The Risk of Using “Consisting Essentially of” in Patent ClaimsThe legal meaning of the transition language “consisting essentially of” is well-established in Federal Circuit case law and is generally construed to mean that the composition or formulation (a) necessarily includes the listed ingredients and (b) is open to unlisted ingredients that do not materially affect the basic and novel properties of the composition.  Similarly, when “consisting essentially of” is used in a process claim, the claim requires that the listed steps are performed, but also may include unlisted steps that do not affect the basic and material properties of the process. Accordingly, a “consisting essentially of” claim is typically understood to signal a middle ground between a closed claim that is written in a “consisting of” format and, thus, excluding any items not expressly recited in the claim, and an open claim that is written in a “comprising” format such that any unrecited items are not excluded. However, the middle ground just became a little less secure for patent holders with the Federal Circuit’s opinion in HZNP Medicines LLC v. Actavis Laboratories UT, Inc. In a nutshell, the phrase “consisting essentially of” is indefinite if any identified basic and novel property is indefinite.

To provide some quick background, HZNP and Horizon own patents covering PENNSAID® 2% – the first FDA-approved twice daily topical diclofenac sodium formulation for the treatment of the pain of osteoarthritis of the knees (Horizon patents). The Horizon patents include the method of use and formulation claims. Actavis asserted that the generic copy of PENNSAID® 2% described in Actavis’ Abbreviated New Drug Application No. 207238 would not infringe any valid and enforceable Horizon patent. Horizon sued Actavis for patent infringement of the Horizon patents in the District of New Jersey.

During the claim construction (Markman) phase, the district court held that the formulation claims, which feature a topical formulation having a viscosity of 500 to 5,000 centipoise “consisting essentially of” certain ranges of diclofenac sodium, dimethyl sulfoxide, ethanol, propylene glycol, hydroxypropyl cellulose, and water were indefinite. More specifically, while the district court found that the specification sufficiently identified five basic and novel properties of the claimed invention — i.e., (1) better drying time; (2) higher viscosity; (3) increased transdermal flux; (4) greater pharmacokinetic absorption; and (5) favorable stability — it concluded that a person of ordinary skill in the art would not be able to have reasonable certainty about the scope of these properties.

On appeal, Horizon tried to convince the Federal Circuit that the Nautilus definiteness standard does not apply to the basic and novel properties of the invention. As a refresher, under Nautilus, Inc. v. Biosig Instruments, Inc., the Supreme Court determined that a claim is invalid for indefiniteness if its language, read in light of the specification and prosecution history, fails to inform with reasonable certainty those skilled in the art about the scope of the invention. In shooting down this argument, the majority clarified that by using “consisting essentially of” in a claim, an inventor incorporates into the scope of the claims an evaluation of the basic and novel properties. Thus, the Nautilus definiteness standard applies to the basic and novel properties.

Horizon also tried to persuade the Federal Circuit that the basic and novel properties are to be considered only as factual determinations of validity and infringement — not at the claim construction stage. Again, the majority was not swayed and explained that the determination of the basic and novel properties of an invention at the claim construction stage is critical to afford clear notice of what is claimed. If any property does not inform a person of ordinary skill in the art with reasonable certainty about the scope of the invention, then the phrase “consisting essentially of” is indefinite in light of the indefinite scope of that property.

On the other side of the podium, Actavis argued that the five basic and novel properties were not identified in the specification as important enough to even be considered basic and novel properties. The majority’s opinion explains that each of the five properties are included in the specification as separate subheadings with discussions of both the importance of each of the properties and the advantages of the invention over prior art with respect to these properties such that the intrinsic record sufficiently identifies the properties as the basic and novel properties of the invention. Despite the basic and novel properties being readily identifiable from the specification, the majority agreed with the district court that one of the five identified basic and novel properties, i.e., better drying time, was indefinite. More specifically, since the two different tests in the specification produced inconsistent results, the majority concluded that a person of ordinary skill in the art would not understand which test to use to evaluate this property. And, as set forth above, if the basic and novel properties are indefinite, so is the phrase “consisting essentially of.”

In sum, if a person of ordinary skill in the art cannot ascertain the bounds of the basic and novel properties of the invention recited in a “consisting essentially of” claim, the claim is indefinite because there is no basis upon which to analyze whether an unlisted item has a material effect on the basic and novel properties.

So what are the key takeaways from this part of the Horizon decision? First, for patent practitioners, be conscientious when employing “consisting essentially of” language in claims.  While the majority’s opinion made it clear that “consisting essentially of” claims are not per se indefinite, ambiguities in the specification as to the basic and novel properties of the invention or what constitutes a material alteration of these properties certainly leave such claims vulnerable to an indefiniteness attack. Since “consisting essentially of” language is typically introduced during prosecution in an effort to distinguish over a cited reference, ensure that any such amendment to the transition language is thoroughly vetted as if you are in the Markman phase of a patent infringement trial. Even though “consisting of” language is narrower in scope than “consisting essentially of” language, if the specification lacks requisite clarity with regard to the basic and novel properties of the invention, you would be better off obtaining a closed claim than a middle ground claim susceptible to attack under 35 U.S.C. § 112.

Second, for accused infringers wanting to challenge the validity of a “consisting essentially of” claim for failure to clearly identify the basic and novel properties or what constitutes a material alteration of these properties, be prepared to do so early in the dispute and no later than the Markman phase. If the only asserted claims are “consisting essentially of” claims, you may be able to end the dispute altogether well before summary judgment. If the asserted claims are not limited to the “consisting essentially of” claims, you at least may be able to significantly narrow the issues for subsequent phases of the litigation, thus reducing litigation costs, as well as possibly gaining considerable leverage for settlement purposes.

As discussed in a previous blog post, since Mayo v. Prometheus, critics of medical treatment patents have advocated that such patents should be banned from patenting. While such arguments seemed futile based on the consistent position taken by the U.S. Court of Appeals for the Federal Circuit (CAFC) that treating a disease or other condition is not merely a “mental process” or “natural law,” the CAFC’s recent decision in INO Therapeutics, LLC v. Praxair Distribution Inc. may have changed that. Indeed, if this decision is followed by other panels of the CAFC, it could have a profound effect on the patenting of personalized medicine in the United States.

The Old Rule: Medical Treatment Informed by Diagnostic Testing Could be Patented

For the First Time, a Medical Treatment Patent Is Ruled Invalid Under Mayo/MyriadPrior to INO, the CAFC consistently ruled that methods of medical treatment are patent-eligible subject matter, regardless of whether they are combined with a diagnostic step. In Classen Immunotherapies Inc. v. Biogen IDEC – the seminal case in this line – the CAFC considered the patent eligibility of a claimed method of immunization of a subject that involved first immunizing a number of other subjects according to two immunization schedules and determining which has the least risk of side effects, then immunizing the subject according to the schedule with the lowest risk.

The unanimous panel found the act of immunizing two groups of subjects and comparing the results to determine the best immunization schedule, without applying that schedule to a subject, not eligible for patenting. However, with the extra step of actually immunizing a subject based on the schedule, the majority of the panel held that the claimed method was patent eligible. Notably, while the majority held that a method of medical treatment is eligible for patenting, even if it involves mental steps, a dissenting judge thought the claims were “a monopoly over the scientific method itself.” The CAFC followed this analysis in several later decisions, including in Natural Alternatives International, Inc. v. Creative Compounds, LLC; Endo Pharmaceuticals Inc. v. Mallinckrodt, LLC; and Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals Int’l Ltd.

In contrast, the CAFC has consistently found patent claims that include only diagnostic steps, without any form of medical treatment, ineligible for patenting. Such cases include Myriad (by the Federal Circuit, before it went to the Supreme Court); PerkinElmer Inc v. Intema Ltd.; Univ. of Utah Research Foundation v. Ambry Genetics Corp.; Cleveland Clinic Foundation v. True Health Diagnostics, LLC; Roche Molecular Systems, Inc. v Cepheid; and Ariosa Diagnostics, Inc. v. Sequenom, Inc.

The INO Rule: Withholding Treatment Dooms the Patent

The invention claimed in INO was directed to a method of treating hypoxia in newborns with nitric oxide while reducing the risk of pulmonary edema (a deadly side effect). The inventors discovered that infants with impaired function of the left ventricle are at elevated risk for pulmonary edema if treated with nitric oxide. The asserted claims of the patents in suit featured a method of diagnosing a hypoxic infant for left ventricular dysfunction (LVD) by echocardiography and administering an appropriate concentration of nitric oxide only in the absence of left ventricular dysfunction.

As in Classen and its progeny, the claims involved a medical intervention based on the result of the diagnostic step. Unlike Classen, the trial court in Mallinckrodt held that the use of previously known treatment methods based on the diagnosis does not add “significantly more” to the understanding of the natural law. You can read more about the trial court decision here.

Two of the three judges on the CAFC panel agreed with the trial court. The majority felt that invention in INO was different from those in Classen, Endo, Natural Alternatives, and Vanda in one significant way: in INO, the diagnostic step determined to which patients nitric oxide should be administered and to which patients it should be withheld, whereas in the other decisions, treatment was administered in some form, although the form differed depending on the results of the test.

The majority cited numerous, separate reasons that the distinction caused the invention to fall under the Mayo/Myriad ban. First, the majority explained that “[t]he effect of [nitric oxide] gas on a newborn with LVD is a matter of human physiology.” The majority then stressed that the use of nitric oxide was not new and, therefore, “the patented method does not propose a new way of treating LVD patients.” Although the patentee argued that the claim in its entirety was new, the majority dismissed this “whole claim” approach, opining that “…the focus of the invention is screening for a particular adverse condition that, once identified, requires iNO treatment be withheld.”

The majority contrasted this case with Vanda and Endo, because in the latter cases, the diagnostic test determined the dosage at which a specific treatment is given. Because treatment is administered regardless of the test results, the majority believes these are properly interpreted to be “methods of treatment.” The INO invention, on the other hand, involves either administration of a specific drug at a specific dosage or non-administration of that drug.

It would seem that the majority’s decision is based on the premise that (1) the claimed treatment with nitric oxide of infants without LVD cannot be considered in the patent eligibility analysis because nitric oxide treatment was already known and (2) the claimed withholding of nitric oxide treatment of infants with LVD is not really a method of treatment because no treatment is administered. In fact, the majority explained that a claim not to treat is akin to not disturbing the naturally occurring processes within the LVD patient’s body and “risks monopolizing the natural processes themselves.” Therefore, the claimed method is merely “instruction” to apply the “law of nature” of how nitric oxide affects human physiology.

Judge Newman – the most senior judge on the CAFC – dissented. Her dissenting opinion took a familiar direction, pointing out that the claimed invention was not a “law of nature” as “it was designed by and is administered by humans.” She further pointed out that all medical treatments rely on the response of human physiology to an artificial intervention. She finally pointed out that the Supreme Court has repeatedly cautioned against dissecting claims into component parts and considering only specific parts in the patent eligibility analysis. As noted by Judge Newman in her dissent, while the claimed method may in fact be invalid under the tests of novelty or obviousness, to declare it patent-ineligible is contrary to preceding decisions from the Supreme Court and the CAFC.

Where Does this Leave Personalized Medicine?

This decision leaves many key questions about patent eligibility unanswered and the future uncertain for personalized medicine patents. Prior to INO, the Vanda decision was regarded as a beacon in the foggy post-Mayo world when it came to patenting personalized medicine. It introduced an unaccustomed level of certainty to the question of subject matter eligibility since Mayo. In fact, published USPTO guidance relies on Vanda to teach that “it is not necessary for method of treatment claims that practically apply natural relationships to include nonroutine or unconventional steps to be considered patent eligible under 35 U.S.C. § 101.”

INO calls all of that into question for a number of reasons. First, the majority did not explain why the Mayo/Myriad ban applies to treatment regimens where a treatment is completely contraindicated by test results but not to regimens where the dosage is changed.

Second, the majority opined that Vanda claimed “an improved set of specific doses” but that INO did not. But in Vanda, the lower dosage in the claim was not more effective to treat the disorder; rather, it had less side effects. This appears to be eerily similar to the claims in INO, except that the INO claims effectively require a “zero dosage” for infants with LVD.

Third, the majority gives no explanation of the relevance of the fact that the use of nitric oxide without reference to LVD was already known. Indeed, the treatment steps in Vanda and Endo were also already known if severed from the diagnostic steps.

In summary, although the majority opinion repeatedly attests that there is no inconsistency between INO and the CAFC’s previous opinions, INO seems to be at odds with established precedent and appears to signal another period of uncertainty and inconsistency regarding the patentability of personalized medicine in the United States. Inventors of personalized medicine inventions would be wise to consider maintaining their innovations as a trade secret or explore markets outside of the United States to protect their inventions.

Detecting Disease Is Not a “Tangible and Useful Result” Eligible for PatentingThe federal appeals court with jurisdiction over questions of patent law has consistently held that methods of diagnosing a disease or other biological condition violate the Supreme Court’s ban on patenting “natural phenomena.” A recent decision reaffirmed this position (in the veterinary sphere), and for the first time in many years clearly articulated the test that a method of diagnosis fails: In the court’s opinion, mere diagnosis of a disease is not a “tangible and useful” result. However, due to the history of this test, it is of questionable value to patent stakeholders.

Diagnosis without Treatment Is Banned from Patenting

Readers of this blog are aware that the Supreme Court decided that a method of determining whether a patient receiving a drug is overdosed or under-dosed was banned from patenting in Mayo Collaborative Services v. Prometheus Laboratories, Inc., for the stated reason that the method was nothing more than a recognition of a “natural phenomenon” (i.e., that the artificial drug in question is effective at certain dosages and toxic at other dosages). The U.S. Court of Appeals for the Federal Circuit (CAFC) has interpreted Mayo to ban patents on methods of diagnosis, but to allow methods of medical treatment that depend on a diagnosis (i.e., personalized medicine). This trend, and the cases that define it, were blogged about in late 2018 in “Patenting Diagnostics and Biomarkers Six Years After Mayo.”

Since 2018, the majority of a triumvirate panel of the CAFC decided that a method of diagnosing previously un-diagnosable cases of myasthenia gravis by detecting a newly discovered biomarker fell under the Supreme Court’s Mayo ban (Athena Diagnostics, Inc v. Mayo Collaborative Services, LLC). The longest serving judge in the CAFC, Pauline Newman, offered a lengthy and thorough dissent. She emphasized that the patented method of diagnosis was new, used a wholly unrecognized approach, and produced a “tangible and useful result.” The “tangible and useful result” standard was taken from the earlier decision in Rapid Litigation Management Ltd., v. Cellzdirect, Inc., in which the CAFC upheld the patent-eligibility of a method of freezing cells. Because effectively preserving cells was considered a “tangible and useful result,” the court allowed the patent in that case to stand.

Diagnosis and Genotyping Not “Tangible and Useful”

The CAFC has again applied the “tangible and useful result” standard in the recent case of Genetic Veterinary Sciences v. LABOKLIN GmbH & Co. KG. In Genetic Veterinary Sciences the patent at issue claimed methods of diagnosing the canine disease known as hereditary nasal parakeratosis, a disease that causes unsightly crusting and fissures in the dog’s nose. The claims were directed to genotyping the SUV39H2 gene, which was discovered to cause the disease. Dependent claims included limitations for specific sequencing techniques, all of which had previously been known and used to sequence other genetic loci. A unanimous panel of the CAFC decided that the invention, as claimed, was not eligible for patenting because the invention was nothing more that the recognition of a natural phenomenon, notwithstanding claims to specific techniques such as PCR (or even the use of specific DNA primers). In comparing this invention to the cell cryopreservation technique in Cellz Direct, the court concluded that “Here, the Asserted Claims provide no tangible result save the observation and detection of a mutation in a dog’s DNA. While a positive and valuable contribution, these claims fall short of statutory patentable subject matter.”

A New Standard of Patent Eligibility?

The CAFC seems to be relying on a test for patent eligibility that rests on shaky ground. The “tangible and useful result” test is actually an old standard, first established by the CAFC in the State Street Bank case. Although this standard was never explicitly overturned, Associate Justice Stephen Breyer has written disparagingly of it in his concurring opinion in Bilksi v. Kappos and his dissent from the refusal of the petition for certiorari in Labcorp v. Metabolite Labs. The USPTO’s internal procedure forbids the use of this standard, as the USPTO interprets Supreme Court precedent as incompatible with it. The CAFC’s recent reliance on a standard that is apparently disfavored by the Supreme Court would seem to be setting the scene for yet another Supreme Court reversal of CAFC precedent. It could be risky for patent stakeholders to rely on this test to evaluate the patent-eligibility of inventions for two reasons. First, the CAFC is notorious for internal divisions, and a panel of different judges from those on the Veterinary Sciences panel might reject the “tangible and useful result” test. Second, this Supreme Court reverses the CAFC frequently, and it is foreseeable that the “tangible and useful result” test could be the subject of such a Supreme Court reversal. Apart from the potential demise of the test, it is anything but clear when an invention produces “tangible and useful” results based on the CAFC’s decisions. Why does a method freezing cells produce a tangible and useful result, but not a method of genotyping dogs? Until questions such as these are resolved, the “tangible and useful result” test remains of dubious value to the regulated public.