The OncoMouse or Harvard mouse is a type of
laboratory mouse
The laboratory mouse or lab mouse is a small mammal of the order Rodentia which is bred and used for scientific research or feeders for certain pets. Laboratory mice are usually of the species ''Mus musculus''. They are the most commonly used ...
(''Mus musculus'') that has been
genetically modified
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the gene ...
using modifications designed by
Philip Leder
Philip Leder (November 19, 1934 – February 2, 2020) was an American geneticist.
Early life and education
Leder was born in Washington, D.C. and studied at Harvard University, graduating in 1956. In 1960, he graduated from Harvard Medical Sc ...
and
Timothy A Stewart
Timothy A Stewart (born 30 September 1952) is a molecular biologist. He graduated from the University of Otago (BScHons, PhD.)
Stewart was born in Christchurch, New Zealand. He was a pioneer in the technique of transferring recombinant genes to ...
of
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
to carry a specific
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
called an activated
oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels. (
v-Ha-ras under the control of the
mouse mammary tumor virus
Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus ''Betaretrovirus''. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to t ...
promoter). The activated oncogene significantly increases the mouse's susceptibility to
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, and thus makes the mouse a suitable model for
cancer research
Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure.
Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate and ...
.
[
OncoMouse was not the first transgenic mouse to be developed for use in cancer research. ]Ralph L. Brinster
Ralph Lawrence Brinster (born March 10, 1932) is an American geneticist, National Medal of Science laureate, and Richard King Mellon Professor of Reproductive Physiology at the School of Veterinary Medicine, University of Pennsylvania.
Early li ...
and Richard Palmiter had developed such mice previously. However, OncoMouse was the first mammal to be patented. Because DuPont
DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...
had funded Philip Leder's research, Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
agreed to give DuPont exclusive rights to any inventions commercialized as a result of the funding. Patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
applications on the OncoMouse were filed back in the mid-1980s in numerous countries such as in the United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, in Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
, in Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
through the European Patent Office
The European Patent Office (EPO) is one of the two organs of the European Patent Organisation (EPOrg), the other being the Administrative Council. The EPO acts as executive body for the organisation (EPO) and in Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
. Initially the rights to the OncoMouse invention were owned by DuPont
DuPont de Nemours, Inc., commonly shortened to DuPont, is an American multinational chemical company first formed in 1802 by French-American chemist and industrialist Éleuthère Irénée du Pont de Nemours. The company played a major role in ...
. However, in 2011 the USPTO
The United States Patent and Trademark Office (USPTO) is an agency in the U.S. Department of Commerce that serves as the national patent office and trademark registration authority for the United States. The USPTO's headquarters are in Alexa ...
decided that the final patent actually expired in 2005, which meant that the Oncomouse became free for use by other parties (although the name is not, as "OncoMouse" is a registered trademark
The registered trademark symbol, , is a typographic symbol that provides notice that the preceding word or symbol is a trademark or service mark that has been registered with a national trademark office. A trademark is a symbol, word, or word ...
[ Trademark: USPTO serial number 75797027]).
The patenting of OncoMouse had a significant effect on mouse geneticists, who had previously shared their information and mice from their colonies openly. Once a strain of mice had been first described in published research, mice were stored and acquired through Jackson Laboratory, a nonprofit research institute. The patenting of OncoMouse, and the breadth of the claims made in those patents, were considered to be unreasonable by many of their contemporaries. More broadly, the patenting of OncoMouse was a first step in shifting academic research away from a culture of open and free (or very inexpensive) shared resources towards a commercial culture of expensive proprietary purchase and licensing requirements. This shift was felt far beyond the mouse genetics community. Harvard later said that it regretted the handling of the OncoMouse patents.
Patent procedures
Canada
In Canada, the Supreme Court
A supreme court is the highest court within the hierarchy of courts in most legal jurisdictions. Other descriptions for such courts include court of last resort, apex court, and high (or final) court of appeal. Broadly speaking, the decisions of ...
in 2002 rejected the patent in ''Harvard College v. Canada (Commissioner of Patents)
''Harvard College v Canada (Commissioner of Patents)'' is a leading Supreme Court of Canada case concerning the patentability of higher organism, life forms within the context of the Patent Act (Canada), Patent Act. At issue was the patentability o ...
'', overturning a Federal Court of Appeal
The Federal Court of Appeal (french: Cour d'appel fédérale) is a Canadian appellate court that hears cases concerning federal matters.
History
Section 101 of the Constitution Act, 1867 empowers the Parliament of Canada to establish "addit ...
verdict which ruled in favor of the patent. However, on 7 October 2003, Canadian patent 1,341,442 was granted to Harvard College. The patent was amended to omit the "composition of matter" claims on the transgenic mice. The Supreme Court
A supreme court is the highest court within the hierarchy of courts in most legal jurisdictions. Other descriptions for such courts include court of last resort, apex court, and high (or final) court of appeal. Broadly speaking, the decisions of ...
had rejected the entire patent application on the basis of these claims, but Canadian patent law allowed the amended claims to grant under rules that predated the General Agreement on Tariffs and Trade
The General Agreement on Tariffs and Trade (GATT) is a legal agreement between many countries, whose overall purpose was to promote international trade by reducing or eliminating trade barriers such as tariffs or quotas. According to its pre ...
, and the patent was valid until 2020.
Europe (through the EPO)
European patent
The European Patent Convention (EPC), also known as the Convention on the Grant of European Patents of 5 October 1973, is a multilateral treaty instituting the European Patent Organisation and providing an autonomous legal system according to w ...
application 85304490.7 was filed in June 1985 by "The President and Fellows of Harvard College
Harvard College is the undergraduate college of Harvard University, an Ivy League research university in Cambridge, Massachusetts. Founded in 1636, Harvard College is the original school of Harvard University, the oldest institution of higher lea ...
". It was initially refused in 1989 by an Examining Division of the European Patent Office
The European Patent Office (EPO) is one of the two organs of the European Patent Organisation (EPOrg), the other being the Administrative Council. The EPO acts as executive body for the organisation (EPO) among other things on the grounds that the European Patent Convention
The European Patent Convention (EPC), also known as the Convention on the Grant of European Patents of 5 October 1973, is a multilateral treaty instituting the European Patent Organisation and providing an autonomous legal system according to w ...
(EPC) excludes patentability of animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s per se. The decision was appeal
In law, an appeal is the process in which cases are reviewed by a higher authority, where parties request a formal change to an official decision. Appeals function both as a process for error correction as well as a process of clarifying and ...
ed and the Board of Appeal held that ''animal varieties'' were excluded of patentability by the EPC (and especially its ), while ''animals'' (as such) were not excluded from patentability. The Examining Division then granted the patent in 1992 (its publication number is ).
The European patent was then opposed by several third parties, more precisely by 17 opponents, notably on the grounds laid out in , according to which "inventions, the publication or exploitation of which would be contrary to "ordre public
A suite, in Western classical music and jazz, is an ordered set of instrumental or orchestral/ concert band pieces. It originated in the late 14th century as a pairing of dance tunes and grew in scope to comprise up to five dances, sometimes with ...
" or morality
Morality () is the differentiation of intentions, decisions and actions between those that are distinguished as proper (right) and those that are improper (wrong). Morality can be a body of standards or principles derived from a code of cond ...
are excluded from patentability
Within the context of a national or multilateral body of law, an invention is patentable if it meets the relevant legal conditions to be granted a patent. By extension, patentability also refers to the substantive conditions that must be met fo ...
. After oral proceedings took place in November 2001, the patent was maintained in amended form. This decision was then appealed and the appeal decision was taken on July 6, 2004.[EPO board of appeal decisio]
T 315/03
of July 6, 2004. The case was eventually remitted to the first instance, i.e. the Opposition Division, with the order to maintain the patent on a newly amended form. However, revocation of the patent was eventually published on August 16, 2006, more than 20 years after the filing date (the normal term of a European patent under ), for failure to pay the fees and to file the translations of the amended claims under .
United States
In 1988, the United States Patent and Trademark Office
The United States Patent and Trademark Office (USPTO) is an agency in the U.S. Department of Commerce that serves as the national patent office and trademark registration authority for the United States. The USPTO's headquarters are in Alexa ...
(USPTO) granted (filed Jun 22, 1984, issued Apr 12, 1988, expired April 12, 2005) to Harvard College claiming “a transgenic non-human mammal whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal…” The claim explicitly excluded humans, apparently reflecting moral and legal concerns about patents on human beings, and about modification of the human genome
The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the n ...
. Remarkably, there were no US courts called to decide on the validity of this patent. Two separate patents were issued to Harvard College covering methods for providing a cell culture from a transgenic non-human animal (; filed Mar 22, 1988, issued Feb 11, 1992, expired Feb 11, 2009) and testing methods using transgenic mice expressing an oncogene (; filed Sep 19, 1991, issued Jul 20, 1999, expires July 20, 2016). Both these patents were found to expire in 2005 by the USPTO due to a terminal disclaimer.[ Dupont is currently bringing suit in the Eastern District of Virginia.][
]
See also
* Biobreeding rat
* Biological patent
A biological patent is a patent on an invention in the field of biology that by law allows the patent holder to exclude others from making, using, selling, or importing the protected invention for a limited period of time. The scope and reach of ...
* Knockout mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
* Animal testing
Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
References
Further reading
*
{{genetic engineering
Bioethics
Genetically modified organisms
Patent law
Laboratory mouse strains
Harvard University
Cancer research