Coming to terms with biocapitalism: Norms and idiosyncrasies of a molecular biology patent
It is pointed out that biochemists and molecular biologists embarking on full time research should be able to respond constructively to the current pressure for commercial exploitation of their achievements, in the form of patents. Learning to do an adequate search and draft an application will save time and money. The requirements of novelty, inventive step, and usefulness are explained briefly. Priority in the event of dispute will hinge on either being first to file or first to invent, with the latter depending on the integrity of the laboratory notebook. Safeguards against premature disclosure are explained. Some idiosyncrasies of biotechnology patents are discussed, as is the importance of identifying a licensee.
When the more senior among us started our careers, the idea of directing our work toward its commercial exploitation was nowhere prevalent. Even in the research institutes of industry and the civil service, the emphasis, very often, was on basic research for its own sake. All this has changed. Most if not all universities have (under various titles) a technology exploitation center, illustrating what some would describe as the triumph of technocapitalism [1, 2]. Now employers want research to make money via its protection within the laws of intellectual property, in other words, by the grant of patents. It is often said that scientists are the worst judges of the patentability of their work, and this is undoubtedly true. They will often look upon their own advances as obvious or trivial when in fact they may readily be commercially exploitable; they may be inventions in the legal sense, and although the scientist may not look upon himself in that light, he is an inventor. The ability to recognize this should be learned at the stage of becoming committed to full time research.
Despite regional organizations, for example, the European Patent Office, patent law is still strictly territorial; international agreements do not override domestic legislation. Because the latter can vary substantially from country to country, the remarks herein represent somewhat broad but hopefully relevant perspectives. Also, they apply to universities rather than industry in which, of course, the impetus toward commercialization is well developed.
The Patent Application
Most jurisdictions require that an inventor apply for a patent in the country in which he is a resident. The rationale is to allow the fruits of the invention to be enjoyed by the society that engenders it and also to give the government first option to acquire a compulsory license in the interests of national security. Simultaneously, or later, a patent may be sought in other countries. This is achieved conveniently via the Patent Cooperation Treaty. The home patent office acts as a postbox for the application in other countries; it is sent to an International Searching Authority, who writes a report; if deemed patentable, the application will then be sent to the designated states under the Patent Cooperation Treaty for detailed examination and processing .
Although a patent agent or attorney can be appointed, the wording in the statutes generally allows “any person” to apply for a patent. It is important to be clear about this, because attorney involvement is extremely expensive, and self-help saves both time and money. In biotechnology, as in other cutting edge activities, the time factor is paramount. A competitor can readily jump in ahead of you if you sit on your invention, and the technology transfer units in universities can only proceed as fast as the resources allotted to them. If the scientist himself can energize the process, especially by drafting out the patent application with a basic knowledge of its requirements, he will be well placed to safeguard the commercial rewards.
Ownerships and Royalties
Most if not all jurisdictions regard an the inventions of an employee as property of the employer. Who then is an employee? In universities the concept is important. Are postdocs (as they are known in the trade) employees? Probably they are. This has been indicated in a case involving the University of Chicago, the reasoning in which would probably be persuasive elsewhere .1 Are postgraduate students employees? Almost certainly not. The work of a postgrad is presumably completely subsumed to the supervisor, but we wait to see a postgrad challenge this in court.
It is of course no good applying for a patent if the invention is already protected, hence the need for a search of the “prior art” (as it is still called in intellectual property law). I would submit that it is in this area that the scientists can most exert self-help. There are very few attorneys sufficiently proficient in the intricacies of molecular biology to discern what really constitutes a new idea or process. Indeed it is known that many attorneys are happy to acquire the agency for an application but send the draft for a search by a more experienced practitioner, sometimes in another country, with an appropriate increment in costs. The Internet has immensely aided search; see Table I.
In the event of dispute over priority, there are two concepts to determine who shall obtain the patent, namely “first to file” (most countries) and “first to invent” (United States). In the former system, priority will go to the first to deposit the papers and fees with the patent office, and in the latter it will go to whosoever can demonstrate the “reduction to practice” of the invention. This is what makes properly maintained laboratory notebooks so important to obtain protection in the United States. Should any dispute arise over priority, the record in the notebook would be decisive . 2 In the international sphere, for protection in the United States and any other country included in the Patent Cooperation Treaty, application must be made through the national patent office to the Patent Cooperation Treaty countries within twelve months of first filing there, unless protection is sought in the originating country and internationally at the same time. This establishes priority. This concept taken aboard, the next step is to draft the patent application itself, making sure that the following requirements are met: novelty, inventive step, and usefulness.
To obtain a patent, in most countries the details of the invention must not be in public domain at the date of filing, or in the case of the United States, at the time of invention (see above). This means that in the former case there must be no public disclosure (oral, written, or diagrammatic) of the invention prior to filing (the novelty requirement). Naturally scientists want to make their work known by publication either in a learned journal or at a conference at the earliest possible date. On first principles, this invalidates the subsequent filing of a patent. In some jurisdictions (e.g. United States and Canada) there is a let-out in the legislation if publication occurs less than 12 months before the date of filing; in some others the premature publication must be by means of a paper to a “learned society.” This proviso could be the subject of judicial interpretation, and it might be as well to take advice before making disclosure in this manner . The window of 12 months is kept short to prevent inventors sitting passively on potentially valuable inventions that competitors might pick up.
Sometimes postgraduate theses deposited in the library contain information germane to a patent, which could invalidate the grant by putting it into the public domain. In that case arrangements should be made to delay depositing the thesis in the library until after filing. It might be as well, also, to put anyone reading a commercially-sensitive report who is not already implicitly under a bar of confidentiality (such as members of the same research team) into that position. This prevents disclosure to any third party who on gaining the information innocently would not be liable. Thus anybody put under a bar of confidence who discloses information rendering a patent invalid for lack of novelty could theoretically be sued, in tort/delict, for damages; whether this would be worthwhile would depend on the circumstances. Material in applications for research grants is generally held to be confidential to the assessors and not in the public domain. In some countries there is a self-assessment system whereby, all other requirements having been met, the patent is issued without formal enquiry as to novelty; it is then open to interested parties to challenge the application after it is published.
The wording in the relevant patent act will generally be something like, “ … the invention must not be obvious to a person well versed in the same technological field” (“skilled in the art” is the old term in many English-speaking jurisdictions). When patent applications for biotechnological inventions fail, it is usually on the grounds of obviousness. In legal terms, you have to persuade the examiners that another biochemist of reasonable competence would not have conceived of the invention, having surveyed the technology at the time. Obviously each dispute will turn on the facts, and judges have a hard time making decisions. In the famous United Kingdom case of Biogen vs. Madeva, involving the design of a hepatitis B vaccine, the original patent was filed in 1978, and the technical arguments on obviousness were bandied to and fro in the courts until 1996.3 To sum up, you might fail to apply for a patent, because being heavily involved in your field your technical advance seemed obvious to you; what the patent examiners are interested in, however, is whether it was obvious to anybody else.
This is the last of the mandatory triad of requirements, after novelty and inventive step. Traditionally it is often called “industrial application.” It is probably the one that gives the least trouble. Almost any biomolecule, especially if its function is known, is potentially useful. There are, however, difficult areas. The patentability of expressed sequence tags, in so far as they represent sequences not known to comprise segments of known genes, remains controversial. Applications for patenting expressed sequence tags in the United States were initially successful if the case could be made that they are potentially probes for elucidating the sequences and functions of the whole genes. The European Patent Office opposed their patenting, and some authorities believe that new guidelines from the United States Patent and Trademark Office are an effective tightening up. The enablement is expressed as, “ … the degree to which the claimed sequence represent a genus of nucleotide sequences, the ability to correlate the structure of the claimed sequence with a function, and the manner in which the claim terms are defined in the specification” [7, 8].
With novelty, inventive step, and utility established, the patent application can be drafted in the correct format, with an existing one as a model, incorporating such technicalities as specifications and claims, which will not be dealt with here. It is notable that very soon application will be possible on-line.
Some Molecular Biology Aspects
If you live in a small country it is obviously insufficient to secure protection there alone, allowing the invention to be exploited by industry elsewhere. It is obvious that protection in the United States, Europe, and elsewhere is even more important than in your own country, so some knowledge of how biotechnology applications are treated in these important jurisdictions is essential.
Base and Amino Acid Sequences—
Most people will be aware of the debate in the media over the patenting of genes. Thus Sir Aaron Klug (Royal Society) and Bruce Alperts (National Institutes of Health) stated that, “The intention … to patent DNA sequences themselves, thereby staking a claim to large numbers of human genes without necessarily having a full understanding of their functioning, strikes us as contrary to the essence of patent law … ” . Notwithstanding, it is clear that genes of known expressivity can be patented in most jurisdictions. The European Patent Convention articulates the enablement simply thus, “Biotechnological inventions shall also be patentable if they concern (a) biological material which is isolated from its natural environment or (b) produced by means of a technical process even if it previously occurred in nature” .
This obviously covers nucleic acids, proteins, and peptides, if they can be shown to be useful. The United States Patent and Trademark Office is even more explicit, stating, “An excised gene is eligible for a patent as a composition of matter or as an article of manufacture, because that DNA does not occur in that isolated form in nature … ” .
Life Forms per Se—
Historically there has been no difficulty in patenting lowly life forms; Louis Pasteur received a patent for a yeast strain in 1873, and in the landmark United States case Diamond vs. Chakraborty (1980), an engineered bacterium was successfully protected by its inventor. Only in recent years, with the possibility of cloning or engineering higher organisms, has a new debate erupted. The Harvard “oncomouse” was patented in the United States although the applications were refused in several other jurisdictions, and it is still subject to opposition in that, if nothing else, the claims are too broad, being made for all mammals and not just mice . Human beings of course are a special case. The patent system in the United States is notoriously enabling, but the 13th Amendment to The Constitution forbids slavery and involuntary servitude of any human beings, and so one presumes that a cloned human being would be refused as an invention, although there is apparently nothing on the United States patent legislation specifically blocking such applications.
There is no doubt that, similarly, legislation in most countries, existing or pending, blocks an application to patent any form of human being; to start, such is implicitly forbidden by Article 4 of the United Nations Universal Declaration of Human Rights, and any modified germline would probably be refused, because this could lead to a usable human form. The rules of the European Patent Convention may again serve as a model. Thus they exclude the following: 1) processes for reproductive cloning of human beings, 2) processes for modifying the germline genetic identity of human beings, 3) use of human embryos for industrial or commercial purposes, 4) processes for modifying the genetic identity of animals likely to cause them suffering without substantial medical benefit to man . It is difficult to believe that in any jurisdiction with an ethical basis in law, this will not be followed. In others, who knows?
Algorithms, Methods, and Processes—
In most countries the patent legislation has moved in the direction of liberalization. Historically, discoveries, theories, artistic works, methods for doing business, and presentation of information (to summarize) were largely excluded. Business methods are now patented in the United States (Amazon.com has received United States patent 6,029,141 for its marketing system, although again, controversy reigns), and there is an Act of Congress to protect inventors who have commercialized processes and then find these are being patented by others outside the United States. Medical procedures or methods were long banned from attracting patents, but again this has changed, though the issues are too lengthy to explore here .
In biochemistry or molecular biology it is difficult to think of any new process or method of doing things, perhaps cutting down the steps or time involved in an isolation, if it works, which is not useful in one way or another. However you may devise a method of producing a specific protein, say, in a way distinct from that in a pre-existing patent for producing the same protein, and the owner of this previous method might challenge your patent application. Such is the situation in the dispute over erythropoietin . Amgen produces the protein by cloning the gene and inserting it into Chinese hamster ovary cells, and Transkaryotic Therapies produces the protein by using human cells and a promoter. The courts seem generally to be favoring Amgen, but the litigation, as the newspapers say, is going to “run and run.” In this situation persistence will depend on the extent to which one's employer is prepared to back up the claim on the basis of expert opinion.
A difficulty also arises when the process is known already but either a new starting material or new product is claimed. For example an already patented cell line could be used to convert compound A into compound B, and either A or B is novel; obviously A could be a gene and B a protein (the word “convert” is being used loosely). Until recently, in the United States (via the celebrated Durden case) such a process was not patentable, but the law was changed by the Biotechnology Patent Protection Act of 1995. In Europe and elsewhere the situation is still fluid.
Good ideas can come in many forms; you can realize that elements of a number of known processes or inventions can be abstracted, combined in some novel way, and made useful in some sense. This is known as “mosaicism” and is often challenged on the grounds of obviousness; however the rejoinder is that if assembly is obvious then somebody else inevitably would have put it together. So it may be that if one can put together a variety of techniques in a novel way, then the result would be patentable. You might for example realize that a certain protein could be produced in large quantities by coprecipitation from the extract with a polyion, dissociation at a denaturing temperature, affinity chromatography, and renaturation. A previous patent describes alcohol precipitation and two stages of ion-exchange chromatography giving a much lesser yield. Should you merit a separate patent? On the basis of your ingenuity (called “inventive step”), it would seem so.
It has to be pointed out that even if an invention is patentable, the cost thereof may be prohibitive unless a clear commercial advantage is likely; for that reason an inventor will be at an advantage if he can identify a company or organization likely to take up a license for so-called technology transfer. In rare cases the invention will be regarded so highly that a spin-off company will be set up with the employee taking an executive or consultancy role. The details of this are for discussion in another paper, but the inventor should be conscious of this aspect as he goes though the patenting process.
A herpes simplex vaccine was developed and patented in the University of Chicago, the team leader being cited as the sole inventor. A former postgrad in the project, Jenny Chou, challenged this in court, which held that she had no standing to sue, because by law the inventions of an employee (which implicitly, therefore, she was) are the property of the employer.
The United States patent attorneys Ladas and Parry suggest inter alia that laboratory notebooks 1) be bound permanently (not loose leaf), 2) have gels and chromatographs mounted permanently, and 3) be scrutinized regularly by a third party and signed. This last is obviously the most difficult to implement.
Biogen vs. Madeva (1996) has been discussed extensively and analyzed in the legal literature, because it was the first biotechnology case to go all the way to the supreme court of the United Kingdom (the House of Lords). This decision is not of course binding in other jurisdictions, but because of the closeness of the reasoning, is likely to be persuasive. The dispute (a challenge by Madeva) involved the method of discovery of a vaccine for hepatitis B. Professor Murray ignored introns and so was described as using a “shotgun” approach, and he succeeded initially in obtaining a patent, because such an approach was considered not to be obvious. At the final appeal however it failed on the grounds of overbroadness of claim.