Family Feuds on Intellectual Property

The med-bio-tech blogosphere is bubbling with commentary on intellectual property issues following last week’s polemical op-ed on gene patents by Michael Crichton in the New York Times, Denise Caruso’s article the week previous (free here), and the recent introduction of the Genomic Research and Accessibility Act in the House (H.R. 977). All three pieces are unanimous, more or less, in their disdain for gene patents.

The general sentiment among my RSS feeds (here, here, here, here, here), especially in regards to Crichton’s piece, is that any outright dismissal of gene patents is foolhardy since it takes an important, complex issue and turns it into a soundbite that is so overly simplistic (“gene patents are bad”), that large numbers of people may actually come to believe it. Much like test tube babies or genetically modified organisms, gene patents are in the category of things that just sound wrong to many people, regardless of whether there is any merit to the belief.

While bold pronouncements like “gene patents are bad” (and the inverse) can be gratifying for the sense of clarity they provide, more often than not their progenitors are guilty of some sort of intellectual cheapness.

If you are interested in dipping your toe in waters of intellectual property and genomics, and you want to an even-handed analysis of many of the big issues, my advice is to forget Michael Crichton and the blogosphere, instead do yourself a favor and read Misha Angrist and Robert M. Cook-Deegan’s very thoughtful recent article in The New Atlantis entitled “Who Owns the Genome?”. Here is a snip:

The race to map the human genome seemed to embody two rival ways of doing science: the public pursuit of human knowledge paid for with public dollars and the private pursuit of useful knowledge paid for with private investments. Each way of doing science has its purist adherents, but in reality the relationship between “public” science and “private” science is a complicated thicket, especially when it comes to the brave new world of genomics. Nation by nation, laboratory by laboratory, regulation by regulation, we are still trying to figure out who “owns” the genome, what the owners actually own, and how best to balance the pursuit of knowledge, the allocation of rewards, and the development of life-improving biotechnologies. Innovation continues apace, but no one really knows how close we are to the optimum policies. The system works, but no one knows how well, because no one can address the crucial question: compared to what?

…And given a realm with so much complexity, so many interests, and so many unknowns, tinkering with the parts is probably the best we can do. But it is also possible that the gathering enthusiasm for “open and collaborative” research, even in the private sector, signals an inflection point. Perhaps we have moved beyond the impassioned rhetoric of public versus private; perhaps we no longer regard the human genome as either “the common heritage of all mankind” immune from IP rights or as a Wild West for speculative patents and endless court fights.

If you do want to get into the details of the impact of patents on genomics, there are many juicy places to start shining your light. The juciest, in my opinion, is a recent court case that involved exactly zero gene patents: LabCorp vs. Metabolite.

Why is it the juiciest? Even though this case did not directly involve gene patents at all, the enforcement of one of the claims in Metabolite’s patent (and others like it) will undoubtedly have a major impact on the development of genomics and personalized medicine as we know it. This is why major players in the genomics industry hired attorneys and got involved when the case was escalated to the Supreme Court.

Even more interesting, two major genomics companies wrote briefs for opposing sides. And even more interesting than that, these two companies are family members (but clearly not kindred spirits on this issue).  One of the companies, Perlegen, is a recent spin-out of the other company, Affymetrix. It was a family feud of the sort that usually only takes place on daytime TV.

To get to the bottom of why this patent case is so important, you probably need to be a legal scholar (which I most definitely am not). Short of that, here are a couple things you can do:

  1. Read a brief history of the LabCorp v. Metabolite case, a good one is here

  2. Familiarize yourself with Claim 13 in Metabolite’s patent (the so-called ‘658 patent) and commit to memory the phrase "test plus correlate", a.k.a. “assay plus correlation”

  3. Read the Supreme Court briefs (thanks Patently-O) and Breyer’s dissent. If you only interested in the gossip, then you can focus on the Perlegen-MDV brief and Affymetrix brief

  4. Understand the concept of inducing patent infringement and understand that this lawsuit was brought by Metabolite because LabCorp purportedly induced infringement by educating physicians about a physiological fact (high amino acid X means low vitamin Y).

  5. Figure out how wide the liability net could be cast for inducing patent infringement via correlations. You might go about this by first figuring out how to get your hands on Lori Andrew’s 2006 piece in the Chronicle (the article is for subscribers only), then figure out if you think this case has the potential of creating a scenario as dire as the one she predicted.  Thought police?

  6. Figure out how high throughput sequencing affects “assay plus correlation”, knowing that today the two steps are closely coupled (I get assay X specifically for correlation Y) and that in the future the two will be uncoupled (I get assay X, like a full genome sequence, for an evolving set of correlations A-Z), and that the actors involved are going to change (hello web)…then revisit #5 above.

  7. Write to me and tell me what you think ;)

For a more thorough look at gene patenting controversies, I also recommend this article:

Caulfield T, Cook-Deegan RM, Kieff FS, Walsh JP. Evidence and anecdotes: an analysis of human gene patenting controversies. Nat Biotechnol. 2006 Sep;24(9):1091-4. (sorry subscribers only)

Want more? Check out Robert Cook-Deegan’s publication page.

History of Patenting Life and Its Parts

Daniel Kevles reviews the history of patenting "life and its parts" in a recent talk at Duke Law School.  The talk provides an overview of the major events that have shaped our current intellectual property regime, including Ananda Chakrabarty and the oil-slick eating bacteria, Philip Leder and the Oncomouse, Stan Allen and the triploid Pacific Oyster, Craig Venter and Expressed Sequence Tags (EST), Myriad’s patent claims on the BRCA genes, and lots of interesting minutiae.   He ends the talk with this comment:

"We all have a stake in human genes, just as for example, down-river residents have a stake in up-river holders of riparian rights.  We limit the rights of the up-river holders to do with their property whatever they wish, the time may well be coming, in fact I think its already here, when we will limit the IP rights in human genes too…"

Watch the streaming webcast

Daniel Kevles "Patenting Life and Its Parts: Ethics and Rights in the Political Economy of Intellectual Property" Duke Law School’s Center for the Study of the Public Domain, April 7, 2005. (streaming webcast)

Daniel Kevles faculty profile at Yale.


Update
: Personal genome sequencing presents some interesting challenges to intellectual property — or perhaps it is the reverse, intellectual property claims present some interesting challenges for personal genome sequencing.  Jay Shendure framed the issue in an excellent paper on the cost of sequencing:

[Ultra low cost sequencing] technologies will probably not be able to avoid the resequencing of patented genes.  Interesting legal issues arise around the question of patients’ rights to have analysed (or to self-analyse) their own DNA sequence versus corporate interests that presumably own the rights to that analysis.

If personal genome sequencing were available cheaply today, this issue might be problematic, to give an example, with the way in which Myriad Genetics exercises their patent claims on BRCA1 and BRCA2.  Daniel Kevles points out they they require that all sequencing of these genes be done at Myriad’s labs.  If other companies adopt similar models to enforce intellectual property rights, the $1000 genome would appear to be dead in the water.  If a person had to send blood or buccal samples to hundreds of labs in order to get a full genome sequence, the shipping costs alone might be more than $1000.

John A. Robertson. "The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals" The American Journal of Bioethics 3(3):W35-W42

Shendure J, Mitra R, Varma C, Church GM (2004) Advanced Sequencing Technologies: Methods and Goals. Nature Reviews of Genetics May;5(5):335-44.

One-Fifth of Human Genes Belong to the “Patome”

A new study reveals that 4382 of 23,688 human genes in NCBI are patented.  The authors of the study actually mapped the patents to their location on the chromosomes using computational techniques familiar to bioinformaticists (cool graphic in the paper shows chromosome 20 with IP righs mapped to it).

While most patented genes have only one IP claim on them, some genes have many claims.  The two most highly patented genes were found to be  BMP7, an osteogenic factor, and CDKN2A, a tumor suppressor gene.  The sequences of these two genes were claimed in more than 20 patents each. 

This research appears to be part of a larger examination on the impact of gene patents on innovation.  The authors of the paper summarize two sides of the intellectual property debate as follows:

Critics [of gene patents]…suggest that overly broad patents might block follow-on research… Alternatively, gene IP rights may become highly fragmented and cause an anticommons effect, imposing high costs on future innovators and underuse of genomic resources…Both situations, critics argue, would increase the costs of genetic diagnostics, slow the development of new medicines, stifle academic research, and discourage investment in downstream R&D…

In contrast, the classic argument in support of gene patenting is that strong IP protection provides incentives crucial to downstream investment…and the disclosure of inventions. Patents are also regarded as the cornerstone of vibrant markets for ideas…and central to the biotech boom of the 1980s and 1990s…

Kyle Jensen and Fiona Murray. "Intellectual Property Landscape of the Human Genome" Science 14 October 2005; 310: 239-240 (sorry subscribers only) Update: See here!

Stefan Lovgren. "One-Fifth of Human Genes Have Been Patented, Study Reveals." National Geographic News. October 13, 2005

Fiona Murray’s homepage

Read more

End of an Era: PCR Patent

WHAT the dominance of Microsoft Windows is to
personal computers, the dominance of the polymerase chain reaction
(PCR) is to biotechnology…
it has transferred large numbers of dollars
from the pockets of its users to those of its patent holder, F.
Hoffmann-La Roche. But on March 28th, the gravy train began to dry up.
The original patents on the technology expired in America (they expire
in March 2006 in Europe).

"Patent ending: The polymerase chain reaction" The Economist. London: Apr 9, 2005. Vol.375, Iss. 8421;  pg. 73 (subscription only)

Resources:

AccessExcellence on PCR

The PCR Project at Berkeley

Videos on PCR at Roche

First Genetic Trust Awarded Patent

First Genetic Trust Gets Patent for Banking System, GenomeWeb, Feb 3 2004. (free registration required)

"First Genetic Trust has received a patent for an electronic genetic banking system, the company said today.  The patent, US patent No. 6,460,211 B1, covers methods, processes, and electronic systems for securely storing, analyzing, and managing genetic data.  First Genetic Trust, headquartered in Chicago, is aiming to develop and commercialize genetic banking and research management applications for biomedical research."

Patent Application #20030104470

Patent Application #20030104470 reads:

"The present invention relates to electronic medical records having polymorphisms data, an electronic library of these electronic medical records, and systems and methods for managing genetic information. For example, the present invention provides system and methods for collecting, storing, and retrieving patient-specific genetic information from one or more electronic databases."

The assignee name is Third Wave Technologies, Inc.