[author: Paul Cole*]
As readers will be aware, members of the public have been invited to submit written comments to the U.S. Patent and Trademakr Office that present their interpretation of the impact of relevant Supreme Court precedent on the legal and technical issues involved in subject matter eligibility analyses during examination of claims reciting or involving laws of nature, natural phenomena, and natural products. The Office invited members of the public who believe that the Supreme Court decisions could be implemented in an alternative manner from the approach taken in the Guidance to:
• present their alternative approach and the legal rationale for the alternative;
• suggest additional examples for use by the Office to create a more complete picture of the impact of Supreme Court precedent on subject matter eligibility;
• provide comments on the subject matter eligibility of particular claims;
• including the sample claims discussed at the 2014 BIO International Convention (see "USPTO Provides Update on Myriad-Mayo Guidance").
The first group of comments has now been published on the USPTO website and can be viewed here.
The present paper provides a brief overview of some early submissions.
Few of the published comments filed deal systematically with the four topics on which the Office has requested information. It is believed that the comments that I filed follow the pattern desired by the Office (save for the BIO claims which had not been published at the time when the comments were submitted), and readers are invited to note the format adopted in the second part of those comments and piggyback on the approach adopted. In particular, amendments suggested page by page and line by line to the existing Guidance and detailed examples and claims analysed using the model contained in the Guidance (with suggested amendments) are more likely to be influential than generalised comments and complaints.
Benjamin Borson argues that the Guidance goes well beyond the Supreme Court's standards under § 101 and might represent "substantive rulemaking" by the Office in contravention of the Administrative Procedures Act (APA). The interpretation of Supreme Court decisions that underlies the Guidance represents policy-driven results that change the way in which patent claims are analysed but without sufficient consideration of legal precedent. In particular he points to the Supreme Court's use in Chakrabarty of the word "characteristics" which he argues is significantly broader than the words "substantially different structure" in the Guidance. If implemented, the standards in the Guidance will significantly and adversely affect the biotechnology, pharmaceutical, and diagnostics industries and will stifle the major purposes of the patent system.
The Japan Patent Attorney Association objects that the content of the Guidance broadens the meaning of the Supreme Court decision in the Myriad case from the field of genes in the human genome to a wide range of natural products. They consider that the Guidance should not apply Myriad so broadly. They point out that the so-called "substance patent system" has been adopted in major jurisdictions including Japan. A substance isolated from a natural environment, for example, a microorganism, antibiotic or a protein with a sugar chain is eligible as a product invention these major jurisdictions. On the other hand, substances isolated from natural products are not eligible in the U.S. according to this guidance. The Guidance therefore goes against efforts to internationally harmonize patent system requirements.
Powerful arguments in favour of the patent-eligibility of natural products are set out in the comments of Thomas DesRosier of Cubist:
Over the coming years, the number of drug compositions derived from naturally occurring small molecules is likely to increase. The development of combinatorial chemistry through the 1990s and 2000s led many pharmaceutical companies to move away from natural products, but that trend is reversing as synthetic small molecule pipelines are drying up. New tools are also emerging to allow scientists to access and study natural products. Scientists have estimated that less than 1% of all microorganisms that have been seen under a microscope have been cultivated. Improved culture procedures are making it possible to grow microorganisms that were previously unavailable, and to study the molecules that they produce. Advances in oceanography and environmental science also are making it possible to collect samples from previously inaccessible areas. Furthermore, recent findings suggest that organisms produce a host of novel products when grown together instead of separately providing new products for researchers to study. Molecular biologists have also discovered silent genes that code for products hidden in bacterial and fungal genomes and they are working to find ways to express and isolate these previously unknown drug candidates.
Researchers must now build upon these discoveries to develop new therapeutic compositions and methods of making and using them. Significant inventive efforts will be required to realize the potential of such naturally-occurring molecules for providing new pharmaceutical treatments. These advances have the potential to produce important new drugs, but only if the economy and the patent system provide appropriate incentives for natural products-related research. Cubist, for example, has invested over $1 billion to bring important life-saving antibiotics to the market, including CUBICIN® and DIFICID®. Unlike diagnostic methods, which were at issue in several of the recent patentable subject matter cases, antibiotics require extensive clinical trials, with substantially more time and resources invested to bring a product to market. If the USPTO now goes beyond the Supreme Court's requirements in refusing to grant patents on inventions derived from or relating to natural products, Cubist and other companies like it will not be able to protect their research and development investments. Therefore, the Guidance should not extend recent Supreme Court decisions to unduly restrict patentable subject matter with respect to natural products-related inventions.
Leslie Fischer of Novartis advocates a "kind"/"degree" test that is in compliance with Hartranft v. Wiegmann, 121 U.S. 609 (1877), which asks whether an object has attained a distinct "name, character, or use" relative to the corresponding raw material. This standard, she argues, has been endorsed, at least implicitly, in patent subject matter eligibility contexts by the Supreme Court in American Fruit, Chakrabarty, and Myriad.
As mentioned, my full submission is available on the website and includes the text previously published here on 4th June under the title: Myriad – An Obvious and Patent-Friendly Interpretation, where it was suggested based on the Hartranft opinion that the Myriad holding should be interpreted in terms of reasons rather than differences, so that isolation accompanied by the additional reason of new utility suffice for eligibility.
My comments also argued that amendment of the Guidance is needed to further clarify that if a claim appears to recite or involve a judicial exception then exclusion is not automatic. For example, materials derived from natural sources do not inevitably fall within the prohibition, and whether or not they do so depends on the form in which they are claimed.
In relation to questions (a) and (g) of the "significantly different" analysis, it is argued that these are unduly restrictive because the only type of difference that is acknowledged is a structural difference. The proposition is repeated in the paragraph following question (l) and in Examples A and E.
Structural difference is neither a necessary nor a sufficient condition for eligibility. If it were a necessary condition, then purified natural products of pharmaceutical use, conceded as being eligible in oral argument in Myriad, would become non-eligible. A fundamental legal change of this kind, affecting the pharmaceutical industry which is one of the most significant classes of user of the patent system, requires explicit language. It should not be imposed by mere assumption of what is implicit in a decision affecting sequences isolated for genetic testing, which is a field of endeavor distant from small molecule natural products or even from isolated plasmids and other sequences useful in genetic engineering e.g. to make products of industrial importance. It is submitted that it was not the intention of the Supreme Court to invalidate protection for natural product inventions such as adrenaline and other compounds set out above. If structural difference were a sufficient condition then the copper plates of the Hartranft example would be eligible because of their raised edges, whereas they were not classified as manufactured articles because insufficient new utility had been demonstrated, the plates being sold by weight and the change in physical form contributing nothing to their value.
As previously explained, the dividing line is therefore a difference leading to new utility. Such differences need not be based on structure but could arise from any human activity leading to new utility including selection, isolation, multiplication, concentration and purification. Questions (a) and (g) therefore require expansion to cover the full range of relevant human activities that could be relevant to eligibility.
Leslie Fischer's approach to example B (Amazonic acid) starts from the tariff cases in the Supreme Court which she argued were not decided based on the potential of the object at issue, but whether the object had, in fact, been changed in such a way that something a new function arose:
Amazonic acid, found in a tree leaf, has the property of being able to inhibit receptor X if administered to humans. Inhibition of receptor X, at a certain level, would be useful to treat the common cold.
Imagine that a human must consume 10,000 pounds of tree leaf to treat the common cold. If one were to administer Amazonic acid in its natural leaf state to a human, Amazonic acid would indeed have the property of inhibiting receptor X, but it would not treat the common cold due to the inordinate (and impossible) amount of leaf that must be consumed. Thus, while one might argue that "function" is inherent, the ultimate "use" is not necessarily so. The use is merely a potential of the natural product. Perhaps the distinction between "use" and "function" is semantic, as the words "use", "function", "quality", "character" and the like are blurred in the English language. Nevertheless, the fact is that purification, isolation, concentration, etc. of Amazonic acid from the leaf is what gives this object the use that is sought, and it is what gives this object value. Indeed, Mr. Hansen, attorney for Petitioner, at oral arguments in front of the Supreme Court in Myriad admitted exactly this, when he conceded that Amazonic acid, isolated from a leaf, could be patent eligible if, in concentrated form, it had a new function.
The suggestion in my comments was to abandon example B entirely and replace it by an example directed to rapamycin (U.S. Patent Nos. 3,929,992 and 3,993,749; for litigation concerning derivatives see the Federal Circuit opinion in Wyeth v Abbott (Fed. Cir. 2013)). It is explained that the naturally-occurring organism Streptomyces hygroscopicus NRRL 5491 was isolated from a sample of soil from Easter Island. It can be cultivated by natural fermentation and produces a triene antibiotic called rapamycin. The antibiotic can be harvested by extraction of the fermentation medium with a water-immiscible solvent such as methylene chloride which can be evaporated to give crude rapamycin as an oily residue. Two stages of preparative column chromatography and precipitation followed by recrystallization give a purified product which was initially of interest for its antifungal properties. A dimethylphosphate derivative of rapamycin has anti-cancer activity. Claims to rapamycin as a colourless crystalline compound, a pharmaceutical composition containing it, and its use for inhibiting the growth of pathogenic fungi are argued as patent-eligible. A real example, it is believed, is more compelling and more difficult to treat dismissively than an over-simplified fictitious example.
A further example of a manufacture relating to a single natural product included in my comments is based on the fact pattern in U.S. Patent No. 4,506,014. Giuseppe Brotzu isolated a library of bacteria from a sewage outfall off the Sardinian coast a fungus called Cephalosporium acremonium, which when cultured, provided crude filtrates having antibacterial activity. Those filtrates were subsequently found to contain cephalosporin antibiotics. Amongst the naturally occurring fungi that he isolated was a strain called Acremonium chrysogenum ATCC 14553. Producing fungal strains with increased productivity for cephalosporin was an unsolved problem. Although genetic engineering using plasmids had become known, success could only be achieved when a plasmid was available which was not immediately eliminated from the host cell which was to be genetically improved, as happens in microorganisms that are unrelated. No such plasmid had been found either in Acremonium or in other closely related strains of fungi. The invention was based on the unexpected discovery of a plasmid in the 14533 strain which had been given the name pAC 1. It was particularly suitable for forming a hybrid vector by cleaving at restriction sites and for inserting a gene for promoting the synthesis of ß-lactam antibiotics.
A claim to the plasmid was assessed as being patent-eligible. In contrast to the BRCA1 sequence considered in Myriad, the plasmid was isolated in vitro and not simply reconstructed in silico and is capable of chemical manipulation using restriction enzymes. Its novelty and utility falls to be judged by a biochemist from the standpoint of practical manipulation to produce hybrid vectors and not simply by a geneticist from the standpoint of its informational content. The plasmid has the new name pAC1. It has new characteristics because in pure form it can be manipulated at defined sites by restriction enzymes, whereas that is not possible with the plasmid as it occurs in nature. It has new utility because it can be used in genetic engineering to form hybrid vectors that can be reintroduced into Acremonium species to promote antibiotic synthesis. It therefore satisfies the Hartranft test approved in Chakrabarty and subsequently approved in Myriad. The use to which the plasmid can be put is a new use and not the mere consequence of its possession (see the dissent of Judge Bryson in Myriad, subsequently approved by Justice Thomas). Selection and isolation has therefore created a new product whose utility goes beyond simple isolation from the surrounding cellular material.
Laurence Shumway and Anne Collins are concerned with personalised medicine and argue for the eligibility of the following process claim:
A method of determining the diagnosis/prognosis of a human patient for disease X, comprising the steps of:
obtaining an isolated biological sample from the patient;
artificially and detectably labelling the isolated biological sample for measuring the level of analyte(s) Y;
measuring the level of the analyte(s) Y using the artificially and detectably labelled biological sample; and
comparing the level of the analyte(s) Y to one or more suitable controls and assigning the patient a diagnosis/prognosis for disease X on the basis of the comparison.
They argued that the proffered claim is more analogous to those in Diehr than to those in Benson, Flook, and Bilski. The proffered claim arguably provides an even stronger case for patent eligibility than did those in Diehr, since, unlike in Diehr, where the equation (analogous to the alleged natural law) was well-known, the "natural principle" (the association of the analyte levels to a diagnosis/prognosis) was not known. The proffered claim also arguably provides that the biological sample is artificially and detectably labelled, which gives an alternative basis to establish patent eligibility.
Although there were 80 attendees at the USPTO Forum on 9 May and it was watched by some 400 people, there have so far been submissions from only two companies or research institutions, two law firms, three IP associations all based in Japan, and 18 individuals. In our profession we tend to file documents just in time before a deadline, which in this case ends at the end of July. Where individuals agree with comments already made, there is, as has been said, an opportunity to piggyback on those comments rather than starting from first principles. However, given the comment at BIO that the Office still considers that its Guidance is fundamentally correct, substantial effort is needed if significant alterations are to be achieved.
* Mr. Cole is a European Patent Attorney and Partner with Lucas & Co. in Warlingham, Surrey, UK and Visiting Professor at Bournemouth University.