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To begin this discussion of patents in pharmaceutical policy, let me first set out two basic points that I think are central to pharmaceutical policy. First, I believe that strong patent protection, at least in developed countries, is an essential component of pharmaceutical policy. Second, I believe that the rapid development and implementation of pharmacogenomics and personalized medicine are absolutely critical for pharmaceutical policy. However, I do not necessarily believe that the development and implementation of pharmacogenomics and personalized medicine require the same breadth of patent protection afforded to the development of new drugs. Patent protection, and with it the rewards of the exclusive rights to make, use, or sell the patented invention, has been a feature of the legal landscape in every country in which significant numbers of new drugs have been developed since the modern pharmaceutical industry began. There have been proposals to do away with patents. Prizes seem to be a recurrent suggested alternative to patents.1 However, I think it is clear that prizes are not a viable alternative reward for the occasional success in a risky and expensive enterprise. No one suggests prizes on the scale of the profits that are earned through patent protection when that risky and expensive enterprise succeeds. It is simply not logical that the amounts of capital required to drive pharmaceutical innovation and drug development would be invested under a prize system, or any other system which significantly reduces the rewards obtainable with strong patent protection. However, that is not to say the details of the current system get the balance right. A number of years ago I suggested that much broader patents should be awarded for the significant innovation that is accomplished by the discovery and validation of a new target for drug development.2 While the Court of Appeals for the Federal Circuit (the principal forum for patent law in the U.S. other than the Supreme Court) has moved further in the other direction (over the vigorous dissent of Judge Rader),3 I still believe in the core of that argument and will expand on that problem in a future post. For now, it is sufficient to say that the validation of new biological targets for pharmaceutical therapy are the biggest (and riskiest) innovations in the drug development enterprise. Ideally the patent system would provide financial rewards that are proportional to the degree of innovation. That is not the system we have, but it is a reasonable and reasonably obtainable goal.
To begin this discussion of patents in pharmaceutical policy, let me first set out two basic points that I think are central to pharmaceutical policy. First, I believe that strong patent protection, at least in developed countries, is an essential component of pharmaceutical policy. Second, I believe that the rapid development and implementation of pharmacogenomics and personalized medicine are absolutely critical for pharmaceutical policy. However, I do not necessarily believe that the development and implementation of pharmacogenomics and personalized medicine require the same breadth of patent protection afforded to the development of new drugs. Patent protection, and with it the rewards of the exclusive rights to make, use, or sell the patented invention, has been a feature of the legal landscape in every country in which significant numbers of new drugs have been developed since the modern pharmaceutical industry began. There have been proposals to do away with patents. Prizes seem to be a recurrent suggested alternative to patents.1 However, I think it is clear that prizes are not a viable alternative reward for the occasional success in a risky and expensive enterprise. No one suggests prizes on the scale of the profits that are earned through patent protection when that risky and expensive enterprise succeeds. It is simply not logical that the amounts of capital required to drive pharmaceutical innovation and drug development would be invested under a prize system, or any other system which significantly reduces the rewards obtainable with strong patent protection. However, that is not to say the details of the current system get the balance right. A number of years ago I suggested that much broader patents should be awarded for the significant innovation that is accomplished by the discovery and validation of a new target for drug development.2 While the Court of Appeals for the Federal Circuit (the principal forum for patent law in the U.S. other than the Supreme Court) has moved further in the other direction (over the vigorous dissent of Judge Rader),3 I still believe in the core of that argument and will expand on that problem in a future post. For now, it is sufficient to say that the validation of new biological targets for pharmaceutical therapy are the biggest (and riskiest) innovations in the drug development enterprise. Ideally the patent system would provide financial rewards that are proportional to the degree of innovation. That is not the system we have, but it is a reasonable and reasonably obtainable goal.
So, what about pharmacogenomics and personalized medicine? Since the
Supreme Court narrowed the availability of patent protection for
human gene sequences and diagnostic methods in
Association for Molecular Pathology v. Myriad Genetics
and
Mayo
Collaborative Servs. v. Prometheus Labs., Inc.,
there have been dire predictions about the consequences for
personalized medicine and pharmacogenomics. Very recently Professor
Chris Holman, who has made great contributions to the discussion of
patents in the context of biotechnology and pharmaceuticals,
responded with similar alarm4
to a recent federal district court decision in Ariosa
Diagnostics, Inc. v. Sequenom, Inc.5
For
purposes of this discussion, the Ariosa
holding
can be boiled down to this: A patent claim to a method of diagnosis
that relies on conventional methods of amplifying and sequencing
naturally occurring DNA is invalid because it is a claim to a
naturally occurring phenomena or a correlation between naturally
occurring phenomenom and a particular result. The Ariosa
district
court found such claims barred by Prometheus
and
Mayo:
The
Supreme Court has never stated that any use of a natural phenomenon
is patentable. To the contrary, the Supreme Court has held that
"simply appending conventional steps, specified at a high level
of generality, to laws of nature, natural phenomena, and abstract
ideas cannot make those laws, phenomena, and ideas patentable."
Prometheus,
132 S. Ct. at 1300.
It is only an innovative or inventive use of a natural phenomenon
that is afforded patent protection. See
Myriad,
133 S. Ct. at 2119....
(Ariosa, "Discussion"
paragraph 5).
The
concern of Holman and others is straightforward: If claims that
use "naturally occurring genetic variations" to
diagnose
disease
or
to diagnose
pharmacologically
relevant characteristics
of a patient are unpatentable, it will
be impossible
for the human
genetic
diagnostics industry to survive and, in that case, pharmacogenomics
and personalized medicine will not develop at a reasonable rate.
That is certainly a valid concern and a logical one, so long as the
underlying premise is true-- which is that the identification of
relevant
human genetic variations
remains an expensive undertaking and utilization of the information
requires a unique device or reagent for each such correlation.
However,
it seems increasingly likely that developments in genetic testing
will rely on whole-genome sequencing ("WGS") technology
along with ever
more
powerful computer technology for genomic analysis.
Let
me elaborate on what this means. In
the past, research to sequence even
a portion of the
genome of a patient's tumor or normal tissue was a costly and
painstaking undertaking that required significant funding dedicated
to that project.
Validation
of any variations found
was also
a painstaking and costly process that took significant time as more
patients' tissues and control tissues were added to the database to
refine the estimates of the
correlation between particular
variations
and the risk of
disease. For example, leaving all other questions of Myriad Genetics
contribution to science and marketplace ethics aside, when Myriad
began offering BRCA1 and BRCA2 testing, the risk estimates
for particular mutations varied widely, the studies that produced
those risk estimates relied on relatively small numbers of subjects,
and each study was a significant investment of time and resources.6
While there are numerous technological issues still to resolve in
the rapidly
increasing clinical
application of WGS,7 it is clear that the direction of genetic analysis
is rapidly moving towards WGS,
improved WGS platform devices, and improved computer algorithms for
reading and analyzing
the
genomic information produced by WGS. Pharmaceutical companies will
be investing in and using pharmacogenomics and should be
required to submit pharmacogenomic data to the FDA to
improve their clinical trial designs, data analysis, and drug use.
Both
diagnosis and personalized medicine will develop at an accelerating
rate as the platform tools are improved. Professor
Holman is a great scholar in the field of pharmaceutical patents and
a real scientist as well as a law professor, but I think his
concerns about the Ariosa
decision
may be unwarranted. Personalized medicine is more likely to be driven
by WGS, pharmaceutical development, and the FDA, without the kinds of
gene patents relied on by diagnostics companies before developments
in genomics changed the game.
1See
for example Linda P. Nussbaum and John D. Radice, Where
Do We Go Now? The Hatch-Waxman Act Twenty-Five Years Later:
Successes, Failures, And Prescriptions For The Future,
41
Rutgers L.J. 229 (2009)
(and sources cited at footnotes 105-110).
2Robert
A. Bohrer, Reach-through Claims for Drug Target Patents: Rx for
Pharmaceutical Policy, 26(1) Nature Biotechnology 55 (January
2008).
3
Ariad Pharmaceuticals, Inc v. Eli Lilly And
Company, 598
F3d 1336 (Fed. Cir. 2010).
4
Christopher M. Holman, The
Holman Report: District Court’s Interpretation of
Mayo in Ariosa Diagnostics
Does Not Bode Well for Patent Eligibility of
Diagnostics and Personalized Medicine, 33
Biotechnology
Law Report 46 (April 2014).
6Anyone
interested in the literature of BRCA1and 2 risk estimation from
before Whole-Genome Sequencing (WGS) became widely available at
increasingly lower costs should read a classic meta-analysis of the
BRCA risk data, A.
Antoniou
et al, Average
Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2
Mutations Detected in Case Series Unselected for Family History: A
Combined Analysis of 22 Studies,
72(5) Am. J. Human Genetics 1117-1130 (April 2003).
7
Frederick E. Dewey, M.D. et al, Clinical Interpretation and
Implications
of
Whole-Genome Sequencing,
311(10) J. Amer. Med. Assoc. 1035
(March
12, 2014).
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