Oncomouse

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	"The Mouse That Changed Science", Distillations Podcast and transcript, Episode 236, November 16, 2018, Science History Institute

Last updated December 05, 2023

The OncoMouse or Harvard mouse is a type of laboratory mouse (Mus musculus) that has been genetically modified using modifications designed by Philip Leder and Timothy A Stewart ^[1] of Harvard University to carry a specific gene called an activated oncogene (v-Ha-ras under the control of the mouse mammary tumor virus promoter). The activated oncogene significantly increases the mouse's susceptibility to cancer, and thus makes the mouse a suitable model for cancer research.^[2]^[3]

OncoMouse was not the first transgenic mouse to be developed for use in cancer research. Ralph L. Brinster and Richard Palmiter had developed such mice previously. However, OncoMouse was the first mammal to be patented. Because DuPont had funded Philip Leder's research, Harvard University agreed to give DuPont exclusive rights to any inventions commercialized as a result of the funding.^[4] Patent applications on the OncoMouse were filed back in the mid-1980s in numerous countries such as in the United States, in Canada, in Europe through the European Patent Office (EPO) and in Japan. Initially the rights to the OncoMouse invention were owned by DuPont. However, in 2011 the USPTO 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 ^[2]^[3]).

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.^[4] 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.^[4]

Patent procedures

Canada

In Canada, the Supreme Court in 2002 rejected the patent in Harvard College v. Canada (Commissioner of Patents) , overturning a Federal Court of Appeal verdict which ruled in favor of the patent. However, on 7 October 2003, Canadian patent 1,341,442 CA 1341442 was granted to Harvard College. The patent was amended to omit the "composition of matter" claims on the transgenic mice. The Supreme Court 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, and the patent was valid until 2020.

Europe (through the EPO)

European patent application 85304490.7 was filed in June 1985 by "The President and Fellows of Harvard College". It was initially refused in 1989 by an Examining Division of the European Patent Office (EPO) among other things on the grounds that the European Patent Convention (EPC) excludes patentability of animals per se. The decision was appealed and the Board of Appeal held that animal varieties were excluded of patentability by the EPC (and especially its Article 53(b) EPC), while animals (as such) were not excluded from patentability.^[5] The Examining Division then granted the patent in 1992 (its publication number is EP 0169672 ).

The European patent was then opposed by several third parties, more precisely by 17 opponents, notably on the grounds laid out in Article 53(a) EPC, according to which "inventions, the publication or exploitation of which would be contrary to "ordre public" or morality are excluded from patentability. 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.^[6] 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 Article 63(1) EPC), for failure to pay the fees and to file the translations of the amended claims under Rule 58(5) EPC 1973.

United States

In 1988, the United States Patent and Trademark Office (USPTO) granted U.S. Patent 4,736,866 (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. 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 ( U.S. Patent 5,087,571 ; filed Mar 22, 1988, issued Feb 11, 1992, expired Feb 11, 2009) and testing methods using transgenic mice expressing an oncogene ( U.S. Patent 5,925,803 ; 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.^[3] Dupont is currently^{[ needs update ]} bringing suit in the Eastern District of Virginia.^[3]

Related Research Articles

The patentability of software, computer programs and computer-implemented inventions under the European Patent Convention (EPC) is the extent to which subject matter in these fields is patentable under the Convention on the Grant of European Patents of October 5, 1973. The subject also includes the question of whether European patents granted by the European Patent Office (EPO) in these fields (sometimes called "software patents") are regarded as valid by national courts.

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 while the Administrative Council acts as its supervisory body as well as, to a limited extent, its legislative body. The actual legislative power to revise the European Patent Convention lies with the Contracting States themselves when meeting at a Conference of the Contracting States.

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 which European patents are granted. The term European patent is used to refer to patents granted under the European Patent Convention. However, a European patent is not a unitary right, but a group of essentially independent nationally enforceable, nationally revocable patents, subject to central revocation or narrowing as a group pursuant to two types of unified, post-grant procedures: a time-limited opposition procedure, which can be initiated by any person except the patent proprietor, and limitation and revocation procedures, which can be initiated by the patent proprietor only.

As with all utility patents in the United States, a biological patent provides the patent holder with the right to exclude others from making, using, selling, or importing the claimed invention or discovery in biology for a limited period of time - for patents filed after 1998, 20 years from the filing date.

The EPC 2000 or European Patent Convention 2000 is the version of the European Patent Convention (EPC) as revised by the Act Revising the Convention on the Grant of European Patents signed in Munich on November 29, 2000. On June 28, 2001, the Administrative Council of the European Patent Organisation adopted the final new text of the EPC 2000. The EPC 2000 entered into force on December 13, 2007.

The opposition procedure before the European Patent Office (EPO) is a post-grant, contentious, inter partes, administrative procedure intended to allow any European patent to be centrally opposed. European patents granted by the EPO under the European Patent Convention (EPC) may be opposed by any person from the public. This happens often when some prior art was not found during the grant procedure, but was only known by third parties.

In certain jurisdictions' patent law, industrial applicability or industrial application is a patentability requirement according to which a patent can only be granted for an invention which is susceptible of industrial application, i.e. for an invention which can be made or used in some kind of industry. In this context, the concept of "industry" is far-reaching: it includes agriculture, for instance. An example of invention which would not be susceptible of industrial application is "a method of contraception [...] to be applied in the private and personal sphere of a human being".

Harvard College v Canada (Commissioner of Patents) is a leading Supreme Court of Canada case concerning the patentability of higher life forms within the context of the Patent Act. At issue was the patentability of the Harvard oncomouse, a mouse that had its genome genetically altered by a cancer-promoting gene (oncogene). In a 5-4 split, the Supreme Court held that the oncomouse and higher life forms in general are not patentable subject matter in Canada.

In patent law, an inventor is the person, or persons in United States patent law, who contribute to the claims of a patentable invention. In some patent law frameworks, however, such as in the European Patent Convention (EPC) and its case law, no explicit, accurate definition of who exactly is an inventor is provided. The definition may slightly vary from one European country to another. Inventorship is generally not considered to be a patentability criterion under European patent law.

In patent law, a disclaimer are words identifying, in a claim, subject-matter that is not claimed or another writing disclaiming rights ostensibly protected by the patent. By extension, a disclaimer may also mean the amendment consisting in introducing a negative limitation in an existing claim, i.e. "an amendment to a claim resulting in the incorporation therein of a 'negative' technical feature, typically excluding from a general feature specific embodiments or areas". The allowability of disclaimers is subject to particular conditions, which may vary widely from one jurisdiction to another.

Maintenance fees or renewal fees are fees paid to maintain a granted patent in force. Some patent laws require the payment of maintenance fees for pending patent applications. Not all patent laws require the payment of maintenance fees and different laws provide different regulations concerning not only the amount payable but also the regularity of the payments. In countries where maintenance fees are to be paid annually, they are sometimes called patent annuities.

G 1/03 and G 2/03 are two decisions of the Enlarged Board of Appeal of the European Patent Office (EPO), which were both issued on April 8, 2004.

This is a list of legal terms relating to patents and patent law. A patent is not a right to practice or use the invention claimed therein, but a territorial right to exclude others from commercially exploiting the invention, granted to an inventor or his successor in rights in exchange to a public disclosure of the invention.

The grant procedure before the European Patent Office (EPO) is an ex parte, administrative procedure, which includes the filing of a European patent application, the examination of formalities, the establishment of a search report, the publication of the application, its substantive examination, and the grant of a patent, or the refusal of the application, in accordance with the legal provisions of the European Patent Convention (EPC). The grant procedure is carried out by the EPO under the supervision of the Administrative Council of the European Patent Organisation. The patents granted in accordance with the EPC are called European patents.

Article 123 of the European Patent Convention (EPC) relates to the amendments under the EPC, i.e. the amendments to a European patent application or patent, and notably the conditions under which they are allowable. In particular, Article 123(2) EPC prohibits adding subject-matter going beyond the content of the application as filed, while Article 123(3) EPC prohibits an extension of the scope of protection by amendment after grant. In addition, Rule 80 EPC limits the types of amendments that can be done during opposition proceedings before the European Patent Office (EPO), and Rule 139 EPC relates to the correction of errors in documents filed with the EPO.

Article 83 of the European Patent Convention (EPC) relates to the disclosure of the invention under the European Patent Convention. This legal provision prescribes that a European patent application must disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.

In United States patent law, a composition of matter is one of the four principal categories of things that may be patented. The other three are a process, a machine, and an article of manufacture. In United States patent law, that same terminology has been in use since the first patent act in 1790.

Under the European Patent Convention (EPC), European patents shall be granted for inventions which inter alia are new. The central legal provision explaining what this means, i.e. the central legal provision relating to the novelty under the EPC, is Article 54 EPC. Namely, "an invention can be patented only if it is new. An invention is considered to be new if it does not form part of the state of the art. The purpose of Article 54(1) EPC is to prevent the state of the art being patented again."

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 biological patents vary among jurisdictions, and may include biological technology and products, genetically modified organisms and genetic material. The applicability of patents to substances and processes wholly or partially natural in origin is a subject of debate.

References

↑ European Patent Register entry for European patent no. 0169672, under "Inventor(s)". Consulted on February 22, 2008.
1 2 Trademark: USPTO serial number 75797027
1 2 3 4 Crouch, Dennis (September 18, 2012). "Harvard's US OncoMouse Patents are All Expired (For the Time Being)". Patently-O. Retrieved 21 April 2013. For now, however, it appears that the mice are finally free although their title (OncoMouse) is still a registered trademark owned by DuPont
1 2 3 "The Mouse That Changed Science: Distillations Podcast and Transcript, Episode 236". Distillations. Science History Institute. November 16, 2018. Retrieved August 28, 2019.
↑ EPO Board of Appeal decision T 19/90 of October 3, 1990.
↑ EPO board of appeal decision T 315/03 of July 6, 2004.