Are Human Genes Patentable?

Efthimios Parasidis

The Supreme Court will consider the patentability of human genes when it reviews the Myriad case this term. As Bill of Health readers are likely to know, the Myriad case centers on Myriad’s patents on gene sequences for BRCA mutations that are associated with the propensity to develop breast or ovarian cancer.  Myriad does not claim ownership over the mutations as they exist in nature, but rather on isolated BRCA sequences that the company has “created”. The Myriad case will give the high Court another chance to clarify the scope of subject matter that is eligible for patent protection. The Court’s track record in this area is less than stellar.

As I have argued (here), the legal uncertainty at to the scope of patentability for claims that implicate products of nature is largely the result of the lack of a uniform framework for determining what areas are excluded from patent-eligible subject matter. More specifically, while patent law prohibits patent protection for inventions that equate to a law of nature, natural phenomenon, mental process, mathematical equation, or abstract idea (collectively referred to as the product of nature doctrine), no court has defined these terms adequately. Uncertainty is bad for business and bad for patients — the Court should seize upon this opportunity and offer clear guidance as to the contours of the product of nature doctrine.

With respect to gene sequences, the mere fact that a sequence is isolated is inconsequential.  Rather, courts should analyze the precise subject matter of the isolated gene sequence to determine if it differs substantially from its natural counterpart. I’ve created a three-part test to help make this determination:

  1. Does the isolated sequence exhibit characteristics or contain properties that are substantially different from the non-isolated sequence?
  2. Is the proximate cause of any difference between the isolated and non-isolated sequences the result of natural phenomenon that govern the properties of the sequence when isolated?
  3. Would a patent on the isolated sequence grant a property interest that extends to anything other than the isolated sequence?

If the answer to these questions is anything other than (1) yes, (2) no, (3) no, the claim must be invalidated pursuant to Section 101 of the patent act because the claim does not constitute patent-eligible subject matter. My article explains why…

Does Whole Genome Sequencing Circumvent Gene Patents?

By Nicholson Price [originally posted at Bio-IT World on Dec. 10, 2012]

What happens when, during the course of whole-genome sequencing (WGS) a patient or research subject, an investigator sequences and analyzes a disease gene that has been patented? The U.S. Supreme Court will shed some light on this question next year when it issues its ruling in the long-running Myriad Genetics saga.

Last month, the Supreme Court voted to hear the case of Association for Molecular Pathology v. Myriad Genetics to consider the question whether human genes are patentable. The plaintiffs—doctors, patients, researchers, and the American Civil Liberties Union—have challenged Myriad’s patents on the breast cancer genesBRCA1 and BRCA2, which cover, among other things, isolated DNA molecules with the sequences of those genes. A federal district court in New York ruled that the patent claims on isolated DNA molecules were invalid, but that ruling was reversed on appeal by the Federal Circuit in D.C. The Supreme Court decided to review the Federal Circuit’s decision and will likely rule on whether isolated human gene sequences are patentable next summer.

This case has profound implications for biotechnology, and diagnostics, as well as the emerging field of personalized medicine. Among the fascinating issues that will likely be addressed is whether WGS—an essential foundation for truly personalized medicine—violates human gene patents.

As WGS involves determining the sequence of an individual’s entire genome, there is concern in many quarters that WGS could violate essentially every patent covering an isolated human DNA sequence—of which there are thousands. Indeed, this concern has been raised by scholars, policy analysts and lawyers, including before the Federal Circuit and in the arguments over whether the Supreme Court should hear the case.

However, a closer look at the technology suggests that rather than violating thousands of gene patents, WGS methods violate few, if any, existing gene patents. Whatever the Supreme Court decides next summer, the widespread adoption of clinical WGS is not particularly threatened by gene patents.

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Elhauge on Solving the Patent Settlement Puzzle

Founding Director of the Petrie-Flom Center, Professor Einer Elhauge, has just published an article with co-author Alex Krueger on an issue that the Supreme Court just granted certiorari on in FTC v. Watson: the proper antitrust analysis of reverse payment patent settlements.  In such settlements, the alleged infringer receives a payment and agrees to stay out of the market for a number of years.  Such settlements have been particularly prevalent in the pharmaceutical industry that has such a large effect on health care costs. The appellate courts have all recognized that such settlements have anticompetitive potential to exclude entry for far longer than merited by the probability of patent victory.  However, the courts have split on whether to find these settlements presumptively anticompetitive or lawful if within the formal scope of a non-sham patent.  The latter courts have focused on the possibility that a settlement might not exclude entry for longer than merited by the probability of patent victory and the administrative difficulty of conducting case-by-case inquiries into that probability.  Professor Elhauge’s article seeks to solve this puzzle by showing that case-by-case inquiries are unnecessary when the reverse payment amount exceeds the patent holder’s future anticipated litigation costs, because one can infer that such settlements will exclude entry for longer than merited by that probability of patent victory, whatever that probability may be.

2012 Global Congress on Intellectual Property and the Public Interest

By Adriana Benedict

The 2012 Global Congress on Intellectual Property and the Public Interest has just come to a close in Rio de Janeiro, Brazil.  The conference brought together global leaders in intellectual property-related fields like access to medicines, access to knowledge, internet freedom, innovation and development, and open educational resources.  I was invited to participate in the various sessions concerning access to medicines, which focused on two sides of this global health challenge.

The first part of the access discussions focused on best practices and threats in the use of TRIPS flexibilities in developing countries.  Participants emphasized the need to look beyond the usual focus on compulsory licenses to set new priorities for understanding and leveraging less-developed flexibilities such as patentability criteria, patent opposition mechanisms and parallel importation.  An important overarching theme in these discussions was reframing flexibilities as rights, as they carry the same legal status as the intellectual property rights which make them necessary.

The other side of the discussions focused on innovation and research and development (R&D) for the developing world, primarily through recent advances by the WHO CEWG report in promoting a binding convention in this realm.  At the forefront of these proposals is the notion that incentives for innovation should be de-linked from product prices in order to address the needs of the developing world.  Participants emphasized that, moving forward, advocates should be careful to ensure that public and institutional debates on alternative R&D models do not narrow their focus from neglected populations to neglected diseases.

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Open Access to Health Research: Highlights from the NIH Public Access Policy panel

By Adriana Benedict

As of 2008, the NIH Public Access Policy requires “that all investigators funded by the NIH submit or have submitted for them to the National Library of Medicine’s PubMed Central an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication.”  Four years later, approximately 80% of NIH-funded research articles make their way into PubMed Central.  Institutional Open Access resolutions such as Harvard’s Open Access Policy have helped accommodate the NIH Public Access Policy requirements, but Harvard Medical School and Harvard School of Public Health have yet to adopt it.

In May, the Harvard Library Faculty Advisory Council issued a public letter calling on faculty to promote open access scholarly publishing, noting that “Many large journal publishers have made the scholarly communication environment fiscally unsustainable and academically restrictive”.  In a Petrie-Flom Center-sponsored Open Access Week panel (moderated by Open Access Liaisons Scott Lapinski and June Casey), Peter Suber, Amy Brand, Winston Hide and Patrick Taylor discussed the challenges and opportunities for progress towards achieving open access to health research.  Highlights from the panel are presented below, and the video should be available on the Petrie-Flom website shortly.

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Reminder: Tomorrow, Institutional Financial Conflicts of Interest in Research Universities

Friday, November 2, 2012
8:30am – 6:30pm (reception to follow)
Milstein Conference Rooms, 2nd Floor
Wasserstein Hall
1585 Massachusetts Avenue
Cambridge, MA

The Petrie-Flom Center and the Edmond J. Safra Center for Ethics will be co-sponsoring a day-long symposium organized by Dr. David Korn on institutional financial conflicts of interest in research universities. The speaker line-up is incredible, including Derek Bok and Zeke Emanuel, among other experts from academia and government.

For more information, and to register (attendance is free), check out the symposium webpage.  We hope to see you there!

FDA Reprimands Genentech for “Drastically Overstat[ing] the Efficacy of Tarceva”

by Jonathan J. Darrow

On October 3, 2012, the FDA’s Division of Professional Drug Promotion issued an untitled letter to Genentech in connection with its cancer drug Tarceva.  Tarceva (erlotinib) was approved in 2004 for the treatment of non-small cell lung cancer, and has since been approved, in combination with Gemzar (gemcitabine), for the treatment of pancreatic cancer. Its approval letter reported a tumor response that was 9 times greater with Tarceva than with placebo (0.9% in placebo versus 8.9% in Tarceva), but relatively modest improvements in 1-year survival rates: approximately 8 of 10 patients on placebo did not survive 1 year, while about 7 of 10 patients on Tarceva did not survive (see page 6, line 102 of the approval letter).  A 2005 New York Times article was less than enthusiastic about Tarceva’s efficacy, noting that it (along with several other cancer drugs that were new at the time) “help[s] most patients only marginally . . . .”  Despite its modest efficacy, Tarceva was reported in the same New York Times article to cost almost $31,000 per year.  A number of patents are listed in the FDA’s Orange Book as covering Tarceva until 2020.

The recent untitled letter accused Genentech’s promotional materials of misleadingly indicating that Tarceva in combination with gemcitabine extended overall survival by 3.7 months in comparison with gemcitabine alone, when the actual increase in survival was only about 12 days.  The FDA characterized the discrepancy as “drastically overstat[ing] the efficacy of Tarceva.”  (The figure of 3.7 months was derived, according to the FDA, “from a retrospective, exploratory subgroup analysis that does not provide substantial evidence to support the efficacy claims cited . . . .”). In addition, the front cover of one of the promotional materials in question contained an image of an hourglass positioned on its side, presented with the claim: “Extending survival for moments that matter.”  Although the claim with its associated image may be literally true (“moments” is left undefined), the FDA characterized the image and claim as “drastically overstat[ing] the overall survival benefit for patients” because it “strongly suggests that time is standing still for the cancer patient because of Tarceva therapy.”  The FDA noted a number of other instances of misleading overstatement of efficacy or minimization of risk.

The October 3 Tarceva letter brings to 23 the total number of Drug Marketing and Advertising Warning Letters (and untitled letters) listed by the FDA’s Office of Drug Promotion as having been sent this year.

Call for Papers – Petrie-Flom Center Annual Conference: The Food and Drug Administration in the 21st Century

We are pleased to announce plans for our annual conference, this year entitled: “The Food and Drug Administration in the 21st Century.”  This one and a half day event will take place Friday and Saturday, May 3-4, 2013, at Harvard Law School in Cambridge, Massachusetts. For details on the event and the call for proposals, see the Call for Papers/Presentations. Abstracts are due no later than December 10, 2012.

FDA’s New Dance with Big Pharma: Are Patients the Band?

Efthimios Parasidis

One week prior to the Supreme Court’s landmark ruling in the health care cases, Democrats and Republicans overwhelmingly voted in favor of health-related legislation (387-5 House; 96-1 Senate).  Industry and HHS were quick to congratulate our elected officials on a triumphant bipartisan achievement, while the FDA enthusiastically welcomed its latest collaboration with Big Pharma.  Lobby groups boasted of their ability to “craft” legislation with FDA and praised the “unprecedented level of public input” into the new law.

We should all be concerned.

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