Patent Law in Biotechnology and Bioethics

The project has to deal with the issues that have arisen in significant patent law cases concerning biotechnology and bioethics. The project will seek to do so by comparing the approach of different patent jurisdictions with respect to the patentability of Harvard Oncomouse. This particular organism is transgenic in nature. Animals are called transgenic in nature when the DNA from other species is artificially introduced into their genome. The need of inducing such genes into animals to produce transgenic animals is required for potentially beneficial applications like medical research, production of proteins and organs and enhanced food production. [1] The genetic manipulation of animals invariably raises a number of ethical issues, which are extremely divisive and controversial.

The Harvard Oncomouse, as the name suggests was one such transgenic organism. In fact it was one of the first transgenic animals to be produced. In the early 1980s’ the researchers in Harvard Medical School, Philip Leder and Timothy Stewart produced this genetically modified mouse, which was found to be highly susceptible to cancer. [2] In order to produce the Oncomouse, scientists introduced a cancer-promoting gene through micro-injection of DNA into a fertilized mouse embryo. The inserted genees were modified also to be expressed in the mammary tissue, for making the mouse a biological model for understanding the development of breast cancer. The mouse was also engineered to exhibit increased sensitivity to toxic substances which allowed medical experts to study carcinogenic environmental factors.

This Oncomouse was immediately seen as a valuable means of furthering cancer research. The Harvard College also sought patent protection in the United States and several other countries.

Patentability of Oncomouse in United States- A battle easily won

It is important to understand the scope and ambit of the phrase “patentable subject matter” which is the phrase used in the statute in United States. In the United States, subject matter is defined as “any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof.” Based on this all- encompassing definition, US Courts have adopted a broad view of statutory subject matter, generally relying on other aspects of the patent statute to invalidate patents. [3] In this judgment, the US Supreme Court also said that patentable subject matter “includes anything under the sun that is made by man.” [4] This decision has clearly made it easier to get a patent for oncomouse in the United States. After the decision of the US Supreme Court in Chakraborty even living matter became patentable. The question before the Court was as to whether a microorganism constituted a manufacture or composition of matter. [5] The invention at issue was a genetically engineered bacterium with the ability to break down crude oil. [6] The invention also had a potential application in the treatment of oil spills. [7] Originally, the U.S. Patent and Trademark Office rejected the patent claims to the bacteria. [8] Thereupon, the Patent Office Board of Appeals also rejected the claims, relying on the 1930 Plant Patent Act as proof that 35 U.S.C. § 101, which describes the subject matter limitation of the U.S. Patent Act, did not cover living things. [9] The Court in Chakrabarty placed a great deal of emphasis on the need to expansively interpret section 101 of the U.S. Patent Act. [10] Thereafter the Court applied the common dictionary definitions of “manufacture” and “composition of matter,” the Court concluded that the claimed bacterium “plainly qualified as statutory subject matter”. [11] Yet the Court refused to consider the moral and policy arguments against granting patents for living matter, finding it beyond the Court’s capabilities and, as such, were more suited to consideration via the legislative process. [12] The Chakrabarty decision paved the way for many subsequent biotechnology patents.

The Harvard Oncomouse easily got a patent in the United States in 1988. The USPTO granted a patent number 4, 736, 866 to Harvard College claiming “a transgenic non-human mammal whose germ cells and somatic cells contain a recombinant oncogene sequence introduced into said mammal.” The claim clearly excluded human beings, which reflected moral and legal concerns about patents on human beings and the perils surrounding modification of the human genome.

In fact it became the first animal, which was given patent protection when the United States Patent and Trademark Office issued a patent to Philip Leder and Timothy Stewart. In fact a broad protection was given for the Oncomouse. The protection was extended to the vectors in which the oncogene got copied, the fertilized mouse egg containing the foreign DNA, and the fully developed Oncomouse. It is to be noted that the USPTO also observed that the animal was “not simply a transgenic mouse with an activated gene; it is any transgenic mammal, excluding human beings, that contains in all its cells an activated oncogene that had been introduced into it or an ancestor at an embryonic stage.” [13] 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 and testing methods using transgenic mice expressing an oncogene.

After the patent was granted to the Oncomouse in the United States in 1988, several other countries adopted similar guidelines. For instance, other countries at the forefront of cancer research like Japan and the European Patent Office also adopted similar guidelines in 1994 and 1992 respectively. Yet there were may people and groups around the world who raised arguments related to ethics and public policy and slammed the approach of patent offices. [14] In this regard it will be very interesting to move on to the next limb of the project which discusses the question of patentability of oncomouse in Canada. It is particularly enlightening because in Canada, the matter was adjuciated by the highest Court of the land.

Patentability of Oncomouse in Canada- A long drawn battle

The Supreme Court of Canada in Harvard College v. Canada (Commissioner of Patents) [15] held by a majority of five to four that higher forms of life are not patentable. The respondents in the instant case were the President and Fellows of the Harvard College. In 1985, Harvard College applied for a patent in Canada. Within the patent application there were 26 claims made by Harvard that sought to protect the process by which the omcomice were produced and the end product of the process, the founder mouse and the offspring whose cells were affected by the oncogene.

Facts:

The facts of the case are very interesting. The respondent applied for a patent on an invention entitled “transgenic animals”. The application had also explained the way the oncomouse was produced by the respondent. An oncogene is injected into fertilized mouse eggs as close as possible to the one-cell stage which were then implanted into a female hose mouse and permitted to develop to term. The offspring of the host mouse are tested for the presence of the oncogene. [16] Those in which the oncogene are found are called “founder” nice which are then mated with mice that has not been genetically altered. Then fifty percent of the offspring will have all of their cells affected by the oncogene making them extremely suitable for carcinogenic research studies.

Claim made by the respondent:

The respondent in its patent application sought to protect both the process by which the oncomice were produced and also the end-product of the process which included the founder mice and the offspring whose cells contained the oncogene. In other words, the claim was for both the process and the product including all non-human mammals.On March 24, 1993 the Canadian Patent Examiner allowed a patent for the process claims but cliams for the transgenic animal itself as the invention or the subject matter of a patent were denied. The appellant Commissioner confirmed the refusal of the product claims. The Federal Court, Trial Division, dismissed the respondent’s appeal from the appellant’s decision. The respondent’s further appeal to the Federal Court of Appeal was allowed. However in 2000, the Federal Court of Appeal overturned the trial judge and concluded that both the process and the mouse could be patented. Ruling 2-1 in favour of the full patent, it said that nothing in the Canada’s 1869 Patent Act outlawed patenting animals, although asserted that human beings cannot be patented under any circumstances. However, this case was further appealed to the Supreme Court of Canada and on December 5th, 2002, the Court decided that higher life forms were not patentable subject matter. [17]

Decision of the Supreme Court of Canada

Majority Opinion [18]

The sole question beofre the Supreme Court was whether the words “manufacture” and “composition of matter”, within the context of the Patent Act, were sufficietnyl broad enough to include higher life forms. The majority could cautioned that the Court’s belief cannot guide the interpretation of a statutory provision. The words of the Patent Act were to be read in their entire context and in their grammatical and ordinary sense harmoiusly with the schme of the Act, the object of the Act and the intention of the Parliament. [19] The Majority judges also cautoned that the compariosn with the patent law of other countries will be of little help in the interpretation of a provision of the Canadian patent law. The majority came to the conlusion that the reading of the words of the Act support the conclusion that higher forms of life are not patentable. [20]

Now the Candian Patent law defines an invention as, “ invention means any new and useful art, process, machine , manufacture or composition of matter, or any new and useful improvement in any art, process, machine, manufacture or composition of matter. The majority came to the conclusion that the choice of an exhaustive definition signalled a clear intention of the legislature to exlude certain subject matter as being outside the confines of the Act. [21] It was emphasized that the defintion of invention did not read as “anything new and useful made by man.” The Court emphazised that the words “composition of matter” are preceded by by words like “machine” and manufacture” which clearly do not imply a living creature. Thus through the rule of “ejusdem generis” the Court came to the conclusion that the words “composition of matter” do not include a higher life form such as the oncomouse. The majority also signified that the word “manufacture”, in the context of the Act, is commonly understood to denote a non-living mechanisitic product or process, not a higher life form. [22]

The majority also stressed on the fact that the higher life forms cannot be conceptualized as mere “compositions of matter” within the context of the Patent Act. It was pointed out that the Parliament might have considered corss bred plants and animals as patentable because they could have been better regarded as “discoveries”. The fundamental premise on which the majority proceeded was that since patenting higher life forms would involve a radical departure from the traditional patent regime, and since the patentability of such life forms is a highly complex and contentious , a clear and unequivocal legislation is required for higher life forms to be patentable as the existing Act does not clearly indicate that higher life forms are patentable. [23] The majority clearly indicated that the Patent Act in its current form was not well suited to address the unique characterisitics possessed by the higher life forms for which the Parliament only has to draft a new legislation. It is submitted that this was largely because of the fact that the majority was not interested in drawing up a list of aspects of human life which would have to be exlcuded from patentability. The Court supported its stand by referring to the Plant Breeders’ Rights Act which was a special legislation for the protection of plant breeders, but did not address other higher life forms. The majority was convinced that the Parliament is the right forum for addressing techincal issues related to biotechnology. The Court also stressed that while lower forms of life like microorganisms are patentable, it will be wrong to apply the same logic in case of higher forms of life like plants and animals. [24]

Minority Opinion [25]

The minority came to the conclusion that the oncomouse was a patentable subject matter because every single cell in the body of an animal which does not in this altered form exist in nature, by human modification of the genetic material of which it is composed is an inventive “composition of matter” within the meaning of Section 2 of the Patent Act.

The minority also stressed that if the genetically altered oncomouse egg was an invention under the Patent Act, there was no basis in the statutory text to conclude that the resulting oncomouse which grows from the patented egg, was not patentable. The minority dismissed the point made by the majority that the legislature never intended to include higher life forms in paten legislation by pointing out that parliament did not contemplate the oncomouse in 1869 when it enacted the definition of “invention”, it aldo did not contemplate moon rockets, antibiotics, telephones, e-mail or hand-held computers either. [26] The minority tried to argue that the based on the language of the Act, the intent could be attributed to the Parliament that it considered it to be in public interest to encourage new and useful inventions without knowing what such invention would turn out to be. It was pointed out that the Commissioner of Patents could not have refused a patent on the grounds of moraility, public interest of the other statutory criteria are met.

The minority has also advocated for the patentability of the oncomouse after referring to the international context. It has commented,

“The mobility of capital and technology makes it desirable that comparable jurisdictions with comparale intellectual property legislation arrive at similar legal results.” [27]

It has been stressed that the expression “composition of matter” was found in the U.S. Patent Act under which the Oncomouse was patented in 1988. The oncomouse was also patented in jurisidictions that cover Austria, Belgium, Denmark, Finland, France, Greece, Ireland, Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden and the United Kingdom. The example of Japan was cited because a simpilar patent was issued there as well. The example of New Zealand was singled out where a patent was issued for a transgenic mouse which was genetically modified to be susceptible to HIV infection. [28] The fact that the massive private sector investemnt in biotechnological research was exactly the kind of research and innovation that the Patent Act was intended to promote. The minority judges also stressed on the fact that the phrase “composition of matter” was an open-ended expression which was not confined to inanimate matter and the Patent Act through its defintion of “invention” never sought to distinguish between “lower” and “higher” life forms. The minority expressed that the job of carving out a subject-matter exception for higher life forms is a policy matter for the Parliament. Furthermore, the idea that oncomouse is not patentable because it invloves only the application of “laws of nature” is wrong because most pharmaceutical drugs utilize the normal bodily processes and functions of humans and animals but are not regarded as unpatentable on that count. [29] The judges accepted that medications like the oncomouse can never be brought into existence without reliance on the laws of nature and biochemistry principles.

The judges also pointed out that the adoption of Plant Breeders’ Rights Act does not mean that the subject matter of patents excludes plants, and other higher life forms like animals because there was no inconsistency between the Act with the Patent Act and thus there was no repeal by implication. The minority concluded by stressing that the lack of a regulatory framework for higher life form inventons could not be a factor for denying patentability to the Oncomouse in Canada. [30] They added that the patenability of human beings is precluded by the law and the braodest claim specifically excludes humans from the scope of transgenic mammals. The judges summed up that neither the Commissioner of Patents nor the courts have the authority to declare a moratorium on higher life patents until Parliament chooses to act. [31]

A Critical Appraisal of the Judgement

The judgment was a clear setback to DuPont as the Oncomouse was licensed to it. The surprising element in the judgment was that it was not expected that such a rigid stand would be taken by the majority. Canada allows single-celled organisms, such as yeasts and bacteria, and GM crops to be patented. It also allows patents for modified human genes and cell lines. Both the najority and minority judgements found the 133 year old Patent Act to be inadequate in addressing the complex ethical and legal problems. The intervention of the Parliament in the matter finds expression in both the opinions. The minority judges have dismissed the prospect that allowing the patent on the Haravard mouse would open the door to patenting humans, as the Canadian Charter of Rights would prohibit ownership of human beings for commercial purposes. But ironically the majority was able to find a counter to that argument and stressed that it is the job of the Parliament to determine as to what are the aspects of human life which shall be excluded from patenting.

The ruling was devastating for numerous Canadian companies which were awaiting patents on plants and animals and the judgemnt was seen as stifling biotechnological research in Canada. It could be gauged from the fact that pending the adjudication by the Supreme Court almost 1, 500 applications for plant and animal patents were put on hold. [32] The judgment of the Court was expected to shape Canada’s policies on cloning and genetic engineering.

Monsanto Canada Inc. v. Schmeiser [33]

The judgment of the Supreme Court of Canada in this case received world wide attention. This case was related to patent rights for biotechnology. The Court did not uphold the validity of the agricultural biotechnology patents held by Monsanto Canada Inc. Now Monsanto’s patent covered only the genetically modified plant cells but not the genetically modified plants themselves, the Court went into the question of whether grwoing genetically modified plants constitutes “use” of the invention of the genetically modified plant cells. The majority came to the conclusion that it does not constitute use.

I am discussing this case in my project because the Court has referred to its decision in the Oncomouse case. The appellant. Schmeiser contended before the Court that the subject matter claimed in the patent by Monsanto was unpatentable. It was argued that giving any protection to the gene or cell will invariably restrict the use of a plant and a seed. Schmeiser relied on reasoning of the majority court in Harvard College v. Canada (Commisisoner of Patents) to contend that plants and seeds were found to be unpatentable higher life forms.

The majority in Monsanto Canada Inc. rejected the contention put forth by Schmeiser and argued that all the judges in Harvard Mouse case had noted in their obiter observations that a fertilized, genetically altered oncomouse egg would be patentable subject matter, regardless of its ultimate anticipated development into a mouse. [34]

The minority in Monsanto Canada Inc. starts off from the premise that the entire matter has to be relooked into in light of the judgment in the Harvard Mouse case. The minority started off its judgment by observing that the lower court decisions allowed Monsanto to do indirectly what Canadian patent law has not allowed them to do directly: namely, to acquire patent protection over whole plants. [35] According to the minority, this was difficult to reconcile with the opinion of the majority in Harvardmosue case as it would invalidate Patent Office’s long-standing policy of not granting exlcusive rights over higher life frms. The minority also states that in Harvard Mouse case, claims for a geetically modified plasmid and the process claims were found to be valid but only the final claim for the mouse was invalidated. In other words, the minority was of the view that the process claims could be valid even if the final produt turns out to be unpatentable subject matter. The minority considered Monsanto’s claims both for products and processes to be valid as neither extend the patent protection to the plant itself, a higher form of life incapable of patent protection. It clarified that the plant cell claim cannot extend past the point where the genetically modified cell begins to multiply and differentiate into plant tissues. [36]

This judgment shows an application of the judgement of the Supreme Court in Harvard Mouse case. The Oncomouse finally got patent protection in Canada on 7th October 2003 when the 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. While the Supreme Court had rejected the entire patent application on the basis of these claims, but now the amended claims were allowed by the Patent Commissioner and the patent remains valid until 2020. [37] It is evident that Canada had to bow down to its international obligations under the TRIPS in light of the fact that the legislature was not coming up with a legisation dealing with the patentability of higher life forms. Article 27 (1) of TRIPS states that Canada has to make patents available for any invention without discrimination as to the field of technology. [38] It is also relevant that the Canadian Biotechnology Advisory Committee, in Patenting of Higher Life Forms and Related Issues in June 2002, suggested that the giving patents to higher life forms might be couterproductive in the long run. The basic premise was that the use of biologically replicating organisms as a vehicle for genetic patents may overcompensate the patentee both in relation to what was invented, and to other areas of invention. [39] The Canadian Biotechnology Advisory Committee has explained that the grant of a patent over a plant, seed or non-human animal covers not only the particular plant, seed or animal sold, but also all its progeny containing the patented invention for all generations until the expiry of the patent term which is for a term of twenty years from the priority date.

Furthermore, Article 27(3)(b) of TRIPS states that members may exlude from patentability plants and animals other than micro-organisms, and essentially biological processes for the production of plants or animals other than non-biological and microbiological processes. It is to be noted that the Oncomouse was able to get a patent in Canada in 2003 only after the “composition of matter” claims on the transgenic mice were rejected.

The next section of the project deals with the extended struggle of DuPont over the Oncomouse before the European Office.

Patentability before the European Patent Office

Biotechnology is a grwoing field and biotechnological inventions have consistently ranked among the ten largest technical fields in terms of patent applications filed with the EPO. Under the regime created by the EPC, biotechnical inventions are patentable with a few exceptions like methods for treatment of the human or animal body, plants and animal varieties and essentially biological processes for the production of plants and animals. [40]

There was a long and protracted battle at several levels at the European Patent Office. The EPO also considered the case at length. Under the EPC, an opposition can be filed by any third party within a period of nine months from mention of grant of the patent amy may result in either revocation of the patent or its maintenance in full or in amended form. The EPO also holds no political views and as an executive organ of the EPO, it examines patent applications on the basis of the relevant law which is the European Patent Convention. [41] The Harvard Oncomouse patent application was EPO’s first-ever application involving an animal. The basic question which was involved was as to whether an animal could be patented under the EPC or not. There were some ethical issues as well which were centred around the fact that commercial profit would be extracted from engineered laboratory animals and a number of groups proclaimed their opposition to laboratory testing on animals in general. The President and Fellows of Harvard College filed an application before the European Patent Office in 1985. It was initially refused in 1989 by an Examining Division of the European Patent Office because, inter alia, that the European Patent Convention excludes patentability of animals per se. The decision was appealed and on October 3, 1990, the Board of Appeal held that animal varieties were excluded of patentability by the EPC by virtue of Article 53 (b) of EPC, while animals, as such, were not excluded from patentability. There were two important conclusions made by the Board of Appeal. Firstly, it was stated that while Article 53 (b) of the EPC excluded animal varieties from patentability, Article 52 (1) which states that patents are avilable for all inventions capable of indusrial application makes it clesr that the exception must be narrowly construed. Secondly, the Board concluded that animals which were genetically altered did not in themselves constitute animal varieties as envisaged in Article 53(b) of the EPC. [42] The Board referred to the Examining division to make a finding if the claim was in contravention of the morality standard envisaged by Article 53 (a). The Examining Division decided that the benefits of the Oncomouse outweighed the risks and the patent was granted. [43]

On 13 May 1992, the EPO granted patent [44] University of Harvard in respect of its European Patent Application of 24 June 1985. Oppositions against the patent were filed within the nine-month period for doing so. This grant was opposed by a large number of non-governmental organizations, religious groups and political parties which were seventeen in number. The main opposition of the groups was that the grant of