Abstract
I. Introduction
O
II. The Supreme Court's Patent Eligibility Criteria (Mayo, Myriad, and Alice) 5
Between 2012 and 2014, the Supreme Court rendered three decisions that have had a profound impact on the patent eligibility of claims, especially in the area of biotechnology. Below, each of these decisions is briefly summarized.
Mayo Collaborative Services v. Prometheus Laboratories
The first of the Supreme Court cases to have a major impact on patent eligibility was Mayo Collaborative Services v. Prometheus Laboratories, 6 a case concerned with claims to a method for adjusting the dosage of a medication provided to a patient. The method required administering 6-thioguanine and then determining the level of the drug (or a metabolite of the drug) present in a blood sample. If the measured level was below a certain threshold, dosage would be increased and if it was above a certain threshold, it would be decreased. 7
In its analysis, the Supreme Court began by summarizing the Supreme Court's historical position that products of nature, natural phenomena, and abstract ideas are not patentable, but that the application of this subject matter to the making of a composition or performance of a process may be.
8
It then characterized the relationship between the blood levels of a drug and the drug's effectiveness as representing a law of nature which is, in itself, excluded from patenting:
Prometheus' patents set forth laws of nature—namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm. … While it takes a human action (the administration of a thiopurine drug) to trigger a manifestation of this relation in a particular person, the relation itself exists in principle apart from any human action. The relation is a consequence of the ways in which thiopurine compounds are metabolized by the body—entirely natural processes. And so a patent that simply describes that relation sets forth a natural law. The question before us is whether the claims do significantly more than simply describe these natural relations. To put the matter more precisely, do the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patent-eligible processes that apply natural laws?
9
The Court concluded that the claimed method was not patent eligible because its steps, considered in the absence of contributions from the subject matter identified as a natural law, only described things that were well known in the art:
The upshot is that the three steps simply tell doctors to gather data from which they may draw an inference in light of the correlations. To put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. For these reasons we believe that the steps are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities.
10
It is worth noting that, to make excluded subject matter patent eligible, the other elements in a claim must not only distinguish it from anything found in nature, but must also not be routine, conventional, or well known. Thus, the analysis involves an odd mixing of patent eligibility criteria under 35 U.S.C. § 101 with concepts usually associated with nonobviousness. However, unlike an obviousness analysis, which considers all of the elements in a claim, contributions to nonobviousness stemming from the excluded subject matter (in this case, a natural law) are disregarded. Since these are usually the most important elements in biotechnology claims with respect to novelty and nonobviousness, the approach taken by the Court creates a substantial bias against a finding of eligibility.
Ass'n for Molecular Pathology v. Myriad Genetics
The patent eligibility criteria provided in Mayo were extended in Myriad. In this case, the inventors had identified gene mutations that are strongly associated with the likelihood of a woman developing breast cancer. 11 Although Myriad's patents included diagnostic methods, the claims before the Court were limited to isolated DNA molecules with sequences matching cancer-related mutations. 12
As in Mayo, the Myriad Court began by identifying subject matter in the claims that it considered to be patent ineligible when taken alone: DNA molecules with sequences matching those found in nature:
It is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes. The location and order of the nucleotides existed in nature before Myriad found them. Nor did Myriad create or alter the genetic structure of DNA. Instead, Myriad's principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within chromosomes 17 and 13. The question is whether this renders the genes patentable.
13
The Court then held that contributions stemming from the identification of a previously unknown genetic sequence were not to be considered in evaluating patent eligibility,
14
and that neither the isolated state nor chemical characteristics (apart from the sequence) of DNA molecules are sufficient to distinguish them from their counterparts in nature:
Nor are Myriad's claims saved by the fact that isolating DNA from the human genome severs chemical bonds and thereby creates a nonnaturally occurring molecule. Myriad's claims are simply not expressed in terms of chemical composition, nor do they rely in any way on the chemical changes that result from the isolation of a particular section of DNA. Instead, the claims understandably focus on the genetic information encoded in the BRCA1 and BRCA2 genes.
15
Overall, the most important aspects of the Myriad decision are that it extends the approach initiated in Mayo to composition claims and establishes that the isolation of genes is insufficient to make them patent eligible. When taken together with Mayo, Myriad suggests that, apart from situations in which the basic methodology used for carrying out assays has been changed, it will be very difficult for claims to diagnostic tests to overcome the patent eligibility hurdle.
Alice Corp. v. CLS Bank International
From the viewpoint of biotechnology, the main value of the Supreme Court's decision in Alice,
16
is that it provides a succinct summary of the Court's patent eligibility test:
In Mayo Collaborative Services v. Prometheus Laboratories, Inc., we set forth a framework for distinguishing patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts. First, we determine whether the claims at issue are directed to one of those patent-ineligible concepts. If so, we then ask, what else is there in the claims before us? To answer that question, we consider the elements of each claim both individually and “as an ordered combination” to determine whether the additional elements “transform the nature of the claim” into a patent-eligible application. We have described step two of this analysis as a search for an “inventive concept”—i.e., an element or combination of elements that is sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the ineligible concept itself.
17
In determining if the particular claim under review “transform[ed] the nature of the claim into a patent-eligible application” the Court looked to whether the claim elements, considered in the absence of contributions from subject matter that had been excluded because it represented an abstract idea, were well-understood, routine, and conventional. 18
Summary
Overall, the approach to patent eligibility taken by the Supreme Court is to: a) identify whether a patent claim recites subject matter that has traditionally been excluded from eligibility (abstract ideas, mathematical formulas, natural products, or natural processes); and b) if this type of subject matter is present, evaluate the other elements in the claim to determine if they, in the absence of the subject matter identified in step a), convey an inventive concept. The primary factor in deciding whether an inventive concept is present is whether the elements, taken individually or together, are well understood, conventional, or routine. The rationale for this process is to ensure that claims will not unacceptably preempt others from using subject matter that has traditionally been considered to be freely available to everyone.
III. Patent Eligibility Decisions at the Federal Circuit in the area of Biotechnology
Since the Supreme Court's decisions in Mayo, Myriad, and Alice, there have been a total of five patent eligibility cases decided by the Federal Circuit in which claims were directed to inventions in the area of biotechnology. Three cases, In Re BRCA1- & BRCA2-Based Hereditary Cancer Test, 19 Ariosa v. Sequenom, 20 and Genetic Technologies Ltd. v. Merial L.L.C., 21 were concerned with diagnostic assays performed using nucleic acid sequences. A fourth case, In re Roslin Inst., 22 involved claims to a cloned animal, and the most recent case, Rapid Litigation Management, Ltd. v. CellzDirect, Inc., 23 was concerned with a method of preserving hepatocytes. These cases are considered individually below.
A. Diagnostic claims based on nucleic acids
In re BRCA1- & BRCA2-Based Hereditary Cancer Test 24
In re BRCA1- & BRCA2 concerned patent claims that were not reviewed during Myriad's appeal to the Supreme Court. Included among these were claims to primers that could be used to amplify BRCA genes. The following is representative:
A pair of single-stranded DNA primers for determination of a nucleotide sequence of a BRCA1 gene by a polymerase chain reaction, the sequence of said primers being derived from human chromosome 17q, wherein the use of said primers in a polymerase chain reaction results in the synthesis of DNA having all or part of the sequence of the BRCA1 gene.
25
This claim is of considerable interest because the single stranded primers are similar to cDNAs and the Supreme Court had suggested that these types of molecules might more readily meet patent eligibility requirements than gene sequences. 26 However, the suggestion was premised on the idea that the cDNAs were generated from mRNAs in which introns had been spliced out and which therefore had a nucleotide sequence different from any found in vivo. 27 The primers under consideration by the Federal Circuit in the present case were short sequences that did not span distinct exons and, using the test set forth by the Supreme Court, they were found to be patent ineligible. 28 Importantly, the court made it clear that it was the sequence that was the determining factor with respect to the novelty of the cDNAs, and that neither the way in which they were synthesized nor the way that they functioned made a difference. 29
The Court also considered two method claims which read as follows:
7. A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid sequence is compared by hybridizing a BRCA1 gene probe which specifically hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and detecting the presence of a hybridization product wherein a presence of said product indicates the presence of said allele in the subject. 8. A method for screening germline of a human subject for an alteration of a BRCA1 gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an alteration in the BRCA1 gene in said subject[,] wherein a germline nucleic acid sequence is compared by amplifying all or part of a BRCA1 gene from said sample using a set of primers to produce amplified nucleic acids and sequencing the amplified nucleic acids.
30
Applying the first step of the Supreme Court's test, the Federal Circuit found the above claims to be patent ineligible because they recite abstract ideas.
31
The Court explained this as follows:
Here, under our earlier decision, the comparisons described in the first paragraphs of claims 7 and 8 are directed to the patent-ineligible abstract idea of comparing BRCA sequences and determining the existence of alterations. The methods, directed to identification of alterations of the gene, require merely comparing the patient's gene with the wild-type and identifying any differences that arise…
32
Then, applying the second step of the test, the court stated:
For this step, Alice dictates that we ask whether the remaining elements, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to “‘transform the nature of the claim’ into a patent-eligible application.” There must be a further inventive concept to take the claim into the realm of patent-eligibility. The second paragraph of claim 7 describes the way in which the sequences are compared: they are compared by 1) hybridizing a BRCA gene probe and 2) detecting the presence of a hybridization product. Similarly, claim 8 requires 1) amplification of the BRCA1 gene and 2) sequencing of the amplified nucleic acids. The non-patent-ineligible elements of claims 7 and 8 do not add “enough” to make the claims as a whole patent-eligible. The district court found, and Myriad does not challenge, that the elements of the second paragraphs of claims 7 and 8 set forth well-understood, routine and conventional activity engaged in by scientists at the time of Myriad's patent applications.
33
The main things to be learned from this case are that, in the area of recombinant DNA technology, it is unlikely that one will be able to distinguish claimed nucleic acids from nucleic acids in nature having the same sequence. Neither the way molecules are made nor the way that they are used is likely to suffice. Apart from this, the case confirms that, in drafting claims, it is generally preferable to avoid claim terms, such as “comparing,” that suggest abstract mental activity.
Ariosa Diagnostics v. Sequenom 34
In 2001, Sequenom obtained U.S. 6,258,540, which was based on the discovery of cell-free fetal DNA (cffDNA) in the blood of pregnant women and the development of a method for detecting the portion of the cffDNA derived from the fetus's father.
35
This DNA was then used diagnostically to evaluate the health and characteristics of the fetus. Claim 1 read:
1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises amplifying a paternally inherited nucleic acid from the serum or plasma sample and detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.
36
Ariosa and another company, Natera, Inc., marketed assays that also used fetal DNA in maternal blood to evaluate characteristics of the fetus and, in response to allegations of infringement by Sequenom, these companies filed declaratory judgment actions in 2011 and 2012. 37 After an initial appeal to the Federal Circuit and remand, 38 the district court granted Ariosa summary judgment based on Sequenom's claims not being patent eligible. 39 In response, Sequenom appealed to the Federal Circuit.
The Court of Appeals began by observing that cffDNA is a natural blood component of pregnant women and was used by Sequenom to generate paternally inherited cffDNA, which is also a natural component of the blood. Based on this, the Court concluded that the claim was directed to “matter that is naturally occurring.”
40
It then completed the analysis as follows:
Using methods like PCR to amplify and detect cffDNA was well-understood, routine, and conventional activity in 1997. The method at issue here amounts to a general instruction to doctors to apply routine, conventional techniques when seeking to detect cffDNA. Because the method steps were well-understood, conventional and routine, the method of detecting paternally inherited cffDNA is not new and useful. The only subject matter new and useful as of the date of the application was the discovery of the presence of cffDNA in maternal plasma or serum. …
41
Thus, in this case, appending routine, conventional steps to a natural phenomenon, specified at a high level of generality, is not enough to supply an inventive concept. Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art. The claims of the '540 patent at issue in this appeal are not directed to patent eligible subject matter and are, therefore, invalid.
42
Probably the most important part of the Court's comments concern preemption:
The Supreme Court has made clear that the principle of preemption is the basis for the judicial exceptions to patentability. … The concern is that “patent law not inhibit further discovery by improperly tying up the future use of these building blocks of human ingenuity.” In other words, patent claims should not prevent the use of the basic building blocks of technology—abstract ideas, naturally occurring phenomena, and natural laws. While preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility. In this case, Sequenom's attempt to limit the breadth of the claims by showing alternative uses of cffDNA outside of the scope of the claims does not change the conclusion that the claims are directed to patent ineligible subject matter. Where a patent's claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are in this case, preemption concerns are fully addressed and made moot.
43
The quotation suggests that the justification for excluding subject matter from patent eligibility is that certain things should belong to everyone, either because they are not new (in the case of natural processes and products of nature), express physical relationships that depend on fundamental universal laws (in the case of mathematical formulas), or express unbounded fundamental concepts (in the case of abstract ideas). Of course, patent claims are, at their heart, a form of preemption but, it has long been established that claims cannot preempt to an unacceptable degree. This is, apparently, the basis for the second step in the Alice test: the presumptive idea being that if, in the absence of the ineligible subject matter, claims are “inventive,” then the degree of preemption should be acceptable. Inventiveness is determined by whether the claim elements, either individually or as a combination, are new and innovative (as opposed to conventional, well known, and routine).
However, these concepts seem poorly suited to the evaluation of preemption. It is not difficult to imagine claims that are made up of conventional, well-known elements, but that are narrow in scope and hardly limit the availability of the claimed subject matter at all. Similarly, it is not hard to imagine claims that are extremely broad but which are novel and nonobvious. Concepts related to the enablement and written description requirements of patentability would appear to be much better suited to the issue of preemption. 44
Moreover, because there are no clear standards for determining how much preemption is too much, patent prosecutors have no way to make a convincing argument that a claim should be patent eligible because it is not unacceptably preemptive. All we know is that: “While preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility.” 45
Finally, the last sentence of the above quote is remarkable because it suggests that the Court has concluded that Sequenom's claims essentially only disclose patent ineligible subject matter. Claim 1 is, in fact, to a method for identifying paternally inherited DNA in serum or plasma samples by amplifying cffDNA present in the samples. It is basically an assay method. While one may argue about whether the claim is sufficiently preemptive (and the claim in its present form may certainly have problems with the written description and enablement requirements of patentability), to conclude that there is essentially nothing in the claim except patent-ineligible subject matter is extreme and reflects the convoluted concept of subject eligibility that has been developed by the Supreme Court.
Genetic Technologies Ltd., v. Merial L.L.C. 46
Genetic Technologies Limited (GTG) obtained a patent (U.S. 5,612,179) which claimed a method of determining the specific alleles present in a person at a multi-allelic site by analyzing noncoding DNA regions either close to, or remote from the alleles. Claim 1 read as follows:
1. A method for detection of at least one coding region allele of a multi-allelic genetic locus comprising: a) amplifying genomic DNA with a primer pair that spans a non-coding region sequence, said primer pair defining a DNA sequence which is in genetic linkage with said genetic locus and contains a sufficient number of non-coding region sequence nucleotides to produce an amplified DNA sequence characteristic of said allele; and b) analyzing the amplified DNA sequence to detect the allele.
47
In 2011, GTG sued several companies, including Merial, for infringement of the '179 patent in the U.S. District Court for the District of Colorado. 48 The case was then transferred to the U.S. District Court for Delaware which granted a motion to dismiss GTG's claims based on their being directed to patent-ineligible subject matter. 49
On appeal, the Federal Circuit again begins by identifying subject matter that reflects a law of nature and, on this basis, concludes that the claim is directed to excluded subject matter:
We begin at step one of the Mayo/Alice test and ask first whether claim 1 is directed to a patent-ineligible concept—e.g., a law of nature, natural phenomenon, or abstract idea. We find that it is. Claim 1 is directed to the relationship between non-coding and coding sequences in linkage disequilibrium and the tendency of such non-coding DNA sequences to be representative of the linked coding sequences—a law of nature.
50
Having concluded that GTG's claim is directed to a law of nature, the court then proceeds to the second step of the Alice test and, not surprisingly, finds that, after disregarding contributions from the relationship between noncoding DNA sequences and the presence of specific alleles, the remaining claim elements lack inventiveness. 51
The GTG case basically confirms the two other Federal Circuit decisions discussed above. It represents the third case in which the Federal Circuit held that diagnostic claims based on recombinant DNA technology are patent ineligible.
B. Cloned animals: In re Roslin Institute (Edinburgh) 52
In 1997, the Roslin Institute gained notoriety by being the first to successfully clone a mammal (a sheep that they named “Dolly”). 53 This was accomplished by taking somatic cells from the animal being cloned and culturing them under conditions that caused the cells to become arrested at a dormant, non-replicating portion of the cell cycle. 54 An oocyte was obtained from a second animal, the nucleus was removed, and the enucleated oocyte was fused with a nucleus taken from the cultured somatic cells. The engineered oocyte created in this manner was then implanted into third animal that served as a surrogate mother. 55
The Roslin Institute filed U.S. application 09/225,233 and, after a lengthy prosecution and many amendments, received a final rejection that was affirmed by the Patent Trial and Appeal Board in February of 2013.
56
The rejection was then appealed to the Federal Circuit for review of patent eligibility. The appealed claims are exemplified by the following:
155. A live-born clone of a pre-existing, non-embryonic, donor mammal, wherein the mammal is selected from cattle, sheep, pigs, and goats. 164. The clone of any of claims 155–159, wherein the donor mammal is non-fetal.
57
In sustaining the rejection of claims, the Federal Circuit focused on a statement by the Supreme Court in a 1980 case
58
indicating that, in order for an invention to be patent eligible, it must, at a minimum, be markedly different from subject matter that is a product of nature:
The patent at issue in Chakrabarty claimed a genetically engineered bacterium that was capable of breaking down various components of crude oil. The patent applicant created this non-naturally occurring bacterium by adding four plasmids to a specific strain of bacteria. Overturning the Board's rejections, the Court held that the modified bacterium was patentable because it was “new” with “markedly different characteristics from any found in nature and one having the potential for significant utility.” As the Court explained, the patentee's “discovery is not nature's handiwork, but his own.” Accordingly, discoveries that possess “markedly different characteristics from any found in nature,” are eligible for patent protection. In contrast, any existing organism or newly discovered plant found in the wild is not patentable.
59
The difficulty that the Roslin Institute faced was that a cloned animal is an exact genetic copy of a donor animal
60
and there were no other characteristics recited in their claims that could be used to distinguish Dolly from its natural counterpart.
61
Nevertheless, Roslin argued that the clone was different from the donor because: a) environmental factors unique to Dolly created phenotypic differences; b) mitochondrial DNA in Dolly was not determined by the nucleus present in the embryo and was therefore not the same as in the donor; and c) Dolly was a “time delayed version” of the donor.
62
The Court however was unpersuaded by these arguments and held that:
There is nothing in the claims, or even in the specification, that suggests that the clones are distinct in any relevant way from the donor animals of which they are copies. The clones are defined in terms of the identity of their nuclear DNA to that of the donor mammals. To be clear, having the same nuclear DNA as the donor mammal may not necessarily result in patent ineligibility in every case. Here, however, the claims do not describe clones that have markedly different characteristics from the donor animals of which they are copies.
63
The decision suggests that, unless one can somehow engineer cloned animals so that they are different from their donors, claims to the clones will not be patent eligible. Differences could potentially be generated by making changes to the genetic material from the donor before transferring it to an oocyte and these, if significant, should result in an animal that is patent eligible. Differences could also be made by manipulating gestational or environmental factors. For example, DNA transferred to oocytes might be chosen based on some particular trait of the donor animals that, when combined with a specific diet, gives rise to animals that are consistently different. However, whether changes of this type would be sufficient to result in patent eligibility is far less certain.
C. Non-recombinant biotechnology (CellzDirect)
The one bright spot in the recent Federal Circuit decisions on patent eligibility is Rapid Litigation Management, Ltd. v. CellzDirect, Inc. 64 (hereinafter “CellzDirect”). This is the first recent case in which claims in the biotechnology area were found to be patent eligible. 65
Part of the reason for the better outcome may have been due to the fact that the technology claimed differed substantially from that in other recent biotechnology cases considered by the Supreme Court and Federal Circuit. Whereas previous cases had been directed to inventions involving recombinant DNA technology or diagnostic assays, the CellzDirect claims were to an improved method for preserving hepatocytes in a frozen state. This is summarized in claim 1 as follows:
1. A method of producing a desired preparation of multi-cryopreserved hepatocytes, said hepatocytes being capable of being frozen and thawed at least two times, and in which greater than 70% of the hepatocytes of said preparation are viable after the final thaw, said method comprising:
(A) subjecting hepatocytes that have been frozen and thawed to density gradient fractionation to separate viable hepatocytes from nonviable hepatocytes,
(B) recovering the separated viable hepatocytes, and
(C) cryopreserving the recovered viable hepatocytes to thereby form said desired preparation of hepatocytes without requiring a density gradient step after thawing the hepatocytes for the second time, wherein the hepatocytes are not plated between the first and second cryopreservations, and wherein greater than 70% of the hepatocytes of said preparation are viable after the final thaw. 66
In judging the patent eligibility of this claim, the court never gets past the first step in the Alice test:
It is enough in this case to recognize that the claims are simply not directed to the ability of hepatocytes to survive multiple freeze-thaw cycles. Rather, the claims of the '929 patent are directed to a new and useful laboratory technique for preserving hepatocytes. This type of constructive process, carried out by an artisan to achieve “a new and useful end,” is precisely the type of claim that is eligible for patenting. … They employed their natural discovery to create a new and improved way of preserving hepatocyte cells for later use.
67
Thus, the court seems to have, just by inspection, concluded that the claim is not directed to a product of nature even though the relationship between the survivability of hepatocytes and repeated freeze/thawing is clearly the basis for the invention. The court distinguishes this decision from the decisions reached in previous patent eligibility cases as follows:
The claims in this case are immediately distinguishable from those we have found patent ineligible in cases since Mayo and Alice. In recent cases, we found claims “directed to” a patent-ineligible concept when they amounted to nothing more than observing or identifying the ineligible concept itself. For example, in Genetic Technologies, the claim recited methods for detecting a coding region of DNA based on its relationship to noncoding regions. Because the relationship between coding and non-coding sequences was a law of nature, the claim amounted to nothing other than identifying “information about a patient's natural genetic makeup.” Likewise in Ariosa, the claims recited methods for detecting paternally inherited cffDNA in the blood or serum of a pregnant female. The existence and location of cffDNA is a natural phenomenon; identifying its presence was merely claiming the natural phenomena itself. And in In re BRCA, the claims recited methods for screening human germline for an altered BRCA1 gene by comparing the target DNA sequence with wildtype sequence. But comparing two sequences to detect alterations is a patent-ineligible “abstract mental process.”. … The same is not true here. The end result of the '929 patent claims is not simply an observation or detection of the ability of hepatocytes to survive multiple freeze-thaw cycles. Rather, the claims are directed to a new and useful method of preserving hepatocyte cells. Indeed, the claims recite a “method of producing a desired preparation of multi-cryopreserved hepatocytes.”
68
Thus, the court draws a distinction between claims where the objective is simply to detect a law of nature and claims where the objective is to use the law to produce something new. Later, the Court also suggests that, because the invention was an improvement over existing technology, it would have found in favor of patent eligibility even if the analysis had proceeded to step 2 of the Alice test:
Even if LTC were correct that the '929 patent, is “directed to” hepatocytes' natural ability to survive multiple freeze-thaw cycles, and that we must proceed to step two, we would find the claims patent-eligible at that point as well. Under step two, claims that are “directed to” a patent-ineligible concept, yet also “improve an existing technological process,” are sufficient to “transform the process into an inventive application” of the patent-ineligible concept. The claims of the '929 patent do precisely that: they recite an improved process for preserving hepatocytes for later use.
69
There are two main things to take away from the CellzDirect case. The first is that, if an applicant can characterize an invention as using a law of nature or using a natural relationship (as opposed to detecting the presence of the law or relationship) and do so sufficiently to avoid having an analysis go to step 2 of the Alice test, the chances of a finding of patent eligibility will be substantially better. The second important thing to learn from this case is that inventions which are claimed as improvements on existing technology also have an improved chance of being viewed favorably.
IV. Caveats
The sections that follow attempt to draw logical inferences from the court decisions discussed above and reach some practical conclusions concerning their effect on different types of inventions in the area of biotechnology. The conclusions and suggestions are based on the assumption that the Federal Circuit decisions are all valid and properly follow the standards set forth by the Supreme Court. However, there are a number of things that need to be borne in mind, particularly with respect to the CellzDirect decision.
The Federal Circuit suggests that the claims in Mayo and Myriad were directed to a natural law in a way that the claims in CellzDirect were not.70 This is not entirely clear. There were limitations in the claims in the Mayo 71 and Myriad 72 cases that could have been used as a basis for distinguishing the inventions from a natural process just as putting cells through a freeze/thaw cycle and then preforming density gradient centrifugation was used in CellzDirect. The difference is that, in Mayo and Myriad, the Court chose to disregard these limitations because they were either insubstantial or well known in the art. 73 It could be argued that the procedures used in CellzDirect were also insubstantial or well known in the art and that what the Federal Circuit actually did was to improperly apply the patent eligibility test set forth by the Supreme Court or unintentionally abandon it altogether. 74
Also the exact basis in the Supreme Court's decisions for the distinction drawn by the Federal Circuit between claims directed to determining if a natural phenomenon is present and claims for using the natural phenomenon to produce something new is unclear. It is also unclear why claims directed to the detection of a natural phenomena, such as the presence of a gene mutation indicative of a propensity to cancer should automatically be patent ineligible. There is no reason, for example, to think that such claims would, by their very nature, be unacceptably preemptive.
These considerations suggest a possibility that the decision in the CellzDirect case might actually not be sustained were it further appealed or, at least that some of its suggestions regarding tests for patent eligibility might be modified. However, it could be a long time before we get further clarification from the Supreme Court on patent eligibility 75 and, until then, we must operate with the guidance that we have available.
V. List of Conclusions From Post-Mayo, Myriad, and Alice Federal Circuit Cases
1. It is the sequence of nucleic acids that is used in determining whether they have counterparts existing in nature. Neither the chemical nature of the nucleic acids (apart from their sequence) nor their physical state (e.g., whether they are isolated) are considerations. 76
2. The way in which nucleic acids are synthesized makes no difference with respect to patent eligibility. 77
3. Practitioners should avoid the use of terms suggesting mental activity such as “comparing,” “evaluating,” “assessing,” estimating,” etc. Under the first step of the Alice test, these will likely be considered a patent-ineligible abstract mental process. 78
4. Although preemption is the rationale underlying the tests for patent eligibility developed by the Supreme Court, arguing that a claim should be patent eligible because it is narrowly drawn and minimally preemptive is likely to be fruitless. 79 All patent claims are preemptive to some degree and there is no standard for how much preemptiveness is too much. Both courts and examiners are, essentially, free to arbitrarily decide that a claim is unacceptable.
5. At a minimum, the products or processes claimed will need to, at least arguably, be markedly different from naturally occurring products or processes to be patent eligible. Manmade copies of subject matter existing in nature (e.g., recombinant genes or cloned animals) will not be patent eligible although the methodology used in making the copies may be. 80
6. The chance of getting claims allowed will increase if an invention can be characterized as an improvement on existing technology or as directed to the use, rather than the identification of, patent-ineligible subject matter. 81 Natural relationships should be integrated as much as possible in claims with the focus on what is being made. The objective is to avoid step 2 of the Supreme Court's patent eligibility test.
7. Although not considered herein, the machine or transformation test is still a viable way for assessing patent eligibility. To the extent that inventions can be characterized as transforming subject matter from one state to another, chances for an allowance should improve. 82
VI. Views of the Patent Office 83
The US Patent and Trademark Office's most recent guidelines on patent eligibility were published on May 16, 2016 and are an extension of guidelines published in 2014. 84 In these, the PTO sets forth the test that should be used by examiners when considering patent eligibility. The test begins with the fairly trivial determination of whether a claim is directed to subject matter recognized as being patentable under 35 USC § 101, i.e., to a process, machine, manufacture, or composition of matter and whether it includes one of the judicially recognized exceptions to patent eligibility, i.e., a law of nature, a natural phenomenon, or an abstract idea. 85
If a judicial exception is found to be present, the claim is considered as a whole to determine whether it is substantially preemptive, i.e., whether it unaccetably prevents others from using the excepted subject matter in the future. If it is not substantially preemptive, then the claim is patent eligible and no further inquiry is needed.
86
However, if preemption still appears to be a potential problem, the analysis proceeds to the final step which the Guidelines describe as follows:
A claim directed to a judicial exception must be analyzed to determine whether the elements of the claim, considered both individually and as an ordered combination, are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself—this has been termed a search for an ‘‘inventive concept.’’ To be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception. It is important to consider the claim as a whole.
87
The primary problem with the test described by the PTO is that it is not well supported by the most recent Supreme Court cases. The idea of an initial examination of a claim as a whole to determine how preemptive it is has no easily identifiable counterpart in Mayo, Myriad, or Alice. These cases teach that once a law of nature, a natural phenomenon, or an abstract idea is identified in a claim, the first step in the analysis is complete. Patent eligibility is then determined in the second step by asking whether the remaining claim elements convey an inventive concept. Preemption may be the underlying rationale behind the analysis but there is no attempt to analyze preemption per se and the evaluation is not performed on the claim as a whole but rather on claim elements in the absence of any contributions from the excluded subject matter. These basic and critically important holdings of the Supreme Court seem to be largely ignored by the Patent Office.
However, the primary objective of this paper is not to consider the merits of the PTO's position but rather to see how this might be used to the advantage of those trying to protect inventions in the area of biotechnology. In this regard, the main point to take away is that the PTO has adopted a position on patent eligibility that, warranted or not, is relatively sympathetic to some inventions in the area of biotechnology. By closely matching example claims provided by the PTO with newly drafted claims, it may sometimes be possible to obtain allowances in areas where case law would suggest ineligibility. It would, however, be foolish to rely entirely on the validity of such claims, and, in this regard, it would be advisable to also include claims that more precisely match the present position of the Supreme Court and/or text that provides support for modifying claims in the future, e.g., by reissue, as further court decisions become available.
VII. Practical Considerations
Until the decisions by the Supreme Court with respect to patent eligibility are altered by a future decision or congressional intervention, patent practitioners and biotechnology companies will need to find some way to deal with them. While there are no certainties, there are at least some conclusions that may be tentatively drawn based on the Supreme Court and Federal Circuit decisions.
Gene-based diagnostic assays and diagnostic assays
In the absence of some significant change in the basic methodology used to carry out gene-based diagnostic assays, claims to these assays will be very difficult to get allowed, even under the criteria of the PTO. Many such claims are likely to be similar to those considered by the Supreme Court in its Myriad decision and every time that claims of this type have come before the Federal Circuit, they have been found to be patent ineligible. Even in the one biotechnology case where the Federal Circuit found claims to be acceptable, the Court made a point of distinguishing between method claims where the objective is to identify a natural law and claims that use a natural law as part of a process with some other objective. 88 The best strategy for applications that include these types of assays is probably to: focus on other subject matter as much as possible; try to recharacterize assays or point to changes in assay methodology; and try to delay prosecution of assay claims in the hope of a more favorable climate in the future.
DNA and proteins
The primary factor in deciding whether claims to DNA molecules are patent eligible will be their sequence. Unfortunately, we do not currently have any case law to tell us the degree to which the sequences of claimed DNA molecules must differ from those of DNA molecules in nature in order for a court to conclude that the claims are patent eligible. Presumably, significant differences in structure as evidenced by changes in function would be sufficient and arguments emphasizing these distinctions probably offer the best chance for success. It is reasonable to assume that similar principles would apply to proteins and, perhaps, to biological molecules in general.
Cloned animals and recombinantly altered cells
Based on the In re Roslyn case, it appears that clones of animals will not be patentable unless there is some substantial difference (preferably genetic) between them and the donors from which they are derived. Similarly, cells recombinantly transformed to match cells in nature (e.g., replacing a defective gene with a normal one) would probably not be patent eligible but, using Chakrabarty as a model, cells transformed to make them different from counterparts in nature probably would be. This is true even though the cells are transformed with a gene that is found elsewhere in nature. 89
Whether vectors used for delivering genes therapeutically would be eligible or not is uncertain. Using the CellzDirect case as a model, a court might apply the first step of the Alice test and simply conclude that the vectors do not exist in nature and are therefore patent eligible. Alternatively, a court might view sequences transferred to vectors to be products of nature and move on to step 2. 90 If this occurs and the court disregards contributions from the transferred sequences in assessing “inventiveness,” the vectors are likely to be judged to be patent ineligible.
Overall, the best approach to the prosecution of these inventions is probably to try draw parallels between a claimed invention and the inventions in Chakrabarty and CellzDirect and to direct arguments at the first step of the Alice test. In the area of biotechnology, no claims have moved to step 2 and been found to be patent eligible.
Other method claims
Based on the Federal Circuit's decision in CellzDirect, a key factor with respect to the patent eligibility of method claims will be whether subject matter that has been traditionally excluded (products of nature, natural processes, and abstract ideas) is being used in a claim to achieve some other objective (e.g., to make a cloned animal or cell) or if the identification of the subject matter is the objective and end result of the method. If an invention can be characterized as an improvement on an already established invention, or as transforming one thing into something substantially different, then the prospects for claims being found to be patent eligible should be improved.
Non-recombinant biotechnology claims
The key case for these types of claims is clearly CellzDirect. Methods that use knowledge regarding a natural relationship or process to bring about a physical or chemical transformation or that improve upon existing technology have a reasonable prospect of being patent eligible. Although not mentioned in the CellzDirect case, the machine or transformation test of Bilski is still valid and can be used as a basis to argue for patent eligibility.
VIII. Final Comments
For many biotechnology companies, the surprising position adopted by the Supreme Court with respect to patent eligibility has resulted in the loss of intellectual property that took years to acquire and has created a future that does not look promising. If these companies are to survive, they will need to develop strategies for protecting inventions in the presence of a Supreme Court that appears to either not recognize, or not care about, their needs.
Perhaps the most obvious thing that can be done is to simply reduce development efforts in those areas where patent protection appears most imperiled: diagnostic assays and gene-based therapies. Of course, this is not an option if a company's entire business is centered in these areas. For those companies, options might include putting a greater emphasis on foreign protection and foreign markets, or relying more heavily on Food and Drug Administration (FDA) provisions for market exclusivity, such as those available under the Orphan Drug Act or Biologics Price Competition and Innovation Act. Companies engaged in industrial biotechnology may consider increased use of trade secrets.
Finally, despite its problems, the patent system in the U.S. may yet right itself. It is clear that there are at least some judges who do recognize the threat that the Supreme Court's decisions have created for the biotechnology industry and who are only reluctantly following its dictates. 91 It is also clear that there is widespread dissatisfaction among companies and trade groups. 92 With time, one can hope that these voices will be heard by either the Supreme Court or Congress. In the meantime, the best patent prosecution strategy may be to achieve what is possible now and to keep open the possibility of obtaining more extensive protection if circumstances become more favorable.