Your Brilliant Partner

Transcription

Your Brilliant Partner
Contract Research Services
YOUR
BRILLIANT
PARTNER
CONTRACT RESEARCH SERVICES
CONTENTS
Greetings 04
History 05
Immunological Analysis
ELISA (enzyme-linked immunosorbent assay) 06
Other Assays/Customized Services 07
Antibody Development
Phage Display Library Screening 08
IgG Conversion & Expression System 09
Genetic Characterization for PDX Tumor Models
Development of Standard guideline for PDX Models 11
IVD-CDx Development
Validation System for IVD-CDx 12
Therapeutic siRNA Development
Hit-Lead-Candidate drug Development/Hit to Lead 14
Lead to Candidate/siRNA PK/TK/PD analysis 15
Molecular Genetic Analysis
Molecular Genetic Analysis/Microarray/Cell Line Authentication 16
Nucleic Acid Quantification & Nucleic Acid Isolation 17
LC/MS/MS Bioanalytical Analysis
Analytic Method Development 18
Histopathological Analysis
Tissue Cross-Reactivity 19
Immunohistochemistry (IHC)/Hematoxylin & Eosin (H&E) Staining 21
Special Stains 22
Slide Preparation 23
ABION CRO – Devices 24
PATENTS 25
ABION CRO Partners 26
04
ABION CRO RESEARCH SOLUTIONS
Y our Br il lia nt Par t ner
Greetings
Since its establishment in 2007, ABION Inc. has served as the pathology core facility
of the College of Pharmacy at Seoul National University and has accumulated extensive experience in biopharmaceutical product analyses.
ABION CRO has provided a broad range of biological analysis services required for
clinical and non-clinical trials. These services have employed small- to medium-sized
laboratory animals and run the gamut from the initial development phase of biologics,
such as therapeutic antibodies, protein drugs, nucleic acid drugs, through the completion of the study report.
ABION CRO will continue to offer excellent biological analysis services in accordance
with our mission to contribute to novel pharmaceutical development infrastructure.
05
You r B ri lli ant P art ner
History
2014
November. Certified as a Family-Friendly Company
Certified as a Safety Laboratory
Secured investment from Solidus Investment (2 Billion Won)
July.
Listed on the KONEX
June.
Renamed the company as ABION Inc.
2013
December. Secured investment from LB Investment (3 Billion Won) and IMM
Investment (3 Billion Won)
September. Awarded Excellence Award by Small- and Medium-sized Business
Administration
April.
Relocated to Guro, Seoul
February. Secured investment from Now IB Capital (1.5 Billion Won)
January. Secured investment from Korean Investment Partners (2 Billion Won)
2012
December. Merged with Research NET Inc.
March.
Merged with Igen Biotech Inc.
2011
September. Licensed-out the prognostic and diagnostic technology for breast cancer
2010
September. Obtained ISO 9001 Certification
August.
Obtained Inno-Biz Certification
2009
December. Certified as a venture company
March.
Established an affiliated research institute (R&D Center)
2007
July.
Established Reference BioLab
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01
Immunological Analysis
The importance of immunological assay methods
for validating the efficacy of pharmacokinetics
and pharmacodynamics of drugs has recently increased due to the rapid growth and development
of bio-therapeutics, including antibody and protein
therapeutics.
In response, ABION CRO aims to offer research
infrastructure optimized for the quantitative and
qualitative analyses of ELISA-based protein therapeutics and high-quality analytical services for
investigators involved in new drug development
and biotechnology-related research through a variety of scientific tools and well-established SOPs.
We conduct method validation in compliance with
ICH Q2 guidelines to guarantee reliable and accurate data.
ELISA (enzyme-linked immunosorbent assay)
ELISA is a widely used assay designed for the accurate detection
and quantitative measurement of antigen or antibody at very low
concentrations. This assay is a highly convenient biochemical
technique and serves as a sensitive analytical tool for the toxicological, immunological, pharmacokinetics, and pharmacodynamics analyses of biologics as part of new drug development.
ABION CRO offers a vast range of ELISA assays, including
direct and indirect ELISA, sandwich ELISA, and multiplex
ELISA. Multiplex ELISA, in particular, is a highly effective beadbased analysis tool that allows simultaneous detection of up to
100 analytes in a single sample and requires less samples,
reagents, and time than conventional single-plex assays.
We also provide customized assay designs for many applications
to suit your analyte combinations or the intended targets in order
to accomplish your specific research goals. We guarantee superior services and ensure effective test results through our integrated
and automated technology platforms, which are coupled with our
extensive expertise.
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ELISA Analysis
Other Assays
Pharmacokinetics (Protein Drug pharmacokinetics)
・Quantitative analysis
・Titer analysis
We have a vast range of services ranging from lab scale
experiments to high-quality antigen-antibody responserelated services, such as surface plasmon resonance (SPR),
designed to meet your research needs. In particular, SPR is
used for screening monoclonal and polyclonal antibodies
during the antibody-based drug development process and
also for measuring the affinity of the selected antibodies.
Pharmacodynamics
・Single target analysis: Cytokine, Chemokine,
Hormone analysis
Immunotoxicity analysis
・Anti-drug antibody quantitative/titer analysis
・Cytokines and chemokine analysis
Western blotting
Flow cytometry
・Immunotoxicity: Immune cell population analysis
Antibody specificity analysis
・Competitive ELISA
Device: FACS Calibur Flow Cytometer (BD)
Device: GENESIS RSP 200/8 Liquid Handling System
(TECAN)
Surface Plasmon Resonance (SPR)
Protein/Drug Interaction
Customized ELISA
Determination of antibody affinity
Non-clinical and Clinical scale kit development
Device: SPR7500DC (Richert)
Commercial kit development (IVD class)
Development steps
・Step. 1: Antibody selection
(Commercial/Development)
・Step. 2: Kit optimization
・Step. 3: Kit validation
・Step. 4: Kit production (Optional)
Kit validation: IHC Q2 guideline
Multiplex ELISA
Pharmacodynamics
Immunotoxicity: Cytokine analysis
Customized Services
ABION CRO has capabilities to provide a wide range of
customized research services that range from drug development to analytical services for non-clinical and clinical trials. We provide solutions for your research challenges and
offer consulting and analytical services for drug development including antibody and drug screening to efficacy
analysis.
Research level support
・Experiment design
・Antibody development (for analysis)
Device: Bio-plex® 200 systems (Bio-Rad)
Non-clinical analysis service
・Animal experiments
・Analysis design consulting
ELISPOT assay
Clinical analysis service
・Clinical Trial Phase I, II, III level analysis
Immunotoxicity: Immune cell activity analysis
[Reference]
ICH guideline Q2 category: Analytical validation (Finalized Guidelines: October 1994/November 1996)
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02
Antibody Development
ABION CRO offers complete services for therapeutic and diagnostic antibody development, including antibody library screenings, antibody
production, serum purification, antibody characterization, and in vivo and in vitro efficacy tests.
All services are flexible from the first experiment
to fully developed antibody production to meet the
individual needs of each client.
Phage Display Library Screening
ABION CRO has scFv synthetic libraries with a diversity of
approximately 1010 fragments and a Fab naïve library with a
diversity of approximately 1012 fragments. In addition, we are
continuously developing new libraries including immune
libraries based on humanized mice. Our scientists have extensive
experience in antibody screening and provide a variety of panning strategies to select the antibodies desired by customer. Highaffinity scFv antibodies against specific antigens are obtained
through three or four rounds of panning.
Advantages of Panning
・Easy to screen a large number of clones
・Easy to amplify the selected phase in E. coli.
・Selection process easy and already in use in various forms.
・Human antibody
Antigen type for Panning
・Peptide (linear or circular form)
・Protein (available proteins with various tags: His, Fc)
・Intact cells
・Selection systems required by the customer
Antigen presentation techniques
・Direct immobilization (immunotube, microplate.)
・Immobilization with magnetic beads
・Antigen presenting cells
Library screening by phage display technology
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IgG Conversion & Expression System
scFv derived from phage library screening can be converted into full human IgG.
We employ two vector systems with separate plasmids for expression of the heavy chain gene and the light
chain sequences, as well as a one vector system with sequences for both chains inserted into the same plasmid. These systems can be used for establishment of stable cell lines.
We have established platforms for small-scale (flask) to large scale (bioreactor) production of IgG in mammalian
cells (CHO or HEK293).
Stable cell line construction service
Antibody characterization
・Affinity measurement analysis using SR7500DC SPR system (Reichert technologies)
・Tissue cross reactivity (Animal and Human organ tissues)
In vitro efficacy & In vivo efficacy
・In vitro efficacy
Proliferationassay,Apoptosisassay,Cellcycleassay,ADCC/CDC
・In vivo efficacy
Animalmodelpreparation
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03
Genetic Characterization
for PDX Tumor Models
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PDX (patient-derived xenograft) tumor models offer clinically relevant models for drug discovery. PDX models
are established in immunodeficient mice by implanting
surgically resected patient. The xenograft tissues can
be serially passaged, cryopreserved, and revived. The
histology of PDX tissues is useful if these tissues retain
the features of the original samples and reflect the heterogeneity of human tumors.
Tumor microenvironment analysis demonstrated PDXs
that maintain molecular similarity with the primary tumors were gradually replaced by murine stroma during
sequential passages. In addition, a decrease in the total
amount of PDXs was observed, while the percentage
of the relative tumor cells and the substrates remained
the same in these models.
Development of Standard guideline for
PDX Models
STR Profiling
Exome Sequencing
・Cancer HotSpot Panel v2 (Life technologies)
・Comprehensive Cancer Panel (Life technologies)
RNA Sequencing
・RNA Cancer Panel (Life technologies)
Hu-Mo ID Test
Thus, the genetic and histological characteristics of the
tumors may be replaced by the original tumors during
the sequential passages of the tissues in PDX models,
and this limitation can be used in the standard guidelines to describe changes in phenotypic and genetic
characteristics of F generations when reporting the therapeutic efficacy of drugs.
ABION CRO aims to provide PDX models and cell line
xenograft studies with the latest genomic characterization technologies to advance cancer research towards
a cure.
[Reference]
Moro M. et al., Patient-derived xenografts of NSCLC: Resurgence of an old model for investigation of mordern concepts of
tailored therapy and cancer stem cells. J Biomed Biotechnol. 2012:568567. doi: 10.1155/2012/568567. (2012)
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04
IVD-CDx Development
In vitro companion diagnostics (IVD-CDx) involves biomarker-based in vitro devices that are intended to assist physicians in
the identification of patient populations that may potentially benefit from a specific treatment.
ABION CRO offers IVD-CDx development services to assist clients in development of a therapeutic product (either a novel
product or an existing product with a new indication) for which the use of an in vitro companion diagnostic device is essential
for safe and effective use of the therapeutic product. This service is also beneficial to clients planning to develop an in vitro
companion diagnostic device that is intended to be used with a corresponding therapeutic product.
ABION CRO also provides comprehensive services for analytical validation and clinical validation to help our clients obtain
approval for medical devices or IVD-CDX products in Korea and abroad.
Validation System for IVD-CDx
We provide a companion diagnostics development platform for anti-cancer therapeutics. This platform includes IHC
(immunohistochemistry) and molecular genetic biomarkers with automated systems (i.e., NGS, qPCR, and microarray). We
perform analytical and clinical validation along with technical and clinical assessment of test performance using FDAapproved IVD-CDx and research use only kits.
FDA approved IVD-CDx Platform
Ventana systems for Herceptin
・INFORM HER-2/NEU
・INFORM HER2 DUAL ISH DNA Probe Cocktail
・PATHWAY ANTI-HER-2/NEU (4B5) Rabbit Monoclonal Primary Antibody
cobas® Oncology Biomarker Tests
Real-Time PCR detects the presence of mutations in cancer genes
Roche cobas z 480 Analyzer
・cobas® BRAF Mutation Test (IVD-CDx) for Zelboraf®
・cobas® EGFR Mutation Test (IVD-CDx) for Tarceva® (erlotinib)
therascreen Oncology Biomarker Tests
Real-Time PCR detects the presence of mutations in cancer genes
・QIAGEN therascreen® EGFR RGQ PCR kit for Gilotrif™(afatinib)
・QIAGEN therascreen® KRAS RGQ PCR kit for Erbitux®(cetuximab) and Vectibix® (panitumumab)
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RUO, IUO & IVD Platform
Droplet digital PCR Oncology Biomarker Tests
ddPCR detects the presence of mutations in cancer genes
・Bio-Rad QX200 Droplet Digital PCR
・QuantaSoft™ Version 1.6.6
NGS Oncology Biomarker Tests
Ion Proton system -Large-scale genetic data analysis
・Exome Sequencing
・RNA Sequencing
・Targeted Sequencing
Roche cobas z 480 Analyzer
・cobas® KRAS Mutation Test (IVD)
[Reference]
In vitro Companion Diagnostic Devices ‘Guidance for industry and FDA staff’ Document issued on: August 6, 2014
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Therapeutic siRNA Development
The RNA interference technique using short interfering RNA (siRNA) is a revolutionary method that can selectively suppress
the expression of target genes. In recent years, many studies have focused on developing therapeutic agents using siRNAs.
ABION CRO offers services to facilitate siRNA nucleic acid drug development, including Hit-Lead-Candidate drug discovery
and PK/TK/PD analyses. Moreover, we have established a variety of tools to identify the level of RNA interference with
siRNAs both in vitro and in vivo.
Hit-Lead-Candidate drug Development
ABION CRO has expertise in performing library screenings, lead discovery and lead validation for efficacy of nucleic acid
therapeutics. Various chemical modifications are performed to increase the stability of nucleic acid drugs and optimize derivation of candidates through the lead optimization process.
Hit to Lead
“Hit-to-Lead” candidate drug discovery is based on the process of establishing at least 10 siRNA sequence designs for the
same target genes using siRNA library screening followed by selection of the highest quality lead siRNAs. In vivo efficacy of
the selected lead siRNAs is then determined in experimental animal models.
Cell line authentication
・Mycoplasma test and STR analysis
In vitro/in vivo assay development
・siRNA physicochemical character ID (Nanoplex size, pH, N:P Ratio etc.)
・siRNA transfection protocol optimization
・in vitro efficacy test (phenotype, cell death and aging, and cell cycle arrest)
・RT-qPCR (mRNA knock-down level)
・Western blotting (protein knock-down level)
・Animal experiment design (Lead Validation)
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Lead to Candidate
Chemical modification: Various modifications can be made to enhance in vivo stability.
Stable derivatives: Sense (S) and antisense (AS) strand are partially modified and combined.
Lead optimization:
・Verification of the safety of siRNA derivatives in human serum is performed using the serum stability test.
・Analysis of siRNA derivatives superior to the lead substances using advanced assays, RT-qPCR, western blotting is conducted for validation of mRNA/protein level changes.
・Optimized siRNA candidate selection and animal experiments using candidate substances are performed.
siRNA pool design: The siRNA pool is designed to reduce the off-target effect by using a lower concentration
than the previously used concentration and to demonstrate superior therapeutic efficacy.
siRNA PK/TK/PD analysis
Modified Stem-loop RT-qPCR quantification
・Selection of optimal primers and probes using a minimum of 8 designs
・Establishment of conditions for cDNA synthesis and stem-loop RT-qPCR through repeat tests
Quantitative method validation and optimization
・siRNA quantitative method validation (in triplicate) and optimization on Naked and formulated siRNA
・Standard and amplification curves
・Verification of siRNA Nanoplex quantitation in plasma
Pharmacokinetics analysis from samples of non-clinical & clinical trials
・Sample tests
Validation of siRNA-directed mRNA Cleavage
・siRNA specific Primer design
・5’-RACE-PCR
[Reference]
・ Jung HS. et al., The synergistic therapeutic effect of cisplatin with Human papillomavirus E6/E7 short interfering RNA on cervical cancer
cell lines in vitro and in vivo. Int J Cancer. 15;130(8):1925-36. doi: 10.1002/ijc.26197. (2012)
・ Jung HS. et al., The potential RNAi-based combination therapeutics. Arch Pharm Res. 34(1):1-2. doi: 10.1007/s12272-011-0100-9.
(2011)
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Molecular Genetic Analysis
In recent years, molecular genetic analysis has
become critical for diagnosis and for verification
of the efficacy of bio-therapeutic products and
companion diagnostics. Rapid expansion of the
field has allowed development and implementation of a vast range of genetic analysis technologies, such as real-time PCR (qPCR and RT-qPCR),
microarray analysis, and NGS (next generation sequencing) have been employed to support the biomarker discovery process.
Next Generation Sequencing
・Large-scale genetic data analysis services:
Life Technologies’ Ion Proton.
・Time and cost efficient services
Ion Proton™ System
Ion PI™ Chip Kit V2 (Life technologies)
Ion PI™ Template OT2 200 Kit v3 (Life technologies)
Ion PI™ Sequencing 200 Kit v3 (Life technologies)
・Exome Sequencing
Ion AmpliSeq™ Exome RDY-OT2 Kit (Life technologies)
Furthermore, method development and analytical
validation have become essential components of
qualitative and quantitative validation in clinical
trials and prospective clinical trials. STR (short
tandem repeat) analysis and Mycoplasma infection analysis, in particular, have become the most
significant analyses for cell line authentication
during the development of novel protein drugs and
therapeutic antibodies
ABION CRO aims to offer these high-quality analytical services and to provide access to a comprehensive range of technologies for researchers
through well-established research systems, a
wide range of technologies, and validated SOPs
for quantitative genomic analysis.
・RNA Sequencing
Ion Total RNA-Seq Kit v2 (Life technologies)
・Targeted Sequencing
Microarray
DNA microarray analysis is a developing technology used to
analyze the expression of thousands of genes during primary
screening and to evaluate expression of specific pre-selected
genes. This methodology is also used to detect mutations in
genomic DNA to facilitate understanding of many different diseases.
Devices: Agilent microarray scanner G2505C
Scan Control 8.5.1
Feature Extraction 10.10
Expression Array
・One-Color Microarray-Based Gene Expression _Version 6.7
Array CGH
・Agilent Oligonucleotide Array-Based CGH for Genomic DNA
Analysis _Version 7.3
miRNA Microarray
・miRNA Microarray System with miRNA Complete Labeling
and Hyb Kit _Version 2.4
Cell Line Authentication
STR (Short Tandem Repeat) Profiling
・Detection of cell line cross-contamination
・DNA fingerprinting identification: STR marker system
STR Kit : AmpFlSTR® Identifier® kit (Applied Biosystems)
Analysis Method: 3730 DNA Analyzer (Applied Biosystems, Foster, CA)
Peak scanner (Applied Biosystems, Foster, CA)
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Mycoplasma Test
・Fast and accurate validation to detect Mycoplasma
contamination in cultured cells
e-Myco™VALiD Mycoplasma PCR Detection Kit (iNtRON
Biotechnology)
MycoTOOL PCR based Mycolplasma Detection Kit (EMA
approved, Roche diagnostics)
Nucleic Acid Quantification
Real-Time PCR (qPCR)
Real-time PCR is an effective and sensitive gene
analysis technique used for a broad range of applications in quantitative gene expression analysis and
gene detection, including siRNA treatment, identification of drug response markers, detection of gene
mutations associated with a particular disease, and
detection of microorganisms and viruses.
・Precise customized analysis using Hydrolysis probes
・Total RNA extraction, RNA QC, cDNA synthesis,
primer & probe design
・All services are in compliance with MIQE guideline
Devices: Roche LightCycler® 480 Instrument II
Roche LightCycler® Software
Quantitative PCR (qPCR)
・Cancer research, developmental research and drug
effect studies
・Bacteria & Virus Detection
・SNP detection/Allelic Discrimination
Reverse Transcription –qPCR (RT-qPCR)
・Reverse Transcription
Transcriptor First Strand cDNA Synthesis Kit (Roche)
・Gene Expression: Cancer research, developmental
research and drug effect studies
microRNA RT-qPCR
・This effective and sensitive method is used to
detect miRNA expression levels and permits discrimination between mature miRNAs and precursor
miRNAs via a stem-loop technique.
TaqMan ® MicroRNA Reverse Transcription Kit (Applied
Biosystems)
TaqMan® MicroRNA Assays (Applied Biosystems)
Digital PCR (ddPCR: droplet digital PCR)
Digital PCR builds on traditional PCR amplification and
fluorescent-probe–based detection methods to provide highly sensitive absolute quantification of nucleic
acids without the need for standard curves.
・Absolute quantification
・Single cell gene expression
・Rare target DNA quantification
・NGS library quantification
Devices: Bio-Rad QX200 Droplet Digital PCR
QuantaSoft™ Version 1.6.6
Nucleic Acid Isolation
Nucleic Acid (DNA/RNA) Isolation
Genomic DNA/Total RNA/miRNA extraction from
various samples
・Cultured cells/Tissues (Frozen, FFPE)/Blood/Body
fluids
・QIAamp® DNA Mini Kit (QIAGEN)
・DNeasy® Blood & Tissue Kit (QIAGEN)
・RNeasy® Mini Kit (QIAGEN)
・RNeasy® FFPE Kit (QIAGEN)
・mirVana miRNA Isolation Kit (Ambion)
・PAXgene Blood miRNA Kit (QIAGEN)
・QIAamp Circulating Nucleic Acid Kit (QIAGEN)
Fully automated DNA and RNA preparation from
FFPE Tissues
Device: Automated Tissue Preparation System
(Siemens Microlabstar System*LET IVD )
・High-throughput DNA/RNA extraction system using
FFPE tissues (48 samples/4 hours)
・CE mark & FDA IVD Certified
QC Control
・Nucleic Acid quality control (QC) is essential prior to
Microarray and NGS for successful analysis.
・NanoDrop® Spectrophotometer :
DNA/RNA purity & quantification measurement
・Qubit® fluorometer :
Precise quantitation using Fluorescence dye
・Agilent 2100 Bioanalyzer :
RNA Integrity Number (RIN) measurement
[Reference]
・ Kwon MJ. et al., Identification of novel reference genes using multiplatform expression data and their validation for quantitative
gene expression analysis. PLoS One. 7;4(7):e6162. doi: 10.1371/journal.pone.0006162. (2009)
・ Korean Patent: Data processing, analysis method of gene expression data to identify endogenous reference genes. 10-2007-0138880
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LC/MS/MS Bioanalytical
Analysis
ABION CRO utilizes a variety of methodologies to
develop, validate, and perform a wide range of
bioanalytical sample analyses. We conduct Pharmacokinetic(PK) and Pharmacodynamic(PD) analyses for clinical and non-clinical studies using a
variety of biological matrices, including plasma,
serum, urine, saliva, feces, cerebral spinal fluid,
and tissues (organs, breasts, oculars, etc.). In addition, we work with our clients to develop suitable bioanalytical methods using quantitative
designs via our LC/MS/MS expertise.
Analytic Method Development
Feasibility Study
・Method design and assessment of analytical feasibility
are conducted with regard to analytic sensitivity, sample
volume, extraction type, matrix effect, and mobile phase.
Method Development
・Method development for PK, TK, and ADME analyses.
・Analytical methods are developed to satisfy the requirements of the current data validation standards (i.e. linearity, accuracy, precision, and deviation). These analytical
methods are established to enhance sensitivity, change
flow rates, save time for the entire process (including
preparation time), and reduce the sample volume.
Method Validation
・Method validation is conducted in accordance with
MFDS guidelines. Options include full validation (preliminary data for submissions to regulatory authorities, clinical and non-clinical trial analysis of samples etc.) or partial
validation (for a research paper or reference data). Data
on recovery, linearity, intra-day, inter-day, and stability is
established.
Representative targets
・Generic drugs
・Chemical compounds
・Metabolites
・Proteins (Bio-markers, Hormones)
・Small molecule of 2000Da or less
Material preparation & extraction
・Protein precipitation
・Liquid-liquid extraction
・Solid phase extraction
Devices:
Triple Quad API 4000™ System (AB SCIEX)
・ IQ, OQ, PQ validated
・ Windows NT® platform-based Analyst® Software facilitates GLP compliance,
including 21 CFR Part 11
Shiseido NANOSPACE SI-2 HPLC System
・ Sample Injection: 0.1 to 400 µL in 0.1 µL increments
・ Injection Precision: RSD less than 1% at 1 µL injection
・ Max. Sample Number: 96 Microplate x 6 (576), or 2mL vial x 144
[Reference]
Guideline on Bioanalytical Method Validation, published in 2013 by the MFDS(Ministry of Food and Drug Safety)
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Histopathological Analysis
ABION CRO is committed to providing affordable, highquality histopathology analysis services including immunostaining services to leading academies, R&D
laboratories, hospitals, and pharmaceutical companies.
We provide a complete analysis service encompassing
sectioning and staining of a full range of specimens, including blood, cells, frozen tissues, FFPEs, and TMAs from
humans and animals. Using our extensive research experience in histopathological analysis, we have established
specific study protocols and well tested immunohistochemistry (IHC) SOPs for more than 300 types of antigens.
We also offer a wide variety of fully optimized services for
staining and specialized staining, tissue slide scanning, tissue microarray (TMA) production, and tissue cross-reactivity (TCR) analysis to ensure fully accurate interpretation
of results in support of your research. Since 2007, our certified pathology staff has been dedicated to providing reliable services in conducting robust TCR studies using
many different antibodies.
Tissue Cross-Reactivity
Tissue cross-reactivity (TCR) studies involve monoclonal antibody screening assays performed to ensure that the experimental antibodies or therapeutic agents bind to the intended target sites without binding to receptors or other epitopes.
These studies are also useful to identify sites of on-target binding that were not previously identified.
ABION CRO is one of Korea’s leading CROs with extensive experience and skills in developing immunocytochemical and
immunohistochemical analyses for different applications including TCR studies for monoclonal antibody development and
detection of biomarker expression in tissue samples. We offer customized TCR services with validated study-specific protocols to reflect your exact requirements and needs. Furthermore, we ensure that our services are in compliance with FDA
and EMEA guidelines in support of your regulatory needs (e.g., investigational new drug [IND] submission, research and
preclinical therapeutic antibody development). All research is performed in compliance with the 2010 MFDS “Testing for
cross-reactivity of the monoclonal antibody products for human use” guidelines.
Toxicity assessment for potential antibody therapeutics (validation requirement for IND approval)
Phase I-III services for antibody and protein development: GLP/non-GLP services
Exceptional services based on strong expertise in immunohistochemistry and immunocytochemistry, and
well-established SOPs
Tissue Quality Control (morphology by H&E, genetic character by qPCR)
SAB/Tyramide IHC/Protein Chip Array analysis
TMAs of a variety of normal human tissues
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We use a three-step approach to provide cost- and time-efficient services and accurate study data.
STEP 1: Initial Characterization and Optimization
・We determine the optimal specificity, staining conditions, and concentrations for the experimental antibody
in immunohistochemical assays using positive and negative control tissues/cell lines to confirm the reliability
of cross-reactivity results.
STEP 2: Preliminary Tissue Cross-Reactivity Screening
・We identify the potential cross-reactivity of the antibody prior to performing the full study on normal or frozen
human or animal standard tissues and FFPE tissues according to the optimized protocols and fully automated
assay.
STEP 3: Full Cross-Reactivity Study
・We stain a complete set of human tissues with the optimal concentration of antibody. The resultant slides are
analyzed by experienced pathologists, and the report is generated based upon FDA recommendations.
Adrenal Gland
Bladder
Blood Cells
Bone Marrow
Breast
Brain Cerebellum
Brain Cortex
Colon
Endothelium
Eye
Fallopian Tube
Gastrointestinal Tract (Stomach)
Heart
Kidney
Liver
Lung
Lymph Node
Ovary
Pancreas
Parathyroid
Pituitary
Placenta
Prostate
Skeletal Muscle
Skin
Spinal Cord
Spleen
Testis
Thymus
Thyroid
Ureter
Uterus (Endometrium)
Uterus (Cervix)
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Immunohistochemistry (IHC)
IHC is a technique that facilitates detection of protein markers in tissue samples for diagnostic and research purposes.
ABION CRO provides a comprehensive range of high-quality IHC services from antibody screening to selection of tissue
sections best suited for testing and evaluating a wide range of IHC antibodies/biomarkers, relying on our extensive experience in optimizing IHC staining conditions.
・Optimized immunohistochemistry staining protocols (SOPs) for more than 300 types of antibodies.
・Titration of primary antibody concentration to maximize the response.
・Accurate IHC results using appropriate positive/negative controls.
・Immunohistochemistry screening
Device: VENTANA® (Roche)
A member of the Roche Group Automated IHC, ISH, and Microarray slide processing system
Human Urinary Bladder, CD24
Human Breast ca, C-erbB2
Mouse Skin, Cox-2
Mouse Liver, E-cadherin
Human Esophagous ca, EGFR
Rat Lung, eNOS
Human Colon, IGFBP3
Human Rectal ca, Ki-67
Human Lymph node, p-mTOR
Mouse Tonsil, von Willebrand Factor
Mouse Tumor, PCNA (red)&CD31 (Brown)
Mouse Tumor,
D16(Red)&Ki-67(qreen)&DAPI(blue)
Hematoxylin & Eosin (H&E) Staining
H&E staining is the most popular staining technique used for histopathological analysis of tissue sections. This staining
process yields color to visualize underlying tissue structures to show a detailed view of the tissues.
ABION CRO provides comprehensive analysis services including interpretation of slides stained with H&E using innovative technology platforms and qualified pathologists. Our services also include preservation of tissue structures, investigation of morphological changes in tissues, frozen section production, and block preparation for DNA/RNA extraction.
Device: Tissue-Tek® Prisma®E2 Automatic H&E Stain System
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Special Stains
Special stains (histochemical methods) are also used to help identify structures and substances in tissue sections.
Oil Red O
Neutral triglycerides and lipids specific staining
Masson’s Trichrome
Keratin and muscle fibers, collagen and bone, cytoplasm and cell nucleus specific staining
Alcian Blue
Staining of acidic polysaccharides such as glycosaminoglycans in cartilages and other
body structures, some types of mucopolysaccharides, sialylated glycocalyx of cells etc.
Toluidine Blue
Mast cell & myelin specific staining
Puchtler’s Picro-Sirius Red
Quantification of the amount of collagen in myocardial tissues
Prussian Blue
Detection of Iron metabolism diseases and Hemochromatosis
Congo Red
Diagnosis of amyloidosis using polarizing microscopy
Safranin O
Detection of cartilage, mucin and mast cell granules
Periodic Acid Schiff (PAS)
Detection of polysaccharides such as glycogen, and mucosubstances such as glycoproteins, glycolipids and mucins in tissues
TUNEL Assay (DAB/Fluorescence)
Detection of DNA fragmentation from apoptotic signaling cascades
BrdU Assay
Detection of proliferating cells in living tissues
* ApopTag® Peroxidase In Situ Apoptosis Detection Kit (Millipore)
* In Situ Cell Death Detection Kit (Roche)
Mouse Embryo, Sarfranin O
Human Amyloidosis, Congo-Red
Mouse Small intestine, PAS
Mouse Spleen, Prussian Blue
Rat Liver, Oil Red O
Mouse Liver, Purchtler’s Picro sirius Red
Mouse Skin, Toluidine Blue
Mouse Lung, Masson’s Trichrome
Mouse Stomach, Alcian Blue
Mouse skin, BrdU
Mouse Tumor, TUNEL(DAB)
Mouse Tumor, TUNEL(Fluorescence)
23
Slide Preparation
Tissue Microarray (TMA)
TMA-based studies enable high-throughput evaluation of tumor markers in disease. As many as 70 different tissue samples
per glass slide can be used to identify molecular targets and validate their clinical relevance in multiple tissue samples.
ABION CRO provides customized human and animal TMA services, including IHC and FISH staining of the tissue
microarrays.
Advantages of our TMA services include:
・Minimization of the edge effect of tissues using capillary gap IHC staining methods;
・High throughput Tissue Microarray services;
・Effective use in antibody screening of various tissue types;
・Fully customized TMA block package services ranging from the preparation of TMA blocks to slide preparation and IHC to meet specific research needs;
・Various core size selection according to the number of tissues and core sizes (∅: 2 mm, 1.5 mm, 1 mm, 0.6 mm).
Device: 3D HISTECH_TMA MASTER
Laser Micro-Dissection (LMD)
This method allows for the isolation and collection of specific regions or tumor cells (cancer tissues) on the
microscope. Quantitative comparative analysis is performed in conjunction with other detectors (e.g., extraction of DNAs or RNAs followed by quantitative comparative analysis using qPCR).
Device: ION LMD
[Reference]
・ Points to consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use” published in February 1997 by the FDA.
・ Guideline on Development, Production, Characterization and Specifications for Monoclonal Antibodies and Related Products”
(EMEA/CHMP/BWP/157653/2007) published in December 2008 by the EMA.
・ Testing for Cross-Reactivity of the monoclonal antibody Products for Human Use, published in January 2013 by the MFDS
24
09
ABION CRO – Devices
Devices for
Histological
Analysis
Devices
Manufacturers
Automatic digital slide scanner
3D HISTECH
Automatic H&E stain
SAKURA
Automatic IHC stain
Ventana
Automatic mounting
SAKURA
Autoprocessing
LEICA
Cryocut microtome
LEICA
Dissection Microscope
NIKON
Embedding center
LEICA
Fluorescence Microscope
OLYMPUS
Laser Microdissection
JW INT
Rotary microtome
LEICA
TMA Master
3D HISTECH
Agilent 2100 Bioanalyzer
Agilent
Agilent microarray scanner
Agilent
®
Devices for
Biological
Analysis
BioDoc-It 220 Imaging System
UVP
Bioplex-HTF
Bio-Rad
COVARIS™ DNA Fragmentation Device
Covaris
ELISA Reader (Tecan GENESIS RSP 200)
TECAN
HydroShear® DNA Shearing Device
GENEMACHNES
Ion Proton Sequencer
LT
LC-MS/MS (API4000)
AB Sciex
Microlab STARlet IVD TPS
Siemens
Microlab STARlet IVD
Hamilton
Nanodrop spectrophotometer
Nanodrop
Qubit fluorometer
invitrogen
QX200 Droplet ddPCR
BIO-RAD
Lightcycler® 480II/96, 384 (Real-Time PCR)
Roche
Roche cobas Z480 IVD
Roche
Tecan GENESIS ELISA workstation
TECAN
®
Veriti 96-Well Thermal Cycler (PCR)
Applied Biosystems
GeneAmp PCR system 9700 (PCR)
Applied Biosystems
Transilluminator
invitrogen
Surface Plasmon Resonance Systems
Reichert
Flow Cytometer (BD FACSCalibur™)
BD
Celigo® Imaging Cytometer
Brooks
Cedex Bio/cell metabolite analyzer
Roche
25
10
PATENTS
KOREA
COUNTRY
KOREA
PATENT
PATENT NO.
FILING DATE
ANTIGEN DERIVED FROM EXTRACELLULAR DOMAIN OF MULTITRANSMEMBRANE PROTEIN AND USES THEREOF
2013-0086591
2013.08.02
ANTIGEN DERIVED FROM EXTRACELLULAR DOMAIN OF MULTI-TRANSMEMBRANE
PROTEIN AND USES THEREOF
1334207
2013.11.22
DATA PROCESSING, ANALYSIS METHOD OF GENE EXPRESSION DATA TO IDENTIFY
ENDOGENOUS REFERENCE GENES
1007926
2011.01.06
HUMAN INTERFERON-BETA MUTEIN
0781666
2007.11.27
COMPOSITION FOR TREATMENT OF HPV-RELATED CANCERS
1197627
2012.10.30
COMPOSITION FOR TREATING HPV-RELATED CANCERS
2014-0018560
2014.02.13
COMPOSITION FOR TREATMENT OF CERVIX CANCER
0962301
2010.06.01
FILING DATE
INTERNATIONAL
COUNTRY
PATENT
PATENT NO.
USA
HUMAN INTERFERON-BETA MUTEIN
8101716
2012.01.24
JAPAN
ヒトインターフェロンベータ変異体
04637913
2010.12.03
BRAZIL
MUTEÌNA HUMANA DE BETA-INTERFERON
PI0517932
2008.10.21
AUSTRIA
HUMANES INTERFERON-BETA-MUTEIN
1809661
2011.05.18
CHINA
人β干扰素突变蛋白
101111519
2012.11.07
WIPO
COMPOSITION FOR TREATING CANCER ASSOCIATED WITH HPV INFECTION
2014021667
2014.02.06
EUROPE
2455878
2012.05.23
JAPAN
METHOD FOR PROCESSING AND ANALYZING GENE EXPRESSION DATA FOR SEARCHING
INSIDE STANDARD GENE
24228249
2012.11.22
USA
20140038833
2014.02.06
USA
ANTIGEN DERIVED FROM EXTRACELLULAR DOMAIN OF MULTI-TRANSMEMBRANE
PROTEIN AND USES THEREOF
20140274755
2014.09.18
USA
METHOD TO INHIBIT CANCER TARGETING CD24
08425906
2013.04.23
CERTIFICATION
2013.09.11
Excellence Award - Innovative Technology Show for Small & Medium-sized Enterprises
2013.09.27
Certificate of Registration: ISO 9001
2014.07.17
Certificate of Registration: Affiliated Research Institute
2014.08.21
Certificate of Registration: Korean Institute of Genetic Testing
2014.09.04
Certificate of Registration: Institutional Review Board (No. 1-70007010-BG-N-01)
2014.11.10
Certificate of Registration: Laboratory Safety Certificate
26
11
ABION CRO Partners
Why
Choose
ABION
CRO?
ABION CRO is one of the leading innovative CROs, serving many
of the premier biopharmaceutical companies and laboratories.
We have established a trusted partnership with our sponsors by
delivering the highest quality services and accurate test results
in a timely and cost-efficient manner. All materials, intellectual
property and confidential information of our clients are legally
protected by a material transfer agreement (MTA) and a confidential disclosure agreement (CDA). We take legal responsibility
to assure absolute confidentiality and protect our clients from
potential liability.
T. +82-2-6006-7622 F. +82-2-2621-7053
http://www.abioncro.com / [email protected]
9th FI, HanWha Biz Metro Bldg, 242 Digital-ro, Guro-gu, Seoul 152-733 Korea

Your Brilliant Partner

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