Stanford’s Method for Inferring Haplotype Phase is Not Patent EligibleStanford University applied for a U.S. patent for statistical methods of predicting haplotype phase. In 2019, the Patent Trial and Appeal Board rejected the application as ineligible subject matter. Last week, a panel of the U.S. Court of Appeals for the Federal Circuit affirmed.

The opinion is interesting for being related to two, often separate fields: software and medicine (specifically genetics and bioinformatics). So, let’s look at what the Federal Circuit said about this computerized method for haplotype estimation.

Haplotype estimation

Gene sequencing is common for determining the genes present in an individual. But standard sequencing techniques cannot always resolve which parent a group of alleles came from — known as haplotype phasing. Stanford’s application describes statistical methods for resolving the haplotype phases for a group of unrelated individuals.

The key statistical model in this technique is a hidden Markov model (HMM). In an HMM, you assume that an observable process is being influenced by something unobservable — “hidden states.” Then, by studying the process, you can learn about the hidden state. In the present case, the observable genotype is assumed to be influenced by the unobservable haplotype. By studying the genotypes of many unrelated individuals, the HMM allows estimation of the individuals’ haplotypes.

The ’982 Application

In U.S. Patent Application No. 13/486,982, Stanford describes a computerized method of estimating (inferring) haplotype phase in a collection of unrelated individuals. The ’982 Application includes two independent claims, of which Claim 1 is representative.

  1. A computerized method for inferring haplotype phase in a collection of unrelated individuals, comprising:

receiving genotype data describing human genotypes for a plurality of individuals and storing the genotype data on a memory of a computer system;

imputing an initial haplotype phase for each individual in the plurality of individuals based on a statistical model and storing the initial haplotype phase for each individual in the plurality of individuals on a computer system comprising a processor a memory [sic];

building a data structure describing a Hidden Markov Model, where the data structure contains:

a set of imputed haplotype phases comprising the imputed initial haplotype phases for each individual in the plurality of individuals;

a set of parameters comprising local recombination rates and mutation rates;

wherein any change to the set of imputed haplotype phases contained within the data structure automatically results in re-computation of the set of parameters comprising local recombination rates and mutation rates contained within the data structure;

repeatedly randomly modifying at least one of the imputed initial haplotype phases in the set of imputed haplotype phases to automatically re-compute a new set of parameters comprising local recombination rates and mutation rates that are stored within the data structure;

automatically replacing an imputed haplotype phase for an individual with a randomly modified haplotype phase within the data structure, when the new set of parameters indicate that the randomly modified haplotype phase is more likely than an existing imputed haplotype phase;

extracting at least one final predicted haplotype phase from the data structure as a phased haplotype for an individual; and

storing the at least one final predicted haplotype phase for the individual on a memory of a computer system.

The novelty of the ’982 Application is in the specific HMM employed. By using imputed haplotypes as the hidden states, Stanford’s method improves the accuracy of haplotype predictions. Importantly, while the claim does attempt to recite hardware limitations, the CAFC noted that “it is hard to imagine a patent claim that recites hardware limitation in more generic terms” than does Claim 1.

Stanford’s computational method of genome analysis fails the Alice test

In applying the first step of the test set forth by the Supreme Court in Alice, the CAFC agreed with the board in that the ’982 Application is directed to “mathematical calculations and statistical modeling.” This is not surprising given the nature of the claims, which even recite specific mathematical formulas. Nor did the recited steps of “receiving, … imputing, … extracting, … and storing” data convert the math into a practical application. According to the Federal Circuit, those steps are too generic and could be implemented with a regular computer.

The CAFC also agreed with the board in that the claims of the ’982 Application do not improve a technological process. In its brief and during oral argument, Stanford leaned heavily on Enfish, arguing that its claims represent an improvement to a technological process in bioinformatics. It based that claim on improvements in accuracy and efficiency of its method over the prior art. The U.S. government argued that any improvement was only to the math itself — an improvement to abstract math is still only abstract math. The court agreed that “[t]he different use of a mathematical calculation, even one that yields different or better results, does not render patent eligible subject matter.”

Finally, as noted above, the court found no inventive concept that could rescue the claims. The steps of manipulating data could be performed on a generic computer. Even considered as an ordered combination, the claimed method is only a “basic tool[] of scientific … work.”

Practice points

First, preserve all arguments so that you can avoid waiver on appeal. At the board, Stanford failed to raise increased efficiency as a technical improvement of its method. When Stanford attempted to argue this point at the CAFC, the court refused to address it since the argument had been waived.

Second, as the U.S. Government said during oral arguments, “narrow math is still math.” No matter how specific the method, it must be more than an abstract idea. The degree of preemption by the ’982 Application would have been narrow to none. But while preemption is a mark of ineligibility, “the absence of complete preemption does not demonstrate patent eligibility.”

Finally — given the complexity and ever-changing nature of the law of subject-matter eligibility under § 101 — involve experienced counsel early. Problems with the initial application can be difficult to correct later, so it is beneficial to frame the application correctly in the first instance. Bradley’s attorneys have significant experience with subject matter eligibility and would be glad to assist with the prosecution of software- and data-related inventions.

“Anything You Say …” -- Terms with Inconsistent Definitions Are IndefiniteLast week, the U.S. Court of Appeals for the Federal Circuit (CAFC) held the term “computer” to be indefinite. That such a familiar term could be indefinite should warn patent practitioners to take care when arguing the scope of a term — even in otherwise unrelated proceedings, possibly separated by years.

Infinity Computer Products, Inc., owns a U.S. patent on using a fax machine as a printer/scanner for a personal computer. As detailed below, one element of an independent claim was “a passive link between the facsimile machine and the computer.” The prosecution history had inconsistent definitions of “passive link,” creating indefiniteness about where the “passive link” begins and the “computer” ends. The CAFC ruled that both terms were therefore indefinite, which invalidated the claim.

Indefinite claims are invalid

Patents — being a kind of sanctioned monopoly — must give the public notice about their precise scope. Conversely, the public needs clear notice of what is still open to them. To this end, Section 112 of the Patent Act requires claims “particularly pointing out and distinctly claiming the subject matter” of the patent. If a patent’s claims fail to do that, we say it is invalid for indefiniteness.

The Supreme Court set the gold standard for indefiniteness in Nautilus v. BioSig: “[A] patent is invalid for indefiniteness if its claims, read in light of … the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention.” One way to fail is for the specification or the prosecution history to use inconsistent definitions of a claim term. For example, in Teva Pharmaceuticals v. Sandoz, the claim at issue had used the term “molecular weight.” But the specification did not say which of three competing definitions of “molecular weight” was intended. In fact, the prosecution history reflected use of two different and inconsistent definitions. So Teva Pharmaceuticals’ patent was invalid for indefiniteness.

Infinity’s claims are indefinite due to conflicting definitions

But how could a term so well understood as is “computer” be indefinite, even to one skilled in the art of interfacing a fax machine with a PC? The answer lies in its interaction with the other indefinite term: “passive link.” Infinity had conceded that, for the claims to be definite, one skilled in the art must be “reasonably certain where the passive link ends and the computer begins.” Indefiniteness in the term “passive link” infected the term “computer” with the same degree of indefiniteness.

Initial prosecution

The term “passive link” is not in the specification, nor was it in the originally submitted claims. Instead, “passive link” had been added during prosecution to overcome a prior-art reference, “Perkins.” Between the fax machine and the PC, Perkins includes an intervening component, e.g., a fax modem. The intervening component could even be a card located “in the computer.” So, Infinity had limited its claims to a passive link between the fax and PC, distinguishing itself from Perkins as not requiring “any intervening apparatus.” More specifically, Infinity had argued that Perkins’ intervening component “should be regarded as a peripheral device” because it “processes data before it is transmitted to the I/O bus of the computer.” Infinity had argued that its own invention had no such intervening device, because the passive link connects directly to the I/O bus of the computer. Crucially, to make this distinction, Infinity relied on drawings that had been added to the specification in a continuation-in-part. The USPTO issued a patent to Infinity on the basis of this distinction (the “’811 Patent”).

Later reexamination

Later the ’811 Patent was subjected to reexamination. This time, the prior art at issue (“Kenmochi”) preceded Infinity’s continuation-in-part. So, Infinity needed to argue the claims were supported by drawings in the original parent application. But each of those earlier figures depicted, internal to the computer, circuitry similar to the internal card of Perkins — i.e., an “intervening component.” To survive the reexamination, then, Infinity fatally argued that “the use of a modulation procedure within the PC and facsimile machine … does not insert an intervening apparatus.”

Infinity had therefore assigned “passive link” to two different, inconsistent scopes. During initial prosecution, to overcome Perkins, “passive link” excluded devices with an internal-card fax modem between the fax machine and the PC. But during reexamination, to pre-date Kenmochi, the scope “passive link” must include such devices. In the first instance, the passive link ends at the port of the computer. In the second instance, the passive link extends all the way through to the I/O bus.

Litigation with Oki Data

The conflicting definitions proved to be a time bomb for Infinity. In litigating the ’811 Patent against Oki Data Americas in the District of Delaware, Oki Data exploited the latent inconsistency. The District Court held the ’811 Patent invalid for indefiniteness. The CAFC agreed.

In its opinion, the CAFC analogized Infinity’s position to that of Teva Pharmaceuticals. Without a consistent definition of “passive link,” one skilled in the art could not know what scope remained open to the public. There could be no reasonable certainty “where the passive link ends and where the computer begins.” So, the ’811 Patent failed to meet the standard for claims under Section 112.

Infinity as the Miranda of patent law

The lesson here is hard, but clear. Say little, and be consistent. Infinity was in a tough spot: Threading the needle between Perkins and Kenmochi would be difficult for anyone (especially if Infinity was unaware of Kenmochi until the reexamination). However, had the “passive link” amendment been left to speak for itself — rather than arguing in detail about the “intervening component” theory — Infinity would have had more room to construe the term carefully. Importantly, it may have been able to delay giving any definition until the reexamination. In that case, Oki Data could not have complained about inconsistent definitions, because there would only have been one. Patent practitioners are friendly, and we often want to help the USPTO side with our clients. But remember: Anything you say can and will be used against you.

Bookcase with numerous foreign languages dictionaries.In IBSA Institut Biochimique v. Teva Pharmaceuticals USA, Inc. a valuable lesson was learned about relying on a translation of a non-English patent application. The IBSA Institut Biochimique (IBSAIB) hired an Italian patent agent to file a patent application in Italian for a thyroid drug formulation. The application was filed in Italy. Within 12 months of filing in Italy, IBSAIB filed a patent application in the United States, citing its Italian patent application under the Paris Convention for Intellectual Property. However, instead of filing the Italian application in the U.S., a poor-quality English translation was filed, and material was added. The translation contained the meaningless term “half-liquid.” Because this term has no established meaning in pharmacology, a district court found the resulting patent to be invalid as indefinite, a finding that was affirmed by the court of appeals.

The Law of Indefiniteness

Section 112 of the Patent Act (as amended by the America Invents Act) requires a minimum level of clarity in the claims of patents. Specifically:

The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.

The courts interpret this section of the act to prohibit claims that are “indefinite.” The Supreme Court further defined this standard in its landmark case of Nautilus v. Biosig: “…we hold that a patent is invalid for indefiniteness if its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention.

The IBSAIB Patent

The patent application at issue in this case claimed a drug formulation containing (among other things) “a soft elastic capsule consisting of a shell of gelatin material containing a liquid or half-liquid inner phase comprising said thyroid hormones.” Based on the contents of the patent itself, the testimony of experts, and the contents of scientific texts, the court found that “half-liquid” was not a term whose meaning was reasonably certain. IBSAIB argued that this term should be interpreted to mean “semi-liquid.” It was not disputed that the term “semi-liquid” is an understood term, but the court disagreed that a person skilled in the art would understand “half-liquid” to be synonymous with “semi-liquid.”

IBSAIB’s argument was based in part on the fact that the original Italian patent contained the term “semiliquido,” which properly translates to “semi-liquid” in English. IBSAIB argued that a person trying to interpret the term “half-liquid” would understand that it was meant to be the English translation of “semiliquido” based on the sworn statement by the inventor that the Italian application was cited under the Paris Convention for Intellectual Property. The Paris Convention requires that, when a person applies for a patent in a first country and then in a second country, the second country treat its patent application as having the filing date in the first country, so long as the patent application in the second country is filed within 12 months of that in the first country. An earlier filing date is advantageous for many reasons, so this treaty is widely used.

The Court’s Rebuke

The court was unpersuaded. It reasoned that the Italian and U.S. patents were separate and distinct; although the U.S. patent was largely a translation of the Italian one, it contained additional information as well. There was nothing in the U.S. patent saying that it should be interpreted to be identical as the Italian one, in whole or in part. As a result, the court based its interpretation only on sources that are usually used under U.S. law: the contents of the patent itself, the prosecution history before the USPTO, and the knowledge of persons skilled in the art at the time of filing.

The Lesson on Foreign Filings

While low-quality patent translations abound (and are difficult to detect), IBSAIB’s problems could have been easily avoided. Under U.S. law one may file a patent application in any language, so long as an English translation is filed within a certain time limit. In such a situation the foreign language application is considered the authoritative version, and the translation merely that. As a result, translation errors can be corrected so long as the original non-English documents shows that they are clearly errors. This differs from IBSAIB’s situation, in which the translation itself was filed as the application.

One may also make an explicit statement in the U.S. application that the foreign application is incorporated by reference into the U.S. application. The USPTO officially recognizes that such an explicit statement allows for the correction of translation errors in section 213.02 of the Manual of Patent Examination Procedure. Had IBSAIB included such a statement in its U.S. patent application, it would have had the opportunity to correct translation errors such as the one that sunk its patent.

When a patent application has been drafted in a language other than English, one should not rely on a third-party translator to draft the patent application in the United States. Instead the foreign language application should either be used as the U.S. patent application or explicitly incorporated by reference, in case corrections need to be made or the foreign language application is needed to understand the English claims. Another option is to ask a U.S. patent agent or attorney to draft an application in English from scratch, which may still cite the foreign application for priority if correctly drafted.