.O.; MOBERG,E.R.; MATHISEN,
`L.C. Analgesic effect of dextromethorphan in neuropathic pain.
`LASP Nice, France. September 2000.
`
`HOEM,N.O. Klinisk farmakokinetikk. Virkeligheteller fata
`morgana? (Clinical Pharmacokinetics — Reality or a distant Mirage?)
`Invited Presentation Population Interest Group Meeting Copenhagen. May
`2000.
`
`HOEM,N.O, JELLIFFE, R. W.. Goal Oriented, Model Based
`Clinical Pharmacokinetics — Invited Presentation Population
`Pharmacokinetics and Simulation Interest Group Meeting Copenhagen. May
`2000.
`
`BOTNEN A, WANG X, JELLIFFE R, THOMASM,and
`HOEM N: Population Pharmacokinetic Modeling via the World
`Wide Web. Poster presentation AnnualMeeting ofthe Population
`Analysis Group in Europe, Basel, Switzerland, June 7-8. 2001.
`
`HOEM N,and JELLIFFE R: An NPEM Populatin Analysis of
`Ciclosporine — Modelling Oral Drug Absorption as a Time-
`Dependent Function. Poster presentation: Annual Meeting ofthe
`Population Analysis Group in Europe, Basel, Saitzerland, June 7-8. 20017
`
`HOEM,N O. Modeling the oral absorption of drugs, an example
`with cyclosporine: Invited oral presentation: Tenth Workshop 2001
`on Adaptive Control ofDrug Therapy: Indiiduahzing Drug Therapy in
`2001- Necessities, Difficulties, and Opportunities”, Hospital Geriatrique
`Antoine Charial, Prancheville, Prance, 27-29 June, 2007,
`
`RIMFROST EXHIBIT 1121 Page 0019
`RIMFROST EXHIBIT 1121 Page 0019
`
`

`

`26.
`
`27,
`
`28.
`
`29,
`
`HOEM,N O. Modeling the oral absorption of drugs, an example
`with cyclosporine: Invited oral presentation: Syposium on Population
`Pharmacokinetics and Doses Adjustment at the 3 Meeting ofthe Federation
`ofthe European Pharmacological Societies, July 6-9,2001, Lyon, France.
`
`BOTNENA, JELLIFFE R, THOMASM, and HOEM N:
`Population Pharmacokinetic/Dynamic Modeling via the World
`Wide Web. Oral Presentation: The 14 IEEE Symposium on Computer
`Based Medical Systems, July 26-27, 2001, Bethesda MD. Proceedings, pp.
`163-168.
`
`HOEM,NO. Optimising Transplant Chemotherapy. Furst Itahan
`Symposium on Population Pharmacokinetics, March 19, 2002.
`
`CARLSSON,KC, HANSEN,H, JELLIFFE, RW,HOEM, NO.
`Establishing a tool for individualised dosing of gabapentin - The
`use of a non-parametric population kinetics model in the MM-
`USCPACKsoftware, a new tool for clinical dosage optimization.
`Annual Meeting ofthe Population Analysis Group in Europe, 12-13 Jane,
`Verona, Italy, 2003
`
`30.
`
`CARLSSON, KC, HOEM, NO, GLAUSER,T, VINKS, AA.
`
`Canclinically useful population PK models for carbamazepine in
`pediatric epilepsy patients be developed based on routine
`therapeutic drug monitoring (TDM) data. AznaualMeeting ofthe
`Population Analysis Group in Europe, 12-13 Jane, Uppsala, Sweden,
`2004
`
`31,
`
`32,
`
`33.
`
`HOEM, NO, BERINGER,P.