Bio-Correlations in Clinical Trials

Bio-Correlations in Clinical Trials: TopoGEN offers powerful and tractable services to assist:

New topo targeting compounds are constantly coming and going. Clinical trials in disease specific applications are active globally. TopoGEN can help with validation, target metrics and lead optimization by providing a framework for predictive response. Here are some of our services:

We can accept cell pellets or tumor samples to quantify total cellular amounts of topoI, topoII, topoII or topoIII. We can make the extracts or we can perform the extractions. This approach offers a way to predict response and determine which patient population may or may not show clinical improvement.

To complement total polypeptide levels from Westerns, we can extract enzymatically active topoI or II to quantify the activity of tumor associated protein. Topoisomerases are subject to post-translational effectors, and it is possible to have high or low total topo polypeptide levels that do not match activity. As above, we can make the salt extracts with your pellets or we can instruct your staff on the processing.

In Vivo Link Kit (ICE Assays). This method can measure the endogenous action of topo in the tumor cell. The method is described (TG1021) and on a YouTube Video . The method is highly relevant clinically since it predicts the action of drug targeting in a cellular (chromatin) context. We direct the client on how to make the lysates and provide all required reagents. These extracts are then sent to use to quantify topo/DNA complexes in the tumor on a per genome basis.

Our Screening Services: Independent Validation, Expediency, Value

At TopoGEN, we developed, trademarked and patented many of the technologies associated with drug effects on DNA. We are leading experts at drug testing and assessment of drug action from a mechanistic standpoint. When you engage our services, we will describe and lay out a logical/rational approach that is rich in content and strongly mechanistic. We offer independent consultants who can validate our findings. Our services offer expediency and value as well. We can significantly accelerate the pace of your research, produce publication quality data and you will own the intellectual property that comes with our studies. We routinely enter into confidentiality agreements on projects, so your results are protected. Our in-house testing program is flexible and efficient. The following are important points associated with our services:

All Postitive & Negative Controls

We demonstrate internally that all testing platforms are perfectly functional. As a result, there is no guessing. Your data will be clear and unambiguous. We stand behind our findings and certify the data.

All Markers Will be Included

To document and validate the results. Again, we certify tractable results that will be internally controlled.

Testing Flexibility

We tailor each contract to offer maximum flexibility and coordinate with you over the course of the project to ensure intellectual flow of ideas and results. We will advise you on the best course of action with all hits. You can select the level of detail for the project that best suits your needs.

Over-Run Flexibility

In most if not all projects, there will be a need to re-examine, re-test or alter the course. How do we correct for work-load adjustments in the mid-stream? Our solution: we include on all projects, a small indirect “over-run fee” that will allow us to perform additional key experiments without asking for additional funds. This is an advantage for clients and ensures that our high standards of data quality will be maintained. For example, if additional testing regimens are required, we carry out the service automatically. Importantly, there is no guessing on the budget and you will not pay additional fees.

Consulting

We are a team of topo experts. All projects include email and direct SKYPE support over the course of the project. Our scientific staff will discuss and suggest future prospects or experiments.

Reporting

For complete flexibility and to ensure cost-effective contracts, we offer two levels of reporting. At a basic level, included in all contracts, we provide well-documented data (powerpoint, PDF or password protected cloud account). We draw conclusions, presented as bullets, on each slide and make a recommendation for further development and maturation of the project. For clients who wish to have a ‘manuscript’ style report, we offer fully referenced publication style reports. These reports are professionally prepared and are suitable for presentation to regulatory agencies. These publication style reports can be reviewed independently by third party opinion leaders in the field and the reviews appended to the final report.

Hands-on Experience

The company has been actively engaged in contract drug testing since the 1990s and we have the experience to get results that will enable ‘go/no go’ decision making on drug development.

Expedience

In most cases, the project will be completed over a period of several business days. We will clearly stipulate how long the project will take and we deliver on time.

A Selection of Enzymes

We can test prokaryotic and eukaryotic systems with highly purified enzymes that are well-controlled reagents. We can provide additional documentation of purity and QC on all preparations. The following enzymes or tractable antibodies are currently in our inventory:

Human DNA Topoisomerase I
Human DNA Topoisomerase IIa
Human DNA Topoisomerase II (in vivo or ICE screens only, see next item below)
Human DNA Topoisomerase III (in vivo or ICE screens only, see next item below)

Advanced Testing in Living Cells

TopoGEN is a pioneer in testing agents that operate in the context of the cell. For eukaryotic systems, we can perform rigorous testing in tissue culture cells. We offer a variety of cell lines suitable for topoI, II and II, testing. For example, we can test your drug (either as CIC or IFP) in virtually any cell line of interest.

"Dual Gel Analytical System"

TopoGEN is unique in offering this service as part of our routine testing regimen. In all projects, we design our experiments to garner new information about your compound. For example, all gels are run in duplicate. One is a non-EB gel system, used to demonstrate unambiguous catalytic activity and the other gel is an EB containing gel to parse clearly the cleavage products. Since the reactions come from the same tube, we can be sure that the results are reproducible and accurate. Importantly, the non-EB gel system also reports whether the drug is a DNA intercalator, which may suggest genotoxicity in cells.