Abstract:
Intellectual property rights are essential in today’s
technology-driven age. A strong intellectual property protection
strategy is crucial in the bioinformatic space as monetary
and temporal resources are tremendous in finding a blockbuster
drug or gene therapy. Current problems and intellectual
property practice in the genomic space are presented and
analyzed. Various strategy and solutions are proposed to
guide bioinformatic companies in forming an aggressive strategy
to protect one’s intellectual property and competitive
positioning.
Overview:
What is bioinformatics? This is a relatively new discipline
that has gained much recognition in the last year. Basically,
bioinformatics is the convergence of analytical and computational
tools with the discipline of biological research. This has
vast influence in biological research as numerous data that
are collected through laboratory experiments can be organized,
analyzed, or prediction made to reduce the time spent in
finding cures to diseases or causes of diseases.
The amount of data collected in biological research is
tremendous especially in the area of genomics. On June 26,
2000, groups of scientist announced the completed survey
of the human genome, the sum total of all the genes in each
cell of the human body. The genome is the entire genetic
blueprint for a human being written in the alphabet of chemical
compounds called nucleotides, adenine (A), guanine (G),
cytosine (C), and thymine (T). A gene is the specific sequence
of the nucleotides that tells the body how to create proteins
that maintain cellular structure of the organism and direct
function of the cell. The human cell has some 100,000 genes
that are specific sequences of DNA and the sum total of
all units of nucleotides results in a mind-boggling 3.1
to 3.2 billion base pairs in the human genome. However,
only 3%-5% of the genome contains genes, which in turn each
produce four to five proteins, the molecules that control
all major functions of life. Thus, computational technology
is required in the sequencing of the database, the studying
of the functions of the specific sequence (gene), and the
management and dissemination of the genetic information.
Figure 1: Enabling Technologies
With the potential vast pay-off of finding a blockbuster
drug or treatment, copious amount of funding both in the
private and public area have gone into the development of
bioinformatic tools in the genomic space. With all the money
going into these bioinformatic companies, these companies
need to protect their technology. In 1999 alone, 289,448
patent applications were filed in the bioinformatic space
and the USPTO has created working groups to deal with the
influx of bioinformatic applications. Although patents in
this area have increased and provides an avenue to protect
ones intellectual property, there is also controversy that
surrounds the patenting of various technology in this area.
For one, the thought of allowing a company to patent and
have a monopoly over a gene sequence that has been around
since the beginning of life is quite disturbing. On the
other hand, the discovering and developing a new gene-based
pharmaceutical product in the United States requires years
of commitment and immense capital resources, sometimes in
the whelm of $500 million. Without the protection of the
patent system, these companies would have no means of recouping
these capital and time investment, and innovation would
be put to a halt.
Figure 2: Companies in the Genomic Landscape
Intellectual Property Protection In Genomic
Discipline
Within the genomic discipline, companies and research can
be divided into three areas: 1) sequencing the genome, 2)
functional genomic, which is finding the functions of the
genes, and 3) information system, which is the software
tools to manage and present the tremendous amount of data.
For each area, different technology is generated and thus,
a different intellectual property strategy should be deployed.
Often, companies participate in one or more of the areas
and should pursue a joint strategy.
Figure 3: Bioinformatic Companies’ Impact on Drug
Discovery Process
Sequencing the Genome
With the hype surrounding the completion of the Human Genome
Project, new technology has been developed for decoding
DNA that provided for the rapid discovery of gene fragments
known as expressed-sequence tags (ESTs). These companies,
such as Incyte Genomics and Celera, have generated large
databases of expressed sequence (EST) data and have aggressively
filed patents on these ESTs. For example, Human Genome Sciences
holds patents on 103 human genes and has patents pending
on 7,500 genes. Incyte Genomics tops the list with some
400 patented genes, while Celera, which only began decoding
DNA last year, has already filed patent claims on at least
6,500 gene sequences.
To fall within patent protection, an invention must be
deemed novel, useful and non-obvious. Often the biological
function of these DNA sequences are unknown and companies
have tried to fulfill the useful criteria by proposing generic
and often frivolous uses, such as forensic probes and sometimes
even cattle feed. Currently, Incyte and similar companies
have filed thousands of provisional patent applications
with the United States Patent and Trademark Office (USPTO)
for ESTs in hopes that, they will someday be able to find
the "usefulness" of the sequence. Numerous opponents
of these tactics have argued that patent rights should be
reserved for whomever uncovers the true biological function
of a complete gene. The USPTO is currently developing guidelines
that require examiners to reject patents that don’t
describe a "specific, substantial and credible"
use for a DNA sequence. Thus, many experts predict that
most of these EST patents would eventually not receive patent
protection.
To combat the high risk that their patent applications
would not be allowed, companies in this area can pursue
various strategic options. One of which is to challenge
the examiner’s rejection by an appeal to the PTO board
of appeals. However, if the appeal process is not successful,
your case can be taken to the Federal Circuit Court of Appeals,
where the new "usefulness" standard has not been
tested. Currently, the case law including Brenner v. Manson
(1966 Supreme Court), Philips Petroleum (1989 Federal Circuit
Court of Appeals), and Bedford v. Hunt (1817) has defined
"useful to mean beneficial in contrast to injurious
to the morals, health, or good order of society." Thus,
the court would need to justify the requirement of the newly
proposed "specific, substantial and credible usefulness
standard."
Another strategic move would be to fortify an application
by performing homology studies on the gene sequence in the
patent. Homology refers to the establishment of a relationship
or common thread between the novel gene sequence in the
patent to another gene that has already been discovered,
but not patented. For example, claiming that gene XYZ is
related to ABC, which has a known function. Thus, making
the argument that gene XYZ performs a related function to
gene ABC’s function. The standard upon which the USPTO
relies on is that an expert in the field would agree that
the common thread is strong. However, as our understanding
of genes increases, the existing definition of what’s
related is constantly shifting and various patents may be
invalidated based on these shifts.
Another tactic would be to conduct several functional assays
in order to better determine gene sequence function. The
inventor can submit a declaration on sequences behavior
asserting that he or she has a strong notion that the sequence
is more likely than not to have some function. Even if a
DNA discovery claims to encode a protein involved in cancer
but later on turns out to be involved in another disease,
the courts would allow the new usage and the invention is
protected. For example, Viagra was originally patented as
a heart remedy.
The most conservative approach would be to go back to the
laboratory and perform analysis until you find a definitive
function. However, when you do find the function, the genetic
sequence probably would have been published already and
you will be too late in the game to claim the use of the
genetic sequence.
With the controversy surrounding the patenting of just
the sequences, companies in this area should explore protecting
intellectual property surrounding the tools to sequence
the genes and the tools to analyze the genetic data. Patents
in this category generally cover computer-implemented methods,
computer-based systems, and computer programs for analyzing
and annotating voluminous nucleotide sequences. For example,
protecting a companies’ proprietary method of locating
boundaries between exons and introns would create value
in licensing revenue and also, more importantly, the protected
intellectual property can be used as bargaining chips in
a cross-licensing of another company’s technology.
Many of these analytic tools are embodied in software and
thus would get automatic protection from copyright protection
for its source code. However, patent protection is a better
venue as the functionality of the invention is protected
versus the literal source code. For example, if a company
obtained a patent for its method of locating boundaries
between exons and introns, one who practices one of the
steps covered in its patent claims would be an infringer
even if a different source code is utilized. Under copyright
protection, the infringer would need to use the exact source
code to infringe.
Functional Genomic
After acquisition of specific sequences, the functionality
of these sequences need to be determine to generate value
in creating targets for new drugs and new genetic therapy
treatments. Many players compete in this area as the monetary
and emotional pay-off is tremendous if one is able to be
the first to find a cure to a certain disease.
Once again the importance of computational power is put
into play as computational methodologies are deployed in
comparative genomic, the comparing of human genetic data
to other organism genomes, which have functions that have
been defined. Patent protection would be invaluable in protecting
methods such as sequence alignments, homology searches,
and metabolic pathway modeling. Protecting these fundamental
methods would create more value than patenting a specific
software product, as intense competition in this area would
create shorter and shorter product life cycles.
Genes do not work in isolation. Finding the pattern of
gene expression is another great area of interest that requires
computational power. Companies, such as Affymetrix and Hyseq,
are engaged in developing assays, tools, and computational
techniques for detecting, monitoring and interpreting gene
expression profiles. For example, a microarray, which is
a collection of probes, -short sequences of nucleotide synthesized
to hybridize with the genes of interest-, are placed in
a grid on a glass slide or chip and exposed to a sample
of unknown DNA. A fluorescent "signaling" enzyme
is attached to the end of the probe that glows when the
probe hybridizes with the gene of interest. Affymetrix,
which pioneered the concept of DNA microarrays based on
computer chip technology, can fit 250,000 probes in a matrix
only 1 square centimeter in size. With an estimated 100,000
genes in the human body, a "universal" microarray
is within reach. Incyte Genomics has announced that its
Synteni division has intention to make a chip containing
the entire human genome in the next few years.
To protect its intellectual property, companies in this
area need to seek patent protection covering the core technology
of these devices and methods. However, an even more valuable
claim would be to protect the generation of expression data
utilizing these methods and devices. In addition, since
the design of the microarrays mirrors chip design technology,
another method of protection to explore would be maskwork
protection. In chip technology, when the chip layout includes
an original circuit design, the layout is protectable. Specifically,
maskworks protect against the unauthorized copying of chip
layout information. Federal registration is relatively quick
and an inexpensive process, but filing must be done within
two years of commercialization of the chip product. Thus,
it is arguable that the layout of the probes for a microarray
can avail itself with maskwork protection.
Information System
As more information is generated from sequencing tools
and functional analysis tools, the managing and sharing
of the information would become increasingly important.
The ability to share, manage, and distribute the information
is extremely important in this space because ethical issues
creates an environment that fosters sharing of the information
and suppresses the patenting of the information. Already
there are advocates who call for an intellectual property
free zone for genomic research, a moratorium on gene patenting,
and a compulsory licensing scheme. In March 2000, President
Clinton and Prime Minister Blair made a joint announcement
that human genome research "should be made available
to scientists everywhere." Thus, a company should not
concentrate all its intellectual property protection on
the information, the genetic sequence, but instead should
try to create value in the analytic tools and the management
of the information.
Companies, such as Incyte Genomics, Celera, and CuraGen,
are developing Internet tools to allow researchers to share
the genetic information in their databases. Also, these
companies are providing researches various tools to analyze
the data, present the data, and store their research results.
This revolution toward content delivery and presentation
can be compared to the Internet revolution where content
is free but the added value is the presentation. Thus, there
is a "silent gold rush in the genomic space" that
mirrors the rush to file Internet business method patents,
such as Amazon’s "one-click" method. Numerous
companies are filing patents to stake out methods for sharing
and manipulating the enormous quantity of genetic data being
put online. For example, one application claims the idea
of using a reward system to compensate scientists with free
purchase for posting information and comments to a private
gene database. Another example is DoubleTwist.com, a start-up
company that is actively filing patents around the software,
the data processing, the data mining that turns "the
raw stuff to the good stuff." However, patenting these
business methods would bring about the same controversy
that surrounds the current Internet patents as opponents
are arguing that these methods of manipulating research
data online have been utilize in the research space for
number of years. Thus, a patent portfolio should include
protection of the enabling tools as well as protecting the
business methods.
Conclusion:
In its intellectual property portfolio, all companies should
aggressively protect their core technology in numerous facets
such as patent protection, copyright, trademarks, maskworks
for chip design, and trade secrets. This is extremely important
in the bioinformatic space as ethical issues create an environment
against patenting of genetic sequence data. In addition
to a defensive strategy of defending its core technology,
companies should also pursue an offensive strategy that
includes analyzing emerging standards and competitor focus
so that companies could acquire a competitive advantage
or entice a cross-licensing of another’s technology.
Footnotes:
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4.- Haseltine, William A. 2000. The Case for Gene Patents.
MIT Technology Review. September/October; 59.
5.- Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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6.- Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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7.- Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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8.- Herrera, Stephan. 2000. Patent Panic. Red Herring. July;
210.
9.- Herrera, Stephan. 2000. Patent Panic. Red Herring. July;
210.
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210.
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12.-Wong and et al. 1999. Genomics-Based Intellectual Property
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3.
13.-Wong and et al. 1999. Genomics-Based Intellectual Property
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14.-Wong and et al. 1999. Genomics-Based Intellectual Property
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15.-Robbins-Roth, Cynthia. 2000. From Alchemy to IPO. The
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17.-Fernandez et al. 1999. Intellectual Property Rights
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18.-Shulman, Seth. 2000. Toward Sharing the Genome. MIT
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19.-Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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20.-Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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21.-Regalado, Antonio. 2000. The Great Gene Grab. MIT Technology
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