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From Our Experts

Tuesday, 28 June 2011 08:42 administrator
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From our expert - questions and answersPreclinical experiments, especially in vivo pharmacology, are by nature complex and often intricate. CrownBio recognize s that protocols, however well defined, do not always capture the insights of years of experience and ofter do not cover all contingencies. To help ensure that your experiments are successful, our experts have put together a set of frequently asked questions to help guide your initial project considerations.

At CrownBio advice is always FREE. We recommend that you take advantage of our in-house experts to design your experiments, answer your questions, and where needed, help troubleshoot your experiments. Ask anything.

Frequently Asked Questions

 

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Questions & Answers

Company History

QWhere is CrownBio located and what year was it founded? EDIT DELETE
Crown Bioscience is a USA company founded in 2006 on two pillars of expertise; structure biology and cancer biology. We ran for one year without generating revenue as we built our infrastructure to set new levels of quality and cost effective processes in place. The company's business model was based on acquiring the over 30% of expertise from deep within academic or industry and to also invest in development of unique assets to enable translational research. CrownBio's current operations and research services are performed in our wholly owned research campuses in Beijing and Taicang (just outside Shanghai).
 
QWhen did CrownBio receive AAALAC and OHLAW authorized and certification? EDIT DELETE

CrownBio-Beijing was granted with AAALAC accreditation in August 2007, and CrownBio-Taicang was accordingly granted with AAALAC accreditation in September, 2009. Both sites were granted with continuous Full Accreditation in February, 2011 after a routine 3-year-post-accrediation site visit. CrownBio received OLAW/NIH’s approval of our institution’s Animal Welfare Assurance in November, 2010.

 
QHow do I ship my compounds to Crown Bioscience? How long does it take to get there? EDIT DELETE
All materials can be shipped to our California site or directly to our research centers in China. CrownBio has strong processes in place to ensure your critical compounds are streamlined through customs and storage conditions continually monitored to ensure its integrety. Typical turnaround from our CA HQ to our sites is 4 days.  If you would like to receive detailed shipping instructions or speak with our logistics experts, simply drop an inquiry to us using the quick quote buttons.
 
QWhat is CrownBio's employee turnover rate? EDIT DELETE
CrownBio has made great investment in cultivating a culture which sustains our employees growth and incentivizes ownership of our endeavors. We lead the industry with the lowest turnover rates year over year averaging 8%. If you would like more detailed information we welcome your inquiries, simple click on the QuickQuote and our management team will get back to you promptly.
 
QWhen did CrownBio receive AAALAC accreditation and OLAW/NIH approval of Animal Welfare Assurance? EDIT DELETE

CrownBio-Beijing was granted with AAALAC accreditation in August 2007, and CrownBio-Taicang was accordingly granted with AAALAC accreditation in September, 2009. Both sites were granted with continuous Full Accreditation in February, 2011 after a routine 3-year-post-accrediation site visit. CrownBio received OLAW/NIH’s approval of our institution’s Animal Welfare Assurance in November, 2010.

 

In Vivo Pharmacology

QHow much material do I need for an efficacy study? EDIT DELETE
For efficacy study, without knowing the dose level for each group, the following formulation helps calculate the amount of compounds needed for efficacy and PK/PD studies. Efficacy study Design: 4 arms ( 10 animals per group, Balb/c mice, IP, QD X 5 for two weeks) In vivo phase XXmg/kg x 0.025kg/mouse x 40 mice x 10 doses x (1+50%)= AMOUNT 1 50%: more spare amount will be needed if the compound is formulated daily right before use. PK/PD study Design: 5 time points (3 animals per), 1 compound (15 total mice) XXmg/kg x 0.025kg/mouse x 15 mice x 1 doses x (1+50%)= AMOUNT 2 Total amount will be the summary of amount 1 and 2. CrownBio trained pharmacologists have years of experience with both small and large molecules. We can easily assist you with dosing ranges and starting points for your studies. It is often key to de-risking your project to run an MTD ( Maximum Tolerated Dose ) study prior to your full scale study. For more info on MTDs, see additional FAQ on MTDs.
 
QHow much material do I need for PK Bioanalysis? EDIT DELETE
We need ca.10mg powder for LC/MS method development for sample analysis. If you do not have bioanalytical method developed, we need more time to develop and validate this specific method as the compound is a peptide which is totally different from small molecule..
 
QWhat is a T/C value mean? EDIT DELETE

The T/C value (i.e., treated to control value) is a measure of the efficacy of a drug.  In CrownBio's assay, the T/C value is determined by comparing tumor volume changes before and after treatment relative to controls. The lower the T/C value, the higher is the efficacy of the drug.

 

In Vitro Cell Biology

QWhat is difference between a relative IC50 and an absolute IC50? EDIT DELETE

The IC50 values are automatically given by the Prism software. Our other customers have also questioned this, especially when the curve can not be fitted into a typical sigmodial curve, when the IC50 values seem making no sense. I can explain this:

The definition of IC50: half maximal inhibitory concentration. it is the half maximal (50%) inhibitory concentration (IC) of a substance. [From Wiki].Seems simple enough. But when you actually go to fit data to determine these values, there are several complexities and ambiguities. [the following are excerpted from the help file of Prism software]

 
The ideal situation

This figure shows an ideal situation:

faq_01 The green symbols show measurements made with controls. The ones on the left (Blank) have no inhibitor, so define "100%". The ones on the right are in the presence of a maximal concentration of a standard inhibitor, so define "0%". The data of the experimental dose-response curve (red dots) extend all the way between the two control values. That is the ideal situation. There is no ambiguity about what IC50 means. [like the positive drugs we used in this CrownBio standardized study]

A situation where IC50 can be defined in two ways

This figure shows an unusual situation where the inhibition curve plateaus well above the control values (NS) defined by a high concentration of a standard drug. This leads to alternative definitions of IC50.

The graph below shows two definitions of the IC50.

faq_02

The relative IC50 is by far the most common definition, and the adjective relative is usually omitted.  It is the concentration required to bring the curve down to point  half way between the top and bottom plateaus of the curve. The NS values are totally ignored with this definition of IC50. This definition is the one upon which classical pharmacological analysis of agonist and antagonist interactions is based.

The concentration that provokes a response halfway between the Blank and the NS value is sometimes called the absolute IC50,  The horizontal dotted lines show how 100% and 0% are defined, which then defines 50%.  This term is not entirely standard. Since this value does not quantify the potency of a drug, the authors of the International Union of Pharmacology Committee on Receptor Nomenclature   think that the concept of absolute IC50 (and that term) is not useful (R. Neubig, personal communication). This is CrownBio's position. The concept (but not the term "absolute IC50") is used to quantify drugs that slow cell growth. The abbreviation GI50 is used for what we call here the absolute IC50.

Hope this explanation helps. Any comments or suggestions are appreciated. We think this kind of IC50 values is better, and when evaluating the compound, we should always take IC50 values, the maximal inhibition and the curve into consideration. However, if you need other forms of analysis, do not hesitate to contact us.
 

Cardiovascular and Metabolic Disease

QWhat is the advantage of cyno vs rhesus non human primate models? EDIT DELETE
Both CrownBio's  cyno and rhesus non human primate models represent the disease state of metabolic disease. One advantage of the cyno to be considered is the smaller size therefore less amount of compound. Currently CrownBio has screened and built large collection of well characterized spontaneous diabetic colonies of the cynos that are available immediately for efficacy studies.
 

DMPK

QDo you have Non Human Primates available for preclinical ADME/PK? EDIT DELETE
Yes we have both rhesus and cyno species availble to for testing.
 

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Last Updated on Saturday, 29 October 2011 05:57  

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