By Paul Cole* —

Is Myriad truly authority for the proposition that naturally occurring nucleic acid sequences and a host of other naturally occurring materials are no longer patent-eligible?  Was it really the intention of the Supreme Court to strip away by a side wind protection for future small molecule innovations of the stature of adrenalin (US 730,176; Parke-Davis v Mulford, 189 F. 95, 103 (1911)), digitalis (US 1,898,199), vitamin B12 (US 2,563,794; Merck v. Olin Mathieson, 253 F.3d 156 (4th Circ. 1958)), vinblastine (US 3,097,137), doxorubicin (US 3,590,028) and rapamycin (US 3,929,992 and 3,993,749)?  According to natural product eligibility guidance issued by the USPTO on 4 March 2014 the answer is "yes" and for a naturally occurring composition of matter the only difference that counts is a marked difference in structure, for example that between a eukaryotic gene and its corresponding cDNA.  That guidance has resulted in a storm of protest both from industry and within the profession.

The Office remains open for comments until the end of the month, and it is therefore timely to enquire whether Myriad and earlier opinions support the dramatic legal changes alleged.

To paraphrase the recent opinion in Nautilus v Biosig, a rule of law derivable from an opinion should be precise enough to afford clear notice of what is intended, otherwise there would be a zone of uncertainty:  in this instance for inventors, the Office, and the public.  For that reason, and also because Justice Thomas majored in English literature, the words in which the opinion of the Court is summarized should be presumed to have been chosen with precision and close semantic attention is merited.

The opinion expresses its ruling in two key paragraphs.  In his opening paragraph Justice Thomas says (emphasis added):

For the reasons that follow, we hold that a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated . . .

and he concludes:

We merely hold that genes and the information they encode are not patent eligible under §101 simply because they have been isolated from the surrounding genetic material.

The relevant sense of mere, according to the Merriam-Webster online dictionary, is "nothing more than", as in "a mere mortal", "a mere hint of spice" or "the mere idea of your traveling alone to Europe".  The word simply in its relevant sense is synonymous with merely, also signifying "nothing more than" as in "eats simply to keep alive".  The primary meaning of because is "for the reason that" as in "rested because he was tired".  The words of limitation in the ruling are unmistakable, as also is the link between eligibility and supporting reasons.

Accordingly there is an arguable hypothesis that the rule of law excludes eligibility for a genetic sequence where the only reason available to support patentability is isolation from the natural environment.  It does not exclude eligibility for a naturally occurring sequence where there are additional reasons supporting eligibility, e.g., new utility.  Indeed, if the proposition is generalized, it amounts to no more than that a difference unaccompanied by anything more such as new function or new utility does not suffice for patentability.  That proposition has been part of US law for two centuries, although it is is normally now stated in the context of § 103 rather than § 101.  It also forms part of European law in the context of problem/solution analysis where technical problem is routinely reconstructed from particular technical success vis-à-vis the closest prior art.

If the hypothesis is correct, and given that a plural reason test is immediately identifiable by and obvious to arts-trained readers outside our profession, an explanation is needed why it is not yet widely accepted as the rule of law handed down in Myriad.  Part of the explanation may be confusion between the factual finding and the underlying legal rule, the immediate reaction especially of scientifically trained readers being that the dividing line is between eligible cDNA and non-eligible genomic DNA.  Those were the different outcomes that could be perceived in Myriad without more detailed legal analysis.  Reinforcing that confusion is an expectation that Supreme Court rulings will be far-reaching and not limited and, in the case of our profession, a mindset focusing on differences rather than reasons.  However, as soon as cDNA is identified as other than a product of nature it loses all relevance to the § 101 enquiry:  the test for eligibility for something that is a product of nature cannot be equated either with the test for eligibility of something that is other than a product of nature or with the test whether or not a composition of matter falls within the definition of a product of nature.

It remains to ascertain whether the plural reason test is consistent with other key opinions on product of nature eligibility.

Hartranft v. Wiegmann, 121 U.S. 609, 615 (1887), is the oldest of the opinions cited in Myriad and was a Supreme Court case concerning liability to import duty rather than patents.  It nevertheless contains illustrative findings that support the plural reason test:

• The application of labor to an article either by hand or by machine does not necessarily make that article a manufactured article within the meaning of the tariff laws.  Blocks of marble cut to convenient size for transport are not regarded as manufactured.

• Cleaning or decontaminating a product also does not necessarily produce a new manufacture.  Washing and scouring wool does not make the resulting wool a manufacture of wool.  Cleaning and ginning cotton does not make the resulting cotton a manufacture of cotton.  In the present case ornamental shells that have been cleaned to remove the epidermis and then polished on an emery wheel to expose the pearly interior remain shells and have not been manufactured into a new and different article having a distinctive name, character, or use from that of a shell.

• Packaging does not necessarily create a new manufacture.  Hay pressed into bales ready for market is not a manufactured article, though labor has been involved in cutting and drying the grass and baling the hay.

• Even a change in physical form does not necessarily create a new manufacture.  Round copper plates turned up and raised at the edges from four to five inches by the application of labor to fit them for subsequent use in the manufacture of copper vessels, but which are still bought by the pound as copper for use in making copper vessels, were held not to be manufactured copper.

• However, India-rubber shoes, made in Brazil by simply allowing the sap of the India-rubber tree to harden upon a mold, were manufactured articles because they were capable of use in that shape as shoes, and had been put into a new form capable of use and designed to be used in such new form.

Analysis of the Hartranft findings shows that an article does not become a manufacture simply on change of form or on isolation from impurities but that, consistently with the present hypothesis, such a change suffices if accompanied by the additional reason of new utility.

The plural reason test finds a paradigm example in US Patent 141,072 issued to Louis Pasteur in 1873.  The problem with which Pasteur was concerned was changes in the condition of brewers' yeast, worts, and beer, and limitations on these keeping beyond a certain time.  He concluded that these problems arose from microorganisms that contaminated the yeast, devised a procedure that would eliminate these contaminants, and claimed:

Yeast, free from organic germs of disease, as an article of manufacture.

The decontaminated yeast does not occur in nature and is markedly different from naturally occurring yeast which has harmful contaminant organisms.  The composition has the new name, germ-free yeast.  It has new characteristics because it does not contain other potentially harmful organisms.  It has new utility because it can be used in brewing to create batches of beer with a reduced risk that a batch will be unusable, and the brewed beer has a better taste and longer shelf life.  It therefore satisfies the Hartranft test approved in Chakrabarty and subsequently in Myriad, and it was implicitly held patent-eligible in Chakrabarty (see footnote 9).

Although it is not strictly speaking a natural product case, another example of the plural reason test may be found in Kuehmsted v. Farbenfabriken of Elberfeld Co. 179 F. 701 (7th Cir. 1910), where acetylsalicylic acid (aspirin) had previously been known but only in an impure form.  The Court affirmed patentability for pure aspirin as follows:

Hoffmann has produced a medicine indisputably beneficial to mankind — something new in a useful art, such as our patent policy was intended to promote.  Kraut and his contemporaries, on the other hand, had produced only, at best, a chemical compound in an impure state.  And it makes no difference, so far as patentability is concerned, that the medicine thus produced is lifted out of a mass that contained, chemically, the compound; for, though the difference between Hoffmann and Kraut be one of purification only — strictly marking the line, however, where the one is therapeutically available and the others were therapeutically unavailable — patentability would follow.  In the one case the mass is made to yield something to the useful arts; in the other case what is yielded is chiefly interesting as a fact in chemical learning.

A further instance where isolation of a natural product to give a new form with new properties was held to give rise to patentable subject-matter involves the 1900 success of Dr. Jokichi Takamine in isolating and purifying adrenalin in fine crystalline form from the adrenal glands of sheep and oxen, for which as explained above he was granted a US Patent.  The new product was said to be storage-stable when dry and when injected into an animal to bring about a rise in blood pressure.  A number of product claims were granted of which the following is representative:

A substance possessing the herein described physiological characteristics and reactions of the suprarenal glands, having approximately the formula C₁₀H₁₅NO₃ and having an alkaline reaction.

Patentability of adrenalin was affirmed by Judge Learned Hand in Parke-Davis & Co. v. H.K. Mulford Co. 189 F. 95, 103 (C.C.S.D.N.Y. 1911), in a ruling that is wholly consistent with the plural reason test:

[E]ven if [Adrenalin] were merely an extracted product without change, there is no rule that such products are not patentable.  Takamine was the first to make it available for any use by removing it from the other gland-tissue in which it was found, and, while it is of course possible logically to call this a purification of the principle, it became for every practical purpose a new thing commercially and therapeutically.  That was a good ground for a patent.

The otherwise puzzling opinion of Justice Douglas in Funk Brothers satisfies the plural reason test, although the facts before the Court differed in some respects from those in Kuehmsted and Parke-Davis.  The claim considered in that case read as follows:

An inoculant for leguminous plants comprising a plurality of selected mutually noninhibitive strains of different species of bacteria of the genus Rhizobium, said strains being unaffected by each other in respect to their ability to fix nitrogen in the leguminous plant for which they are specific.

It had been known to make inoculants containing more than one strain of the different bacterial species, but these were mutually inhibitive.  The only novel feature in the inoculant as claimed was that it succeeded whereas previous inoculants had not, the bacteria having gone through some process of selection that was left wholly undefined, as were the bacteria themselves.  The situation was therefore the reverse of that in Myriad with new utility defined but not any supporting difference.  It is not surprising in the circumstances that Justice Douglas refused to borrow invention from the discovery of the natural principle itself, but nothing more.  The concurring opinion of Justice Frankfurter concluded that the particular strains by which compatibility was achieved should have been adequately identified, but this had not happened either in the claims or in the supporting description and the claimed strains were identifiable only by their compatibility.  References in subsequent opinions to the bacteria in Funk being unaltered should be understood against this factual background:  the bacteria in the inoculants supplied to farmers had indeed been altered by isolation, selection, and cultivation, but none of these features had been specified in any way in the subject-matter claimed.

The bacterium in Chakrabarty which was oil-digesting by virtue of additional plasmids creating new metabolic pathways was, strictly speaking, not a product of nature but was held to be a product of human ingenuity having a distinctive name, character, and use as in Hartranft.  However, the reasoning here was again consistent with the plural reason test.

The opinion in Myriad is (unsurprisingly) consistent with the plural reason test if the factual situation before the Court is correctly analyzed.  In his dissent in the Federal Circuit, Judge Bryson relied on Chakrabarty and held that as between what is claimed and what is found in nature the focus should be firstly on the similarity in structure and secondly on the similarity in utility.  His analysis, which like that of Justice Thomas was from the standpoint of a geneticist rather than a chemist, emphasized the absence of any new utility for the isolated wild-type BRCA1 gene:

The structural differences between the claimed "isolated" genes and the corresponding portion of the native genes are irrelevant to the claim limitations, to the functioning of the genes, and to their utility in their isolated form.  The use to which the genetic material can be put, i.e., determining its sequence in a clinical setting, is not a new use; it is only a consequence of possession.  In order to sequence an isolated gene, each gene must function in the same manner in the laboratory as it does in the human body.  Indeed, that identity of function in the isolated gene is the key to its value.  The naturally occurring genetic material thus has not been altered in a way that would matter under the standard set forth in Chakrabarty.  For that reason, the isolation of the naturally occurring genetic material does not make the claims to the isolated BRCA genes patent-eligible.

Justice Thomas agreed that Chakrabarty was central to the enquiry, and that qualifying subject-matter had to be a product of human ingenuity having a distinctive name, character, and use.  In relation to the wild-state gene Myriad had not created anything.  As previously explained, he ruled that genes and the information that they encode are not patent-eligible under § 101 simply because they had been isolated from the surrounding genetic material.  In relation to genomic BRCA1 all that could be said in favor of eligibility was that it had been claimed as an isolated sequence, and that was not enough.

Isolation or purification of a naturally occurring substance leading to a non-natural composition of matter with desirable new properties has provided basis for patent grant for over a century in the US and continues to provide such basis in the UK, before the EPO, and before the patent offices of substantially every country in the industrialised world.  What is remarkable about the Parke-Davis opinion is how seldom it has been challenged in the century since it was handed down notwithstanding the multiplicity of patents for naturally-occurring products of great utility and commercial value that have been granted during that time, and how widely the same logic has been adopted in other countries.  It is submitted that this long standing line of authority and established practice, implicitly approved in Chakrabarty can only be overruled by clear language, and that such language is not found in Myriad or in any earlier opinion on the eligibility of products of nature.

It will be recalled that during oral argument in Myriad Justice Ginsberg expressed concern that in rejecting the patentability of isolated genomic sequences US law would be differing from that in every other industrialised nation and the US would be in a singular position.  However, if the present plural reason test is accepted then much the same considerations would apply under § 101 in the US as apply under § 56 EPC in Europe, and the perceived difference would have been reduced substantially to vanishing point.

* Mr. Cole is a European Patent Attorney and Partner with Lucas & Co. in Warlingham, Surrey, UK and Visiting Professor at Bournemouth University.