SPI Infoamtion

Table of Contents

Executive summary

An introduction to monoclonal antibodies
Identifying non-human monoclonal antibodies
Optimizing full-length antibodies
Fully human monoclonal antibodies
Antibody conjugates
Novel binding molecules derived from antibodies

Chapter 1 An introduction to monoclonal antibodies

Summary
Introduction
Antibodies in nature
Advantages of monoclonal antibodies as drugs

Target range
Predictability
Pharmacokinetics
Technology protection

Challenges and opportunities for the next generation of monoclonal antibodies

Target selection
Species specificity
Pharmacokinetics
Manufacture

Monoclonal antibody drugs already at market

Orthoclone OKT3
Remicade
Rituxan
Zenapax
Synagis
Humira
Vectibix
Simponi
Lucentis
Cimzia
Tysabri

Preclinical development of therapeutic drugs

Proof of concept
Safety profile
Conclusions

Chapter 2 Identifying non-human monoclonal antibodies

Summary
Introduction
Technology platforms

Hybridoma technology
RabMAbs
SLAM
Human Response Platform
DIAAD
ImmuneY2
iMAB
Fusion Expression Technology
ProMIS
AbScreen
AbProt
BioArctic platform
FunctionFIRST

Case studies

Abbott Labs
AbGenomics
Alethia
Amorfix
Arrowsmith Technologies
AVEO
BioSceptre
Canadian Bio Med Systems
Cangene
CellAct
CoGenesys
Crucell
CSL
Daewoong
DKFZ
Epitomics
Fusion Antibodies
Ganymed Pharmaceuticals
GeNeuro
Genitope
GSK
Heat Biologics
Immuno-Biological Labs
ImmunoGen
Immutep
InflaRx
Innate Pharma
Inotek
Intercell
LigoCyte
MedImmune
Morphotek
NeoGenix
Northwest Biotherapeutics
Novartis
Novo Nordisk
OncoMed
Perseis Therapeutics
Pfizer
Pharma Research Toronto
Prana Biotech
Quest PharmaTech
Recepta Biopharma
Receptor-Logic
Roche
Shanghai CP Guojian
Suzhou Stainwei Biotech
Therapure
ThromboGenics
Thrombotargets
Tolerx
Trillium
Vaccinex
Wilex
ZymoGenetics

Conclusions

Chapter 3 Optimizing full-length antibodies

Summary
Introduction
Technology platforms

Chimeric antibodies
CDR grafting
SMART
Superhumanisation
Framework Patching
Composite Human Antibody
ATLAb
Humaneering
MLG
DeImmunisation
Humanation
Human Engineering
FcX
The LEX System
Potelligent
Complegent
BestMAb
ImmunoBody
EB66
Synageva Expression Platform
XmAb
Sugar Engineered Antibodies
Wox

Case studies

Abbott Labs
Advanced Immune Therapeutics
Alder Biopharm
Alethia
Alexion
Antisoma
Arana
Attenuon
AVEO
BioArctic Neuroscience
Biogen Idec
Biolex
BioXell
China Synthetic Rubber Corp
CSL
CureTech
Direvo
DSX
Eli Lilly
Epitomics
Faron Pharm
Femta Pharm
Forerunner Pharma Research
Fusion Antibodies
Galaxy Biotech
Galileo Oncologics
Genentech
Glenmark
GlycoForm
Glycotope
ImmunoCellular Therapeutics
Immunomedics
Innate Pharma
InNexus Biotech
Intellect Neurosciences
Isu Abxis
Janssen Alzheimer Immunotherapy
KaloBios
Keel Pharm
LigoCyte
Lpath
Mabion
MacroGenics
MaimoniDex
MAT Biopharma
MedImmune
Medtronic
Micromet
NKT Therapeutics
Opsona
Percipio
Pharma Research Toronto
ProtAb
Scancell
Selexys
SinoMab Bioscience
Synageva
TaiMed
Trillium
United Biomedical
Vascular Pharm
VasGene
Vegenics
Vybion
Xencor

Conclusions

Chapter 4 Fully human monoclonal antibodies

Summary
Introduction
Technology platforms

Phage display
MBAS
CBAS
HuCAL
MAbstract
ActivMAb
Adimab platform
XenoMouse
UltiMAb
VelocImmune
Open Monoclonal Technology
Xenerex
SEBVI
Cloning the Human Response
Viventia platforms
Natural Human Antibodies
MabIgX
Reverse Translational Medicine
I-STAR
CellSpot
iBioLaunch

Case studies

Adimab
Acorda Therapeutics
Affitech
Agensys
Alopexx
AstraZeneca
BioFactura
Biotherapix
CellAct
Celldex
Centocor
Crucell
CSL
Dyax
Emergent BioSolutions
Functional Genetics
GenMab
Crucell
GSK
Humabs
Human Antibodomics
Humanyx
iBio
ImClone
IMED
Immune System Therapeutics
IQ Therapeutics
Kenta Biotech
Kyowa Hakko Kirin
MabVax
Mapp Biopharmaceutical
Medarex
MedImmune
Merck & Co
Micromet
MorphoSys
NatImmune
Neurimmune
NovImmune
Novo Nordisk
Omeros Corp
Oncaidia
OncoMed
Oxford BioTherapeutics
Panacea
Patrys
Peregrine
PharmAbcine
sanofi-aventis
Theraclone
Trellis Bioscience
U3 Pharma
Vaccinex
Vegenics
Xoma

Conclusions

Chapter 5 Antibody conjugates

Summary
Introduction
Technology platforms

Antibody Drug Conjugate
Targeted Antibody Payload
Probodies
Antibody cloaking
Targeted Photodynamic Therapy
AlbudAb
hyFc
Ligand traps
CovX-Body
Dynamic Cross-Linking
LEC technology

Case studies

Algeta
Aphios
ArmaGen Technologies
Asan Medical Center
Bayer Schering
Beijing ABT
Biogen Idec
BioTransformations
Boehringer Ingelheim
Celldex
Cytoguide
CytomX
Dompe
EnGeneIC
FDA
Forerunner Pharma Research
Galileo Oncologics
Genentech
Genexine
ImmunoGen
Immunomedics
InNexus Biotech
Medarex
MedImmune
Merrimack
Morphotek
Mycenax
NCI
Oncaidia
OncoTherapy Science
Panacea
Peregrine
Pfizer
Pivotal BioSciences
Seattle Genetics
Symphogen
Transgene Biotek
Viventia

Conclusions

Chapter 6 Novel binding molecules derived from antibodies

Summary
Introduction
Technology platforms

Fab
TetraMABs
scFv
Immuna
[scFv]2
BiTE
Avibodies
TandAb
Flexibody
V-NAR
Nanobody
Domain Antibodies
Heteropolymer
UniBody
Domain Exchanged Antibodies
SMIP
SCORPION
DVD-Ig

Case studies

Abbott Labs
Ablynx
AdAlta
Affimed
Avipep
Beijing ABT
Biogen Idec
Calmune
Elusys
ESBATech
Galileo Oncologics
Glycotope
GSK
Inmunova
MAT Biopharma
Micromet
Novartis
PharmAbcine
Trubion
Suzhou Stainwei Biotech
Taligen
Vegenics

Conclusions

Appendix

Primary research methodology
Glossary
Index

List of Figures
Figure 1.1: The B-cell receptor
Figure 1.2: Immunoglobulin G, subclass 1
Figure 1.3: Immunoglobulin G, subclass 3
Figure 1.4: Features of monoclonal antibody technology
Figure 3.5: Chimeric antibody technology
Figure 3.6: CDR grafting
Figure 3.7: Complegent® technology
Figure 5.8: An Antibody Drug Conjugate
Figure 5.9: Probody™ technology
Figure 5.10: An AlbudAb™
Figure 5.11: An EGF ligand trap
Figure 6.12: Antigen binding fragment (Fab)
Figure 6.13: A [Fab]2 fragment
Figure 6.14: A single chain variable fragment (scFv)
Figure 6.15: An [scFv]2 molecule
Figure 6.16: A diabody
Figure 6.17: A triabody
Figure 6.18: A tetrabody
Figure 6.19: A TandAb
Figure 6.20: A Flexibody
Figure 6.21: A shark antibody (IgNAR)
Figure 6.22: A V-NAR fragment
Figure 6.23: A camelid antibody
Figure 6.24: A Nanobody®
Figure 6.25: A Domain Antibody (dAb)
Figure 6.26: A bivalent Dual-targeting dAb™
Figure 6.27: An IgG-like Dual-targeting dAb™
Figure 6.28: A mAb-dAb
Figure 6.29: An antibody heteropolymer
Figure 6.30: A UniBody®
Figure 6.31: A Domain Exchanged Antibody
Figure 6.32: A SMIP™
Figure 6.33: An scFv-based SCORPION™ antibody
Figure 6.34: A Dual-Variable Domain Immunoglobulin™

List of Tables
Table 2.1: Preclinical mAbs with no known humanization or engineering
Table 2.2: Preclinical mAbs with no known humanization or engineering (ctd 1)
Table 2.3: Preclinical mAbs with no known humanization or engineering (ctd 2)
Table 2.4: Preclinical mAbs with no known humanization or engineering (ctd 3)
Table 2.5: Preclinical mAbs with no known humanization or engineering (ctd 4)
Table 2.6: Preclinical mAbs with no known humanization or engineering (ctd 5)
Table 3.7: Antibody engineering technologies
Table 3.8: Antibody engineering technologies (ctd 1)
Table 3.9: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns
Table 3.10: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns (ctd 1)
Table 3.11: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns (ctd 2)
Table 3.12: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns (ctd 3)
Table 3.13: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns (ctd 4)
Table 3.14: Preclinical mAbs with engineered amino acid sequences or glycosylation patterns (ctd 5)
Table 4.15: Preclinical ‘fully human’ mAbs
Table 4.16: Preclinical ‘fully human’ mAbs (ctd 1)
Table 4.17: Preclinical ‘fully human’ mAbs (ctd 2)
Table 4.18: Preclinical ‘fully human’ mAbs (ctd 3)
Table 4.19: Preclinical ‘fully human’ mAbs (ctd 4)
Table 4.20: Preclinical ‘fully human’ mAbs (ctd 5)
Table 4.21: Preclinical ‘fully human’ mAbs (ctd 6)
Table 4.22: Preclinical ‘fully human’ mAbs (ctd 7)
Table 5.23: Preclinical antibody conjugates
Table 5.24: Preclinical antibody conjugates (ctd 1)
Table 5.25: Preclinical antibody conjugates (ctd 2)
Table 5.26: Preclinical antibody conjugates (ctd 3)
Table 5.27: Preclinical antibody conjugates (ctd 4)
Table 6.28: Antibody-derived binding molecules in preclinical development
Table 6.29: Antibody-derived binding molecules in preclinical development (ctd 2)
Table 6.30: Antibody-derived binding molecules in preclinical development (ctd 3)
Table 6.31: Antibody-derived binding molecules in preclinical development (ctd 4)