Over the past year or so, any company or academic department that has a name that includes terms like “bio,” “life sciences,” or the like has been home to individuals who have probably experienced some level of anxiety and uncertainty about the impact of recent federal court decisions relating to biotechnology patent law on their research and development work. If you are one of those individuals, please allow me to validate your feelings of frustration and confusion. You are not alone. What you are experiencing is a normal and healthy response. As they say, the first step is recognizing the problem.
Now, I don’t have some Twelve-Step Program for dealing with this shifting legal landscape. But what I hope to offer are some practical tips for developing or revising your United States patent strategy in light of these recent changes.
However, before we launch into the nitty-gritty details, let me make sure we’re all clear on nomenclature by first presenting a quick overview of the utility requirement for patentability under United States patent law.
The Utility Requirement Under United States Patent Law
To obtain a utility patent 1 in the United States, the inventor(s) must submit an application to the U.S. Patent and Trademark Office (“USPTO”) and demonstrate that the invention meets the statutory requirements for patentability. These requirements include:
- Novelty; 2
- Written description;4 and
However, the primary focus of this article relates to another statutory requirement for patent eligibility known as “the utility requirement.”6 Utility in the context of United States patent law means that an invention must perform some function that is beneficial to society. The invention must also fall within a category of subject matter that is eligible for patenting.
Historically, the subject matter aspect of the utility requirement was interpreted fairly broadly. For example, in the 1980 United States Supreme Court case of Diamond v. Chakrabarty (“Chakrabarty”), the Court quoted from the legislative history of the 1952 Patent Act to show that the intent of the Act was to allow for the patenting of “anything under the sun that is made by man."7 However, the Court also recognized certain exceptions to patent-eligible subject matter: laws of nature; physical phenomena; and abstract ideas. As the Court explained, these exceptions are necessary because “[s]uch discoveries are manifestations of…nature, free to all men and reserved exclusively to none."8 That did not mean that such excluded subject matter could not be used to create patentable methods or products applying, for example, laws of nature in a new and nonobvious way, just that those underlying laws of nature could not be patented in and of themselves.9
What Has Changed With Respect to United States Patent Protection for Biotechnological Inventions?
A lot. First, let’s deal with the elephant in the room. On June 13, 2013, the United States Supreme Court ruled unanimously in Association for Molecular Pathology v. Myriad Genetics (“Myriad”)10 that isolated genomic DNA is not eligible for patenting under 35 U.S.C. § 101 of the Patent Act, but that “synthetic” cDNA (complementary DNA) is eligible for patenting.
Myriad reversed 30 years of USPTO policy. Since the early 1980s, the USPTO had granted thousands of patents claiming isolated naturally-occurring DNA. It was the USPTO’s policy that a particular gene could be patentable if it was isolated from its natural state and purified from other molecules with which it was naturally associated (thereby satisfying the “made by man” portion of the “anything under the sun” holding in Chakrabarty). This policy also seemed to be in line with case law relating to naturally-occurring chemical compounds isolated from their natural environment.11
However, in Myriad, the Supreme Court held that naturally-occurring DNA is not eligible for patenting just because it has been isolated from its natural state. Naturally-occurring DNA remains a “product of nature” even after isolation and, therefore, falls under the “laws of nature” exception to patent eligibility described above. In other words, isolation of naturally-occurring DNA is not enough for the naturally-occurring DNA to be considered man-made.
In its holding, the Supreme Court appeared to draw a new line between products of nature and man‑made products. While naturally-occurring DNA is not patent eligible just because it has been isolated, the Court held that cDNA is patentable. cDNA is synthetically-created DNA that contains the same protein‑coding information found in a segment of natural DNA but omits portions within the DNA segment that do not code for proteins. In so doing, the Court held that DNA that has been synthetically created or modified from its naturally-occurring form may still be patented. The Court was also careful to qualify its holding by noting that the patent ineligibility of isolated naturally-occurring DNA does not apply to methods of using DNA, new applications of knowledge about naturally-occurring genes, or the patentability of DNA in which the order of the naturally-occurring nucleotides has been altered.
In spite of the caveats and carve-outs (or, in some cases, perhaps because of them), the full impact of Myriad is not yet clear. Although Myriad was limited to isolated naturally-occurring DNA, the test applied by the Court could potentially render patents to other isolated naturally-occurring biomolecules such as therapeutic proteins and peptides invalid as well. However, this is a gray area, since Myriad appears to provide bases for arguments on either side of this application of its holding.
For example, on one hand, some portions of Myriad may provide support for arguments that an application of Myriad to any and all isolated naturally-occurring biomolecules is overly broad. For example, the Court acknowledged that the claims at issue were functional in format and did not rely on any chemical changes resulting from the isolation of a particular section of DNA (the claims were directed to “[a]n isolated DNA coding for a BRCA1 polypeptide” or, in other words, an isolated DNA sequence with the genetic information that instructs a cell to produce a BRCA1 polypeptide).12 One could argue that in the context of claiming isolated naturally-occurring proteins or peptides, it may be enough to distinguish Myriad by specifying a certain level of purity coupled with a limitation for a specific level of sequence homology to a specified amino acid sequence/structure, provided further that such proteins or peptides have “markedly different characteristics” from their naturally-occurring unpurified forms.13
On the other hand, however, one could just as easily argue that isolated naturally-occurring proteins or peptides are directly analogous to the isolated naturally-occurring DNA found to be patent ineligible in Myriad, about which the Court noted that “Myriad’s principal contribution was uncovering the precise location and genetic sequence of the BRCA1 and BRCA2 genes within [the relevant] chromosomes.” Yet the “location and order of the [claimed] nucleotides existed in nature before Myriad found them” and since “Myriad [did not] create or alter the genetic structure of DNA,” “Myriad did not create anything."14 This argument would further state that no matter how important and useful the isolated biomolecule may be, or how extensive the research efforts involved in identifying and isolating the biomolecule, “separating [it] from its surrounding [natural state] is not an act of invention"15 and “extensive effort alone is insufficient to satisfy the demands of § 101.”16
On this issue, the USPTO has historically taken the position that “[p]urer forms of known products may be patentable” and that “[p]ure materials are novel vis-à-vis less pure or impure materials because there is a difference between pure and impure materials.”17 Unfortunately, Myriad stands as an example that the Supreme Court will not show deference to the policies and practices of the USPTO, going so far as to note that “Congress has not endorsed the views of the [USPTO] in subsequent legislation”18 and instead placed weight on the views of the U.S. Department of Justice over that of the U.S. Department of Commerce.
Clear as mud? Unfortunately, I believe we’re going to have to wait for additional case law to develop before we get an answer regarding the patentability of isolated naturally-occurring proteins or peptides.
What is clear is that patent claims drawn to biomolecules that are chemically distinct from their naturally-occurring counterparts (e.g., recombinant polynucleotides, labeled polynucleotides, vectors, transfected host cells, non-naturally-occurring or chemically-modified proteins and peptides, etc.) are still patent eligible following Myriad.
Now remember how the Court in Myriad was so careful to qualify its holding by noting that it did not apply to methods of use or new applications of knowledge relating to isolated naturally-occurring DNA? So that means that novel and nonobvious methods of using isolated naturally-occurring DNA is fair game for patenting, right? Not so fast.
Mayo Collaborative Servs. v. Prometheus Labs., Inc.
One tricky aspect of patenting methods of use or new applications of knowledge relating to isolated naturally-occurring DNA relates to another recent United States Supreme Court case. In Mayo Collaborative Servs. v. Prometheus Labs., Inc. (“Mayo”),19 the Court held that certain diagnostic methods were not patentable because they involved routine conventional steps (e.g., administering a known drug and analyzing a blood sample) coupled with what the Court viewed as an unpatentable law of nature (e.g., adjusting dosage based on observed metabolite concentrations in the blood sample).
In Mayo, the Supreme Court held that the process by which the drug is metabolized in the body is a natural process, and so the relationship between the amounts of metabolites and the effectiveness of drug dose is a law of nature. In other words, merely observing such a naturally-occurring relationship, without adding anything else, was not enough to make the claims patentable. Mayo has had an impact on diagnostic methods patents that involve correlations between diseases and certain biomarkers (like specific proteins or gene mutations), and imposes an important limitation on the caveats listed by the Court in Myriad with respect to methods of using isolated naturally-occurring DNA.
Following Mayo, the Court of Appeals for the Federal Circuit (“Federal Circuit”) has since invalidated a diagnostic claim as being directed to patent-ineligible subject matter in PerkinElmer v. Intema (“PerkinElmer”).20 Although PerkinElmer was nonprecedential, it may forecast how other diagnostic claims will be treated in United States courts and the USPTO following Mayo.
At issue in PerkinElmer was whether claims directed to methods of determining the risk of fetal Down’s Syndrome were patent eligible. In general, the claims recited the steps of measuring a screening marker during the first trimester, measuring a screening marker during the second trimester, and determining the risk of Down’s Syndrome by comparing the measured marker levels with a frequency distribution of the appropriate marker levels in Down’s Syndrome pregnancies versus unaffected pregnancies. The markers included markers individually known to be associated with Down’s Syndrome, and the claims did not require any action to be taken after determining the correlation (e.g., that a doctor act on the calculated risk). In reaching its decision, the Federal Circuit characterized the determining step as a mental process, and the relationship between screening marker levels and the risk of Down’s Syndrome as a law of nature.21 The Court noted that measurements and comparisons could be made using routine and conventional activity, and that the claims as a whole did not sufficiently convert the mental comparison step and natural law into a patent-eligible application.
PerkinElmer also distinguished the claims at issue from the claims of one of an earlier Federal Circuit case, Classen Immunotherapies v. Biogen IDEC (“Classen”).22 In Classen, certain patent-eligible claims involved a “further act” that moved an abstract scientific principle to a specific application. The claims at issue in Classen were directed to a method of immunization comprising a screening step that effectively comprised mental steps, followed by an immunization step in which the subject was physically immunized according to the result of the screen. It was the addition of this concrete, physical step that the Federal Circuit found “moves [a claim] through the coarse filter of § 101…from [abstract scientific] principle to application.”23
Although Classen predates the Supreme Court’s decisions in Mayo and Myriad, the holding in Classen was not clearly modified by either of the Mayo or Myriad decisions. Accordingly, although Mayo and Myriad have clearly limited the scope of patents in the United States relating to biotechnological inventions, there are approaches to drafting claims that can put some wind back in the sails of inventors in the biotechnology field.
The bottom line is that it’s still possible to obtain patents relating to methods of using DNA or new applications of knowledge relating to naturally-occurring genes. However, Mayo, now in combination with Myriad, has made it more challenging to show that the methods involve additional elements that take the claims beyond what could be construed to be a combination of a natural principle with conventional methods or reagents. It’s tricky — if claims are too broad, they may be struck down; but if they are too narrow, they may not adequately protect the claimed method from copycats.
Implications of Myriad and Mayo for the Biotechnology Industry
The impact of the Myriad decision on the biotechnology industry is a mixed bag. If you have a company with a business model based solely on the sale or use of naturally-occurring genes, then, of course, Myriad is going to be a big problem for you. However, most biotechnology companies these days, including those in the genetic diagnostic testing arena, are not based on a single patent around an isolated naturally-occurring DNA sequence. As recently stated by Richard Marsh, General Counsel for Myriad Genetics, “The types of patents that we’re now seeing in the molecular diagnostic space are no longer with respect to specific genes….What you’re seeing today is a shift from molecular diagnostic testing focused on a single gene or a small set of genes rather to what we call panels of genes.”24 Marsh also stated, “Candidly, the future of molecular diagnostic testing…will probably be more contingent on the Mayo type of case…Your claims to the patents are now going to recite to the method of determining disease identification based upon this panel as opposed to claiming a specific isolated gene.”25 In fact, Myriad Genetics is currently pursuing preliminary injunctions against two companies that introduced alternative genetic diagnostic tests for the BRCA1 and BRCA2 genes in early June, based on patent claims that were not invalidated by Myriad.26 Myriad Genetics contends that the Myriad decision regarding claims covering the isolated naturally-occurring DNA itself does not have much of an effect on its ability to exclude others from offering a competing test since Myriad Genetics still holds patents with valid claims to, among other things, methods covering processes for diagnosing breast cancer.27
Even companies that have relied on patent claims to isolated naturally-occurring DNA (like Amgen’s blockbuster anemia treatment based on the human protein erythropoietin) also generally have patents with claims covering either the types of synthetic DNA that the Supreme Court said are patent eligible, or covering the types of technology the Court explicitly carved out of its decision, such as methods of using DNA and new applications of knowledge about naturally-occurring genes. In fact, most genetic patents acquired during the last decade have been for synthetic sequences, so some in the industry view synthetic DNA as the most commercially-important form of DNA. For example, agricultural biotechnology companies work with plant DNA, but most of the time they are modifying or combining naturally-occurring genes in new ways, such as to make better seeds. It’s not that you can’t patent DNA sequences; it’s how you go about doing it.
Potential losers within the biotechnology industry following Myriad actually have nothing to do with genetic diagnostic testing. That’s because although Myriad was limited to isolated naturally-occurring DNA, the test applied by the Court could potentially render patents to other isolated naturally-occurring biomolecules, such as proteins and peptides, invalid as well. This could impact companies with patents claiming isolated naturally-occurring industrially-useful or therapeutic proteins. For example, many naturally-occurring enzymes have been identified and isolated for uses ranging from the production of ethanol to the processing of paper. On the therapeutic side, the most powerful antibodies against HIV are antibodies that have been isolated from untreated subjects who have failed to control their HIV infection for many years. Such subjects have developed so-called broadly-neutralizing antibodies (“bNAbs”). These bNabs do little to help the people who produce them, but they may be isolated to target different parts of the virus. Myriad places such isolated naturally-occurring biomolecules in a gray area for patent eligibility in the United States. While it is true it should still be possible to patent combinations of such isolated proteins that do not occur naturally, or recombinant versions of such isolated naturally-occurring proteins, it is clear that Myriad has implications beyond just isolated naturally-occurring DNA.
On the research front, researchers may now have more freedom to engage in gene sequencing because they won’t have to worry about a slew of isolated DNA patents covering individual sequences. Some have speculated, however, that because early‑stage research on newly discovered DNA sequences cannot be patented, it may encourage companies to be more secretive about those early-stage discoveries, or to pursue trade secret protection for potentially valuable discoveries.
So What Is and Is Not Patentable in the United States for Biotechnological Inventions?
Where do we go from here? We have a combination of clear case law, unclear implications of case law, and guidelines released by the USPTO outlining the approach its Examiners should take in examining certain types of claims in view of Mayo and Myriad.28 For example, with respect to the USPTO guidelines outlining the examination approach for method claims after Mayo, the guidelines set forth a three-step test for determining patent eligibility under § 101:
- Determine whether the claim is directed to a process (i.e., a method);
- Determine whether the claim focuses on a natural principle; and
- Determine whether the claim includes additional elements or a combination of elements that integrate the natural principle into the claimed invention along with a practical implementation that is significantly more than the principle itself.
The third step asks whether the claim is more than simply a law of nature plus an instruction to apply it and, if the answer is “no,” then the USPTO will likely reject the claim.
Myriad is also important because it stands as an example that the United States Supreme Court will not show deference to the policies and practices of the USPTO. Unfortunately, in the absence of clear case law, it’s the next best source we have for guidance.
Let’s run through some specific examples.
DNA, Proteins, and other Biomolecules
As stated above, biomolecules that are chemically distinct from their naturally-occurring counterparts are still patent eligible following Myriad. Such biomolecules include recombinant polynucleotides, labeled polynucleotides, vectors, transfected host cells, non-naturally-occurring or chemically-modified proteins and peptides (e.g., protein conjugates).
What about isolated naturally-occurring biomolecules that are identified as therapeutics? For example, are bNabs, as described above, patentable in the United States?
It depends. Isolated naturally-occurring bNabs would fall into the gray area described above for the patent eligibility of isolated naturally-occurring proteins or peptides. However, combinations of bNabs that do not occur naturally, or recombinant bNabs that comprise modifications from the naturally-occurring proteins, should be patentable in view of Myriad.
Diagnostic method claims relating merely to correlations between biomarkers and a certain outcome (e.g., a correlation between a genetic mutation or the presence or absence of a specific protein and the diagnosis of a given disease) will require “something more” to be eligible for patent protection in the United States. Additional elements must integrate the natural principle into the claimed invention along with a practical implementation that is significantly more than the principle itself. What is that “something more”?
Let’s start with what likely is not “something more.” Conventional or known elements or steps that are appended to the correlation would not be sufficient to impart patent eligibility in the United States. For example, a claim to diagnosing an infection that recites the step of correlating the presence of a certain bacterium in a person’s blood with a particular type of bacterial infection would not become patent eligible simply by adding a step of recording the diagnosis on a chart. Other examples of additional elements that likely would not impart patent eligibility to a naturally-occurring correlation include adding a comparison to a control, adding the steps of a well-known assay (e.g., ELISA, Immunohistochemistry, PCR, etc.), or adding a value such as a detection threshold.
O.K., so what does qualify as “something more” that would integrate a natural principle into the claimed invention along with a practical implementation that is significantly more than the principle itself?
One possibility is the addition of new or unconventional reagents or methods (e.g., the use of a defined reagent or device that provides an increase in sensitivity or specificity to the method). For example, assume that a new antibody is discovered or is selected from a library of reagents based upon the discovery that it binds to a specific discovered portion of protein Y. Incorporation of that new or selected antibody may be enough to impart patent eligibility to a claim of the following format:
A method for diagnosing disease X in a patient, comprising the steps of:
- obtaining a serum sample from a patient; and
- detecting the presence or absence of protein Y in the sample using antibody A;
wherein the patient is diagnosed with disease X if protein Y is detected in the sample.
Accordingly, where possible, specifically incorporate into the claims the use of new or unconventional:
- Reagents or devices;
- Genetic probes or other biomarkers;
- Screening libraries;
- Screening methods for a specifically defined subset of compounds; and/or
Another possibility is the addition of a specific combination of assays or biomarkers that work better than individual assays or biomarkers. The key here is that the assays or biomarkers need to either be new or not routinely used together or in the claimed manner. However, the claimed assays or biomarkers need to be specifically recited; otherwise they are likely to be viewed in the same light as the claims struck down in PerkinElmer. An example of such a claim might take the following form:
A method for diagnosing disease X in a patient, comprising the steps of:
- obtaining a serum sample from a patient; and
- detecting the presence or absence of proteins X, Y, and Z in the sample;
wherein the patient is diagnosed with disease X if proteins X, Y, and Z are detected in the sample.
Yet another possibility is to turn to Classen and add an “administering” step to the claims. Such a claim might take the following form:
A method for diagnosing and treating disease X in a patient, comprising the steps of:
- obtaining a serum sample from a patient; and
- detecting the presence or absence of protein Y in the sample;
wherein the patient is diagnosed with disease X if protein Y is detected in the sample, and administering treatment Z to the patient.
A potential downside of this approach is that infringement of such a claim would likely involve divided infringement (i.e., where the diagnosis and treatment are carried out by separate parties). However, divided infringement was more of a concern in the past, since recent cases have upheld induced infringement claims under 35 U.S.C. § 271(b) where more than one entity is induced to perform the steps of a method.29
Another potential approach could include claims that involve samples comprising a non-naturally-occurring intermediate such as an antibody-biomarker complex. An example of such a claim might take the following form:
A method for diagnosing disease X in a patient, comprising the steps of:
- obtaining a serum sample from a patient;
- applying an antibody specific for biomarker Y to the sample, wherein presence of the biomarker creates an antibody-biomarker complex;
- applying a detection agent that detects the antibody-biomarker complex; and
- diagnosing disease X by detecting the detection agent of step c).
Think Globally; Act Locally
Finally, it’s important to remember that the case law and patent office policies described above are specific to the United States. If you’re a patent applicant in the biotechnology field, it’s likely that you aren’t interested in filing for a patent only in the United States. Outside of the United States, broader claims may be available. Accordingly, it would be wise to include claims of varying scope in your application to provide the flexibility of pursuing broad claims in countries where they are available, while allowing for the presentation of fallback claims in the United States meeting one or more of the criteria described above.