MD Biosciences Catalog

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P r o d u c t & S e r v i c e C a t a l o g

description

Catalog of all products and services offered by MD Biosciences

Transcript of MD Biosciences Catalog

Page 1: MD Biosciences Catalog

p r o d u c t & S e r v i c e C a t a l o g

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Disease Induction Reagents

ELISA Kits and Assays

Antibodies

Natural & Recombinant proteins

Cell Culture Related Kits

Disease Models

Mode of Action

In Vitro

Inflammation

Neurology

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Contents

Research Products

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placing an order with MD Biosciences is easy with these options:

Web: Fill out an order form at www.mdbiosciences.com/order.html

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Fax: place your order by fax using the number for the corresponding office below

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productstools for inflammation and neurology research

MD Biosciences carries products in the following categories:

Disease Induction•ELISAs•Natural & Recombinant proteins•Antibodies•Cell Culture Related kits•

Our products can be used in many applications. Visit our website to see a list of references and the applications in which they have been used. You will also find online troubleshooting guides and protocols for common applications.

Immunoassay Technology

MD Biosciences carries several Immunoassays as well as products that can be used in Immunoassay development. Immunoassays utilize the specific reaction between an antigen and an antibody and is applicable to any molecule that can elicit an antigenic response directly or indirectly. Immunoassays are widely used for specific and quantitative measurement of analytes. There are two main types of ELISAs: competitive assay (EIA) and sandwich assay (ELISA). EIAs use a single antibody to measure small molecules and is based on the principle that two reactants, labeled and unlabeled analyte, compete for binding to the limited number of antibody sites.

ELISAs work on the principle that two antibodies “sandwich” the ana-lyte to be measured. The two antibodies are optimized to be capture and detection antibodies and are typically in excess compared to the amount of antigen in the sample.

Development of Immunoassays

MD Biosciences takes into account several factors when developing ELISAs. If you are using separate reagents to develop your own ELISA then you will want to consider these factors as well.

Antibody Selection1.

One of the most important components in an ELISA is the antibody. Antibodies recognize antigenic epitopes with varying affinities. Low affinity/avidity interactions can be replaced by higher affinity/avidity interactions. The antibodies that MD Biosciences has selected for its Immunoassays bind with high affinity so that non-specific substances such as complement, heterophilic antibodies etc do not interfere.

Use these criteria when selecting an antibody for use in an ELISA:

purity of the antibody•high signal to noise ratio•affinity/avidity•coupling capacity•

Protein selection for use as standard2.

Analytes used as a standard in immunoassays need to be carefully chosen and calibrated as the analyte concentration in the sample will be compared to the standard. Accuracy is critical to allow the comparison between assays.

Reagents and Buffers3.

Immunoassay technology is based on antibody-antigen complex. Non-specific substances in the sample can often interfere with these complexes (matrix effect) which will affect the accuracy and valid-ity of the assay. Selecting and optimizing buffers can aid in eliminating or reducing this interference.

Performance Characteristics

MD Biosciences takes into consideration the above factors when manu-facturing its ELISAs to produce ready-to-use ELISAs with the following performance characteristics:

Accuracy - Criteria such as the proteins, antibodies and buffers used provides high binding affinities and minimal interference from non-specific substances giving accurate results.

Specificity - The specificity of an ELISA is the degree to which the results are not influenced by cross-reacting substances or closely related molecules. MD Biosciences tests closely related molecules in its assays to ensure high specificity.

Precision/Reproducibility - MD Biosciences evaluates the inter- and intra-assay precision as well as linearity, drift and recovery to determine the precision and reproducibility of an assay.

Sensitivity - MD Biosciences assays are manufactured to provide the greatest sensitivity allowing you to measure the lowest concentration of the analyte that is distinguishable from zero.

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4R E S E A R C H P R O D U C T S | D I S E A S E I N D U C T I O N R E A G E N T S

In vIvo dIsease models allow researchers the abIlIty to evaluate lead compounds under physIologIcal condItIons and observe InteractIons among the dIfferent cell types and tIssues that wIll closely mImIc the envIronment that the drug Is Intended for. for researchers who have the abIlIty to run In vIvo dIsease models In-house, md bIoscIences provIdes reagents and technIcal assIstance to perform the dIsease models. for those who use a combInatIon of In-house and outsourced dIsease models, they can be assured that the same reagents are beIng used by both theIr In-house labs and our contract research organIzatIon.

Arthritis Induction ReagentsDescription Size Catalog #

ArthritoMab™ Antibody Cocktail 50 mg CIA-MAB-50

Bovine Collagen Type II (lyophilized or soluble) 10 mg 804001

Chicken Collagen Type II (lyophilized or soluble) 10 mg 804002

Rat Lathrytic Collagen Type II 0.5 mg 8041001

Rat pepsin-Digested Collagen Type II 0.5 mg 8041002

pG-pS 10S 10 mg 3036001

pG-pS 100p 10 mg 3036002

Multiple Sclerosis/EAE Induction ReagentsDescription Size Catalog #

Myelin proteolipid protein (pLp-139-151) 15 mg 301008

Myelin Oligodendrocyte Glycoprotein (MOG 35 - 55) 25 mg 3038001

AdjuvantsDescription Size Catalog #

Complete Freund’s Adjuvant, 4 mg/mL* 5 mL 501009

Complete Freund’s Adjuvant, 3 mg/mL* 5 mL 501010

Incomplete Freund’s Adjuvant 5 mL 501011

ArthritoMab™ Antibody CocktailCatalog # CIA-MAB-50

Benefits of ArthritoMab™

Rapid model: • results in as little as 7 days reducing costs associated with expensive compounds, controls, scoring and administration periods

Synchronized disease onset: • animals develop arthritis at the same time, eliminating complicated administration schedules based on disease onset of each mouse in the CIA

Histology Results: • provides researchers valuable data in days com-pared to months in CIA model

Susceptibility: • susceptibility in DBA/1, B10.RIII and C57Bl strains as well as CIA-resistant mice such as Balb/c

Incidence in ACAIA goes from 0 to 100% within 48 hours of giving LPS, but incidence in CIA does not reach 100% until 10 days after collagen boost.

*Other concentrations available by request. Please inquire.

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5R E S E A R C H P R O D U C T S | E L I S A K I T S A N D A S S A Y S

enzyme-lInked Immunosorbent assays (elIsas) can provIde a useful measurement of antIgen or antI-body concentratIon. they combIne the specIfIcIty of antIbodIes coupled to an easIly-assayed enzyme such as horseradIsh peroxIdase. there are several types of elIsa assays, maInly “IndIrect,” “competI-tIve” and “sandwIch” assays where antIgen/antIbody InteractIons are detected by the enzyme whIch Is converted to a detectable sIgnal. md bIoscIences elIsas are manufactured to provIde ease of use for the researcher. our qualIty control program ensures that results are sensItIve, precIse and reproducIble.

Description Species Catalog #

ACTH ELISA human, mouse, rat ACTH.96

Aggrecanase Activity ELISA human ACT-AGG.96

Sensitive Aggrecanase Activity Assay human SEN-AGG.96

IGD Aggrecanase Activity ELISA various species IGD-AGG96

Calcitonin ELISA human CALC.96

Collagen Type II ELISA chicken/human/mouse/porcine/rat/bovine CII96

Collagen Immunohistochemistry Kit for use on cells CIIST

Mouse IgG anti-Bovine Collagen Type II ELISA mouse CIIAB96-B

Mouse IgG anti-Chicken Collagen Type II ELISA mouse CIIAB96-C

Mouse IgG anti-Human Collagen Type II ELISA mouse CIIAB96-H

Mouse IgG anti-Mouse Collagen Type II ELISA mouse CIIAB96-M

Mouse IgG anti-porcine Collagen Type II ELISA mouse CIIAB96-p

Mouse IgG anti-Rat Collagen Type II ELISA mouse CIIAB96-R

Mouse IgG2a anti-Bovine Collagen Type II ELISA mouse CII2A96-B

Mouse IgG2a anti-Chicken Collagen Type II ELISA mouse CII2A96-C

Mouse IgG2a anti-Human Collagen Type II ELISA mouse CII2A96-H

Mouse IgG2a anti-Mouse Collagen Type II ELISA mouse CII2A96-M

Mouse IgG2a anti-porcine Collagen Type II ELISA mouse CII2A96-p

Mouse IgG2a anti-Rat Collagen Type II ELISA mouse CII2A96-R

Mouse IgG2b anti-Bovine Collagen Type II ELISA mouse CII2B96-B

Mouse IgG2b anti-Chicken Collagen Type II ELISA mouse CII2B96-C

Mouse IgG2b anti-Human Collagen Type II ELISA mouse CII2B96-H

Mouse IgG2b anti-Mouse Collagen Type II ELISA mouse CII2B96-M

Mouse IgG2b anti-porcine Collagen Type II ELISA mouse CII2B96-p

Mouse IgG2b anti-Rat Collagen Type II ELISA mouse CII2B96-R

Animal COMp ELISA bovine/canine/mouse/rat/sheep A-COMp.96

β-Endorphin EIA bovine/camel/equine/human/ovine/porcine/rat EDRF.96

Erythropoeitin (EpO) ELISA human EpO.96

Leucine-Enkephalin EIA human L-ENKL.96

Human Activated MMp-13 ELISA human ACT-MMp13.96

Mouse OVA-IgE ELISA mouse OVA-IGE96

Intact-pTH ELISA human pTH.96

Rat prolactin ELISA rat RpRL.96

Substance p EIA human/mouse/rat SUBp.96

Vitamin H (Biotin) ELISA human VITH.96

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6R E S E A R C H P R O D U C T S | A N T I B O D I E S

Collagen Size Application Catalog #

Antibodies for Bovine Collagen

purified rabbit anti-bovine type I 0.5 mL IFA, IHC, ELISA, WB MD20121

purified rabbit anti-bovine type II 0.5 mL IFA, IHC, ELISA, WB MD20221

purified rabbit anti-bovine type III 0.5 mL IFA, IHC, ELISA, WB MD20321

purified rabbit anti-bovine type IV 0.5 mL IFA, IHC, ELISA, WB MD20421

purified rabbit anti-bovine fibronectin 0.5 mL IFA, IHC, ELISA, WB MD24921

Antibodies for Chicken Collagen

purified rabbit anti-chicken type I 0.5 mL IFA, IHC, ELISA, WB MD20131

purified rabbit anti-chicken type II 0.5 mL IFA, IHC, ELISA, WB MD20231

purified rabbit anti-chicken type III 0.5 mL IFA, IHC, ELISA, WB MD20331

purified rabbit anti-chicken type V 0.5 mL IFA, IHC, ELISA, WB MD20531

purified rabbit anti-chicken type IX 0.5 mL IFA, IHC, ELISA, WB MD20931

purified rabbit anti-chicken fibronectin 0.5 mL IFA, IHC, ELISA, WB MD24931

Antibodies for Fish Collagen

purified rabbit anti-goldfish type I 0.5 mL IFA, IHC, ELISA, WB MD20171-G

purified rabbit anti-salmon type I 0.5 mL IFA, IHC, ELISA, WB MD20171-S

purified rabbit anti-tuna fish type I 0.5 mL IFA, IHC, ELISA, WB MD20171-T

Antibodies for Human Collagen

purified rabbit anti-human type I 0.5 mL IFA, IHC, ELISA, WB MD20111

purified rabbit anti-human type II 0.5 mL IFA, IHC, ELISA, WB MD20211

purified rabbit anti-human type III 0.5 mL IFA, IHC, ELISA, WB MD20311

purified rabbit anti-human type IV 0.5 mL IFA, IHC, ELISA, WB MD20411

purified rabbit anti-human type V 0.5 mL IFA, IHC, ELISA, WB MD20511

purified rabbit anti-human type VI 0.5 mL IFA, IHC, ELISA, WB MD20611

purified rabbit anti-procollagen type III 0.5 mL IFA, IHC, ELISA, WB MD23311

purified rabbit anti-human laminin 0.5 mL IFA, IHC, ELISA, WB MD24811

purified rabbit anti-human fibronectin 0.5 mL IFA, IHC, ELISA, WB MD24911

purified rabbit anti-human elastin 0.5 mL IFA, IHC, ELISA, WB MD25011

purified guinea pig anti-human elastin 0.5 mL IFA, IHC, ELISA, WB MD20513

Antibodies for Mouse Collagen

purified rabbit anti-mouse type I 0.5 mL IFA, IHC, ELISA, WB MD20151

purified rabbit anti-mouse type II 0.5 mL IFA, IHC, ELISA, WB MD20251

purified rabbit anti-mouse type IV 0.5 mL IFA, IHC, ELISA, WB MD20451

purified rabbit anti-mouse laminin 0.5 mL IFA, IHC, ELISA, WB MD24851

purified rabbit anti-mouse fibronectin 0.5 mL IFA, IHC, ELISA, WB MD24951

Antibodies for Porcine Collagen

purified rabbit anti-porcine type I 0.5 mL IFA, IHC, ELISA, WB MD20191

md bIoscIences offers monoclonal (mAb) and polyclonal (pAb) antIbodIes that can be used In a wIde varIety of applIcatIons such as:

elIsa•neutralIzatIon/blockIng•Immunofluorescence (Ifa)•Immunoblot (Ib)•ImmunoprecIpItatIon (Ip)•

ImmunohIstochemIstry (Ihc)•flow cytometry (fc)•cell sortIng (cs)•western blot analysIs (wb)•facs analysIs•

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7R E S E A R C H P R O D U C T S | A N T I B O D I E S

Collagen cont...

Antibodies for Rat Collagen

purified rabbit anti-rat type I 0.5 mL IFA, IHC, ELISA, WB MD20141

purified rabbit anti-rat type II 0.5 mL IFA, IHC, ELISA, WB MD20241

purified rabbit anti-rat type III 0.5 mL IFA, IHC, ELISA, WB MD20341

purified rabbit anti rat type IV 0.5 mL IFA, IHC, ELISA, WB MD20441

purified rabbit anti-rat type V 0.5 mL IFA, IHC, ELISA, WB MD20541

purified rabbit anti-rat fibronectin 0.5 mL IFA, IHC, ELISA, WB MD24941

purified rabbit anti-rat elastin 0.5 mL IFA, IHC, ELISA, WB MD25041

Proteases

Human Cathepsin K polyclonal Ab 100 µL ELISA, FC, IB, IFA, IHC, Ip 2028043

Human Dipeptydlpeptidase mAb 100 µL ELISA, FC, IB, IFA, IHC, Ip 2028042

Aggrecan

Aggrecan mAb to N-terminal neoepitope ARG (clone BC3) 0.1 mg/mL WB, ELISA, IHC 1042001

Aggrecan mAb to N-terminal neoepitope DIpEN (clone BC4) 0.1 mg/mL WB, ELISA, IHC 1042002

Aggrecan mAb to N-terminal neoepitope NITEGE (clone BC13) 0.1 mg/mL WB, ELISA, IHC 1042003

Aggrecan mAb to N-terminal neoepitope FFGV (clone BC14) 0.1 mg/mL WB, ELISA, IHC 1042004

Aggrecan mAb 0.1 mg/mL WB, ELISA, IHC 1042005

Mouse anti-human aggrecan N-terminal sequence ARGSVIL 100 µL WB 1028023

Matrix Metalloproteinases

Rabbit anti-human MMp-1 (interstitial collagenase) pAb 100 µg ELISA, FC, IB, IFA, IHC, Ip 2028035

Rabbit anti-human MMp-2 (gelatinase B) pAb 100 µL ELISA, FC, IB, IFA, IHC, Ip 2028036

Rabbit anti-human MMp-3 (stromelysin 1) pAb 100 µg ELISA, FC, IB, IFA, IHC, Ip 2028038

Rabbit anti-human MMp-9 (gelatinase B) pAb 100 µg ELISA, FC, IB, IFA, IHC, Ip, RIA 2028039

Rabbit anti-human MMp-13 (collagenase-3) pAb 100 µL WB, ELISA 2028019

Mouse anti-human MMp-13 (latent & active collagenase-3, clone M53) mAb 100 µL WB, ELISA 1028020

Mouse anti-human MMp-13 (procollagenase-3, clone M33) mAb 100 µL WB, ELISA 1028021

Mouse anti-human MMp-13 (procollagenase-3, clone M66) mAb 100 µL IHC 1028022

Rabbit anti-MMp-14 (anti-MT1-MMp) pAb 100 µL WB, ELISA 2028017

Rabbit anti-MMp-15 (anti-MT2-MMp) pAb 100 µL WB, ELISA 2028018

Tissue Inhibitor of MMP (TIMP)

Mouse anti-human TIMp-2 (clone T12) mAb 100 µL WB, ELISA 1028040

Mouse anti-human TIMp-2 (clone T75) mAb 100 µL WB, ELISA 1028041

T cell Antibodies

Mouse anti-human ST2L mAb 200 µg FC, FACS, IHC, CS 101002

Mouse anti-human ST2L mAb, FITC 200 µg FC, FACS, IHC, CS 101002F

Mouse anti-human ST2L mAb, Biotinylated 200 µg FC, FACS, IHC, CS 101002B

Rat anti-mouse T1/ST2 mAb 0.5 mL FC, Ip 101001

Rat anti-mouse T1/ST2 mAb, Biotinylated 0.5 mL FC, Ip 101001B

Rat anti-mouse T1/ST2 mAb, FITC 0.5 mL FC, Ip 101001F

Rabbit anti-human IL-18R pAb 0.5 mL FACS, CS, IHC 201006

TCR, D011.10 mAb 0.2 mg/mL FC 1042006

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8R E S E A R C H P R O D U C T S | N A T U R A L & R E C O m B I N A N T P R O T E I N S

Collagen Size Source Catalog #

Bovine Collagen Type II, (lyophilized or soluble) 10 mg fetal bovine articular cartilage 804001

Chicken Collagen Type II, (lyophilized or soluble) 10 mg chicken sternum 804002

Rat Lathrytic Collagen Type II 0.5 mg, 1.0 mg rat SWARM chondrosarcoma 8041001

Rat pepsin-Digested Collagen Type II 0.5 mg, 1.0 mg rat SWARM chondrosarcoma 8041002

Protease

Human Cathepsin G 10 ug, 200 ug human neutrophils 5028033

rHuman Cathepsin K 10 ug, 200 ug E. coli 5028034

Human Neutrophil Elastase 10 ug, 200 ug human neutrophils 5028032

rhHtrA1 (his-tagged) 5 ug, 100 ug insect cells 5028031

Aggrecan

rhADAMTS4 (Aggrecanase 1) truncated, His-tagged 5 ug, 100 ug insect cells 5028001

rhADAMTS1 truncated, His-tagged 5 ug, 100 ug insect cells 5028002

rAggrecan Interglobular Domain 100 ug, 500 ug E. coli 5028003

Matrix Metalloproteinase

MMp-1 (interstitial collagenase) 10 ug, 200 ug human fibroblasts 5028024

rhMMp-2 (gelatinase A) 10 ug, 200 ug Sf-9 insect cells 5028013

rMMp-3 (stromelysin 1) 10 ug, 200 ug E. coli 5028026

MMp-9 (gelatinase B) monomer 10 ug, 200 ug human blood 5028012

rhMMp-13 (procollagenase-3) 10 ug, 200 ug Sf-9 insect cells 5028014

rhMMp-13 (collagenase-3) catalytic domain 10 ug, 200 ug E. coli 5028015

rMMp-14 ( MT1-MMp) catalytic domain 10 ug, 200 ug E. coli 5028004

rMMp-14 (MT1-MMp) prodomain catalytic domain 10 ug, 200 ug E. coli 5028005

rMMp-14 prodomain-catalytic domain hemopexin domain 10 ug, 200 ug E. coli 5028006

rMMp-14 hemopexin domain 10 ug, 200 ug E. coli 5028007

rMMp-15 (MT2-MMp) catalytic domain 10 ug, 200 ug E. coli 5028008

rMMp-15 hemopexin domain 10 ug, 200 ug E. coli 5028009

rMMp-16 (MT3-MMp) catalytic domain 10 ug, 200 ug E. coli 5028010

rMMp-17 (MT4-MMp) catalytic domain 10 ug, 200 ug E. coli 5028011

rMMp-24 (MT5-MMp) catalytic domain 10 ug, 200 ug E. coli 5028016

Tissue Inhibitor of MMP (TIMP)

rhTIMp-1 10 ug, 200 ug Sf-9 insect cells 5028028

rhTIMp-2 10 ug, 200 ug Sf-9 insect cells 5028029

Proteoglycan

proteoglycan from Septum Cartilage 1 mg human septum cartilage 5028044

proteoglycan from Joint Cartilage 1 mg human joint cartilage 5028045

the choIce to use recombInant proteIn or a proteIn from a natural source can largely depend on how much materIal Is requIred and Its ease of extractIon from the source. typIcally recombInant proteIns are over-expressed In bacterIal, yeast, Insect or mammalIan systems, gIvIng greater yIeld of pure proteIn per gram than can be obtaIned from natural sources. md bIoscIences has both natural and recombInant proteIns for use In InflammatIons research. recombInant proteIns are normalIzed for actIvIty or bIndIng affInIty wIth each preparatIon.

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9R E S E A R C H P R O D U C T S | C E L L C U L T U R E R E L A T E D K I T S

cell cultures are used every day as part of research methods. you rely on those cultures to be healthy, yet up to 35% of all cultures may be contamInated by mycoplasma. mycoplasma contamInatIon affects many cell functIons IncludIng metabolIsm, morphology, proteIn synthesIs and cell prolIferatIon. all lead to unrelIable results, lost tIme and resources. sInce contamInatIon Is not typIcally vIsIble by turbIdIty, routIne screenIng for mycoplasma contamInatIon Is essentIal.

md bIoscIences provIdes a rapId and sensItIve pcr method for monItorIng your cultures-- savIng tIme over classIc screenIng methods--as well as an assay to check for cell vIabIlIty and prolIferatIon.

Cell Proliferation KitProduct Description Size Catalog #

Cell proliferation Kit with XTT Reagent 1000 assays 409005

Cell proliferation assays are widely used in cell biology for the study of growth factors, cytokines and media components, for the screening of cytotoxic agents and for lymphocyte activation. The need for a reliable, sensitive and quantitative assay that would enable analysis of a large number of samples led to the development of methods such as:

Use of radioactive thymidine to label DNA in live cells•Use of Brdu to label DNA in live cells (as a substitute for radioactive thymidine)•

The advantages of using our cell proliferation kit can be summarized with the following attributes:

Easy-to use: there is no requirement for additional reagents and/or cell washing procedures•Speed: multiwell plates and a plate reader are used for reading results•Sensitivity: can be assayed even in low cell concentrations•Accuracy: dye absorbance is proportional to the number of cells in each well•Safety: there is no need for radioactive isotopes•

PCR Mycoplasma Test KitProduct Description Size Catalog #

pCR Mycoplasma Test Kit 20 assays 409010

pCR Mycoplasma Test Kit is designed to detect the presence of mycoplasma contaminating biological materials such as cultured cells. Mycoplasma detec-tion by the direct culture method is time-consuming, and some mycoplasma species are difficult to cultivate. With pCR testing, results are obtained within a few hours since the presence of contaminant mycoplasma can be easily detected simply by verifying the bands of amplified DNA fragments in electro-phoresis. There is no need to prepare probes labeled with radioisotopes or to calculate enzyme, dNpTs or buffer concentrations. Instead, a ready-to-use, optimized pCR mix is supplied. The primer set allows detection of various mycoplasma species (M. fermentans, M. hyorhinis, M. arginini, M. orale, M. salivarium, M. hominis, M. pulmonis, M. arthritidis, M. bovis, M. pneumoniae, M. pirum and M. capricolum) as well as Acholeplasma and Spiroplasma species with high sen-sitivity and specificity.

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Servicesmodels of inflammatory and neurological disease

Benefits of Outsourcing:

Outsourcing areas of your pre-clinical drug discovery process allows you to preserve your R&D focus, eliminates investments in expensive infrastructure, provides a wide range of scientific expertise, and increased flexibility. Recognizing your various reasons for outsourcing can aid in selecting the appropriate vendor.

Benefits to working with the Discovery Service Groups at MD Biosciences:

Quick start dates and timely delivery of data•All scientists are specialized and have experience with small molecules •and biologicalsStandard and specialized routes of administration•Customized protocols•Development of novel models•

preclinical capabilities include:

Efficacy studies in several therapeutic areas•Mode of Action platforms•Bioanalysis using immunoassay techniques•Histopathology processing and/or scoring•

Guideline to outsourcing:

Many factors including time, quality and flexibility can lead to a successful contract resource relationship. Before selecting a contract research organization (CRO), you need to have a plan developed. Start with your end objective so that you and/or the CRO can put the appropriate plan in place to reach your goals.

What is the research goal and study objective?1. Identify what drives your outsourcing needs (i.e. increased resources, 2. different scientific expertise, technology or capability)What is your timeline?3. What is your budget?4.

Having these answers in place will help you narrow down the appropriate vendor.

Choosing a CRO

Now that you know the criteria for your outsourcing, you can begin to evaluate outsourcing providers. There are a few key issues to consider when evaluating vendors.

Scientific Evaluation1.

Is the CRO an expert within your target disease(s) in order to under-•stand disease mechanisms and provide suggestions?

Does the CRO have experience with the type of molecule that you •are working with?Does the CRO have experience with the species and route of •administration?

MD Biosciences employs scientific experts in each of the disease fields we focus on. This gives you access to insight and strategies that can put your pre-clinical program on a systematic, focused and efficient progression towards clinical trials.

Quality Assurance2.

Does the CRO have complete and thorough SOps put in place?•What are the report formats?•Is the equipment maintained and calibrated appropriately?•

MD Biosciences follows a detailed and thorough SOp system for every step. All equipment is maintained and calibrated on a regular basis.

Time3.

How long does it take from protocol design to study implementa-•tion?What is the turn-around time from study completion to final •reports?

MD Biosciences is typically able to implement a study within a few weeks of an approved protocol. With outsourcing on the rise, there is an increased capacity at outsourcing facilities often causing delays up to several months, requiring you to plan around this wait time.

Once we start your study, we provide regular updates while your study is being conducted and preliminary data is available within 10 days of termination. A detailed final report is normally available within 4 weeks.

Customer Service4.

Does the CRO have good customer service?•Are responses timely, complete and helpful?•Does the CRO have a reputation for quality?•Is the CRO respected in the scientific community?•

MD Biosciences provides you with superior customer service. Upon the initial inquiry, your request is moved quickly towards the appropriate scientific director who will work with you directly to design a protocol. Our scientific staff is available to conference with your scientific staff to establish a strategy with your end objective in mind.

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11D I S E A S E m O D E L S | m O D E O F A C T I O N

the abIlIty to determIne the mechanIsm of actIon and target dIsease choIce for compounds sImultaneously Is crItIcal for decreasIng dIscovery tIme lInes and reducIng late-phase faIlures. the current approach to mode of actIon and target valIdatIon wIthIn drug dIscovery often faIls to take advantage of the systems and technologIes now avaIlable. md bIocIences offers both In vItro and In vIvo mechanIsm of actIon studIes, allowIng you to target the approprIate dIsease choIce and progress to clInIcal stages In a more systematIc, effIcIent and focused progressIon.

Capabilities

In addition to offering these capabilities as an end-readout with in vivo or in vitro services, we are also able to provide these as stand alone services.

Multiplex Testing Service

MD Biosciences utilizes multiplex assays for detection of cytokines, chemokines, growth factors, MMps, kinase/phosphorylated proteins in human, mouse or rat samples.

Benefits of using a multiplex assay:small sample size - 50 μL•up to 20 analytes within 50 μL •ability to customize desired analytes •sensitivity of 10 pg/mL offers relevant measurements•precise, accurate and reproducible results•low background and high specificity so your results withstand •scrutiny

Biomarker Analysis

MD Biosciences offers biomarker analysis as a stand alone service or as an end readout to our in vitro and in vivo efficacy studies. Biomarkers are available for:

collagen/bone markers•metabolism/obesity/diabetes•renal and liver function/lipid peroxidation/oxidative stress•inflammation cytokines and chemokines•

Gene Expression Analysis

In addition to examining protein production, we also offer gene expres-sion analysis in many of our in vitro and in vivo models. Using branched DNA (bDNA) signal amplification in association with bead-based mul-tiplex technology1, we can analyze up to 30 genes in a single sample allowing for high-throughput screening of small volume samples. Sample types include whole blood, cultured cells, fresh or frozen tissues and formalin fixed or paraffin embedded tissue. providing high sensitiv-ity, a high dynamic detection range and a high level of reproducibility, our gene expression service allows the ability to compare effects of gene induction in different tissues as well as investigate effects of drug treat-ment on disease.

Histology

H & E staining in a variety of samples such as joints, colons, lungs•pathological scoring of prepared slides •

1. QuantiGene plex 2.0 System, panomics, Inc.

In Vitro Molecular Mode of Action Extracellular cues are transmitted through the cell by a network of sig-nal transduction molecules. A compound’s mode of action can be further characterized by identifying affected pathways such as:

Identify inhibitors or agonists of cell signaling pathways by determining •the phosphorylation state of intracellular proteins such as Akt, CREB, ERK1/2, GSK-3β, HSp27, IκBα, JNK, p38 MApK, p70S6K and ZAp-70. Con-centrate on a specific pathway, such as T cell activation, or screen mul-tiple pathways at once.

Screen compounds for their ability to activate or inhibit a specific •pathway using cell lines harboring a luciferase reporter gene under the control of NFκB, STAT-1, STAT-3, Ap-1, CREB or NFAT responsive elements.

Determine second messenger levels, such as cAMp or calcium, in •compound treated cells.

Screen compounds for their ability to inhibit enzyme activity: kinase •activity, cyclooxygenase activity (COX-1, COX-2), monoamine oxidase activity (MAO), aggrecanase activity, matrix metalloproteinase activity.

In Vivo Senerga® Mode of Action

The Senerga® Mode of Action program offers the opportunity to avoid the target disease dilemma by allowing a more systematic, efficient and focused progression towards clinical studies. The effective result is the avoidance of expensive and time-consuming screens of compounds in a range of disease models. The technology behind Senerga Mode of Action enables visualization of key events that are common to all immune respons-es. By examining the common events that underlie all diseases resulting from an inappropriate immune response, not only are multiple potential target diseases screened, but the mode of action of a compound is also discovered in the process. Traditional models offer post event analy-sis whereas Senerga, through T and B cell transfer methods, offers event analysis as it happens along with mechanistic dissection.

Implementing a program such as Senerga® has an integral place in a research strategy. Compounds can be evaluated in the Senerga® program in as little as 2 weeks, simultaneously discovering the mode of action and the target disease choice. Compounds can then be evaluated for efficacy in the appropriate disease models. This provides a great advantage to compounds that are in the first discovery process as well as existing drugs that are in indication discovery.

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12D I S E A S E m O D E L S | I N V I T R O

In vItro assays are an Important tool In drug dIscovery as they offer rapId turn-around tIme for data analysIs as well as the abIlIty to evaluate multIple doses of a compound quIckly and typIcally at a lower cost than In vIvo models. In vItro cell based assays allow the researcher to quIckly Interpret and predIct many bIologIcal propertIes of a compound whIle provIdIng correlatIon to human dIsease. because In vItro assays exclude the mIcroenvIronmental Influences found In In vIvo studIes, they are an approprIate tool for use In early screenIng and In combInatIon wIth In vIvo models.

ImmuneProfiler™ In vitro screening of compounds for anti-inflammatory activity

MD Biosciences offers Immuneprofiler™ as a series of successive in vitro assays beginning with a general screen to evaluate anti-inflammatory activity in cultured primary human peripheral blood mononuclear cells (pBMCs).

Following the results of this initial screen, our immunologists will design a series of in vitro assays that will profile the immunomodulatory activity or your compound. This can then lead to mode of action studies and target disease models using an efficient and focused strategy.

Benefits:

Rapid turnaround time•Cost effective assay•potential to expand therapeutic application of an approved drug•Results include strategic outline from specialized immunologists•

Stimulants:

LpS•pHA•anti-CD3 mAb•

Analysis

Cytokine analysis by multiplex•Cell proliferation•Gene expression analysis by bDNA signal amplification•

General In Vitro Inflammation Models Species/Cell System Stimulant Assessment

General Anti-Inflammatory Screen Human pBMCs, RAW 246 macrophage LpS, pHA Cytokine panels

T cell Activation Assay Human pBMCs T cell activation cocktail Cytokine panels

Leukocyte Migration Assay Neutrophils, T cells or monocytes -- Cell migration

Endothelial Cell Adhesion Endothelial cells TNFα Bound cells

Integrin-Mediated Adhesion Leukocytes -- Bound cells

T cell proliferation Human pBMCs, murine spleenocytes anti-CD3/CD28, OVA Cell proliferation

B cell proliferaton Human pBMCs, murine spleenocytes anti-CD3/CD28, anti-Igm, LpS Cell proliferation

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13D I S E A S E m O D E L S | I N F L A m m A T I O N

md bIoscIences InflammatIon dIscovery servIces provIdes well establIshed preclInIcal dIsease models for Inflammatory dIseases such as arthrItIs, asthma, Ibd and multIple sclerosIs. our specIalIzed scIentIsts are specIalIzed and provIde you wIth In-depth expertIse to desIgn an approprIate preclInIcal program for your potentIal therapy. short lead tImes from contract to study InItIatIon and quIck turnaround tImes for data reports allow you to move through your preclInIcal program effIcIently.

In VivoModel Length Species Positive Control Assessments Options

Collagen-Induced Arthritis (CIA) 35-42 days

Various Dexamethasone, Methotrexate, Enbrel

Clinical signs, body weight, clinical score, paw measurements

Histology, cytokine analysis

Collagen Antibody-Induced Arthritis (CAIA)

7+ days Balb/c, DBA1, B10.RIII, C57BI/6 mice

Dexamethasone, Enbrel

Clinical signs, body weight, clinical score, paw measurements

Histology, cytokine analysis

Adjuvant-Induced Arthritis 35 days Balb/c or Lewis rat Dexamethasone Clinical score, body weight Histology, cy-tokine analysis, pain assessment (for rats)

Antigen-Induced RA 17 days Balb/c Dexamethasone Clinical signs, body weight, clinical score, paw measurements

Histology, cytokine analysis

DSS-induced IBD 7 days C57/Bl mice N/A Body weight, clinical observation, record of diarrhea, record of blood in feces, colon weight, colon length

Histology, cytokine analysis

TNBS-induced IBD 7 days Balb/c mice Sulfasalazine Body weight, clinical observation, record of diarrhea, record of blood in feces

Histology, cytokine analysis

SCID IBD 8 weeks SCID mice TBD Body weight, clinical observation, record of diarrhea, record of blood in feces, colon weight, colon length

Histology, cytokine analysis

OVA-Induced Allergic Asthma 16-28 days

Balb/c mice Dexamethasone Cell differentials in BALF, IgE levels, cytokine in BALF

AHR, lung histology

Lung Fibrosis 14 days C57Bl/6 mice -- BALF, lung histology, collagen staining in lung

AHR

passive Cutaneous Anaphylaxis 1 day Balb/c mice, rats Dexamethasone Evans blue dye content in ears, area and score of evans blue diffusion in skin on back

--

FITC or DNCB-induced Contact Dermatitis

14 days Balb/c mice Dexamethasone Ear thickness Histology, biopsy, weights

Oxazolone-induced DTH Model 7 days Lewis rat Dexamethasone Ear thickness Histology

LpS Lung Inflammation Model 4 hours Balb/c mice Dexamethasone Cell counts in BALF, TNFα --

Endotoxic Shock 90 min-6 hours

Balb/c mice Dexamethasone TNFα, IL-1β, cell counts in BALF Additional pro-inflammatory cytokine analysis

In VitroAssay Name Cell System Stimulant Assessment Indication

Synoviocyte Culture Assay Synovial fibroblast cells Cytokines MMps, IL-8, IL-6, GMCSF Arthritis

Bone Resorption Assay Human osteoclast precursor cells RANK ligand, MCSF Type I collagen release Arthritis

Lung Epithelial Assay Lung epithelial A549 cells TNFα, IL-1β Inflammatory mediators Respiratory

Bronchial Smooth Muscle Assay Human bronchial smooth muscle cells TNFα, IL-1β Inflammatory mediators Respiratory

Adenocarcinoma Cell Assay HT29 human adenocarcinoma cell line TNFα pGE2, IL-8, 1β-10, MIp-3α IBD

Intestinal Cell Damage Assay Caco-2 human colon adenocarcinoma cells

LpS TEER IBD

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14D I S E A S E m O D E L S | N E U R O L O G Y A N D P A I N

md bIoscIences neurology dIscovery servIces provIdes well establIshed preclInIcal dIsease models of neurodegeneratIve dIsorders such as parkInson’s and alzheImer’s dIsease, demyelInatIng dIseases of the nervous system such as multIple sclerosIs and neuropathIc, nocIceptIve, post-operatIve and Inflammatory paIn. our scIentIsts are specIalIzed and provIde you wIth In-depth expertIse to desIgn an approprIate preclInIcal program for your potentIal therapy. short lead tImes from contract to study start and quIck turnaround tImes for data reports allow you to move through your preclInIcal program effIcIently.

NeurologyModel Disease Length Strain

Acute MpTp Model parkinson’s 7 days C57/Bl mice

Chronic MpTp Model parkinson’s 8 weeks C57/Bl mice

6-OHDA Model parkinson’s 14 days SD rats

Gliosis Model Gliosis 7 days Lewis rats

MOG-Induced EAE Multiple Sclerosis 35 days C57Bl/6 mice

MBp-Induced EAE Multiple Sclerosis 14 days Lewis rats

Relapsing pLp-Induced EAE Multiple Sclerosis 21 days SJL mice

PainIn Vivo Models for Pain Type of Pain Length Strain

CCI Sciatic Nerve Ligation (Bennet & Xie Model) Neuropathic 14-28 days SD rats

Spinal Nerve Ligation (Chung Model) Neuropathic 2-5 weeks SD rats

Taxol-Induced Neuropathy Neuropathic 14 days SD rats

STZ-Diabetic Neuropathy Neuropathic 4 weeks SD rats

Carrageenan-Induced Acute Inflammatory pain Inflammatory 3-24 hours SD rats

CFA-Induced Acute Inflammatory pain Inflammatory 24 hours SD rats

post-incisional pain in rats (Brennan Model) post-operative 3-6 days SD rats

post-incisional pain in pigs post-operative 3-6 hours Domestic piglets

Tail Flick Test Nociceptive 10 minutes SD rats or ICR mice

Visceral pain (acetic acid writhing test) Nociceptive 10 minutes ICR mice

Capsaicin Nociceptive 10 minutes ICR mice

Adjuvant-Induced Arthritic pain Arthritic 28 days SD rats

PLP-Induced EAE for MS

EAE and MS are characterized by a relapsing-remitting disease course with subsequent progressive disability. EAE, common model used to study MS due to clinical and pathological similarities, is characterized by chronic inflammatory demyelination of the central nervous system and involves autoimmune CD4+ Th1 cells. These cells develop in the peripheral lymphoid organs and travel to the CNS causing an immune response. The development of T cells is controlled largely by the expression of various cytokines as well as cellular adhesion molecules. The pLp-induced EAE model is appropriate for evaluating the effect of a compound on the relapsing-remitting disease course.

Figure: PLP-induced EAE model showing relapse

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Implementing a strategy that will put your preclinical drug discovery program on a systematic, efficient and focused progression.

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Inflammations Discovery Services

Literature

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