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 "The Mouse That Changed Science", Distillations Podcast and transcript, Episode 236, November 16, 2018,Science History Institute |
TheOncoMouse orHarvard mouse is a type oflaboratory mouse (Mus musculus) that has beengenetically modified using modifications designed byPhilip Leder andTimothy A Stewart[1] ofHarvard University to carry a specificgene called an activatedoncogene (v-Ha-ras under the control of themouse mammary tumor virus promoter). The activated oncogene significantly increases the mouse's susceptibility tocancer, and thus makes the mouse a suitable model forcancer research.[2][3]
OncoMouse was not the first transgenic mouse to be developed for use in cancer research.Ralph L. Brinster andRichard Palmiter had developed such mice previously. However, OncoMouse was the first mammal to be patented. BecauseDuPont 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 theUnited States, inCanada, inEurope through theEuropean Patent Office (EPO) and inJapan. Initially the rights to the OncoMouse invention were owned by DuPont. However, in 2011 theUSPTO 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 aregistered 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 throughJackson 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]
In Canada, theSupreme Court in 2002 rejected the patent inHarvard College v. Canada (Commissioner of Patents), overturning aFederal Court of Appeal verdict which ruled in favor of the patent. However, on 7 October 2003, Canadian patent 1,341,442CA 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 theGeneral Agreement on Tariffs and Trade, and the patent was valid until 2020.
European patent application 85304490.7 was filed in June 1985 by "The President and Fellows ofHarvard College". It was initially refused in 1989 by an Examining Division of theEuropean Patent Office (EPO) among other things on the grounds that theEuropean Patent Convention (EPC) excludes patentability ofanimals per se. The decision wasappealed and theBoard of Appeal held thatanimal varieties were excluded of patentability by the EPC (and especially itsArticle 53(b)EPC), whileanimals (as such) were not excluded from patentability.[5] The Examining Division then granted the patent in 1992 (its publication number isEP 0169672 ).
The European patent was thenopposed by several third parties, more precisely by 17 opponents, notably on the grounds laid out inArticle 53(a)EPC, according to which "inventions, the publication or exploitation of which would be contrary to "ordre public" ormorality are excluded frompatentability. 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 underArticle 63(1)EPC), for failure to pay the fees and to file the translations of the amended claims underRule 58(5)EPC 1973.
In 1988, theUnited States Patent and Trademark Office (USPTO) grantedU.S. patent 4,736,866 (filed Jun 22, 1984, issued Apr 12, 1988, expired April 12, 2005) to Harvard Collegeclaiming "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 thehuman 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]
For now, however, it appears that the mice are finally free although their title (OncoMouse) is still a registered trademark owned by DuPont