Diagnostic Kits/Interviews

Interviews with experts. Questions:

1. What are diagnostics kits?
2. What is the typical development pipeline for a diagnostic?
3. At what stages in the pipeline is there IP activity?
4. Is there a "pipeline problem" for diagnostics?

Jim Hardy

Jim Hardy
Hemacell Perfusion
4539 Metropolitan Court
Frederick, MD 21704
(301) 639-6718

contacted 8/27/09 (headset not working, had to take paper notes)

• Jim was involved in the commercialization of the first FDA-approved DNA diagnostic test. It discriminated between benign and cancerous HPV tumors.
• Involved radiolabeled southern blot (IP protected)

Mark Redmond (via LinkedIn)

I solicited answers in response to my Research Question through a variety of avenues, including LinkedIn. Mark Redmond responded:

Dear Mac,

This is a question with a broad spectrum of answers since diagnostic kits are a broad spectrum of product. Speciality companies as well as general laboratory suppliers distribute Kits. Some kits are available in pharmacies and drug stores for testing for flu, diabetes, etc. Complex tests may also be performed by sending the developer who has the expertise to use the kit as well as the detection equipment necessary to read the kit's results.

The product life-cycle is typically method development, internal validation, clinical validation, and regulatory approval.

The method is typically:

Target + Detection reagent → Detector → Result

If required, the target is captured:

Capture reagent + Target + Detection reagent → Detector → Result

There are kits for a broad range of targets ranging from hormones, infectious diseases, metabolites, antibodies, and tumour antigens to name but a few. Biomarkers has become the accepted term for disease specific

There is a lot of work required to develop the reagents and the working dilutions for each of the reagents as well as ensuring there are no undesirable high backgrounds, false positives or false negatives produced in the test.

Once assembled, the complete kit may be protectable. Detection reagents and sequence probes and the methods to produce probes for examples primers, as well as proprietary cell lines used to prepare reagents, and antibodies may be proprietary as intellectual property..

Sample preparation of the target in the form of patient samples and specimens is also critical. Sampling tools and associated equipment are the subjects of intellectual property e.g. specialized nasal swabs and capture systems for flu detection (see the Flutest reference)..

The diagnostic method is also driven by the method of detection, for example, ELISA, RIA, PCR, and fluorescence as well as the phases of detection, liquid-solid, liquid-liquid, and tissue staining on microscope slides. The latest technology drive is towards arrays for multiple target screening - this method is also called lab-on-a-chip. [Detection methods and the equipment used for the detection are the subjects of intellectual property]

A major determinant in the utility of the test is the sensitivity and specificity of the assay. The more sensitive and more specific test the more useful and valuable it will be.

Having completed the development the next stage is evaluation and validation. Two types of evaluation are performed: (1) Analytical Evaluation where performance characteristics are measured and (2) Clinical Evaluation, where clinically annotated samples are available. Clinical evaluation is the demonstration of association of test results with a particular clinical condition or prediction of treatment response. Comparisons between similar assays can be drawn using the same standard clinical samples and analytes.

Test results are provided in a standardized format for ease of submission to FDA for review. FDA review and approval is the final stage before marketing as a validated test and a medical device for a specific indication.

I hope that this is a helpful broad overview and answer to your question.

Good luck with your project.

Links:

• http://www.ibl-america.com/?gclid=CKmYqt6qwJwCFSn6agodUEelmA
• http://www.flutest.com/rapid-flu-test

Andrew Torrance

Notes taken on etherpad:

Andrew W. Torrance http://papers.ssrn.com/sol3/cf_dev/AbsByAuth.cfm?per_id=625609&reason=0 Bio: http://www.law.ku.edu/faculty/faculty/torrance.shtml (worked at Inverness Bio IT Word: Patent Rights and Civil Wrongs (Big Issue) http://www.bio-itworld.com/comment/2009/07/06/ACLU-lawsuit.html

• look into the Bilski case (can't patent human steps)
• this may determine the patentability of claims

Patent People (will come out in Columbia Journal) he will give us an early copy

Diagnositics invivo invitro ?

Basic questions (60 second answers)

What is the basic business model in the IVD industry?* Identify potential new invention demonstrate profitability of invention

What are the stages of development for an IVD?* (mac) innovation, validation, regulatory approval, clinical utility etc, marketing chassis (foundation of device / test) is often standard & relatively simple testing for antigen w/ antibodies, for instance, is actually pretty simple operation very first step is finding biomarker don't know for most diseases; difficult when disease is polygenic or multifactorial (i.e. heart disease) "most IVD profit comes from immunological-based tests, they are so simple." (mac) literature says demonstrating clinical validity of experimental markers is hard biomarkers are cryptic; so companies get a bunch of expert academics from top flight schools universities; hire as consultant; build clinical validity with these guys

(carol) are biomarkers patentable? as a chemical, often no, but method of use (for specific diagnostic, can include algorithm), yes genetic markers can be patented this way as well Experts are key after FDA approval as well Second uses (offlabel) are key to reducing FDA costs and maximizing test value experts are needed to give confidence in the secondary use By targeting inventors (and not universities) the companies are able to benefit from key innovators without illegally making agreements for inventions before they are developed.

Key Universities Stanford Harvard hospitals (not the unversity)

database for diagnostic test biomarkers for "orphan diseases" for genetic biomakers, linkage studies? hapmap? Tradesecret is used to protect biomarkers

When is there IP activity (which stages)?*

Classify the types of things being protected: (mac) measurement techniques, analytes, algorithms, trials data? biomarkers, particular diagnostic tool chassis, relevant publications http://www.bio-itworld.com/comment/2009/07/06/ACLU-lawsuit.html SSRN physiological steps paper colombia science & tech law review: "patenting people" the underlying rule is that anything that happens within the human body

Trade Secret (EXPAND THIS IF POSSIBLE/ANDREW) is used to early development, and it supplements patent protection later in the value chain Strong confidentially, non-solicitation, assignment, & Noncompete Agreements (carol) Even with a patent, the knowledge is not enough to reverse engineer Have you seen the industry trend towards consolidation effect patent behavoir? (Labcorp of America, Corning, and Beecham)

How is value anticipated in commercialization An FDA focused emplyee will often be used to make sure that in office connections are used to anticipate problems and move things along FDA testing is not as rigorous for dianostics as it is for therapeutics

Collaboration / Commons-building questions

Commons can be classified with two parameters: access and regulation. What, if any, examples of commons exist in the IVD industry?

What phases of IVD development do you envision could benefit from commons-based resources?

What forces inhibit the formation of commons-based resources? Conversely, what (potential) incentives would drive the adoption?

• Commons examples
  • Scottish government required compulsory licensing ourside of field of practice
  • FDA releases data after approval
  • Lobbying commons
    • Opportunity: platforms which are an input for innovation
    • shared use of the platform coudl be a useful form of the commons
    • why compete when the competition is not for the sale of the platform

Licensing Questions

• Are there industry norms for licensing of IVD patents
• Do these norms favor exclusive or nonexclusive licensing?
• Do these norms differ significantly for academic use as compared to commercial use?
  • cross licensing (collusion in some ways)
  • categories
  • a settlement method
  • or suing causes stocks to dips, then predatory purchasing of stock

There is a strong push towards consolidation- smaller companies aim to acquire IP for a disease and they wait to be acquired

Are patent clearing-house or patent pool models feasible in today's market? Would they cause more problems than they solve (ie. antitrust, high maintainence costs associated with administration) In the case of clearinghouses, would standardizd license use be possible? Our research ahs shown that there are efficencies involved in a common licensing scheme but is this a good fit for the IVD industry?

• No evidence of a push for this
• control over areas as units is a standard strategy
• ie. they want to own diabetes testing
• ownership of 2 out of 10 patents doesn't matter much, the aim is to move towards total ownership

Is confusion over patent ownership or enforcment a significant barrier to IVD research and development? some firms innovate through aquisition, this seems to frustrate downstream licensees. Is there a need for better reporting of patent assignment/licensing agreements?

Diagnostics is increasingly linked with theraputics (IMPORTANT BUNDLING BEHAVIOR)

• loss leading diagnostics that show that their drug is a good fit
• this is a way to create a drug market

fav questions:

• current examples of IVD commons
  • (mac) hapmap, theraputics + diagnotic pairs, common trials & validation platforms
• Andrew: look for platforms (even plastic casette / chassis) that have
• phases of IVD development that could benefit most from commons
  • will happen when government mandates sharing
• incentives & disincentives for commons development at those locations
• Are there industry norms for licensing of IVD patents?

Andrew's last words:

• diagnostics increasingly linked to theraputics
  • diagnostic identifies new market; could be given away for free as loss-leader for test-specific drugs
  • FDA doesn't regulate drugs, diagnostics, food; it regulates the CLAIMS about those things
• It is the knowledge of what to test that is valuable. The platform is known.
• (mac/carol) other people to talk to: diagnostic scientists?
• only two machines in country for tay-sachs

In-Meeting notes

The GAME: http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1411328

Carol's intro: How do stakeholders in different fields govern information with commons-based arrangements? How do actors in different field cooperate and share knowledge?

• aught they to privatize it all, or is sharing important in certain economic situations?
• first, understand value chain in given sector, main players, how consolidation happens
• then ask, where does knowledge sharing & commons-building happen on value chain?
  • in genomics, there is a lot of sharing with discovery. As it gets closer to the consumer, however, sharing happens less often.
• main classes of resources that are shared- or not: data, narratives & tools

Big Picture: what are the forces that move certain markets towards closed models or conversely open models? How can the pattern be repeated in different markets?

Bio v. Software Patent discussion discrete units (molecule) v. unclear units (algorithms) history of the field (long hisotry of patenting) v. history of the field (brief history of patenting) Biotech has culture of patenting from beginning

discusssion of quadrent model for understanding the commons

Follow Up

• Find the international classification for gene ownership
• quote about value and necessity of patents (from his slides?)
• ask about contacts who could provide more insight
• add to monthly report
• list of patented genes that are likely to be infringed (via sequencing)
• make pizza graph of top 4 companies holding patents relevant to a particular diseases