Board of Trustees of the Leland Stanford Junior University v. Chinese University of Hong Kong (Fed. Cir. 2017)

by McDonnell Boehnen Hulbert & Berghoff LLP

Detection of paternal cell-free fetal DNA (cffDNA) in maternal blood (the technology at issue in Ariosa v. Sequenom) was in a different incarnation the subject of an interference between professors at two universities; the decision of the U.S. Patent and Trademark Office Patent Trial and Appeal Board in favor of Dennis Lo and the Chinese University of Hong Kong was reversed on July 3, 2017 and remanded for further proceedings, in Board of Trustees of the Leland Stanford Junior University v. Chinese University of Hong Kong.

This embodiment of the technology was directed to detecting aneuploidies, or an abnormal number of chromosomes in a cell; noted examples include Downs Syndrome (trisomy 21) and Turner's syndrome (XO).  While the opinion recognizes Dr. Lo as the discoverer of cffDNA in 1996, Stanford's professor (Dr. Stephen Quake) developed a new method for detecting small changes in the number of chromosomes characteristic of aneuploidy, employing a technology the Court terms "digital analysis," which did not distinguish between paternal and maternal sources of DNA.  There were four steps to Dr. Quake's claimed method as set forth in the opinion:

(1) obtaining a maternal tissue sample, preferably blood; (2) distributing single DNA molecules from this sample to a number of discrete reaction samples; (3) "[d]etecting the presence of the target in the DNA in a large number of reaction samples"; and (4) performing "[q]uantitative analysis of the detection of the maternal and fetal target sequences."

The opinion also sets forth disclosure from Dr. Quale's specification relating to the use of "second generation massively parallel sequencing [(MPS)] methods and PCR amplification of chromosome DNA as being useful in the practice of the invention.

Dr. Lo's invention, according to the opinion, was claimed in U.S. Patent Application Nos. 12/178,181; 13/070,275; 13/070,240; 12/614,350; 13/070,251; and 13/417,119.  The claims of these applications were directed to "random sequencing" of cffDNA followed by sequence alignment to a reference human genome sequence to detect DNA sequence fragments specific for each chromosome, using MPS methods as in Dr. Quake's patents and application.  Aneuploidies for each chromosome where they exist are detected by finding a greater frequency of aligned fragments for particular chromosomes than others.

At issue in the interference were Stanford U.S. Patent Nos. 7,888,017 and 8,008,018 and U.S. Application No. 12/393,833.  Dr. Lo and CUHK application in interference was U.S. Application No. 13/070,275.  Three interferences were declared, identified as lack of written description.  Quake v. Lo, No. 105,920 (P.T.A.B. Apr. 7, 2014); Lo v. Quake, No. 105,923 (P.T.A.B. Apr. 7, 2014); and Lo v. Quake, No. 105,924 (P.T.A.B. Apr. 7, 2014); In a footnote, the Federal Circuit opinion notes that the Board's opinion in all three interferences "contained largely the same findings" and to the opinion cited the '920 interference throughout as being applicant to all three interferences.  Dr. Quakes was accorded the benefit of his earliest provisional filing, February 2, 2007; Dr. Lo's priority date as disclosed in the Declaration of Interference was July 3, 2007.  Thus, Dr. Lo and CUHK were designated as the Junior Party and would have the burden of establishing an earlier date of invention should the interference reach the priority phase.

Both parties requested the PTO declare the interferences, which were all declared in 2013, and during each of the proceedings, CUHK filed preliminary motions that Stanford's '018 patent and '833 application were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a) (this posing a threshold question in the interference wherein Junior Party Lo would prevail if its motion was persuasive to the Board).  At least part of the basis for this allegation was that Dr. Quake changed the claims pending in the application that matured into the '018 patent to more closely parallel Dr. Lo's claims; indeed, Junior Party Lo contended that Senior Party Quake had copied the pending claims of CUHK's '181 application.  These motions were supported by expert testimony, as were Stanford's rebuttals to these motions.  The Board was persuaded by CUHK's motions and granted them, thus ending the interference and invalidating Stanford's patents.  In these decisions, the Board (according to the panel opinion) "repeatedly credited the testimony of [CUHK's expert] Dr. Gabriel, including in finding that (1) the specification of the '018 patent is directed to the use of 'digital analysis' of predetermined targeted sequences in a sample, and (2) 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 in the art 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'" (and was not persuaded by Stanford's attacks on that testimony).  In summary, the Board stated that:

Though the Quake inventors may have possessed parts of such a method, including massively parallel sequencing, randomly fragmenting DNA, and aligning sequences to genomic sequences, the facts do not indicate that those of ordinary skill in the art would have understood the inventors had put these pieces together into a complete method of sequencing random DNA fragments and identifying the sequenced fragments to determine aneuploidy.

Stanford appealed this decision to the District Court under 35 U.S.C. § 146 in the Northern District of California (Judge Susan Illston of Sequenom fame).  However, based on its decision in Biogen MA, Inc. v. Japanese Found. for Cancer Research, 785 F.3d 648 (Fed. Cir. 2015), that the provisions of the Leahy-Smith America Invents Act precluding appeals to the district courts should apply, the parties jointly asked the District Court to transfer the appeal to the Federal Circuit, and this opinion followed.

The Federal Circuit reversed, in an opinion by Judge O'Malley, joined by Judges Reyna and Chen.  The panel rejected Stanford's invitation to "rethink" its Biogen decision regarding whether appeals from interferences could no longer be brought before the district courts under § 146.  On that question the opinion states that Biogen is the law in this circuit and we, as a panel, will not revisit it.  Similarly, the panel refused to consider the evidence adduced during the brief discovery period before the California District Court and the Biogen decision, because the District Court did not have subject matter jurisdiction under the panel's appreciation of the law after Biogen ("the activities in the district court are a nullity when the district court lacks subject matter jurisdiction to consider a matter," citing Ruhrgas AG v. Marathon Oil Co., 526 U.S. 574, 577 (1999)) and CUHK cannot waive lack of subject matter jurisdiction.  Having made this decision, the Federal Circuit's review was limited to the "four corners" of the record before the PTAB, and the panel agreed with CUHK that it would "treat the district court proceedings as if they never occurred."

Turning to the merits (which the Court reviewed for substantial evidence as the question of written description is one of fact; In re Gartside, 203 F.3d 1305, 1314 (Fed. Cir. 2000)), the panel held that the PTAB had erred in invalidating Stanford's patents.  The basis for this determination was found in CUHK's expert's testimony and some of the references upon which her conclusions had been based.  The deficiency arose based on the lack of correspondence between what was expressly disclosed in Stanford's patents and applications and what the references relied upon by CUHK's expert disclosed (and upon which she based her conclusion on the adequacy of disclosure question).  According to the opinion:

All of the published references on which the Board relies focus on the Roche 454 platform, not the Illumina platform actually referenced in the specification.  The Board did not cite evidence to connect targeted sequencing on the Roche 454 platform to targeted sequencing on the Illumina system, nor has the Board explained what it found persuasive about the Roche 454 platform references.

The evidence put forward by Stanford was that its disclosure related to a so-called "second generation" (Illumina) sequencing apparatus and that CUHK's expert relied on references directed to a "first generation" (Roche 454) machine.  In addition (and perhaps providing the panel's best support for its opinion), "Dr. Gabriel and the Board failed to cite to the Roche 454 references with specificity, leaving us with no reviewable record to conclude that the disclosed methods or platform would have been applicable to Illumina on Quake's priority date."  It is one thing to give deference to the PTAB and apply the substantial evidence standard; it is apparently another thing not to provide a reviewing court (or at least the Federal Circuit) with sufficient evidence for the substantiality thereof to be assessed.

The panel was also unimpressed with the distinctions raised by CUHK's expert regarding targeted versus random MPS:

The Board's finding that the '018 specification's language does not preclude targeted MPS ignores the fact that the same description might be able to disclose both random and targeted sequencing.  Put another way, even if the '018 specification could indicate targeted sequencing, it could also disclose random sequencing, or it could disclose both random and targeted sequencing.  The Board frames its finding in terms of an erroneous premise: 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.

In addition, this was another instance where the Federal Circuit believed the PTAB had not properly explained its reasoning:  "The Board's error on this issue is compounded by its failure to explain the meaning of key sentences and phrases in the specification's discussion of the sequencing process, and its failure to compare these statements to the claim limitations."

On remand, the panel directed the PTAB to "examine whether a person of ordinary skill in the art would have known, as of the priority date, that the '018 specification's reference to Illumina products meant random MPS sequencing as recited in the claims," based on the understanding in the art at the priority date, and should "examine whether a person of ordinary skill would have understood that the '018 patent's specification disclosed random MPS sequencing, as opposed to whether the specification did not preclude targeted MPS sequencing."  Of course, should the Board find that the evidence does not support invalidating any or all of Stanford's patents or application, the interference should proceed to address other motions and ultimately put CUHK to its priority proofs regarding who was the first inventor of the claimed technology.

Board of Trustees of the Leland Stanford Junior University v. Chinese University of Hong Kong (Fed. Cir. 2017)
Panel: Circuit Judges O'Malley, Reyna, and Chen
Opinion by Circuit Judge O'Malley

DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.

© McDonnell Boehnen Hulbert & Berghoff LLP | Attorney Advertising

Written by:

McDonnell Boehnen Hulbert & Berghoff LLP

McDonnell Boehnen Hulbert & Berghoff LLP on:

Readers' Choice 2017
Reporters on Deadline

"My best business intelligence, in one easy email…"

Your first step to building a free, personalized, morning email brief covering pertinent authors and topics on JD Supra:
Sign up using*

Already signed up? Log in here

*By using the service, you signify your acceptance of JD Supra's Privacy Policy.
Custom Email Digest
Privacy Policy (Updated: October 8, 2015):

JD Supra provides users with access to its legal industry publishing services (the "Service") through its website (the "Website") as well as through other sources. Our policies with regard to data collection and use of personal information of users of the Service, regardless of the manner in which users access the Service, and visitors to the Website are set forth in this statement ("Policy"). By using the Service, you signify your acceptance of this Policy.

Information Collection and Use by JD Supra

JD Supra collects users' names, companies, titles, e-mail address and industry. JD Supra also tracks the pages that users visit, logs IP addresses and aggregates non-personally identifiable user data and browser type. This data is gathered using cookies and other technologies.

The information and data collected is used to authenticate users and to send notifications relating to the Service, including email alerts to which users have subscribed; to manage the Service and Website, to improve the Service and to customize the user's experience. This information is also provided to the authors of the content to give them insight into their readership and help them to improve their content, so that it is most useful for our users.

JD Supra does not sell, rent or otherwise provide your details to third parties, other than to the authors of the content on JD Supra.

If you prefer not to enable cookies, you may change your browser settings to disable cookies; however, please note that rejecting cookies while visiting the Website may result in certain parts of the Website not operating correctly or as efficiently as if cookies were allowed.

Email Choice/Opt-out

Users who opt in to receive emails may choose to no longer receive e-mail updates and newsletters by selecting the "opt-out of future email" option in the email they receive from JD Supra or in their JD Supra account management screen.


JD Supra takes reasonable precautions to insure that user information is kept private. We restrict access to user information to those individuals who reasonably need access to perform their job functions, such as our third party email service, customer service personnel and technical staff. However, please note that no method of transmitting or storing data is completely secure and we cannot guarantee the security of user information. Unauthorized entry or use, hardware or software failure, and other factors may compromise the security of user information at any time.

If you have reason to believe that your interaction with us is no longer secure, you must immediately notify us of the problem by contacting us at In the unlikely event that we believe that the security of your user information in our possession or control may have been compromised, we may seek to notify you of that development and, if so, will endeavor to do so as promptly as practicable under the circumstances.

Sharing and Disclosure of Information JD Supra Collects

Except as otherwise described in this privacy statement, JD Supra will not disclose personal information to any third party unless we believe that disclosure is necessary to: (1) comply with applicable laws; (2) respond to governmental inquiries or requests; (3) comply with valid legal process; (4) protect the rights, privacy, safety or property of JD Supra, users of the Service, Website visitors or the public; (5) permit us to pursue available remedies or limit the damages that we may sustain; and (6) enforce our Terms & Conditions of Use.

In the event there is a change in the corporate structure of JD Supra such as, but not limited to, merger, consolidation, sale, liquidation or transfer of substantial assets, JD Supra may, in its sole discretion, transfer, sell or assign information collected on and through the Service to one or more affiliated or unaffiliated third parties.

Links to Other Websites

This Website and the Service may contain links to other websites. The operator of such other websites may collect information about you, including through cookies or other technologies. If you are using the Service through the Website and link to another site, you will leave the Website and this Policy will not apply to your use of and activity on those other sites. We encourage you to read the legal notices posted on those sites, including their privacy policies. We shall have no responsibility or liability for your visitation to, and the data collection and use practices of, such other sites. This Policy applies solely to the information collected in connection with your use of this Website and does not apply to any practices conducted offline or in connection with any other websites.

Changes in Our Privacy Policy

We reserve the right to change this Policy at any time. Please refer to the date at the top of this page to determine when this Policy was last revised. Any changes to our privacy policy will become effective upon posting of the revised policy on the Website. By continuing to use the Service or Website following such changes, you will be deemed to have agreed to such changes. If you do not agree with the terms of this Policy, as it may be amended from time to time, in whole or part, please do not continue using the Service or the Website.

Contacting JD Supra

If you have any questions about this privacy statement, the practices of this site, your dealings with this Web site, or if you would like to change any of the information you have provided to us, please contact us at:

- hide
*With LinkedIn, you don't need to create a separate login to manage your free JD Supra account, and we can make suggestions based on your needs and interests. We will not post anything on LinkedIn in your name. Or, sign up using your email address.