Why The Federal Circuit Revisited Written Description

In Stanford University v. The Chinese University of Hong Kong (Fed Cir. No 2015-2011, June 27, 2017), the Federal Circuit vacated and remanded interference decisions on the ground the Patent Trial and Appeal Board (“Board”) applied the incorrect standard in determining whether a patent specification satisfies the written description requirement. The decision is interesting because it is yet another review of patents related to prenatal detection of fetal DNA, and because the Federal Circuit addressed when post-filing evidence can be used to establish possession of a claimed invention.

The Claimed Technology – Detecting Fetal Aneuploidies

The claimed technology relates to “testing methods for fetal aneuploidies, conditions in which a fetus either has an abnormally high number of chromosomes (e.g., Down’s syndrome, a result of trisomy 21) or an abnormally low number of chromosomes (e.g., Turner’s syndrome, a result of a missing copy of an X chromosome).” Slip Op. at 2-3. Stanford professor Stephen Quake and Chinese University of Hong Kong professor Dennis Lo both developed methods that relied on detecting cell-free fetal DNA (“cff-DNA”) present in maternal blood in small amounts. A technical challenge in detecting cff-DNA in a maternal blood sample is distinguishing the maternal DNA from fetal DNA.

Quake developed a technique to account for the interfering maternal DNA. His technique relied on a “digital analysis” method to detect small changes in the quantity of an aneuploid chromosome relative to one or more normal chromosomes, without distinguishing between maternal and fetal DNA. Quake’s U.S. Patent No. 8,008,018 (‘018 patent) describes the technique as involving the “separation of extracted genomic material into discrete units so that the detection of a target sequence (e.g., chromosome 21) may be simply quantified as binary (0,1) or simple multitudes, 2, 3, etc.” Slip Op. at 3, citing col. 1, lines 49-52 of the ‘018 patent.

Quake’s digital analysis method requires a large number of samples because only a small amount of cff-DNA is present in the maternal sample. The ‘018 patent notes that the digital PCR technique, which uses target-specific primers, is the preferred method for amplifying and detecting target sequences. Slip Op. at 4. The patent also discloses that second generation massively parallel sequencing (“MPS”) can perform Quake’s method using, for example, Illumina’s sequencing platform that was disclosed in the patent specification as a means to carry out the method.

Lo’s method to account for interfering maternal DNA relies on a random sequencing method that uses random MPS. Random MPS does not require the detection of specific target sequences; rather, DNA present in the maternal sample is sequenced using random MPS and the sequenced fragments are aligned to a reference genome to determine a chromosomal region of origin for each sequence. After the sequences are mapped to the chromosome, the numbers of mapped sequences are compared. A disproportionate number of aligned sequences to chromosome 21 is indicative of Down’s syndrome trisomy. Lo filed a patent application describing the random sequencing method.

Quake’s first patent (which issued as U.S. Patent No. 7,888,017) claimed the targeted method to analyze cff-DNA. Quake filed a continuation application which ultimately issued as the ‘018 patent. Quake’s ‘018 patent claimed a method that randomly sequenced DNA fragments. Claim 1 of the ’018 patent recites:

  1. A method for determining presence or absence of fetal aneuploidy in a maternal tissue sample comprising fetal and maternal genomic DNA, wherein the method comprises:

a. obtaining a mixture of fetal and maternal genomic DNA from said maternal tissue sample;

b. conducting massively parallel DNA sequencing of DNA fragments randomly selected from the mixture of fetal and maternal genomic DNA of step a) to determine the sequence of said DNA fragments;

c. identifying chromosomes to which the sequences obtained in step b) belong;

d. using the data of step c) to compare an amount of at least one first chromosome in said mixture of maternal and fetal genomic DNA to an amount of at least one second chromosome in said mixture of maternal and fetal genomic DNA, wherein said at least one first chromosome is presumed to be euploid in the fetus, wherein said at least one second chromosome is suspected to be aneuploid in the fetus, thereby determining the presence or absence of said fetal aneuploidy.

Slip Op. at 6, citing ‘018 patent, col. 22, lines 48-67 (emphasis added).

The Interference History

In 2011, Quake added for the first time, claims to methods that explicitly cover random MPS methods in an application that ultimately issued as the ‘018 patent. Both Quake and Lo requested interferences to determine who invented the random sequencing method, and when the method was invented. Slip Op. at 7. Three interferences were declared.

Lo attacked Quake’s ‘018 patent as unpatentable for lack of written description. Lo’s expert, Dr. Stacy Gabriel, alleged that Quake’s specification describes the digital analysis method and not the random sequencing method invented by Lo. Quake countered and pointed to language of the specification that he alleged disclosed every aspect needed to detect aneuploidy using random MPS.

The Board sided with Lo, finding that the ‘018 patent specification disclosed targeted and not random sequencing and that the “specification would not have indicated to one of ordinary skill in the art that Quake was in possession of the claimed MPS method.” Slip Op. at 8. The Board found Dr. Gabriel’s testimony persuasive that the ‘018 patent specification is directed to digital analysis of targeted sequences, and that “the language relied upon by Quake could have related to either random or targeted sequencing but that, because ‘the main focus of the Quake ‘018 patent [was] on diagnosing aneuploidy with digital PCR, those of skill would have understood the discussion of massively parallel sequencing to refer to sequencing targeted, predetermined portions of the DNA in a sample, not sequencing of random DNA.” Slip Op. at 8. The Board also determined that the specification’s reference to the Illumina platform could support random MPS and targeted sequencing.

Stanford and Dr. Quake appealed.

Written Description

The Federal Circuit reviewed the Board’s legal conclusions de novo. The court began by noting that:

“Substantial evidence supports a finding that the specification satisfies the written description requirement when ‘the essence of the original disclosure’ conveys the necessary information – ‘regardless of how it’ conveys such information, and even when the disclosures ‘words’ [a]re open to different interpretation[s].’”

Slip Op. at 13-14, citing In re Wright, 866 F.2d 422, 424-25 (Fed. Cir. 1989).

In this case, the Federal Circuit determined that the Board erred in evaluating the testimony offered by Lo’s expert, Dr. Gabriel. The court stated that both the Board and Dr. Gabriel did not cite any evidence of targeted or random sequencing on the Illumina platform, prior to Quake’s filing date. The evidence offered by Dr. Gabriel were two post-dated references that discussed the use of targeted sequencing methods. The Board did not, however, rely on this evidence in support of its decision. The other evidence offered by Dr. Gabriel related to sequencing on a Roche platform, not the Illumina platform cited in the ‘018 patent.

The court also determined that the Board applied the incorrect standard in evaluating the teachings of the ‘018 patent specification. As stated by the court, “the Board’s task was to determine whether the ‘018 patent’s written description discloses random MPS sequencing, as recited by the later-added claims, not whether the description does not preclude targeted MPS sequencing.” Slip Op. at 18.

As a result of the aforementioned errors, the court vacated the interference decisions and remanded to the Board to reconsider whether the Quake patents and applications satisfy the written description requirement by examining the record evidence to pre-filing evidence related to Illumina’s products. Any post-filing evidence can only be relied upon as far as they contain evidence of random MPS sequencing or Illumina products that existed as of the filing date. Slip Op. at 19.

In sum, the court instructed the Board to examine “whether a person of ordinary skill in the art would have understood that the ‘018 patent’s specification disclosed random MPS sequencing, as opposed to whether the specification did not preclude MPS sequencing.” Slip Op. at 20.

USPTO Extends Cancer Immunotherapy Pilot Program

On June 29th, 2016, the USPTO announced the Cancer Immunotherapy Pilot Program to allow expedited examination of patent applications that pertain to cancer immunotherapy. Under the Program and after proper petition, the USPTO has examined qualifying applications out of turn thereby expediting examination. The Program was implemented to support the National Cancer Moonshot and was scheduled to expire on June 28th, 2017. While only in effect for just less than one year, over 80 petitions for Program participation have been filed and 9 patents have been granted to date. On June 23rd, 2017, the USPTO announced that the Program is now extended until December 31, 2018.

To qualify for the fee-free program, the patent application must contain one or more claims to a method of treating cancer using immunotherapy. The Program is open to:

  • Any application that has not yet received a first Office Action;
  • Any application where the petition is filed with a Request for Continued Examination; or
  • Any application that is not under final rejection if the claimed therapy is the subject of an active Investigational New Drug (IND) application that has entered Phase II or Phase III (FDA) clinical trials.

Additional information and the appropriate forms can be found at this USPTO web address.

The USPTO also announced on June 23rd that it may further extend the Program (with or without modifications) or terminate it depending on feedback received, continued interest, and program effectiveness.

NIH Begins Beta Test of Million Patient Cohort

The National Institutes of Health announced the enrollment of the first participants as beta testers of the “All of Us research program. Initially branded as the “Precision Medicine Initiative®” Cohort Program, “All of Us” will be the largest health and medical research program on precision medicine.

The mission of the All of Us Research Program is to accelerate health research and medical breakthroughs, enabling individualized prevention, treatment and care for all of us.

The program follows and is built upon recommendations from a Precision Medicine Working Group organized by the NIH to develop a framework for the program for collecting, protecting, and analyzing medical data collected from volunteers. The program will start small and gradually expanded to more than 100 sites nationally during the beta phase.

Presently, enrollment in the program is by invitation only with enrollment to be expanded at partner sites at different times. Citizens that receive care at a participating a health care provider organization may be contacted to participate as a beta tester. Interested individuals can subscribe for email updates on the program at https:://www.joinallofus.org/.

Federal Circuit’s Primer on Equivalence Infringement of Chemical Process Patents

In an appeal characterized as “unusual,” the Federal Circuit affirmed the grant of a preliminary injunction, holding it likely that plaintiff patent holder would succeed on the merits its claim of infringement of a patent claiming a purified chemical compound, but reversed a finding of infringement under the doctrine of equivalents of related chemical process patents. Mylan Institutional LLC v Aurobindo Pharma Ltd., 2017-1645 (May 19, 2017 Fed. Cir.). The decision is an interesting read because, as the court admitted, “of the sparse and confusing case law concerning equivalents, particularly the paucity of chemical equivalents case law, and the difficulty of applying the legal concepts to the facts.” Slip Op at 12. Continue reading this entry

Breaking Down Barriers Between Pre-clinical and Clinical Adoption of Personalized Medicine

Personalized medicine will change how health care is delivered and disease is prevented and treated. But first, how disease and health is defined, as well as the clinical development and adoption of new therapies must align with current theories of disease and treatment. Continue reading this entry