The Patent, the Mouse and You

April 26, 2018

In 1980, genetically altered living organisms were deemed eligible for patent protection as the result of a Supreme Court ruling in Diamond v. Chakrabarty447 U.S. 303, 206 USPQ 193 (1980), which held that a human-made microorganism (bacterium capable of breaking down crude oil) was patentable as a “manufacture” or “composite of matter.” Prior, such subject matter was excluded from patent protection, included with items exempted by statutory prohibition or judicial interpretation, including products of nature and laws of nature. However, the Court ruled a live, human-made micro-organism is patentable subject matter under 35 U.S.C. § 101.

The Diamond v. Chakrabarty ruling opened the cage door so to speak for patented research mice, specifically the Harvard OncoMouse. On June 22, 1984, Harvard College researchers Philip Leder and Timothy A. Stewart filed a U.S. patent application titled, “Transgenic Non-Human Mammals,” which was patented April 12, 1988 (patent no. 4,736,866). A transgenic organism contains artificially introduced genetic material from an unrelated organism and, in this case, a heritable cancer-causing gene that increases the probability of the development of malignant tumors. Future generations of the Harvard OncoMouse were bred to test materials suspected of being carcinogenic; used as antioxidant tester animals; and used as a source for cell culture. A second, related patent application was filed by the researchers in 1988 (patent no. 5,087,571), and a third in 1991 (patent no. 5,925,803). Applications were also filed in Canada, Europe and Japan. All three patents have since expired, though the OncoMouse name is a live, registered trademark owned by E.I. Dupont de Nemours and Company, Inc. (research at Harvard Medical School was funded in part by Dupont).

Much is remarkable about the Harvard OncoMouse patents—genetic engineering, contributions to cancer research, ethical issues of transgenic technology itself—but particularly interesting is its status as the first patented animal. According to the Manual of Patent Examining Procedure (MPEP), following Diamond v. Chakrabarty, the Board of Patent Appeals and Interferences determined that animals are patentable subject matter under 35 U.S.C. § 101. In Ex parte Allen, 2 USPQ2d 1425 (Bd. Pat. App. & Inter. 1987), the Board decided that a non-naturally occurring Pacific coast oyster could have been the proper subject of a patent under 35 U.S.C. § 101 if all the criteria for patentability were satisfied. Shortly after the Allen decision, the Commissioner of Patents and Trademarks issued a notice (Animals—Patentability, 1077 O.G. 24, April 21, 1987) stating that the Patent and Trademark Office considers nonnaturally occurring, non-human multicellular living organisms, including animals, to be patentable subject matter within the scope of 35 U.S.C. § 101.

What is also remarkable about the Harvard OncoMouse patents is what they are not: pertaining to humans, other than being a human invention. All three patents include “non-human” verbiage, meaning that the claimed inventions—genetic alterations in living organisms—are limited to non-humans. More broadly, the Leahy-Smith America Invents Act (AIA), § 33(a) states, “Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.” In light of AIA legislative history, this means, according to MPEP § 2105, that while the USPTO has issued patents on genes, stems cells, animals with human genes, and non-biologic products used by humans, it has not issued patents on claims directed to human organisms, including human embryos and fetuses. Thus, § 33(a) of the AIA codifies existing USPTO policy that human organisms are not patent-eligible subject matter and, if the broadest reasonable interpretation of the claimed invention as a whole encompasses a human organism, then a rejection under 35 U.S.C. § 101 and AIA sec. § 33(a) must be made. Additionally, claimed inventions must be examined with regard to all issues pertinent to patentability, and any applicable rejections under 35 U.S.C. § 102, § 103, or § 112 must be made, as well.

What was once exempt from patent protection pre-1980 and the Diamond v. Chakrabarty ruling—a live, non-human (though human-made) micro-organism—is patent-eligible, as evidenced by subsequent patents such as the Harvard OncoMouse. But now so is human genetic material—as noted in AIA § 33(a): the USPTO has issued patents on genes, stems cells, animals with human genes, and non-biologic products used by humans. The Diamond v. Chakrabarty case threw open the gates of innovation to biomedical research, genetic technologies and the Human Genome Project. According to the American Medical Association “Gene Patenting” report on its website, after the human genome was mapped in the year 2000, private and public entities unleashed a flood of patent requests for genes and small pieces of gene sequences. The total number of human genes is estimated to be about 30,000 and, until recently, up to 20 percent of those genes were patented by private companies, the government and individuals.

Human gene patents are not without controversy. According to “Intellectual Property and Genomics” on the National Human Genome Research Institute website, critics argue genes are naturally occurring and, while much intellectual effort may have gone into discovering them within the DNA sequence, discovery is not the same as invention. Additionally, patents issued for genetic technologies limit the use of basic genetic information, which was once in the public domain, thereby inhibiting biomedical research.

One critic is Donna R. MacLean, a British poet who voiced her opposition to human gene patents quite creatively. MacLean filed a patent application on January 5, 2000, with the U.K. Intellectual Property Office—for herself. Titled “Myself” and accorded patent no. GB0000180.0, MacLean argued that she satisfied the usual patent criteria: she was novel, inventive and useful. MacLean said she had many industrial applications, as noted in “After the Gold Rush: Patent Law and Biological Inventions” by Matthew Rimmer (Law in Context 2006): her genes could be used in medical research to extremely profitable ends so she wished to have sole control of her own genetic material. MacLean’s opposition-statement application was terminated before grant.

Critics of gene patenting gained ground in June 2013, when the Supreme Court  ruled unanimously that naturally occurring genes and genetic sequences are not patentable. In Association for Molecular Pathology, v. Myriad Genetics, Inc., 569 U.S. 576 (2013), the case focused on patents on the genes BRCA1 and BRCA2, which are normal genes found in all humans, but mutations increase the risk for breast cancer. The Association of Molecular Pathologists, the American Civil Liberties Union, and a coalition of other groups, filed a lawsuit in 2009 against Myriad Genetics, the USPTO, and the University of Utah Research Foundation challenging the constitutionality and validity of the BRCA1 and BRCA2 gene patents. The case wound its way through the courts—U.S. District Court for the Southern District of New York, Court of Appeals for the Federal Circuit, reexamination at the Court of Appeals and, finally, the U.S. Supreme Court. The Supreme Court found that that isolated but otherwise unmodified genes were products of nature and therefore not patent eligible subject matter. However, the court did find that cDNA, synthetic DNA molecules that contain only the exons of a gene, do involve an inventive step and, thus, remain patent eligible.

The takeaway from this story is what began with a human-made bacterium morphed into a transgenic mouse, then grew into a genetic patent gold rush, which ended up at the steps of the U.S. Supreme Court, twice. Surely more story is yet to come.