DIPEPTIDYL
`DIPEPTIDYL
`AMINOPEPTIDASES IN
`AMINOPEPTIDASESIN
`HEALTH AND DISEASE
`HEALTH AND DISEASE
`
`MPI EXHIBIT 1100 PAGE 1
`
`MPI EXHIBIT 1100 PAGE 1
`
`MPI EXHIBIT 1100 PAGE 1
`
`
`DIPEPTIDYL
`AMINOPEPTIDASES IN
`AMINOPEPTIDASESIN
`HEALTH AND DISEASE
`HEALTH AND DISEASE
`
`MPI EXHIBIT 1100 PAGE 1
`
`MPI EXHIBIT 1100 PAGE 1
`
`MPI EXHIBIT 1100 PAGE 1
`
`
`
`ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
`
`Editorial Board:
`
`NATHAN BACK, State University of New York at Buffalo
`
`IRUN R. COHEN, The Weizmann Institute of Science
`
`DAVID KRITCHEVSKY, Wistar Institute
`
`ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
`
`RODOLFO PAOLETTI, University of Milan
`
`Recent Volumes in this Series
`
`Volume 515
`NEUROPILIN: From Nervous System to Vascular and Tumor Biology
`Edited by Dominique Bagnard
`
`Volume 516
`TRIPLE REPEAT DISEASES OF THE NERVOUS SYSTEM
`Edited by Lubov T. Timchenko
`
`Volume 517
`DOPAMINERGIC NEURON TRANSPLANTATION IN THE WEAVER MOUSE
`MODEL OF PARKINSON’S DISEASE
`Edited by Lazaros C. Triarhou
`
`Volume 518
`ADVANCES IN MALE MEDIATED DEVELOPMENTAL TOXICITY
`Edited by Bernard Robaire and Barbara F. Hales
`
`Volume 519
`POLYMER DRUGS IN THE CLINICAL STAGE: Advantages and Prospects
`Edited by Hiroshi Maeda, Alexander Kabanov, Kazurori Kataoka, and Teruo Okano
`
`Volume 520
`CYTOKINES AND AUTOIMMUNE DISEASE
`Edited by Pere Santamaria
`
`Volume 521
`IMMUNE MECHANISMS IN PAIN AND ANALGESIA
`Edited by Halina Machelska and Christoph Stein
`
`Volume 522
`NOVEL ANGIOGENIC MECHANISMS: Role of Circulating Progenitor Endothelial Cells
`Edited by Nicanor I. Moldovan
`
`Volume 523
`ADVANCES IN MODELLING AND CLINICAL APPLICATION OF INTRAVENOUS
`ANAESTHESIA
`Edited by Jaap Vuyk and Stefan Schraag
`
`Volume 524
`DIPEPTIDYL AMINOPEPTIDASES IN HEALTH AND DISEASE
`Edited by Martin Hildebrandt, Burghard F. Klapp, Torsten Hoffmann,
`and Hans-Ulrich Demuth
`
`A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume
`immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact
`the publisher.
`
`MPI EXHIBIT 1100 PAGE 2
`
`MPI EXHIBIT 1100 PAGE 2
`
`
`
`DIPEPTIDYL
`AMINOPEPTIDASES IN
`HEALTH AND DISEASE
`
`Edited by
`
`Martin Hildebrandt, Burghard F. Klapp
`
`Medical Faculty Charité, Humboldt University Berlin
`Berlin, Germany
`
`Torsten Hoffman and Hans-Ulrich Demuth
`
`Probiodrug SG
`Halle (Saale), Germany
`
`KLUWER ACADEMIC PUBLISHERS
`NEW YORK, BOSTON, DORDRECHT, LONDON, MOSCOW
`
`MPI EXHIBIT 1100 PAGE 3
`
`MPI EXHIBIT 1100 PAGE 3
`
`
`
`eBook ISBN:
`Print ISBN:
`
`0-306-47920-6
`0-306-47717-3
`
`©2004 Kluwer Academic Publishers
`New York, Boston, Dordrecht, London, Moscow
`
`Print ©2003 Kluwer Academic/Plenum Publishers
`New York
`
`All rights reserved
`
`No part of this eBook may be reproduced or transmitted in any form or by any means, electronic,
`mechanical, recording, or otherwise, without written consent from the Publisher
`
`Created in the United States of America
`
`Visit Kluwer Online at:
`and Kluwer's eBookstore at:
`
`http://kluweronline.com
`http://ebooks.kluweronline.com
`
`MPI EXHIBIT 1100 PAGE 4
`
`MPI EXHIBIT 1100 PAGE 4
`
`
`
`Contributors
`
`Catherine A. Abbott
`School of Biological Sciences, Flinders University, GPO Box 2100,
`Adelaide SA 5001, Australia
`
`Katerina Ajami
`Centenary Institute, Royal Prince Alfred Hospital, Locked Bag No 6,
`Newtown, NSW, 2042, Sydney, Australia
`
`Siegfried Ansorge
`IMTM, Magdeburg, Germany
`
`Dorit Anthonsen
`Biochemistry Laboratory C, IMBG, The Panum Institute, Blegdamsvej 3,
`DK-2200 Copenhagen N, Denmark
`
`Petra C. Arck
`Department of Internal Medicine/Psychosomatics, Charité Campus Mitte,
`Luisenstr. 13A, Berlin, Germany
`
`Marco Arndt
`Institute of Experimental Internal Medicine, Otto-von-Guericke University
`Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany
`
`Koen Augustyns
`Laboratory of Medical Biochemistry, Dept. of Pharmaceutical Sciences,
`University of Antwerp, Universiteitsplein 1 S-6, 2610 Wilrijk, Belgium
`
`v
`
`MPI EXHIBIT 1100 PAGE 5
`
`MPI EXHIBIT 1100 PAGE 5
`
`
`
`vi
`
`Contributors
`
`William W. Bachovchin
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Joachim Bär
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Oliver Baum
`Institut für Molekularbiologie und Biochemie, Freie Universität Berlin,
`Arnimallee 22, 14195 Berlin, Germany
`
`A. Belyaev
`Dept of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein
`1, B-2610 Wilryk, Belgium
`
`Sergei A. Belyakov
`R & D, Guilford Pharmaceuticals Inc., 6611 Tributary St., 21224 Baltimore,
`MD, USA
`
`Felix Bermpohl
`Institut für Molekularbiologie und Biochemie, Freie Universität Berlin,
`Arnimallee 22, 14195 Berlin, Germany
`
`Maria G. Bernengo
`Dermatologic Clinic,
`Department of Medical and Surgical Specialities,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Gregory A. Bohach
`Department of Microbiology, Molecular Biology and Biochemistry,
`University of Idaho, S. Line St./P.O. Box 443052, 83843 Moscow, ID, USA
`
`Ilona Born
`Institut für Biochemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-
`Mothes-Str. 3, 06120 Halle, Germany
`
`Ernst Brandt
`Research Center Borstel, Parkalle 22, 23845 Borstel, Germany
`
`Wolfgang Brandt
`Institute of Plant Biochemistry, Leibniz-Institute Halle, Weinberg 3, D-
`06120 Halle, Germany
`
`MPI EXHIBIT 1100 PAGE 6
`
`MPI EXHIBIT 1100 PAGE 6
`
`
`
`Contributors
`
`vii
`
`Alicja Bukowska
`Institute of Experimental Internal Medicine, Otto-von-Guericke University
`Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany
`
`Petr Bušek
`1st Faculty of Medicine of Charles University, U Nemocnice 5, 12853
`Prague 2, Czech Republic
`
`Richard D. Carr
`Pharmacology Research 1, Novo Nordisk A/S, Novo Allé, DK-2880
`Bagsværd, Denmark
`
`Tong Chen
`School of Biological Sciences, Flinders University of South Australia,
`Adelaide, Australia
`
`Wen-Tien Chen
`Dept of Medicine/Medical Oncology, SUNY, HSC T-15, Rm 053, 11794-
`8154 Stony Brook, N.Y., USA
`
`Blas Cigic
`Institute Jozef Stefan, Department of Biochemistry and Molecular Biology
`Jamova 39, 1000 Ljubljana, Slovenia
`
`Alessandra Comessatti
`Department of Medical and Surgical Specialities, Dermatologic Clinic,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Oscar J. Cordero
`Departamento de Bioquímica e Bioloxía Mol., Facultade de Bioloxía,
`Universidade de Santiago de Compostela, Campus Sur, 15782 Santiago de
`Compostela, Spain
`
`Guy Cox
`Electron Microscope Unit, University of Sydney, Sydney, Australia
`
`William C. Davis
`Washington State University, Pullman, WA 99163, USA
`
`Ingrid De Meester
`Dept of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein
`l, B-2610 Wilryk, Belgium
`
`MPI EXHIBIT 1100 PAGE 7
`
`MPI EXHIBIT 1100 PAGE 7
`
`
`
`viii
`
`Contributors
`
`Carolyn F. Deacon
`Department of Medical Physiology, Panum Institute, Blegdamsvej 3, DK-
`2200 Copenhagen N, Denmark
`
`Hans-Ulrich Demuth
`Probiodrug AG, Biozentrum, Weinbergweg 22, 6120 Halle (Saale),
`Germany
`
`H. Dong
`Department of Medicine/Medical Oncology, State University of New York,
`Stony Brook, New York 11794-8154, USA
`
`Timothy Doty
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Jan A. Ehses
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Lori Estes
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`Hua Fan
`Department of Molecular Biology and Biochemistry, Freie Universität
`Berlin, Arnimallee 22, 14195 Berlin, Germany
`
`Sabiha Fatima
`Department of Biochemistry, Aligarh Muslim University, 202002 Aligarh
`U.P., India
`
`Jürgen Faust
`Institut für Biochemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-
`Mothes-Str. 3, 06120 Halle, Germany
`
`Maria T. Fierro
`Department of Medical and Surgical Specialities, Dermatologic Clinic,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Axel Fischer
`Dept. of Internal Medicine, Psychosomatics/Psychotherapie, Humboldt-
`University, Charite Campus Mitte, Liusenstraße 13A, 10117 Berlin, Germany
`
`MPI EXHIBIT 1100 PAGE 8
`
`MPI EXHIBIT 1100 PAGE 8
`
`
`
`Contributors
`
`ix
`
`Herbert Fliege
`Dept of Internal Medicine/ Psychosomatics, Charité, Humboldt University
`Berlin, Luisenstraße 13A, 10117 Berlin, Germany
`
`Lawrence K. Fox
`Washington State University, Pullman, WA 99163, USA
`
`Daniel Friedrich
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Petra Fuchs
`Institute of Biochemistry, Department of Biochemistry/Biotechnology,
`Martin-Luther-University, Halle-Wittenberg, Germany
`
`Vilmos Fülöp
`Department of Biological Sciences, University of Warwick, Gibbet Hill
`Road, Coventry, UK
`
`Bernd Gerhartz
`Novartis Pharma AG, Klybeckstr. 141, CH-4057 Basel, Switzerland
`
`Giulio Ghersi
`Department of Cellular and Developmental Biology, Università di Palermo,
`Viale delle Scienze, 90138 Palermo, Italy
`
`L.A. Goldstein
`Department of Medicine/Medical Oncology, State University of New York,
`Stony Brook, New York 11794-8154, USA
`
`Mark D. Gorrell
`Dept of Gastroenterology, Royal Prince Alfred Hospital, Locked Bag No 6,
`Sydney Newtown, NSW, 2042, Australia
`
`David A. Groneberg
`Dept. of Internal Medicine, Psychosomatics/Psychotherapie, Humboldt-
`University, Charite Campus Mitte, Liusenstraße 13A, 10117 Berlin, Germany
`
`Vanessa Gysbers
`Dept of Gastroenterology, Royal Prince Alfred Hospital, Locked Bag No 6,
`Sydney Newtown, NSW, 2042, Australia
`
`Achiel Haemers
`Laboratory of Medical Biochemistry, Dept. of Pharmaceutical Sciences,
`University of Antwerp, Universiteitsplein 1 S-6, 2610 Wilrijk, Belgium
`
`MPI EXHIBIT 1100 PAGE 9
`
`MPI EXHIBIT 1100 PAGE 9
`
`
`
`x
`
`Contributors
`
`L. Hakkinen
`University of British Columbia, Division of Periodontics, 2199 Westbrook
`Mall, Vancouver, BC V6T 1Z3, CANADA
`
`Ross Haller
`VA Medical Center, University of Minnesota, Minneapolis, MN, USA
`
`Gregory S. Hamilton
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`Ulrich Heiser
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Martin Hildebrandt
`Dept of Internal Medicine/ Psychosomatics, Charité, Humboldt University
`Berlin, Luisenstraße 13A, 10117 Berlin, Germany
`
`Simon A. Hinke
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Maw Hliang
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Torsten Hoffmann
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Jens J. Holst
`Department of Endocrinology, The Panum Institute, Blegdamsvej 3, 2200
`Copenhagen, Denmark
`
`Kazuhiko Ino
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan
`
`Annelore Ittenson
`Institute of Immunology, Otto-von-Guericke University Magdeburg,
`Leipziger Strasse 44, D-39120 Magdeburg, Germany
`
`Paul Jackson
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`MPI EXHIBIT 1100 PAGE 10
`
`MPI EXHIBIT 1100 PAGE 10
`
`
`
`Contributors
`
`xi
`
`Eleanor Kable
`Electron Microscope Unit, University of Sydney, Sydney, Australia
`
`Thilo Kähne
`Research Center of Immunology, Institute of Experimental Internal
`Medicine, University of Magdeburg, Magdeburg, Germany
`
`Hiroaki Kajiyama
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai-cho 65, Showa-ku, 466-8550 Nagoya, Japan
`
`Fumitaka Kikkawa
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai-cho 65, Showa-ku, 466-8550 Nagoya, Japan
`
`Joanna Kitlinska
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`Burghard F. Klapp
`Department of Internal Medicine/Psychosomatics, Charité Campus Mitte,
`Luisenstr. 13A, Berlin, Germany
`
`1st Faculty of Medicine of Charles University, U Nemocnice 5, 12853
`Prague 2, Czech Republic
`
`Sina Koch
`Biochemistry Laboratory C, IMBG, The Panum Institute, Blegdamsvej 3,
`DK-2200 Copenhagen N, Denmark
`
`Stephan Korom
`Abteilung f. Thoraxchirurgie, Universitätsspital Zürich, Rämistrasse 100,
`8091 Zürich, Switzerland
`
`Kerstin Kühn-Wache
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Yumi Kumagai
`Department of Microbiology, Nippon Dental University, Tokyo, Japan
`
`Jack Lai
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`MPI EXHIBIT 1100 PAGE 11
`
`MPI EXHIBIT 1100 PAGE 11
`
`
`
`xii
`
`Contributors
`
`Anne-Marie Lambeir
`Laboratory of Medical Biochemistry, Dept. of Pharmaceutical Sciences,
`University of Antwerp, Universiteitsplein 1 S-6, 2610 Wilrijk, Belgium
`
`H.S. Larjava
`University of British Columbia, Division of Periodontics, 2199 Westbrook
`Mall, Vancouver, BC V6T 1Z3, CANADA
`
`Edward W. Lee
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`Sang-Un Lee
`University of Idaho, Moscow, ID 83844, USA
`
`Uwe Lendeckel
`Institut für Experimentelle Innere Medizin, Universitätsklinikum, Otto-von-
`Guericke-Universität, Leipziger Str. 44, 39120 Magdeburg, Germany
`
`Miriam T. Levy
`Dept of Gastroenterology, Royal Prince Alfred Hospital, Locked Bag No 6,
`Sydney Newtown, NSW, 2042, Australia
`
`Lijun Li
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`David C. Limburg
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`Juan Lojo
`University of Santiago de Compostela, Department of Biochemistry and
`Molecular Biology, 15782 Santiago de Compostela, Galicia, Spain
`
`X.M. Lu
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`Andreas Ludwig
`Research Center Borstel, Parkalle 22, 23845 Borstel, Germany
`
`Francis Lynn
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`MPI EXHIBIT 1100 PAGE 12
`
`MPI EXHIBIT 1100 PAGE 12
`
`
`
`Contributors
`
`xiii
`
`P. Majer
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`Radek Malík
`1st Faculty of Medicine of Charles University, U Nemocnice 5, 12853
`Prague 2, Czech Republic
`
`Susanne Manhart
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Vladislav Mareš
`1st Faculty of Medicine of Charles University, U Nemocnice 5, 12853
`Prague 2, Czech Republic
`
`Didier Marguet
`Centre d’Immunologie INSERM-CNRS de Marseille-Luminy, Marseille,
`France
`
`George Marinos
`Gastroenterology Department, Prince of Wales Hospital Sydney, Sydney,
`Australia
`
`Geoffrey W. McCaughan
`Dept of Gastroenterology, Royal Prince Alfred Hospital, Locked Bag No 6,
`Sydney Newtown, NSW, 2042, Australia
`
`Christopher H.S. McIntosh
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Rolf Mentlein
`Anatomisches Institut, Universität Kiel, Olshausenstr. 40, 24098 Kiel,
`Germany
`
`Shigehiko Mizutami
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai-cho 65, Showa-ku, 466-8550 Nagoya, Japan
`
`Hubert Mönnikes
`Department of Internal Medicine, Division of Gastroenterology, Charité,
`Humboldt University, Luisenstrasse 13a, Berlin, Germany
`
`MPI EXHIBIT 1100 PAGE 13
`
`MPI EXHIBIT 1100 PAGE 13
`
`
`
`xiv
`
`Contributors
`
`Carmen Mrestani-Klaus
`Institute of Biochemistry, Martin-Luther-University Halle-Wittenberg, Kurt-
`Mothes-Str. 3, 06120 Halle, Germany
`
`Klaus Neubert
`Institut für Biochemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-
`Mothes-Str. 3, 06120 Halle, Germany
`
`Jan H. Niess
`Department of Internal Medicine, Division of Psychosomatics and
`Psychotherapy, Charité, Humboldt University, Luisenstrasse 13a, Berlin,
`Germany
`
`André Niestroj
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Montserrat Nogueira
`University of Santiago de Compostela, Department of Biochemistry and
`Molecular Biology, 15782 Santiago de Compostela, Galicia, Spain
`
`Mauro Novelli
`Department of Medical and Surgical Specialities, Dermatologic Clinic,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Nathalie Pamir
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Yong-Ho Park
`Seoul National University, Seoul, Korea
`
`Raymond A. Pederson
`Department of Physiology, University of British Columbia, 2329 West Mall,
`V6T 1Z4 Vancouver, Canada
`
`Christian Peiser
`Dept. of Internal Medicine, Psychosomatics/Psychotherapie, Humboldt-
`University, Charite Campus Mitte, Liusenstraße 13A, 10117 Berlin, Germany
`
`Astrid Plamboeck
`Department of Medical Physiology, Panum Institute, Blegdamsvej 3, DK-
`2200 Copenhagen N, Denmark
`
`MPI EXHIBIT 1100 PAGE 14
`
`MPI EXHIBIT 1100 PAGE 14
`
`
`
`Contributors
`
`xv
`
`Jennifer Pons
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`Sarah Poplawski
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`J. Andrew Pospisilik
`Department of Physiology, University of British Columbia, 2329 West
`Mall, V6T 1Z4 Vancouver, Canada
`
`Paul Proost
`Rega Institute of Medical Science, Catholic University of Leuven, Leuven,
`Belgium
`
`Pietro Quaglino
`Dermatologic Clinic,
`Department of Medical and Surgical Specialities,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Dean Rea
`Department of Biological Sciences, University of Warwick, Gibbet Hill
`Road, Coventry, UK
`
`Dirk Reinhold
`Institute of Immunology, Otto-von-Guericke-University Magdeburg,
`Leipziger Strasse 44, Magdeburg, Germany
`
`Werner Reutter
`Institut für Molekularbiologie und Biochemie, Freie Universität Berlin
`Arnimallee 22, 14195 Berlin, Germany
`
`Camilo J. Rojas
`R & D, Guildford Pharmaceuticals Inc., 6611 Tributary St., 21224
`Baltimore, MD, USA
`
`Fred Rosche
`Probiodrug AG, Weinberweg 22, D-06120 Halle, Germany
`
`Matthias Rose
`Dept of Internal Medicine/ Psychosomatics, Charité, Humboldt University
`Berlin, Luisenstraße 13A, 10117 Berlin, Germany
`
`MPI EXHIBIT 1100 PAGE 15
`
`MPI EXHIBIT 1100 PAGE 15
`
`
`
`xvi
`
`Contributors
`
`Jens Rüter
`Dept of Internal Medicine/ Psychosomatics, Charité, Humboldt University
`Berlin, Luisenstraße 13A, 10117 Berlin, Germany
`
`Francisco J. Salgado
`University of Santiago de Compostela, Department of Biochemistry and
`Molecular Biology, 15782 Santiago de Compostela, Galicia, Spain
`
`David G. Sanford
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Paola Savoia
`Dermatologic Clinic,
`Department of Medical and Surgical Specialities,
`University of Turin, Via Cherasco 23, Turin 10126, Italy
`
`Simon Scharpé
`Laboratory of Medical Biochemistry, Dept. of Pharmaceutical Sciences,
`University of Antwerp, Universiteitsplein 1 S-6, 2610 Wilrijk, Belgium
`
`Florian Schiemann
`Research Center Borstel, Parkalle 22, 23845 Borstel, Germany
`
`Dagmar Schlenzig
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Georg Schmidbauer
`Department of General and Thoracic Surgery, Justus Liebig University,
`Giessen, Germany
`
`Detlef Schuppan
`Klinik für Innere Medizin I, Abt. Hepatologie, Universität Erlangen-
`Nürnberg, Ulmenweg 18, D-91054 Erlangen, Germany
`
`Konrad Schwemmle
`Department of General and Thoracic Surgery, Justus Liebig University,
`Giessen, Germany
`
`Aleksi Sedo
`Institute of Biochemistry and Experimental Oncology, 1st Faculty of
`Medicine of Charles University, U Nemocnice 5, 12853 Prague 2, Czech
`Republic
`
`MPI EXHIBIT 1100 PAGE 16
`
`MPI EXHIBIT 1100 PAGE 16
`
`
`
`Contributors
`
`xvii
`
`Jan Ševč(cid:2)k
`1st Faculty of Medicine of Charles University, U Nemocnice 5, 12853
`Prague 2, Czech Republic
`
`Kiyosumi Shibata
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai(cid:1)cho 65, Showa(cid:1)ku, Nagoya 466(cid:1)8550, Japan
`
`Akhouri A. Sinha
`University of Minnesota Cancer Center, University of Minnesota,
`Minneapolis, MN, USA
`
`Hans Sjöström
`Biochemistry Laboratory C, IMBG, The Panum Institute, Blegdamsvej 3,
`DK(cid:1)2200 Copenhagen N, Denmark
`
`Hanne Skovbjerg
`Biochemistry Laboratory C, IMBG, The Panum Institute, Blegdamsvej 3,
`DK(cid:1)2200 Copenhagen N, Denmark
`
`Joel W. Slaton
`University of Minnesota Cancer Center, University of Minnesota,
`Minneapolis, MN, USA
`
`B.S. Slusher
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`Sabine Stehling
`Institut für Molekularbiologie und Biochemie, UKBF, Freie Universität
`Berlin, Arnimallee 22, D(cid:1)14195 Berlin, Germany
`
`Joseph P. Steiner
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`Beate Stiebitz
`Institut für Biochemie, Martin(cid:1)Luther(cid:1)Universität Halle(cid:1)Wittenberg, Kurt(cid:1)
`Mothes(cid:1)Str. 3, 06120 Halle, Germany
`
`Andrea Stöckel(cid:3)Maschek
`Department of Biochemistry and Biotechnology, Martin(cid:1)Luther(cid:1)University
`Halle(cid:1)Wittenberg, Postfach 8, 06099 Halle, Germany
`
`MPI EXHIBIT 1100 PAGE 17
`
`MPI EXHIBIT 1100 PAGE 17
`
`
`
`xviii
`
`Contributors
`
`Jörg Stork
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`James L. Sudmeier
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Takahiro Suzuki
`Department of Obstetrics and Gynecology, Nagoya University Graduate
`School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8550, Japan
`
`Janine Tadje
`Institute of Experimental Internal Medicine, Otto-von-Guericke University
`Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany
`
`Q. Thai Dinh
`Dept. of Internal Medicine, Psychosomatics/Psychotherapie, Humboldt-
`University, Charite Campus Mitte, Liusenstraße 13A, 10117 Berlin, Germany
`
`A.G. Thomas
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`T. Tsukamoto
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`J. J. Vornov
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`Otto B. Walter
`Department of Internal Medicine, Division of Psychosomatics and
`Psychotherapie, Charité, Humboldt University, Luisenstrasse 13a, Berlin,
`Germany
`
`Xin M. Wang
`Dept of Gastroenterology, Royal Prince Alfred Hospital, Locked Bag No 6,
`Sydney Newtown, NSW, 2042, Australia
`
`Neil F. Wasserman
`University of Minnesota Cancer Center, University of Minnesota,
`Minneapolis, MN, USA
`
`MPI EXHIBIT 1100 PAGE 18
`
`MPI EXHIBIT 1100 PAGE 18
`
`
`
`Contributors
`
`xix
`
`Michael Werman
`Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany
`
`Douglas E. Wilkinson
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`Michael J. Wilson
`Research Service, University of Minnesota, VA Medical Center, One
`Veterans Drive, 55417 Minneapolis, MN, USA
`
`Carmen Wolke
`Institute of Experimental Internal Medicine, Otto-von-Guericke University
`Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany
`
`K.M. Wozniak
`Guilford Pharmaceuticals Inc., 6611 Tributary Street, Baltimore, Maryland
`21224, USA
`
`Sabine Wrenger
`Institute of Immunology, Otto-von-Guericke-University Magdeburg,
`Leipziger Strasse 44, Magdeburg, Germany
`
`Wengen Wu
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Yong-Qian Wu
`Guilford Pharmaceuticals, Inc., Tributary St., Baltimore, MD, USA
`
`Shuling Yan
`Institut für Molekularbiologie und Biochemie, UKBF, Freie Universität
`Berlin, Arnimallee 22, D-14195 Berlin, Germany
`
`Y.Yeh
`Department of Medicine/Medical Oncology, State University of New York,
`Stony Brook, New York 11794-8154, USA
`
`Yuhong Zhou
`Department of Biochemistry, Tufts University School of Medicine, 136
`Harrison Avenue, Boston, MA 02111, USA
`
`Zofia Zukowska
`Department of Physiology and Biophysics, Georgetown University Medical
`Center, 3900 Reservoir Rd., NW, Washington, DC, USA
`
`MPI EXHIBIT 1100 PAGE 19
`
`MPI EXHIBIT 1100 PAGE 19
`
`
`
`Preface
`
`In recent years, the research on Dipeptidyl Aminopeptidases has led from
`basic science to first concepts of pharmaceutical applications. The complex
`role of these enzymes in physiological processes as well as in the
`pathophysiology of diseases such as diabetes mellitus, rheumatoid arthritis,
`autoimmune disease, transplant rejections and cytokine-mediated abortions
`has become evident and provides a rationale for therapeutic interventions by
`a modulation of their respective enzymatic activity.
`The International Conference on Dipeptidyl Aminopeptidases, held in
`Berlin, Germany, in September 2002, was initiated in an attempt to bridge
`basic science, results of clinical studies and strategies for therapeutic
`applications. Experts in the field presented a state-of-the-art view on the
`various aspects of Dipeptidyl Aminopeptidases, thus contributing to a sound
`basis for decisions on research and therapeutic strategies. The conference,
`fueled by the presentation of the crystallographic structure of DPP IV by Dr.
`D. Webb, was concluded by a panel discussion on perspectives and
`limitations of DPP IV inhibitors.
`Selected authors have shared their opinion on basic science, clinical
`applications and therapeutic interventions with the audience, and they extend
`their view to the readers of this book. By doing so, they have generously
`supported us in our attempt to provide a comprehensive overview over
`Dipeptidyl Aminopeptidases at a time when the therapeutic implications of
`enzyme inhibitors are imminent, demanding a critical risk assessment based
`on a detailed understanding of the complex function that these enzymes
`appear to exert.
`A conference on Dipeptidyl Aminopeptidases hosted by a Department of
`Internal Medicine/Psychosomatics with an interest in these enzymes may be
`
`xxi
`
`MPI EXHIBIT 1100 PAGE 20
`
`MPI EXHIBIT 1100 PAGE 20
`
`
`
`xxii
`
`Preface
`
`surprising, but reflects the current state of research on these enzymes, with a
`growing understanding of specific clinical implications and therapeutic
`options. A glance at a preliminary list of substrates of DPP IV (Table 1) may
`help to understand such interest: DPP IV-mediated turnover of peptide
`hormones in various areas of relevance for the body-mind relationship must
`thrill every one
`interested
`in
`functional
`thinking. Especially a
`psychosomaticist in psychoanalytical tradition is reminded of the expectation
`of Freud, the founder of
`century’s mainstream psychosomatics, that one
`day every psychological event will be understood from the underlying
`physiological and biochemical processes. The contributions
`to our
`conference and to this book nurture the idea that research on DPP IV is an
`example for a step towards a biochemical, or even molecular founded
`psychosomatics.
`
`Although hypothetical at this stage, an integrative concept as presented in
`Figure 1 may help to appreciate consequences of changes in DPP IV activity
`or of DPP IV inhibitors. The potential of such inhibitors for novel treatment
`approaches of type II diabetes has served as a spearhead in the search for
`
`MPI EXHIBIT 1100 PAGE 21
`
`MPI EXHIBIT 1100 PAGE 21
`
`
`
`Preface
`
`xxiii
`
`substances with inhibitory activity, and continues to fuel research on
`structure and function of DPP IV as well as on the growing number of DPP
`IV-like enzymes. The targeted modulation of these enzymes in distinct sites
`of the organism represents a pharmacodynamic and pharmakokinetic
`challenge for the development of novel drugs and prodrugs. Given the
`complexity of the biological processes affected by inhibitors of Dipeptidyl
`aminopeptidases, their clinical use cannot be fully appreciated yet.
`
`At this stage, it may be helpful to label these novel and potent substances
`Peptide modulators, denominating a process rather than a clinical indication
`and thus avoiding a premature narrowing on a single disease entity.
`Furthermore, the risk assessment in the exploitation of inhibitory substances
`should take potential side effects such as an impact on hunger and satiety,
`pain perception or immunomodulation into account.
`The Berlin Conference has continued a series of similar conferences on
`this topic; a further continuation in 2004 was announced by Uwe Lendeckel
`and Dirk Reinhold from Magdeburg, members of a team that pioneered in
`the research on Dipeptidyl Aminopeptidases. We are convinced that major
`advancements justifying further conferences can be expected in the next
`future.
`
`Burghard F. Klapp and Martin Hildebrandt
`Department of Internal Medicine/ Psychosomatics
`Charité, Humboldt University
`Berlin, Germany
`
`1. Hildebrandt, M., Reutter, W., Arck, et al., 2000, Clin Sci (Colch)., 99(2): 93-104.
`2. De Meester, I., Durinx, C., Bal, G., et al., 2000, Adv.Exp.Med.Biol.477: 67-87.
`
`MPI EXHIBIT 1100 PAGE 22
`
`MPI EXHIBIT 1100 PAGE 22
`
`
`
`Acknowledgments
`
`We are indebted to Joanna Lawrence and Joanne Duggan from Kluwer
`Academic/Plenum Publishers, for their continuing support in the editing
`process.
`Furthermore, we thank Dr. Jens Rüter, Medical Faculty Charité, Berlin,
`and Florian König, Kingsize Event, Berlin, as members of the Organizing
`Committee of the International Conference on Dipeptidyl Aminopeptidases,
`Berlin, September 2002. The conference formed the basis from which the
`decision was made to compile and edit this volume. The success of this
`conference
`is clearly attributable
`to
`their commitment and highly
`professional work.
`The International Conference on Dipeptidyl Aminopeptidases received
`support from the following organisations:
`
`Abbott Laboratories, Abbott Park, IL, USA
`Essex Pharma GmbH, München, Germany
`Fonds der Chemischen Industrie im Verband der Chemischen Industrie e.V.,
`Frankfurt, Germany
`Merck Research Laboratories, Rahway, NJ, USA
`Probiodrug AG, Halle/S., Germany
`
`Berlin, October 2002
`The Editors
`
`xxv
`
`MPI EXHIBIT 1100 PAGE 23
`
`MPI EXHIBIT 1100 PAGE 23
`
`
`
`Contents
`
`Structure and Function of Dipeptidyl Aminopeptidases
`
`Dipeptidyl Peptidase IV Substrates
`Ingrid de Meester, Anne-Marie Lambeir, Paul Proost, and
`Simon Scharpé
`
`Structure-Function Relationship of DPP IV: Insights into its
`Dimerisation and Gelatinase Activity
`Oliver Baum, Werner Reutter, and Felix Bermpohl
`
`3
`
`19
`
`Exploration of the Active Site of Dipeptidyl Peptidase IV From
`Porphyromonas gingivalis
`Anne-Marie Lambeir, Dean Rea, Vilmos Fülöp, Yumi Kumagai,
`Koen Augustyns, Ingrid de Meester, Achiel Haemers, and Simon Scharpé
`
`29
`
`Modification of the Biological Activity of Chemokines by Dipeptidyl
`Peptidase IV – a Side Effect in the Use of Inhibitors?
`Rolf Mentlein, Florian Schiemann, Andreas Ludwig, and Ernst Brandt
`
`Molecular Chimeras and Mutational Analysis in the Prolyl Oligopeptidase
`Gene Family
`Katerina Ajami, Catherine A. Abbot, Vanessa Gysbers, Thilo Kähne,
`Geoffrey W. McCaughan, and Mark D. Gorrell
`
`37
`
`49
`
`xxvii
`
`MPI EXHIBIT 1100 PAGE 24
`
`MPI EXHIBIT 1100 PAGE 24
`
`
`
`xxviii
`
`Contents
`
`The Specificity of DP IV for Natural Substrates is Peptide Structure
`Determined
`KerstinKühn-Wache, Torsten Hoffmann, Susanne Manhart,
`W. Brandt, and Hans-Ulrich Demuth
`
`New Results on the Conformations of Potent DP IV (CD26) Inhibitors
`Bearing the N-terminal MWP Structural Motif
`Carmen Mrestani-Klaus, Wolfgang Brandt, Jürgen Faust, Sabine
`Wrenger, Dirk Reinhold, Siegfried Ansorge, and Klaus Neubert
`
`Different Inhibition Mechanisms of Dipeptidyl Peptidase IV by
`Tryptophan Containing Peptides and Amides
`Angela Stöckel-Maschek, Beate Stiebitz, Jürgen Faust, Ilona Born,
`ThiloKähne,Mark D. Gorrell, and Klaus Neubert
`
`57
`
`65
`
`69
`
`Re-Uptake Mechanisms of Peptide Fragments after DPP IV-Mediated
`Proteolysis in the Peripheral Nervous System
`73
`Q. Thai Dinh, Christian Peiser, Axel Fischer, and David A. Groneberg
`
`DPP IV-Like Enzymes
`
`Dipeptidyl Peptidase IV Gene Family
`79
`Tong Chen, Katerina Ajami, Geoffrey W. McCaughan, Mark D. Gorrell,
`and Catherine A. Abbott
`
`Seprase-DPPIV Association and Prolyl Peptidase and Gelatinase Activities
`of the Protease Complex
`87
`Giulio Ghersi, H. Dong, L.A. Goldstein, Y. Yeh, L. Hakkinen,
`H.S. Larjava, and W-T. Chen
`
`Dipeptidyl Peptidase-IV Activity and/or Structure Homologues
`(DASH) in Transformed Neuroectodermal Cells
`Radek Malik, Petr Bušek, Vladislav Mareš,
`and Aleksi Šedo
`
`Characterisation of Human DP IV Produced by a Pichia pastoris
`Expression System
`Joachim W. Baer, Bernd Gerhartz, Torsten Hoffmann, Fred Rosche,
`and Hans-Ulrich Demuth
`
`Isolation and Characterization of Attractin-2
`Daniel Friedrich, Kerstin Kühn-Wache, Torsten Hoffmann,
`and Hans-Ulrich Demuth
`
`95
`
`103
`
`109
`
`MPI EXHIBIT 1100 PAGE 25
`
`MPI EXHIBIT 1100 PAGE 25
`
`
`
`Contents
`
`Investigation of DP IV-dependent Protein-Protein Interactions using
`Surface Plasmon Resonance
`Joerg Stork, Torsten Hoffmann, and Hans-Ulrich Demuth
`
`Immune Mechanisms and Immune Disorders
`
`Synergistic Action of DPIV and APN in the Regulation of T Cell
`Function
`Uwe Lendeckel, Marco Arndt, Alicja Bukowska, Janine Tadje,
`Carmen Wolke, Thilo Kähne, Klaus Neubert, Jürgen Faust,
`Annelore Ittenson, Siegfried Ansorge, and Dirk Reinhold
`
`xxix
`
`115
`
`123
`
`CD26/DPP IV in Experimental and Clinical Organ Transplantation
`Stephan Korom, Ingrid de Meester, A. Belyaev, Georg Schmidbauer,
`and Konrad Schwemmle
`
`133
`
`CD26 is Involved in the Regulation of T-Cell Plasma Membrane
`Compartmentation
`Juan Lojo, Francisco J. Salgado, Montse
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
