ORGANOTECHNIE PEPTONES to Enhance Protein Expression in Mam malian Cell Lines

Peptones selected by The Scientific Community and The Industry :

TRYPTONE N1 TRYPTONE PLUS

New C-Cell Peptones for Mammalian Cell Lines :

MICROFILTERED BATCH SELECTED THROUGH OUR OWN PERFORMANCE TEST BASED ON MAMMALIAN CELL LINES

ULTRAFILTERED PROTEIN FREE (0 % > 10 KDA)

HIGH TITER Protein Expression in Mammalian Cell Lines  HEK 293  CHO 

REFERENCES

“Transient Gene Expression in HEK293 Cells: Peptone Addition Posttransfection Improves Recombinant Protein Synthesis”, ANIMAL CELL TECHNOLOGY GROUP SECTOR, BIOTECHNOLOGY RESEARCH INSTITUTE, NATIONAL RESEARCH COUNCIL, MONTREAL (CANADA), BIOTECHNOLOGY AND BIOENGINEERING, VOL. 90, N°3, MAY 2005

P.L. Pham S. Perret B. Cass  E. Carpentier  G. St-Laurent  L. Bisson  A. Kamen  Y. Durocher

‘‘Encyclopedia of Cell Biology’’, UNIVERSITY OF CALIFORNIA (USA), WASHINGTON UNIVERSITY SCHOOL OF MEDICINE (USA), JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE, BALTIMORE (USA), ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE, NORTH CHICAGO (USA), PENN STATE UNIVERSITY COLLEGE OF MEDICINE, HERSHEY (USA); MOLECULAR CELL BIOLOGY ELSEVIER (I) 54-65, 2016

Ralph A. Bradshaw  Philip D. Stahl

‘‘H-IPSE Is a Pathogen-Secreted Host Nucleus-Infiltrating Protein (Infiltrin) Expressed Exclusively by the Schistosoma haematobium Egg Stage’’, STANFORD UNIVERSITY SCHOOL OF MEDICINE, CALIFORNIA (USA), SCHOOL OF PHARMACY, UNIVERSITY OF NOTTINGHAM (UK), BIOMEDICAL RESEARCH INSTITUTE, MARYLAND (USA), AMERICAN SOCIETY FOR MICROBIOLOGY  INFECTION AND IMMUNITY, SEPTEMBER 2017

Luke F. Pennington Abdulaziz Alouffi Evaristus C. Mbanefo  Debalina Ray  David M. Heery  Theodore S. Jardetzky  Michael H. Hsieh  Franco H. Falcone

‘‘Expression of antibodies using single open reading frame (sORF) vector design’’, ABBVIE, WORCESTER, MA USA, MABS 5:4, 595-607  LANDES BIOSCIENCE, JULY/AUGUST 2013

Wendy R. Gion  Rachel A. Davis-Taber  Dean A. Regier Emma Fung  Limary Medina  Ling C. Santora  Sahana Bose  Alexander V. Ivanov  Barbara A. Perilli-Palmer  Chris M. Chumsae  Joseph G. Matuck  June Z. Kunes  Gerald R. Carson

‘‘Effects of Peptone Supplementation in Different Culture Media on Growth, Metabolic Pathway and Productivity of CHO DG44 Cells; a New Insight into Amino Acid Profiles’’, BIOTECHNOLOGY RESEARCH CENTER, PASTEUR INSTITUTE OF IRAN, TEHRAN; SCIENCE AND RESEARCH BRANCH, ISLAMIC AZAD UNIVERSITY OF ARAK, IRAN, IRANIAN BIOMEDICAL JOURNAL (IBJ), 19(4), 194-205, OCTOBER 2015

Fatemeh Davami  Farnaz Eghbalpour  Leila Nematollahi  Farzaneh Barkhordari  Fereidoun Mahboudi

‘‘Effect of Peptone Feeding on Transient Gene Expression Process in CHO DG44’’, BIOTECHNOLOGY RESEARCH CENTER, PASTEUR INSTITUTE OF IRAN, TEHRAN; SCIENCE AND RESEARCH BRANCH, ISLAMIC AZAD UNIVERSITY OF ARAK, IRAN, AVICENNA JOURNAL OF MEDICAL BIOTECHNOLOGY (AJMB), 6(3), 147-155, MARCH 2014

Fatemeh Davami  Farnaz Eghbalpour  Leila Nematollahi  Farzaneh Barkhordari  Fereidoun Mahboudi

‘‘Peptone Supplementation of Culture Medium Has Variable Effects on the Productivity of CHO Cells’’, LABORATORY OF CELLULAR BIOTECHNOLOGY, ECOLE POLYTECHNIQUE FÉDERALE DE LAUSANNE, SWITZERLAND BIOTECHNOLOGY RESEARCH CENTER, PASTEUR INSTITUTE OF IRAN, INT J MOL CELL MED, 3, AUGUST 2014

Fatemeh Davami  Lucia Baldi  Yashas Rajendra  Florian M. Wurm

‘‘High level transient production of recombinant antibodies and antibody fusion proteins in HEK 293 cells’’, DEPARTMENT OF BIOTECHNOLOGY, TECHNISCHE UNIVERSITÄT BRAUNSCHWEIG, INSTITUTE OF BIOCHEMISTRY, BIOTECHNOLOGY AND BIOINFORMATICS, GERMANY; BIOMED CENTRAL (BMC) BIOTECHNOLOGY 13, 52, 1472-6750, 2013

Volker Jäger  Konrad Büssow  Andreas Wagner  Susanne Weber  Michael Hust  André Frenzel  Thomas Schirrmann

‘‘Transient production of scFv-Fc fusion proteins in mammalian cells’’, TECHNISCHE UNIVERSITÄT BRAUNSCHWEIG, INSTITUT FÜR BIOCHEMIE UND BIOTECHNOLOGIE, DEPARTMENT OF BIOTECHNOLOGY, GERMANY; ANTIBODY ENGINEERING, VOLUME II, 2010

Thomas Schirrmann  Konrad Büssow

‘‘A robust transfection reagent for the transfection of CHO and HEK 293 cells and production of recombinant proteins and lentiviral particles – PTG1’’, BIOTECHNOLOGY JOURNAL  SYSTEMS & SYNTHETIC BIOLOGY  NANOBIOTECH  MEDICINE; SEPTEMBER 2014

Cristine Gonçalves  Fabian Gross  Philippe Guégan  Hervé Cheradame  Patrick Midou

‘‘High-titer expression of recombinant antibodies by transiently transfected HEK 293-6E cell cultures’’, RECOMBINANT PROTEIN EXPRESSION GROUP, HELMHOLTZ CENTRE FOR INFECTION RESEARCH, GERMANY; BIOMED CENTRAL (BMC) PROCEEDINGS, 9, 40, DECEMBER 2015

Volker Jäger  Johanna Groenewold  Dominik Krüger  Dennis Schwarz  Veith Vollmer

‘‘Optimization of recombinant protein expression in HEK 293 cell line’’, UNIVERZITA KARLOVA V PRAZE, PRIRODOVEDECKA FAKULTA, KATEDRA BIOCHEMIE, FACULTAS RERUM NATURALIUM, 2010

Jan Blaha

‘‘Pyroglutamate and O-Linked Gycan Determine Functional Production of Anti-IL17A and Anti-IL22 Peptide-Antibody Bispecific Genetic Fusions’’, PFIZER BIOTHERAPEUTICS RESEARCH AND DEVELOPMENT, CAMBRIDGE, MASSACHUSETTS AND PFIZER COVX RESEARCH, SAN DIEGO, CALIFORNIA, JBC PAPERS IN PRESS, NOVEMBER 2012

Xiaotian Zhong  Elizabeth Kieras  Eric Sousa  Aaron D’Antona  J. Christian Baber  Tao He  Joel Desharnais  Lauren Wood  Deborah Luxenberg  Mark Stahl  Ronald Kriz  Laura Lin  Will Somers  Lori J. Fitz  Jill F.Wright

Patent No. US 9,217,039 B2, ‘‘Anti-HER3 Antibodies and Compositions’’, SYMPHOGEN A/S, LYNGBY (DK), DECEMBER 2015

Mikkel Wandahl Pedersen  Helle Jacobsen  Klaus Koefoed

Patent No. US 2017/0029515 A1, ‘‘Method of Inhibition of Leukemic STEM Cells’’, CSL LIMITED, PERKVILLE, VI (US), UNIVERSITY HEALTH NETWORK, TORONTO (CA), FEBRUARY 2017

John Edgar Dick  Liqing JIN  Gino Luigi Vairo  David Paul Gearing  Samantha Jane Busfield

Patent No. US 2016/0222356 A1, ‘‘High Titer Recombinant AAV Vector Production in Adherent and Suspension Cells’’, AMGEN INC., THOUSAND OAKS, CA (US), AUGUST 2016

Huiren Zhao  Ki Jeong Lee  Thomas Wolfe  Cherylene Plewa  Jackie Z. Sheng

‘‘Rôle des Protéoglycanes à Héparane Sulfate dans le Transfert de Gène des Cellules CHO et HEK 293’’, MONTREAL UNIVERSITY, DEPARTEMENT DE BIOCHIMIE ET DE MEDECINE MOLECULAIRE, MAY 2016* *THESIS AVAILABLE ONLY IN FRENCH

Laurence Delafosse

‘‘Conception et évaluation d’un nouveau système de transfection ciblée, basé sur l’utilisation du système E/Kcoil’’, MONTREAL UNIVERSITY, DEPARTEMENT DE BIOCHIMIE ET DE MEDECINE MOLECULAIRE, FACULTE DE MEDECINE, JUNE 2015* *THESIS AVAILABLE ONLY IN FRENCH

Elodie Louvier

‘‘Single Chain Antibodies as Tools to Study transforming growth factor-β-Regulated SMAD Proteins in Proximity Ligation-Based Pharmacological Screens”, DEPT. OF IMMUNOLOGY, UPPSALA UNIVERSITY, SWEDEN, MOLECULAR & CELLULAR PROTEOMICS, FEBRUARY 2016

Andries Blokzijl  Agata Zieba  Michael Hust  Thomas Schirrmann Saskia Helmsing Karin Grannas Ellen Hertz Anita Moren Lei Chen Ola Soderberg Aristidis Moustakas Stefan Dubel Ulf Landegren

‘‘An anti-TL1A antibody for the treatment of asthma and inflammatory bowel disease”, TEVA PHARMACEUTICALS, R&D, BIOLOGICS, LEAD ANTIBODY DISCOVERY, SYDNEY, AUSTRALIA; TEVA PHARMACEUTICALS, R&D, BIOLOGICS, ASSAYS AND TECHNOLOGY, TAYLOR & FRANCIS GROUP, LLC © TEVA PHARMACEUTICALS AUSTRALIA PTY LTD, 2018

Adam W.Clarke Lynn Poulton Doris Shim David Mabon Danyal Butt Matthew Pollard Vanya Pande Jean Husten Jacquelyn Lyons Chen Tian & Anthony G. Doyle

‘‘A Cyclic Peptidic Serine Protease Inhibitor: Increasing Affinity by Increasing Peptide Flexibility”, DANISH-CHINESE CENTRE FOR PROTEASES AND CANCER, FUJIAN INSTITUTE OF RESEARCH ON THE STRUCTURE OF MATTER, CHINESE ACADEMY OF SCIENCES, FUZHOU, CHINA; DANISH-CHINESE CENTRE FOR PROTEASES AND CANCER, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, AARHUS UNIVERSITY, DENMARK; NANOSCIENCE CENTER AND DEPARTMENT OF CHEMISTRY, UNIVERSITY OF AARHUS, DENMARK; DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, UNIVERSITY OF COPENHAGEN, DENMARK; PLOS ONE 9(12):E115872, 2014

Baoyu Zhao Peng Xu Longguang Jiang Berit Paaske Tobias Kromann-Hansen Jan K. Jensen Hans Peter Sorensen Zhuo Liu Jakob T. Nielsen Anni Christensen Masood Hosseini Kasper K. Sorensen Niels Christian Nielsen Knud J. Jensen Mingdong Huang Peter A. Andreasen

Patent No. CA2614039A1, “Compositions and methods of treating disease with fgfr fusion proteins”, FIVE PRIME THERAPEUTICS INC., 2015

Lewis T. Williams Elizabeth Bosch Stephen Doberstein Kevin Hestir Diane Hollenbaugh Ernestine Lee Minmin Qin Ali Sadra Justin Wong Ge Wu Hongbing Zhang

“Transfection of HEK293-EBNA1 Cells in Suspension with Linear PEI for Production of Recombinant Proteins”, NATIONAL RESEARCH COUNCIL CANADA, COLD SPRING HARBOR PROTOCOLS, 2008

Roseanne Tom Louis Bisson Yves Durocher

“Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite”, DEPARTMENT OF IMMUNOLOGY AND INFECTIOUS DISEASES, HARVARD; T.H. CHAN SCHOOL OF PUBLIC HEALTH, BOSTON, USA; DEPARTMENT OF BIOLOGICAL ENGINEERING, MASSACHUSETTS INSTITUTE OF TECHNOLOGY, CAMBRIDGE, USA, Nature communications, 2015

Selasi Dankwa Caeul Lim Amy K. Bei Rays H.Y. Jiang James R. Abshire Saurabh D. Patel Jonathan M. Goldberg Yovany Moreno Maya Kono Jacquin C. Niles  Manoj T. Duraisingh

“Development of Human-Like scFv-Fv Neutralizing Botulinum Neurotoxin E. “, TECHNISCHE UNIERSITAT BRAUNSCHWEIG, INSTITUT FUR BIOCHEMIE, BIOTECHNOLOGIE UND BIOINFORMATIK, ABTEILUNG BIOTECHNOLOGIE, BRAUNSCHWEIG, GERMANY; DIVISION OF BACTERIOLOGY, NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL (NIBSC), UK, INSTITUT DE RECHERCHE BIOMEDICALE DES ARMEES, FRANCE; PLOS ONE, 2015

SEBASTIAN MIETHE Christine Rasetti-Escargueil Arnaud Avril Yvonne Liu Siham Chahboun Hannu Korkeala Christelle Mazuet Michel-Robert Popoff Thibaut Pelat Philippe TFhullier Dorothea Sesardic Michael Hust

“Stable high volumetric production of glycosylated human recombinant IFNalpha2b in HEK293 cells”, NATIONAL RESEARCH COUNCIL CANADA, ANIMAL CELL TECHNOLOGY GROUP, BIOPROCESS SECTOR, BIOTECHNOLOGY RESEARCH INSTITUTE, MONTREAL, CANADA; INSTITUTE FOR BIOLOGICAL SCIENCES, OTTAWA, CANADA; DEPARTMENT OF BIOMEDICAL ENGINEERING, FACULTY OF MEDICINE, MONTREAL, CANADA; BIOMED CENTRAL BIOTECHNOLOGY, 2008

Martin Loignon  Sylvie Perret  John Kelly  Denise Boulais  Brian Cass  Louis Bisson  Fatemeh Afkhamizarreh  Yves Durocher

“Structure and function of C-type lectin NK cell receptors studied by recombinant expression and protein crystallography”, CHARLES UNIVERSITY IN PRAGUE, FACULTY OD SCIENCE, DEPARTMENT OF BIOCHEMISTRY, PRAGUE, 2010

*Thesis

Ondrej Vanek

“Pyroglutamate and O-Linked Glycan Determine Functional Production of Anti-IL17A and Anti-IL22 Peptide-Antibody Bispecific Genetic Fusions”, PFIZER BIOTHERAPEUTICS RESEARCH AND DEVELOPMENT, CAMBRIDGE, MASSACHUSETTS; PFIZER COVX RESEARCH, SAN DIEGO, CALIFORNIA; JBC PAPERS IN PRESS, 2012

Xiaotian Zhong  Elizabeth Kieras  Eric Sousa  Aaron D’Antona  J. Christian Baber  Tao He  Joel Desharnais  Lauren Wood  Deborah Luxenberg  Mark Stahl  Ronald Kriz  Laura Lin  Will Somers  Lori J. Fitz  Jill F. Wright

“Expression and purification of soluble and stable ectodomain of natural killer cell receptor LLT1 through high-density transfection of suspension adapted HEK293S GnTI- Cells”, DEPARTMENT OF BIOCHEMISTRY, FACULTY OF SCIENCE, CHARLES UNIVERSITY IN PRAGUE, CZECH REPUBLIC; INSTITUTE OF ORGANIC CHEMISTRY AND BIOCHEMISTRY, ACADEMY OF SCIENCES OF THE CZECH REPUBLIC; INSTITUTE OF MICROBIOLOGY, ACADEMY OF SCIENCES OF THE CZECH REPUBLIC; ELSEVIER – PROTEIN EXPRESSION AND PURIFICATION 109 7-13; 2015

Jan Blaha  Petr Pachl  Petr Novak  Ondrej Vanek

Patent No. US 2012/0321626 A1 “Multi-specific FAB Fusion Proteins and methods of use”, FABION PHARMACEUTICALS INC, SAN DIEGO, US; 2012

Hongxing Zhou

“Multi-host expression system for recombinant production of challenging proteins”, DEPARTMENT OF MOLECULAR STRUCTURAL BIOLOGY, HELMHOLTZ CENTRE FOR INFECTION RESEARCH, BRAUNSCHWEIG, GERMANY ; PLOS ONE – E68674, 2013

Steffen Meyer  Carmen Lorenz  Bahar Baser  Mona Wordehoff  Volker Jager  Joop van den Heuvel

“Generation of Recombinant Antibodies against the beta-(1,6)-Branched beta-(1,3)-D-Glucan Schizophyllan from Immunized Mice via Phage Display”, DEPARTMENT FOR BIOTECHNOLOGY, INSTITUTE OF BIOCHEMISTRY, BIOTECHNOLOGY AND BIOINFORMATICS, TECHNISHE UNIVERSITAT BRAUNSCHWEIG, GERMANY; INSITITUTE FOR PHYSICAL AND THEORETICAL CHEMISTRY, TECHNISHE UNIVERSITAT BRAUNSCHWEIG, GERMANY; YUMAB GMBH, BRAUNSCHWEIG, GERMANY; BIOTECHNOLOGY RESEARCH INTERNATIONAL, V2017 – RESEARCH ARTICLE; 2017 Jorn Josewski Sabine Buchmeier  André Frenzel  Philip Tinnefeld Stefan Dubel Udo Rau

“Novel CH1:CL interfaces that enhance correct light chain pairing in heterodimeric bispecific antibodies”, CHRISTIAN DOPPLER LABORATORY FOR ANTIBODY ENGINEERING AT DEPARTMENT OF CHEMISTRY AND DEPARTMENT OF BIOTECHNOLOGY, BOKU – UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES, VIENNA, AUSTRIA; INSTITUTE FOR ORGANIC CHEMISTRY AND BIOCHEMISTRY, DARMSTADT, GERMANY; DEPARTMENT OF CHEMISTRY, BOKU- UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES, VIENNA, AUSTRIA; PROTEIN ENGINEERING AND ANTIBODY TECHNOLOGIES, MERCK, DARMSTADT, GERMANY ; PROTEIN ENGINEERING, DESIGN & SELECTION, VOL. 30, NO.9; 2017

Maximilian Bonisch Carolin Sellmann Daniel Maresch Claudia Halbig Stefan Becker Lars Toleikis  Bjorn Hock  Florian Ruker

“Exploring Site-Specific N-Glycosylation of HEK293 and Plant-Produced Human IgA Isotypes”, DEPARTMENT OF APPLIED GENETICS AND CELL BIOLOGY, UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES, MUTHGASSE, VIENNA, AUSTRIA; DEPARTMENT OF CHEMISTRY, DIVISION OF BIOCHEMISTRY, UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES, VIENNA, AUSTRIA; JOURNAL OF PROTEOME, 16, 2560-2570, 2017

KATHRIN GORITZER Daniel Maresch Friedrich Altmann  Christian Obinger Richard Strasser

“Exploring site-specific N-glycosylation of HEK293 and plant-produced human IgA isotypes”, DEPARTMENT OF APPLIED GENETICS AND CELL BIOLOGY, UNIVERSITY OF NATURAL RESOURCES AND LIFE, VIENNA; DEPARTMENT OF CHEMISTRY, DIVISION OF BIOCHEMISTRY, UNIVERSITY OF NATURAL RESOURCES AND LIFE, VIENNA; 2017

RICHARD STRASSER

“Generation and characterization of protective antibodies to Marburg virus”, US ARMY MEDICAL RESEARCH INSTITUTE FOR INFECTIOUS DISEASE, USA; UNITE DE BIOTECHNOLOGIE DES ANTICORPS, INSTITUT DE RECHERCHE BIOMEDICALE DES ARMEES, FRANCE; BIOTEM, APPRIEU, FRANCE; TECHNISCHE UNIVERSITAT BRAUNSCHWEIG, INSTITUT FUR BIOCHEMIE, BIOTECHNOLOGIE UND BIOINFORMATIK BRAUNSCHWEIG, GERMANY ; YUMAB GMBH, BRAUNSCHWEIG, GERMANY ; DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY, ALBERT EINSTEIN COLLEGE OF MEDICINE, BRONX, USA. ; MABS VOL. 9, NO. 4, 696-703; 2017

Jeffrey W. Froude  Thibaut Pelat Sebastien Miethe Samantha E. Zak  Anna Z. Wek  Kartik Chandran  Jennifer Mary Brannan Russel R. Bakken Michael Hust  Philippe Thullier John M. Dye

“Engineering elastic properties into an anti-TNF monoclonal antibody”, ABBVIE BIORESEARCH CENTER, USA; COGENT BIOLOGY, VOL.4 : 1469387, 2018

RAMKRISHNA SADHUKHAN NATHAN BROWN DAVID OUELLETTE DAVID BANACH DANA I. FILOTI DAVID WINARTA REEMA RAGHAVENDRA SILVINO SOUSA ANHDO DARCY LESLIE ALESSANDRI ALEXANDER IVANOV SAHANA BOSE LUCIA EATON GREGORY PRESTON JEREMY FREEMAN IVAN CORREIA

Patent No.: US 2016/0333418 A1 “Activin Inhibitor Response Prediction and uses for Treatment”; SANTA MARIA BIOTHERAPEUTICS, INC., SOUTH SAN FRANCISCO, CA (US);2016

CHRISTOPHER MICHAEL HAQQ

Patent No.: US 2010/0168020 A1 “Stabilized Receptor Polypeptides and uses Thereof”; AMGEN INC., THOUSAND OAKS, CA (US); 2010

JEONGHOON SUN LEI-TING TONY TAM MARK LEO MICHAELS THOMAS C. BOONE ROHINI DESHPANDE YUE-SHENG LI  HQ HAN “A Cyclic Peptidic Serine Protease Inhibitor: Increasing Affinity by Increasing Peptide Flexibility”, DANISH-CHINESE CENTRE FOR PROTEASES AND CANCER, FUJIAN INSTITUTE OF RESEARCH ON THE STRUCTURE OF MATTER, CHINESE ACADEMY OF SCIENCES, FUZHOU, CHINA; DANISH-CHINESE CENTRE FOR PROTEASES AND CANCER, DEPARTMENT OF MOLECULAR BIOLOGY AND GENETICS, AARHUS UNIVERSITY, DENMARK ; NANOSCIENCE CENTER AND DEPARTMENT OF CHEMISTRY, AARHUS UNIVERSITY, DENMARK ; DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE, UNIVERSITY OF COPENHAGEN, DENMARK ; PLOS ONE 9(12):E115872; 2014

ZHAO B XU P JIANG L PAASKE B KROMANN-HANSEN T ET AL.