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Tag Archives: Companion Diagnostics

Supreme Court Asked for Further Clarity on Patent-Eligibility of Diagnostic Claims

Posted by Antoinette Konski on Posted in Biomarkers; Companion Diagnostics; Personalized Medicine

Did the Federal Circuit incorrectly interpret and apply the holding of the U.S. Supreme Court’s decision regarding patent-eligibility of medical methods as set forth in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S.Ct. 1289 (2012)(“Mayo“)? Intema Ltd. (“Intema”) asserts that yes, the Federal Circuit did err when it determined that Intema’s diagnostic patent claims are invalid for failing to satisfy 35 U.S.C. Section 101. (See PerkinElmer, Inc. v. Intema Ltd., 496 F. App’x 65, 105, U.S.P.Q.2d 1960 (Fed. Cir. 2012)). Late last month, Intema petitioned the U.S. Supreme Court to reverse the Federal Circuit’s holding that the claims of U.S. Patent No. 6,573,103 are invalid as patent-ineligible under Section 101. Intema contends that the Federal Circuit erred by misapplying Mayo in a manner that creates erroneous, rigid rules for determining patent-ineligibility in cases involving laws of nature. Failure to reverse the Federal Circuit’s decision, Intema argues, will have the practical effect of rendering most diagnostic, screening and personal medicine tests unpatentable.

The ’103 Patent

U.S. Patent No. 6,573,103 (the ’103 Patent) entitled “Antenatal Screening For Down’s Syndrome” issued on June 3, 2003. All twenty-four claims relate to methods for determining whether a pregnant woman is at an increased risk of having a fetus with Down’s syndrome. Claim 1 is representative:

1. A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down’s syndrome, the method comprising the steps of:

measuring the level of at least one screening marker from a first trimester of pregnancy by:

 (i) assaying a sample obtained from the pregnant woman at said first trimester of pregnancy for at least one first biochemical screening marker; and/or

 (ii) measuring at least one first ultrasound screening marker from an ultrasound scan taken at said first trimester of pregnancy;

measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one first screening marker from the first trimester of pregnancy, by:

 (i) assaying a sample obtained from the pregnant woman at said second trimester of pregnancy for at least one second biochemical screening marker; and/or

 (ii) measuring at least one second ultrasound screening marker from an ultrasound scan taken at said second trimester of pregnancy; and

determining the risk of Down’s syndrome by comparing the measured levels of both the at least one first screening marker from the first trimester of pregnancy and the at least one screening marker from the second trimester of pregnancy with observed relative frequency distribution of marker levels in Down’s syndrome pregnancies and in unaffected pregnancies.

The Federal Circuit’s Asserted Errors

Intema argues that the Federal Circuit erred when it ignored material differences between the claims of the ’103 Patent and the claims held invalid by the Supreme Court’s Mayo decision. Such errors include, for example:

  • the failure of the Federal Circuit to recognize the claims of the ’103 Patent are more than the use of a law of nature – the claims embody the use of data gathered was completely non-standard when developed, and improved screening efficacy;
  • the failure of the Federal Circuit to acknowledge that the measuring step, achieves a simple and useful test result using statistical analysis when it wrongly characterized the measuring steps as conventional and obvious presolution activity;
  • the failure of the Federal Circuit to give proper weight to the steps of selecting the measured marker levels during two separate trimesters of pregnancy and the integration of that in a carefully specified manner;
  • the Federal Circuit’s finding that the determining step is insufficient as being a “known and conventional” algorithm;
  • the Federal Circuit’s interpretation of the “assaying” portion of the measuring steps to be insufficient to impart patent-eligibility to the claims because it could be performed without transforming the sample should science develop a totally different system for assaying for a biochemical marker that did not involve such a transformation; and
  • the Federal Circuit’s error in concluding that a transformation, if it existed, would be insufficient relying on another rigid rule excluding all transformations from consideration under Section 101.

Personalized Medicine and Diagnostic Patents

The Supreme Court’s Mayo ruling has created uncertainty for diagnostic technologies that support and promote personalized medicine. Inventions simply defined by correlating a natural biomarker with a clinical outcome or therapeutic treatment are now ineligible for patent protection as a result of the Mayo decision. For inventions that offer more than a simple correlation, patent protection may still be available. However, how much “more” is necessary to move an invention involving a biomarker and correlation to patent-eligibility is still an open question. With that in mind, more clarity and direction would be welcome, provided the Supreme Court does not take the opportunity to further restrict patent protection for these important technologies.

A copy of Intema’s petition is attached.  PerkinElmer’s reply is due June 19, 2013.

Personalized Medicine and the Gene Patenting Debate

Posted by Antoinette Konski on Posted in Gene Patents; Genetic Testing; Personalized Medicine

The transcript for today’s Supreme Court oral argument in The Association for Molecular Pathology v. Myriad Genetics, Inc., No. 12-398 (2013) has been released, and the importance of the gene patenting debate to personalized medicine was discussed. The Court was well briefed on the issues and questioned the parties and U.S. government regarding why isolated genes should or should not be patent-eligible, the distinctions between DNA probes or primers and claims to full length sequences (isolated genomic DNA and cDNA) and the difficulty in crafting a test that would exclude broadly claimed inventions under Section 101 of the patent act rather than limiting broadly claimed inventions as failing under Section 102 (novelty) and/or Section 103 (obviousness). Continue reading this entry

FDA Regulation of Laboratory Developed Tests: Benefit or Unnecessary Burden?

Posted by Antoinette Konski on Posted in Companion Diagnostics; Diagnostic Methods; FDA; Personalized Medicine; Uncategorized

The U.S. Department of Food and Drug Administration (“FDA”) has previously announced an interest in regulating diagnostic tests used in providing personalized medicine clinical care. Interested stakeholders such as the American Clinical Laboratory Association, the College of American Pathologists, and the Association for Molecular Pathology, have weighed in on whether the FDA can and should expand its jurisdiction to laboratory developed tests (“LDTs) performed by clinical laboratories. Continue reading this entry

Personalized Medicine Patenting Update

Posted by Antoinette Konski on Posted in Personalized Medicine; Prometheus

Patenting diagnostic methods is more challenging in the wake of the U.S. Supreme Court’s Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. __ (2012) (Prometheus) and the USPTO’s application of the decision, as set forth in its Guidance Document distributed to patent examiners. Patent examiners are advised to follow the Guidance Document in examining a process claim (e.g., medical method claim) in which a law of nature, a natural phenomenon, or naturally occurring relation or correlation (collectively referred to as a natural principle in the Guidance Document) is a limiting element or step. Thus, a medical diagnostic claim that correlates or relates to a genetic marker or physiological measurement (typical in personalized medicine) is subject to the Guidance Document as the claim necessarily includes an element interpreted by the USPTO as a natural principle. Continue reading this entry

Gene Patents and Diagnostics: The Economics of Innovation

Posted by Antoinette Konski on Posted in Gene Patents

The increasing importance of genetic markers and diagnostic tests in the drug approval process and the delivery of health care requires consideration of who will underwrite the necessary research and development, Michael Hopkins and Stuart Hogarth argue in the recent issue of Nature Biotechnology. “Biomarker patents for diagnostics: problem or solution?” Nature Biotechnology, Vol. 30(6): 498-500. Consistent with the biomedical model, many innovators have relied on patents and the temporary monopoly patents provide to recoup the cost of innovation, but the appropriateness of this model is being challenged. Whether are not patents covering diagnostic medical tests support or spurn innovation was considered in the U.S. Supreme Court’s Mayo Collaborative Services v. Prometheus, Inc., decision, (see our March 20th post) and is currently under review by the U.S. Patent and Trademark Office (see our January 25th post). The issue also is central to the ACLU’s challenge to the patenting of isolated DNA now before the Federal Circuit in the Association for Molecular Pathology v. Myriad Genetics et al. or the ”gene patenting case” recently sent back to the Federal Circuit for reconsideration in light of the U.S. Supreme Court’s Mayo decision (see our March 26th post.) Patents for this technology are argued to be unnecessary as the cost of providing the tests are low and could prevent clinical scientists in hospital laboratories from developing and offering their services.

A Missed Opportunity

The co-authors suggest that whatever judgments are made against gene patents, the debate thus far has missed an opportunity to consider the wider issue of diagnostic patents and their role in innovation. The conclusions drawn by the co-authors were informed by a seminar convened in London in 2010 by the Human Genetics Commission, whose membership included hospital staff, diagnostic and pharmaceutical firms, research funders, lawyers and ethicists. The co-authors also note that the context of the debate differs between Europe and the United States. However, several important points are raised by the co-authors that are relevant to the ongoing debate in the United States.

Changing Regulations

For too long, the co-authors note, the gene-patenting debate has been framed by an innovation model that assumes low regulatory barriers to market entry and an easy path to market and clinical adoption. Recent evidence suggests that low-cost and therefore easy market entry is no longer the norm. Test developers are now being asked to provide more evidence, not less, and more quickly, and conventional business models do not support large-scale trials of the utility of new biomarkers. In addition, as noted in our January 24th post, the U.S. Food and Drug Administration will begin regulating laboratory developed tests offered as companion diagnostics.

The SACGHS Report

The Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) for the U.S. Department of Health and Human Services has often been cited by those who oppose the patenting of this technology. The SACGHS committee concluded that the exclusivity provided by patents or licenses had not been necessary to ensure that tests were developed and made available to patients. What is lost in the discussion but noted by Hopkins and Hogarth is that the evidence informing the SACGHS report and conclusion was mainly limited to tests for the diagnosis of rare genetic disorders. Tests related to, for example, infectious agents and drug metabolism were neglected in the SACGHS analysis. The co-authors report that the approach SACGHS took on framing the issues and evidence split their committee, with dissenters writing that the burden of regulatory compliance and the need for clinical utility were pushing up R & D costs for test development. IP was therefore required to incentivize companies to invest in this technology.

Who Will Pay for Personalized Medicine?

The co-authors also argue that extensive evidence is necessary for a biomarker’s acceptance by drug regulators and health care providers. Such evidence includes, for example, that the biomarker accurately and reliably identifies the target population. If the biomarker is tied to a drug under development by a pharmaceutical company, the drug company has the economic incentive to fund the necessary research.  IP can serve additional strategic roles – stakeholders such as diagnostic developers, pharmaceutical companies and regulators are increasingly eager to control who provides diagnostic tests in the future, because safe, speedy and effective prescription of drugs will depend on reliable diagnostics. However, if the test is not tied to the company’s drug, incentives to fund the development of the diagnostic are less obvious. Hopkins and Hogarth cite the case of Roche’s AmpliChip CYP450 as an example of a test that has been approved by the FDA but not widely adopted because follow-up studies to establish its clinical utility were not completed. Although Roche shepherded the test through the FDA, it did not invest in the necessary clinical studies demanded for wide-spread adoption of the technology. The co-authors note that Roche holds no patents or exclusive licenses on the genes encoding CYP450 and that therefore any investment it makes in building the clinical evidence would also benefit rival companies who have entered the CYP450 market or are preparing to do so.

No Easy Answers

Hopkins and Hogarth provide no simple solution to the question of what should be done to ensure that well-validated diagnostics are made available to patients. They encourage continued public debate by all stakeholders to address the contentious issues that surround funding of research and development to generate evidence on the safe and effective use of diagnostics with clinical utility. In concluding this informative report, the co-authors argue that one point is clear: supporting innovation in the diagnostics sector while ensuring patient access to valuable new tests will require different strategies for different circumstances. Even previously controversial options, such at patented diagnostics and exclusive licenses that restrict market entrants, may have a part to play.

Personalized Multiplex Test on Market

Posted by Antoinette Konski on Posted in Uncategorized

A multiplex test that can analyze tumors for over 200 genes is now available from Foundation Medicine Inc., the Wall Street Journal reported today. The test will be used by Novartis, Sanofi SA, Johnson & Johnson and Celgene to analyze patients in early-stage clinical trials of new cancer drugs to identify patients most likely to benefit from the drug and to accelerate the drug approval process. Continue reading this entry

Patent-Eligibility of Diagnostic Patents Reconsidered in Canada

Posted by Antoinette Konski on Posted in Diagnostic Methods; Gene Patents; Genetic Testing

The Canadian Patent Office released today practice guidelines regarding the patent-eligibility of medical diagnostic methods and medical methods. The practice guidance are in effect immediately and until further notice, and in place of any contrary guidance presently in the Canadian Manual of Patent Office Practice (MOPOP, the Canadian equivalent to the US MPEP, setting forth examination criteria for patent applications).

Diagnostic Methods

The guidance document indicates that many diagnostic methods can be thought of as comprising two distinct aspects: data acquisition steps and data analysis steps. A claim often contains one or more data acquisition steps, such as a step for determining, measuring, identifying, assaying, etc. which may be implicit or explicit. Diagnostic methods are patentable before the Canadian Patent Office if the claim describing the method satisfies all the requirements of patentability, i.e., novelty, inventive, useful, sufficiently disclosed and unambiguously defined and contains an inventive concept that is statutory.

In order to be patentable, the inventive concept of the diagnostic method claim must provide a solution to a technical problem and either have physical existence or manifest a discernible effect or change. If the claim includes at least on step of physically acquiring data from an analyte (such as a substrate, marker, tissue, body, for example) then the inventive concept is statutory. However, where a known analyte had been previously assessed using the same or similar technique to those in the claim, the inventive concept may therefore be limited to the significance, understanding or interpretation of the acquired data. In these situations, the claim is not statutory because the inventive concept is limited ot the interpretation of the acquired data.

Medical Uses

The guidance also emphasizes that medical methods are not statutory in Canada, while medical use claims are permitted, as long as do not equate to medical or surgical methods and they satisfy all other requirements of patentability.

For patent-eligibilty, the inventive concept of a medical use claim must provide a solution to a technical problem and have either physical evidence or manifest a discernible effect or change. If a claim to a medical use includes a dosage regime or range for the purpose of defining patentability, the inventive concept does not need to include that dosage regime or range if the use itself meets all the requirements for patentability. In contrast, if the inventive concept requires a dosage regime or range, then the inventive concept is considered to be a methods of medical treatment, and therefore not patent-eligibility.

Similarly, where the inventive concept necessary to support patentability only serves to instruct a medical professional “how” or “when” to treat a patient, rather than “what” to use, this may not be patent-eligible as the claim would encompass a method of medical treatment.

Prometheus’ Claims in Canada

As those in the medical industry reconsider US patent strategies in light of Prometheus and the expected US PTO guidance for examiners for medical diagnostic methods, (see our posts of March 20, 2012 and March 25, 2012), the patenting of similar technologies in other jurisdications is of concern as global patenting strategies adopt to the uncertainty of the application of Prometheus by the US PTO.

Canada’s recent guidance appears to follow the US Supreme Court holding that such claims are not patent-eligible for failing to claim a patent-eligible method.

The  “determining” step of the Prometheus claims was stated by the US Supreme Court to add nothing of signficance to the art, and merely told doctors to engage in well-understood, routine, conventional activity previously engaged in by scientists who work in the field. In interpretating the “determining” element under the Canadian guidelines, the inventive concept would be limited to significance, understanding or understanding of the acquired data (as stated by the “wherein” clause of the claim) because the element was previously assessed using the same or equivalent analytical techniques known in the art.

The “wherein” clause would also fail to rescue the claim under the Canadian guidelines as it could be argued to be an expression of the understanding of the discovery of the significance of the acquired data. 

Finally, the “administering” step also was admitted to be known to those in the art and could be precluded from the claim in Canada as being directed to claiming a method of medical treatment.

However, if a diagnostic method is tied to the use of a therapeutic and that use would meets all the other requirements of patentability then the claim is more likely to possess the requisite inventive concept. In addition, if the “determining” step of the claim utilizes analytical techniques unknown to the skilled artisan, the claim is more likely patent-eligible.

A copy of the practice guidelines is available here.

Video Interview: Discussing Mayo v. Prometheus With LXBN TV

Posted by Antoinette Konski on Posted in Companion Diagnostics; Gene Patents; Genetic Testing; Prometheus

The other day I had the opportunity to speak with Colin O’Keefe of LXBN TV on the subject of Mayo Collaborative Services v. Prometheus Laboratories, Inc. In the short interview, I explain the background of the case, offer my thoughts on why Prometheus’ patent wouldn’t have a detrimental impact on medical research and give my thoughts on what this means for the Myriad “gene patenting” case.

Speak UP – USPTO Seeking Comments on Second Opinion Genetic Tests

Posted by Antoinette Konski on Posted in Companion Diagnostics; Genetic Testing; Patent Reform

Today’s Federal Register includes a notice to the public inviting comments on independent second opinion genetic tests where patents and exclusive licenses exist that cover primary genetic diagnostic tests. The comments are collected for the purpose of preparing a report on the subject as required by Section 27 of the America Invents Act (“AIA”).  In addition to soliciting comments, the USPTO will hold two public hearings in support of the genetic testing studies. Continue reading this entry

Patent-Eligibility of Medical Methods Considered By U.S. Supreme Court

Posted by Antoinette Konski on Posted in Companion Diagnostics; Diagnostic Methods; Gene Patents; Genetic Testing

This post is co-authored by Antoinette F. Konski and Jacqueline D. Wright Bonilla

The U.S. Supreme Court entertained oral argument today in Mayo Collaborative Services v. Prometheus Laboratories, Inc. The case is being closely monitored by the pharmaceutical and biotechnology industry, and in particular those in the industry that patent diagnostic methods and companion diagnostics.  At its core, the case addresses whether certain patent claims directed to diagnostic methods or methods of optimizing therapeutic efficacy for treatment recite patent eligible subject matter under 35 U.S.C. § 101.

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Making The Case for Personalized Medicine

Posted by Antoinette Konski on Posted in Biomarkers; Companion Diagnostics; Diagnostic Methods; FDA; Health Care IT

The Personalized Medicine Coalition recently published the third edition of its state of the industry report, The Case for Personalized Medicine (“Report”). While the Coalition acknowledges greater adoption of the principles of personalized medicine by the health care industry and the public; technical, legal, regulatory and payor issues are highlighted for improvement to recognize the industry’s full potential and benefits. This post summarizes the Coalition’s view of the state of the industry and the issues identified as critical to the ongoing development and adoption of personalized medicine.

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Subject Matter Jurisdiction Challenged in Supreme Court’s Review of Mayo v. Prometheus

Posted by Antoinette Konski on Posted in Companion Diagnostics; Gene Patents; Genetic Testing

An international intellectual property association filed an amicus curie brief urging the U.S Supreme Court to dismiss the dispute and issue presented in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 131 S.Ct. 3027 (2011), arguing that the district court and Federal Circuit lacked subject matter jurisdiction. The amici argued that for reasons that are not clear, the district court and the Federal Circuit unapplied, misapplied, or simply overlooked Congress’ legislative efforts to achieve a globally-desired limitation of exclusive patent rights.

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USPTO – Seeking Comments On Patent Reform Bill

Posted by Antoinette Konski on Posted in Companion Diagnostics; Patent Reform

The U.S. Patent and Trademark Office (USPTO) announced that it is proactively seeking public comments on the Leahy-Smith America Invents Act (AIA), H.R. 1249, passed by the U.S. House of Representatives on June 23, 2011, and currently pending before the U.S. Senate.  The AIA requires the USPTO to undertake a series of rulemakings to implement the Act.  Because several provisions of the AIA require implementation within a period of one year from enactment, the USPTO is anticipating that expeditious rulemaking proceedings will be required.

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FDA “Draft Guidance” for Companion Diagnostic Devices

Posted by Jackie Wright Bonilla on Posted in Companion Diagnostics; Diagnostic Methods; FDA; FDA Guidelines

On July 14, 2011, the FDA issued “Draft Guidance” relating to regulatory approval of in vitro companion diagnostic devices/tests, also called “IVD companion diagnostic devices.” The FDA intends the Guidance to assist those (1) who develop a therapeutic product that depends on the use of such a device/test for the product’s safe and effective use, and (2) who develop a companion diagnostic device intended for use with a corresponding therapeutic product.  The FDA invites comments and suggestions regarding the Draft Guidance within 60 days. 

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Inducing Infringement of a Diagnostic Method: Consult the Supreme Court’s New Test

Posted by Antoinette Konski on Posted in Companion Diagnostics; Diagnostic Methods; Infringement

A patent’s value is determined by the economic monopoly provided to the patent holder.  The claims of the patent define the monopoly and therefore are the core of its value.  Infringement of a patent claim is the legal cause of action asserted by a patent holder, and one does not infringe a claim unless all elements of that claim are practiced.  Nevertheless, under section 271(b) of the patent statute, one can still be held to infringe a claim if one actively encourages or urges another to infringe.

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