Diagnostic Kits/Paper

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Are patents clogging the pipeline: The effects of intellectual property on commercialization and access to genetic diagnostics
(A Summary Paper of our Research to date)
By Carolina Rossini, Andrew Clearwater, and Mackenzie Cowell

Last Draft: December 3, 2009

Introduction

Description of the GDx Market

The Pipeline: Samples(MTAs?), Narratives -> Basic Research -> Dx genes & biomarkers, Narratives -> TTOs (patents) -> Commercialization (licenses) -> Trials / Peer Review -> Marketing

Questions / notes:

  • How are human tissue samples controlled during the basic research stage?
  • Are putative Dx genes and biomarkers always patented by the TTO before publication? Or are some described in literature before IP?
  • The value of a research output a TTO protects is often unclear, hence the TTO is willing to negotiate for an exclusive license to make the protected technology as desirable from a commercialization perspective as possible
    • Often small start-ups obtain exclusive licenses from the TTOs. Are they often then acquired by large corporations? Is it easier for large companies to purchase small ones w/ exclusive licenses rather than negotiating w/ TTOs to begin with?

Image of Pipeline diagram provided in: Priorities for Personalized Medicine, prepared by your Council of Advisors on Science and Technology (PCAST). Available at: http://www.ostp.gov/galleries/PCAST/pcast_report_v2.pdf

Defining Genetic Diagnostics

from Give_an_overall_picture_of_the_Kits'_sector

To quantify the Diagnostic Kit Market, we must start with a working definition. We use the phrase Diagnostic Kit to cover the In-Vitro Diagnostics (IVD) Market. The IVD market is composed of products which produce clinical data from a sample of tissue taken out of a patient (note that other diagnostic products such as medical imagers and in-vivo diagnostics are not included).

IVDs can be categorized based on the location of testing. The vast majority of routine tests are performed in-house hospital labs or in reference labs. These tests may be supplied as a complete kit to the testing laboratory or may be developed in-house with Analyte Specific Reagents (ASRs). ASR-based diagnostics are interesting because the ASRs are sold alone, without specific testing procedures, instructions, or supporting materials. Instead of purchasing a complete kit, labs (which must be CLIA high-complexity certified) purchase just the ASR and develop their own tests around it. Lastly, some kits are available directly to consumers over-the-counter. Of these, some can be operated in the home, such as pregnancy tests and blood glucose tests, while others require the user to ship a sample to a remote reference lab. DNA Direct is a company that operates in this space, providing gene-based OTC diagnostic kits that are evaluated in a remote lab.

Brief History of GDx and Related Technology

  • chemical patents at turn of century (see Palombi's work)

The recent history of the diagnostic kits market is a history of consolidation. "[T]he 1980s and 1990s saw the establishment of some 7000 independent reference labs." (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 13) By 2008 that number had collapsed to less than half with 3000 small reference labs in the U.S." (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 13) By the mid nineteen nineties there were clear leaders: Labcorp of America, Corning, and SmithKline Beecham (Beckman) (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 13) In 1997 Corning created Quest Diagnostics as an entity to hold their laboratories and in 1999 Quest Diagnostics purchased the laboratories of SmithKline Beecham (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 13) Since 1999, LabCorp and Quest have been the two largest independent labs in the U.S.

Overview of IP Landscape

Sources: Overview picture of the Kits' sector added most of kits overview & Economics of IP added all of ECO & IP


Patent Protection

20%
Understanding the intellectual property landscape requires discussion about a of a wide variety of protections including: patents, trade secrets, nondisclosure agreements, non-compete agreements, non-solicitation agreements, confidentiality agreements. While all these protections play an important role in the development of diagnostic test, patents are the most important protection. The results of a study carried our by Jensen and Murray shows “20% of human genes are explicitly claimed as U.S. IP” (Jensen, K. & Murray, F., 2005). The patent coverage is not evenly distributed. “Although large expanses of the genome are unpatented, some genes have up to 20 patents asserting rights to various gene uses and manifestations including diagnostic uses, single nucleotide polymorphisms (SNPs), cell lines, and constructs containing the gene” (Jensen, K. & Murray, F., 2005). These areas of concentrated patent protection raise concern about the possibility for a patent thicket to develop. Basically, if we stand on the shoulders of giants and build upon the innovations of others, then "a dense web of overlapping intellectual property rights that a company must hack its way through in order to actually commercialize new technology" acts as a barrier to innovation. (Shapiro, 2001) The rise of patent protections over genetic testing research has to potential to cause labs to decline to develop new tests and stop their current genetic test offerings. (Cho et al. 2003) Patenting of genetic testing can “increase the costs of genetic diagnostics, slow the development of new medicines, stifle academic research, and discourage investment in downstream R&D” (Jensen, K. & Murray, F., 2005) Concern over patent thickets may be premature. Esther van Zimmeren et al. found conflicting information about the existence of a patent thicket. (Esther van Zimmeren et al. 2006) The Committee on Intellectual Property Rights in Genomic and Protein Research and Innovation (US National Research Council of the National Academies) concluded there is "no substantial evidence for the existence of a patent thicket or a patent-blocking problem in genetics." [1] On the other hand, patent holders of gene based diagnostics are more active in asserting their patents which gives some support for the conclusion that diagnostic kit research is currently being inhibited. (Esther van Zimmeren et al. 2006)

Market Structure
Merz claims market structure is primarily influenced by "the number of patents related to a test", "the simplicity of a test may favor pure competition", and "prevalence of a disease or condition." (Merz, J.F., 1999) Merz is most concerned with the effect of patents on the market structure. (Merz, J.F., 1999)

Patents as Incentives
In order for patents to justify the monopoly they allow, the need for the monopoly as a market incentive to innovate is often cited. Genetic diagnostic kits specifically may not fit within this justification. "Several reports from national and international bodies note that genetic testing applications require far less investment after initial gene discovery than development of therapeutic proteins, and so the rationale for exclusive intellectual property rights may be less compelling." (Pressman, L. et al., 2006) Merz also found that there is evidence that patents are not necessary for the quick transformation of the genetic markers to a clinical test. (Merz, J.F. et al., 2002)

Market Patent History
"Myriad Genetics, Athena Laboratories (now part of Thermo Fisher) and Nymox Pharmaceuticals were among the first companies to offer their patented and proprietary assays as a service in their own laboratories." (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 26) When patenting of genetic diagnostic kits began, the practice was considered controversial. The lack of access was "seen as unethical and preventing widespread access to what were considered important tests. Further, both companies pursued labs that infringed on their patent positions by offering these tests and threatened litigation." (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing page 26) The widespread controversy over these patent protections has diminished over time but still continues on a smaller scale.

Insert Patent Filings Chart

SACGHS

  • Report
  • Criticism of the report

The US Secretary’s Advisory Committee on Genetics,Health, and Society (SACGHS) has recommended the “creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient care purposes”.146 A more convoluted and narrow exemption could not have been thought up and it begs the question: how can an independent committee made up of experts in the fields of intellectual property law and the relevant sciences conclude that a human gene is an ‘invention’ and therefore legally entitled to patent protection? Is not the patent system only about protecting ‘inventions’ and not discoveries? ( PCAST, 2008, page 28)

The President's Council of Advisors on Science and Technology (PCAST) believes there is a need for strong intellectual property rights fro genomics-based molecular diagnostics. They recently prepared a report on genomics-based molecular diagnostics and concluded that "[t]he ability to obtain strong intellectual property protection through patents has been, and will continue to be, essential for pharmaceutical and biotechnology companies to make the large, high-risk R&D investments required to develop novel medical products, including genomics-based molecular diagnostics." (PCAST, 2008, page 21) The counsel's genomics-based molecular diagnostics patent concerns included: the common law development of a more restrictive nonobviousness standard, the possible nonpatentability of diagnostic correlations, an expanding research and development exemption, the increased difficulty of injunctive relief, and the proposed but unpassed Patent Reform Act of 2007. Some of these concerns don't seem to match the reality of recent caselaw and practice. For example, the §271(e)(1) safe harbor and common-law research exemption have arguably narrowed in the last decade. In the 2002 case the court stated that "the district court had an overly broad conception of the very narrow and strictly limited experimental use defense" Madey v. Duke. 307 F.3d 1351 (2002) More recently, the Supreme Court addressed this issue and added that § 271(e)(1)'s exemption from infringement does not categorically excludes "either (1) experimentation on drugs that are not ultimately the subject of an FDA submission or (2) use of patented compounds in experiments that are not ultimately submitted to the FDA. Under certain conditions, we think the exemption is sufficiently broad to protect the use of patented compounds in both situations." but this hardly seems like an expanded exemption. (Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005)) (PCAST, 2008, page 21) The counsel strongly recommended a follow up study to address patent laws issues but no public notice of the implementation of this recommendation was found.


Bayh-Dole

AUTM

BIO BIO is the largest biotechnology organization in the world. BIO is strongly in favor of the patent protection of university research.(Source: Biotechnology Industry Organization (BIO)) A BIO member surbey "shows that university-based technology transfer serves as a foundation for the creation of many biotechnology companies and industry job growth. Half of surveyed companies were founded on the basis of obtaining an in-license agreement with significant, subsequent job growth." (Source: Biotechnology Industry Organization (BIO))

Licensing

When IP Does and Does Not Work Effectively

Our Research Questions

Our Methodology

Literature Review

Forces affecting the GDx Industry

Revolutionary technical advances

Regulatory process

payer system (public & private insurance)

Intellectual Property

Patenting Trends

  • 'Patents

The market for genetic diagnostic kits shows a trend towards consolidation (Diagnostic Test Service Commercialization in Multiplex and Esoteric Testing) At the same time, there has been "an increase in patents on the inputs to drug discovery (“research tools”)." (Cohen et. al., 2003) Despite this increase in patents in patent activity, no substantial patent barriers have been found as a result of this increase in patents on the inputs to drug discovery (Cohen et. al., 2003). There has been incongruity between the concern expressed about patents and empirical evidence from recent studies. In fact, The perception of rising patent litigation rates in the area of DNA-based patents is most likely false (Mills, A.E. & Tereskerz, P., 2008) A recent study found that the rate of litigation involving genetic patents has decreased in recent years. “Between 2000 and 2005, the rate of patent litigation for the patent classifications studied dropped significantly from 14/3,827 to 1/2,772” (Mills, A.E. & Tereskerz, P., 2008)


START HERE

Palombi, L. The Search for Alternatives to Patents in the 21st Century. (2009) Available at http://cgkd.anu.edu.au/menus/publications.php#palombi "are patent monopolies the most efficient and effective form of encouraging innovation and capacity building?" page 3

SEE ALSO Gene Cartel



  • Justifiable scope of protection for gene patents
    • This topic is rarely discussed in the literature (Verbeure, et al., 2005) but the implications of broad or narrow claim recognition are important to our research.

move this?

  • Bayh-Dole

The Bayh-Dole Act may not be serving its purpose in the genetic testing context. If genetic research is inhibited by current patenting behaviors then the fact that at least one study found “[t]he majority of the patent holders enforcing their patents were universities or research institutes, and more than half of their patents resulted from government-sponsored research” means that the act holds a central role in creating a barrier to access (Cho et al. 2003). While Cohen et. al. found substantially no patent barriers to university research there was "some evidence of delays associated with negotiating access to patented research tools, and there are areas in which patents over targets limit access and where access to foundational discoveries can be restricted. There are also cases in which research is redirected to areas with more intellectual property (IP) freedom. Still, the vast majority of respondents say that there are no cases in which valuable research projects were stopped because of IP problems relating to research inputs." (Cohen et. al., 2003)

Petitions for march-in rights are allowed under the Bayh-Dole Act (U.S.C. 203). The right can be exercised by the funding agency and it allows the agency to require the rights holder grant additional licenses to other reasonable applicants and if this is refused, the funding agency may make reasonable grants themselves. This grant is limited to four situations under that statue:

  1. "action is necessary because the contractor or assignee has not taken, or is not expected to take within a reasonable time, effective steps to achieve practical application of the subject invention in such field of use;" (U.S.C. 203)
  2. "action is necessary to alleviate health or safety needs which are not reasonably satisfied by the contractor, assignee, or their licensees;" (U.S.C. 203)
  3. "action is necessary to meet requirements for public use specified by Federal regulations and such requirements are not reasonably satisfied by the contractor, assignee, or licensees; or" (U.S.C. 203)
  4. "action is necessary because the agreement required by section 204 has not been obtained or waived or because a licensee of the exclusive right to use or sell any subject invention in the United States is in breach of its agreement obtained pursuant to section 204." (U.S.C. 203)

This check on patent power sounds powerful in theory but it has been weak in practice. March-in rights have been petitioned for several times in the history of the act but they have never been used.

The National Institutes of Health has received several public request that have provided some precedent for evaluating when march-in rights are appropriate. In 1998 CellPro petitioned for the use of march-in rights claiming "Hopkins and Baxter have failed to take reasonable steps to commercialize the technology" (In the Case of Petition of CellPro, Inc.) CellPro requested that a license be given to them because the current license holders, Becton-Dickinson and Baxter Healthcare Corporation, had taken effective steps to achieve practical application within a reasonable period of time and a public health need warranted march-in rights to be used. At the time of the request, CellPro was the only company that had an FDA-approved device commercially available. (In the Case of Petition of CellPro, Inc.) The National Institutes of Health evaluated whether, "(1) Baxter has failed to take, or is not expected to take within a reasonable time, effective steps to achieve practical application of the subject inventions; and, (2) there exists a health or safety need which is not reasonably satisfied by Hopkins or Baxter" and found that the use of march-in right was not appropriate for the situation. (In the Case of Petition of CellPro, Inc.) As a result of this decision to not exercise march-in rights, and the earleir patent infringement case brought by Johns Hopkins, CellPro was driven out of business. (policy flaws complicate commercialization of federally funded university discoveries)

In 2004, The National Institutes of Health received another request to exercise it's march-in rights. (In the Case of NORVIR) Essential Inventions, Inc. requested the exercise of march-in rights and requested a license to use six patents related to the manufacture of ritonavir used for the treatment of patients with HIV/AIDS. A price increase in Norvir® was alleged to have anti-competitive effects. (http://www.ott.nih.gov/policy/March-in-norvir.pd%7C In the Case of NORVIR) The National Institutes of Health responded saying that "it is important to the NIH that pharmaceutical companies commercialize new health care products and processes incorporating NIH-funded technology thereby making the technology available to the public. A central purpose of the Bayh-Dole Act involves the development and commercialization of such products out of federally-funded research." (http://www.ott.nih.gov/policy/March-in-norvir.pdf In the Case of NORVIR) The NIH denied the petition finding no grounds to exercise its march-in rights because ritonavir had reached practical application and there wasn't a health need that warranted the use of the rights. (http://www.ott.nih.gov/policy/March-in-norvir.pdf In the Case of NORVIR)

Also in 2004, The National Institutes of Health received letters concerning the high price of Xalatan in the United States as compared to Canada or Europe. In the Case of Xalatan Xalatan is a treatment for glaucoma and "is covered by licenses and patents and marketed by Pfizer for the treatment of patients with Glaucoma." In the Case of Xalatan The National Institutes of Health found Xalaton to be similar to the two proceeding cases and concluded that the standard for achieving practical application of the applicable patents had been met. In the Case of Xalatan

Case Law

The bounds of patentable subject matter are constantly being being developed through case law. The caselaw that specifically comments on the patentability of diagnostic processes often revolves around the "the machine or transformation of nature test. A patent must meet the requirements of subject matter, novelty, nonobviousness, utility, and industrial application.

  • not patentable subject matter: law of natures, natural phenomenon, or abstract ideas
  • Prometheus Laboratories, Inc. v. Mayo Collaborative Services 2009 WL 2950232 C.A.Fed. (Cal.,2009)
    • decided September 16, 2009
    • Issue: Whether the claims are patentable?
    • Facts: patents claiming methods for calibrating proper dosage of drugs
      • Prometheus sued Mayo for infringement of the patents
    • Reasoning:
      • "A process is not patent-eligible if it claims 'laws of nature, natural phenomena, and abstract ideas.'"
      • "An application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.’“ Bilski, 545 F.3d at 953
      • The step must not be insignificant
    • Holding: the "methods of treatment claimed in the patents in suit squarely fall within the realm of patentable subject matter"
    • News Reaction:
      • Patent Docs: Biotech and Pharma Patent Law and News Blog:Medical Diagnostics Claims Are Patentable Subject Matter

        "Over the past few years, Federal Circuit decisions in In re Bilski and Classen Immunotherapeutics, Inc. v. Biogen Idec, combined with Justice Breyer's dissent in Laboratory Corp. v. Metabolite Labs., Inc. ("LabCorp"), have created more than a frisson of anxiety in the biotechnology and medical diagnostics community, due the apprehension that medical diagnostics claims might generally be deemed not to be patent-eligible subject matter under 35 U.S.C. § 101. These fears may be alleviated to some degree by the decision today in Prometheus Laboratories, Inc. v. Mayo Collaborative Services, where the Court held that a diagnostics claim satisfies the machine-or-transformation test enunciated in Bilski."

      • Harvard Journal of Law & Technology:The Federal Circuit Provides Protection to Medical Diagnostics

        "The Federal Circuit’s successful application of the Bilski “machine-or-transformation” test to the treatment method in Prometheus secures patent protection for the medical diagnostics industry. This security may be temporary however as the diagnostics industry anxiously awaits the Supreme Court’s review of Bilski later this year."

      • Genetic Engineering & Biotechnology News Court Ruling May Impact Life Science Patents

        "Further, the Federal Circuit’s footnote 26 suggests indirectly that the patentability of certain medical diagnostic process claims could be challenged under Bilski... In Classen Immunotherapies, Inc. v. Biogen IDEC, Fed. Cir. No. 2006-1634 (December 19, 2008) process claims related to risk-assessment of protocols for vaccination followed by immunization were found to be invalid for not meeting either of requirements (1) or (2) under Bilski. The Classen decision is nonprecedential however, and the single paragraph opinion leaves many speculating how to interpret it."

  • Prometheus Labs., Inc. v. Mayo Collaborative Servs. (pdf), 2008 WL 878910 (S.D. Cal. Mar. 28, 2008)
  • Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co. (pdf) 560 F.3d 1366 C.A.Fed. (Mass.),2009
    • ARIAD PHARMACEUTICALS, INC., Massachusetts Institute of Technology, The Whitehead Institute for Biomedical Research, and The President and Fellows of Harvard College, Plaintiffs-Appellees, v. ELI LILLY AND COMPANY, Defendant-Appellant.
    • Facts:
      • Infringement action
      • Patent claims a methods with a single step for reducing Nuclear Factor Kappa B (NF-kB) activity in eukaryotic cells.
    • Holding:
      • patent is invalid, failed to provide adequate written description
    • News Reaction:
  • Classen Immunotherapies, Inc. v. Biogen IDEC, 304 Fed. Appx. 866 (Fed. Cir. 2008)
    • "In light of our decision in In re Bilski, 545 F.3d 943 (Fed.Cir.2008) (en banc), we affirm the district court's grant of summary judgment that these claims are invalid under 35 U.S.C. § 101. Dr. Classen's claims are neither “tied to a particular machine or apparatus” nor do they “transform[ ] a particular article into a different state or thing.” Bilski, 545 F.3d at 954."
  • In re Bilski, 545 F.3d 943 (C.A.Fed., 2008.)
    • a trading method, not a diagnostic test method was analyzed
    • the test that governs whether a process qualifies patentable subject matter under 35 USC 101.
  • In re Fisher, 421 F.3d 1365, 1371 (Fed.Cir. 2005)
    • involved “expressed sequence tags” ESTs
    • EST claims were held invalid for lack of enablement and utility
    • Patent non-gene sequences has been made more difficult by this case.
  • Lab. Corp. of Am. Holdings v. Metabolite Labs., Inc., 370 F.3d 1354 (2004)
    • Facts: processes for testing a patient and correlating the test data with the patient's health. This correlation required mental reasoning by the physician.
    • Issue:the patentability of a diagnostic process but the case was decided on other grounds the Supreme Court dismissed after initially granting certiorari and hearing oral arguments, in the dissent to the Supreme court dismissal, the process was characterized as unpatentable natural phenomenon
    • Prometheus used its own “machine or transformation” test and found Labcorp to be nonbinding.
  • Diamond v. Chakrabarty, 447 U.S. 303 (1980)
    • recognized the patentability of a genetically engineered bacteria
    • patentable subject matter under § 101 embraces “anything under the sun made by man.” Chakrabarty, 447 U.S. at 309
    • Courts "should not read into the patent laws limitations and conditions which the legislature has not expressed.” Chakrabarty, 447 U.S. at 308.
  • Gottschalk v. Benson, 409 U.S. 63 (1972) ... 9
    • Holds unpatentability due to preemption of every possible implementation that could come from recognizing a fundamental principle.
    • Test: whether the machine or transformation is central to the purpose of the claims.
    • “Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Bilski, 545 F.3d at 952, citing Benson, 409 U.S. at 67
  • Funk Brothers v. Kalo, 333 U.S. 127 (1948) ... 10-11, 15
    • “If there is to be invention from such a discovery, it must come from the application of the law of nature to a new and useful end.” Funk Brothers v. Kalo, 333 U.S. 127, 130 (1948).
    • A transformation of matter that is part of a natural process remains “the handiwork of nature” and is not patentable. Id. at 131.
    • Basic scientific facts “are part of the storehouse of knowledge of all men.” Funk Bros., 333 U.S. at 130.
  • O'Reilly v. Morse, 56 U.S. 62 (1853)
    • Facts:
    • Morse was the first and original inventor of the electro-magnetic telegraph, for which a patent was issued to him in 1840, and reissued in 1848. His invention was prior to that of Steinhiel of Munich, or Wheatstone or Davy of England. O'Reilly, 56 U.S. at 62
      • Claim 8 that was foudn to be invalid: ‘I do not propose to limit myself to the specific machinery or parts of machinery described in the foregoing specification and claims; the essence of my invention being the use of the motive power of the electric or galvanic current, which I call electro-magnetism, however developed, for making or printing intelligible characters, signs or letters at any distances, being a new application of that power, of which I claim to be the first inventor or discoverer.’ O'Reilly, 56 U.S. at 62
    • Holding:
      • "he claims an exclusive right to use a manner and process which he has not described and indeed had not invented, and therefore could not describe when he obtained his patent. The court is of opinion that the claim is too broad, and not warranted by law." O'Reilly, 56 U.S. at 113

Proposed Alternative Protection Schemes

  • Patent Pools
  • Patent Clearing Houses

Licensing

  • Licensing Approaches

Van Overwalle defines four licensing approaches (Geertrui Van Overwalle et al., 2005) First, access to the genetic sequences is free but commercial test kits require a royalty. Second, the license for the commercial test kit to labs is set at a price that makes access to the genetic sequences more expensive. Third, an exclusive license is given to laboratories in a way that limits access. Lastly, there are open licenses which allow improvements to the patent to be shared as a way to facilitating cooperative invention (ie. Biological Innovation for Open Society). Given these options presented by Van Overwalle, there were several trends in licensing behavior that are important to the development of genetic diagnostic tests. The likelihood of granting a license for patented DNA sequences was found to be similar for firms and nonprofits but nonprofits were far more likely to grant exclusive licenses. This use of exclusive licensing demands further study to find out if the use of these licenses is justified or merely a default practice with little substantive justification. (Henry, M. et al. 2002) Next, it is important to consider that changes in patent ownership and licensing complexities can have measurable effect on the development and performance of genetic testing. (Merz, J.F. et al., 2002) A industry trend towards greater complexity has not been shown but Merz demonstrates a case where the transaction costs due to changes in patent ownership and licensing reduced innovation and research for that area of genetic diagnostic tests.

  • Licensing Behavior

Licensing behavior varies by entity. The study conducted by Henry et. al found that for profit and non-profit entities approach patent and licenses differently. (Henry, M.R. et. al., 2003) Patenting behavior of for-profit entities showed a tendency towards filling patent applications for all new technologies and then deciding what to pursue based on commercial interest. Non-profit entities, on the other hand, were more selective about when to apply for a patent. Licensing behavior was found to be fairly uniform with both types of entities, licensing was most often used as a method of commercialization with licensing for research was very infrequently. Despite these similarities, nonprofits were more than twice as likely to license exclusively as compared to for-profit companies (Henry, M.R. et. al., 2003).

Licensing behavior can have a measurable effect on the development and performance of genetic testing laboratory studies. Many changes in ownership and degree of patent enforcement lead to market confusion, which has a chilling effect on new and current research. (Merz, J.F. et al., 2002) On the other hand, these licensing effects may actually be a decrease in market rather than effects of licensing behavior (Merz, J.F. et al., 2002)


  • Compulsory Licensing

Trade Secret

  • The importance of this was made clear in our interview with Andrew W Torrance
  • Trade Secret is used to early development, and it supplements patent protection later in the value chain
  • Strong confidentially, non-solicitation, assignment, & Noncompete Agreements enable the protection of Trade Secret data.
  • Even with a patent license, the knowledge transferred by the patent is often not enough to reverse engineer

MTA

Material Transfer Agreements (MTAs) are contracts that governs the transfer of research materials. [2] The agreement describes the rights that are being given, as well as those rights which are withheld, when the material is transferred. Biological materials are often transferred under agreement between universities as well as companies. The transactional barriers associated with material transfer are a cause for concern in other areas of laboratory science but their specific affect on genetic diagnostic kits is probably limited.

START HERE

  • Access to Bio-Knowledge: From Gene Patents to Biomedical Materials
    • "Recent empirical studies, however, indicate that access to materials is a much more serious problem than patents are for basic biomedical researchers, and access to materials is also a critical problem for producers of biomedical end products like biopharmaceuticals." (quoting the abstract)
    • Specific Legislative Efforts
      • Genomic Research and Diagnostic Accessibility Act of 2002 (proposed)
      • The Genomic Research and Accessibility Act of 2007 (proposed)
    • Definition of Biological Knowledge
      • Yochai Benkler’s framework for knowledge classification (page 26)
        • information
        • human knowledge,
        • information-embedded tools
        • information-embedded goods
      • Patent information protects: usually "sequence and function of a given gene" which does not prevent an access problem to basic research (page 28)
      • The access problem is in "information-embedded tools"
        • See Zhen Lei, Rakhi Juneja & Brian D. Wright, Patents Versus Patenting: Implications of Intellectual Property Protection for Biological Research, 27 NATURE BIOTECHNOLOGY 36, 37 (2009) (a survey of ninety-three US agricultural biology faculty)
          • barriers found:
            • not patents
            • material transfer agreements (MTAs)
              • use has increased
              • delay has increased: "Thirty-four faculty (42%) experienced a total of ninety-seven delays in research, with an average delay of 8.7 months" (page 28 of [3])
        • John P. Walsh, Wesley M. Cohen & Charlene Cho, Where Excludability Matters: Material Versus Intellectual Property in Academic Biomedical Research, 36 RES. POL’Y 1184, 1191 (2007)
          • Of the academics surveyed, "about 75% had made at least one request for materials or data in the past two years, but 18% of requests to academics and 33% of requests to industry went unfulfilled (page 29 of [4]
          • non-compliance with MTA requests is an important barrier
        • This access problem is governed by social norms
          • Adhering to this norm increases the transaction cost of sharing
          • How can this cost be reduced? "This cost may be reduced both through initiatives to streamline the contracts covering transfers and through increased use of material depositories." (page 34 of [5])
          • Possible Solution: Science Commons Biological Materials Transfer Project

Existing and Evolving GDx Models

Commercialization of Basic Research

  • Licensing of research to existing GDx company
  • Licensing of research to new GDx start-up
  • Usage of research in public domain by existing GDx company? (multiplex kits?)

Paths to Market

  • ASRs
  • Kits
  • DTC

Discussion

Why is there a lack of empirical evidence about patents as a barrier to innovation?

Case Studies

Myriad

  • The ACLU Case (Association for Molecular Pathology, et al. v. United States Patent and Trademark Office, et al.)
    • [Rights and Civil Wrongs: The ACLU Lawsuit]
    • [Challenges Patents on Breast Cancer Genes]
    • mutations: BRCA1 and BRCA2
    • As a result of the PTO granting patents on the BRCA genes to Myriad Genetics, Myriad's lab is the only place in the country where diagnostic testing can be performed (ACLU Challenges Patents On Breast Cancer Genes)
    • "Myriad's monopoly on the BRCA genes makes it impossible for women to access other tests or get a second opinion about their results, and allows Myriad to charge a high rate for their tests - over $3,000, which is too expensive for some women to afford." (ACLU Challenges Patents On Breast Cancer Genes)
    • Obstacles to the lawsuits success: (Patent Rights and Civil Wrongs: The ACLU Lawsuit)
      • genes are considered patentable subject matter (see Diamond v. Chakrabarty).
      • Standing: "none of the plaintiffs who sued Myriad have themselves been sued for infringing Myriad’s patents." (Patent Rights and Civil Wrongs: The ACLU Lawsuit)

Conclusions

Possible Solutions

Bibliography

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