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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


Contents Research Products Disease Induction Reagents

4

ELISA Kits and Assays

5

6-7

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

Natural & Recombinant Proteins

8

Phone: Place your order by phone using the number for the corresponding office below

Cell Culture Related Kits

9

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

Antibodies

Disease Models Mode of Action

11

In Vitro

12

Inflammation

13

Neurology

14

= Whitepaper available for download

$

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

US/Canada 1000 Westgate Dr., Suite 162 St. Paul, MN 55114 651-641-1770 1-888-USMDBIO toll free 651-641-1773 fax info-us@mdbiosciences.com International and Headquarters Division of Morwell Diagnostics Postfach, Gewerbestrasse 9 8132 Egg b. Z端rich, Switzerland Tel: +41-44-986-2628 Fax: +41-44-986-2630 info@mdbiosciences.com Israel Sapir Street 3, Weizmann Science Park, Nes-Ziona, 74140 Israel Free: 1-800-200-MDB (632) Tel: +972 (0)8 9396884 Fax: +972 (0)8 9396885 info-il@mdbiosciences.com

= Request a quote

0308

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Products tools 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 analyte 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. 1. Antibody Selection 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

2. Protein selection for use as standard 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. 3. Reagents and Buffers 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 validity 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 manufacturing 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.


4

RESEARCH PRODUCTS | DISEASE INDUCTION REAGENTS

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 Reagents Description

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

Description

Size

Catalog #

Myelin Proteolipid Protein (PLP-139-151)

15 mg

301008

Myelin Oligodendrocyte Glycoprotein (MOG 35 - 55)

25 mg

3038001

Description

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

Multiple Sclerosis/EAE Induction Reagents

Adjuvants

*Other concentrations available by request. Please inquire.

ArthritoMab™ Antibody Cocktail Catalog # 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 compared 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.

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

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5

RESEARCH PRODUCTS | ELISA KITS AND ASSAYS

Enzyme-linked immunosorbent assays (elisas) can provide a useful measurement of antigen or antibody 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,” “competitive” 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

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

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6

RESEARCH PRODUCTS | ANTIBODIES

md biosciences offers monoclonal (mAb) and polyclonal (pAb) antibodies that can be used in a wide variety of applications such as:

• • • • •

Collagen

• • • • •

elisa

neutralization/blocking

immunofluorescence (ifa) immunoblot (ib)

immunoprecipitation (ip)

immunohistochemistry (ihc) flow cytometry (fc) cell sorting (cs)

western blot analysis (wb) facs analysis

Size

Application

Catalog #

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

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

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

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

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

0.5 mL

IFA, IHC, ELISA, WB

MD20191

Antibodies for Bovine Collagen

Antibodies for Chicken Collagen

Antibodies for Fish Collagen

Antibodies for Human Collagen

Antibodies for Mouse Collagen

Antibodies for Porcine Collagen Purified rabbit anti-porcine type I

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

$


7

RESEARCH PRODUCTS | ANTIBODIES 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

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 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

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

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

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

Proteases

Aggrecan

Matrix Metalloproteinases

Tissue Inhibitor of MMP (TIMP)

T cell Antibodies

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

$


8

RESEARCH PRODUCTS | Natural & Recombinant Proteins

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.

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

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

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

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

rhTIMP-1

10 ug, 200 ug

Sf-9 insect cells

5028028

rhTIMP-2

10 ug, 200 ug

Sf-9 insect cells

5028029

Proteoglycan from Septum Cartilage

1 mg

human septum cartilage

5028044

Proteoglycan from Joint Cartilage

1 mg

human joint cartilage

5028045

Protease

Aggrecan

Matrix Metalloproteinase

Tissue Inhibitor of MMP (TIMP)

Proteoglycan

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

$


9

RESEARCH PRODUCTS | CELL CULTURE RELATED KITS

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.

PCR Mycoplasma Test Kit Product 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 detection 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 electrophoresis. 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 sensitivity and specificity.

Cell Proliferation Kit Product 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

US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

$


Services

models 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 biologicals Standard 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. 1. 2. 3. 4.

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

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.

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. 2. Quality Assurance • • •

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. 3. Time • •

How long does it take from protocol design to study implementation? 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. 4. Customer Service • • • •

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.

1. Scientific Evaluation •

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

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11

DISEASE MODELS | MODE OF ACTION

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.

In Vitro Molecular Mode of Action Extracellular cues are transmitted through the cell by a network of signal 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. Concentrate on a specific pathway, such as T cell activation, or screen multiple 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 responses. 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 analysis 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.

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 expression analysis in many of our in vitro and in vivo models. Using branched DNA (bDNA) signal amplification in association with bead-based multiplex 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 sensitivity, 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 treatment 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. US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

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12

DISEASE MODELS | IN VITRO

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.

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

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

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13

DISEASE MODELS | INFLAMMATION

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 Vivo Model

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, cytokine 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 proinflammatory cytokine analysis

In Vitro Assay 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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14

DISEASE MODELS | NEUROLOGY AND PAIN

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.

Pain In 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

Model

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

Neurology

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 relapsingremitting disease course.

Figure: PLP-induced EAE model showing relapse

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Data Sheets & Technical Guides

Data sheets and technical guides detailing all of our disease models and research products.

Citations & Application Notes

References citing MD Biosciences products and applications are listed on our website. ∙ Send us your publications using one of our products and receive a free gift and discount on a future purchase. ∙ Send us your application note using our products and be featured in our monthly e-Newsletter and receive a free gift. US/Canada (888) USMDBIO | Europe (+41-44) 986 26 28 | info-us@mdbiosciences.com | www.mdbiosciences.com

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