2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Gene Patents and Personalized Medicine
Overview: The use of genetic information to design and guide
therapies and to develop novel diagnostic procedures creates
important patent issues. Patents on human gene sequences
have likely helped stimulate the introduction of new biologics;
however, their role and that of patents on genotype-phenotype
THE PRACTICE of personalized medicine has been
described as giving the right drug, to the right patient,
at the right dose, at the right time. Central to the concept of
personalized patient management is knowledge and application
of somatic and heritable molecular pathologic (molecular
genetic) changes associated with disease susceptibility,
prognosis, therapeutic responsiveness, and susceptibility to
side effects. Although we are far from achieving truly individually
designed care for most patients, in oncology the era
of targeted therapies linked to measurable biomarkers has
arrived. Diagnostic tests have long been important in cancer
management, but the high sensitivity, specificity, and direct
relationship to therapy of many nucleic acid-based analyses
adds enormously to their utility.
Because they have been rationally designed to directly
influence biochemical pathways implicated in malignant
progression, targeted cancer therapies potentially offer patients
greater benefits with less morbidity than most currently
used chemotherapeutic agents. Moreover, by allowing
for prospective selection of individuals most likely to benefit
from a given therapy, molecular pathology-guided approaches
benefit patients by rescuing antineoplastic agents,
the efficacy of which is confined to select populations. Without
the ability to specifically identify potential responders,
such drugs may mistakenly be abandoned. Finally, personalized
medicine encourages cost-effective use of expensive
therapies by restricting administration to patients most
likely to benefit and least likely to suffer harms from them.
Gene Patents and Personalized Medicine
The use of molecular pathologic information to develop
and prescribe therapies raises important new patent issues.
In the United States, patents confer on the patent holder
the right to exclude others from making, using, or selling an
invention for 20 years from the filing date. Under the Patent
Act, patentable inventions must be novel, nonobvious, and
useful. 1 Patent claims define an invention’s features much
as a deed delineates the boundaries of a plot of land. Patent
applications are submitted to the U.S. Patent and Trademark
Office (USPTO) where they are rejected or allowed and
issued. Importantly, “[p]rocesses, machines, manufactures,
and compositions of matter” can be patented, 2 but patents
may not be obtained on products of nature or, under the
“natural phenomenon doctrine,” “laws of nature, natural
phenomena, and abstract ideas.” 3
Patents have been integral to the discovery and commercialization
of drugs and biologics. The product exclusivity
patents confer has been instrumental in ensuring that
manufacturers can raise sufficient capital to identify, test,
obtain regulatory approval for, and bring to market new
therapeutic agents. Absent enforceable patent rights for
new drugs, investment dollars would likely be redeployed to
By Roger D. Klein, MD, JD
correlations in diagnostic testing is highly controversial.
Genotype-phenotype associations are at the heart of personalized
medicine. The intellectual property rules by which these
biologic relationships are governed have profound implications
for the growth of individualized medicine.
areas with a more favorable risk-reward balance. So clear
are the positive incentives patents provide the pharmaceutical
industry, even patent system critics have acknowledged
them. 4 Similarly, the stimulatory effects of patent
protection on pharmaceutical development may extend to
patents granted on human genes, when patented genes are
cloned to produce biologic therapies and vaccines. 5
By contrast, patents on relationships between genetic
variants and clinical phenotypes are controversial. Such
patents have been widely criticized and their legitimacy
challenged, whether the patents directly claim genotypephenotype
associations or gene sequences themselves. 5,6
Because genotype-phenotype associations are the center of
personalized medicine, the intellectual property rules by
which these biologic relationships are governed have profound
implications for its growth.
Clinical implementation of molecular pathology procedures
is substantially less costly than the discovery, development,
and commercialization of in vivo pharmaceuticals.
Manufacturers typically invest hundreds of millions of dollars
over a prolonged period of time to bring a drug or
biologic to market. Drug candidates must be extensively
tested in preclinical and clinical studies before U.S. Food
and Drug Administration (FDA) approval. Unlike therapeutics,
most molecular pathology procedures are designed,
developed, and validated by individual diagnostic laboratories
at limited expense. The wide availability of automated
nucleic acid extractors, thermal cyclers, and DNA sequencing
instruments combined with broad licensing of standard
molecular methods and the free accessibility of online gene
sequence databases has rendered development straightforward
for many molecular pathology procedures.
Laboratory quality is ensured by the Clinical Laboratory
Improvement Amendments, accreditation by the College of
American Pathologists and other professional societies, and
individual state requirements. Most molecular pathology
services do not undergo FDA clearance or approval, although
laboratories serving New York patients submit tests
to the state’s Clinical Laboratory Evaluation Program for
pre-implementation review. The small minority of molecular
pathology procedures manufactured and sold as kits to
clinical laboratories must be cleared or approved by the
FDA. However, this process is much less burdensome and
orders of magnitude less expensive for in vitro diagnostic
kits than for drugs.
From the Medical College of Wisconsin, Milwaukee, WI.
Author’s disclosure of potential conflicts of interest are found at the end of this article.
Address reprint requests to Roger D. Klein, MD, JD, 27500 Cedar Road #808, Beachwood,
OH 44122; email: roger.klein@aya.yale.edu.
© 2012 by American Society of Clinical Oncology.
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