THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Plaintiff-Appellant
THE CHINESE UNIVERSITY OF HONG KONG, Defendant-Appellee
from the United States District Court for the Northern
District of California in No. 3:12-cv-00865-SI, Judge Susan
R. Reines, Weil, Gotshal & Manges LLP, Redwood Shores,
CA, argued for plaintiff-appellant. Also represented by DEREK
C. WALTER, MlCHELE Gauger.
Charles E. Lipsey, Finnegan, Henderson, Farabow, Garrett
& Dunner, LLP, Reston, VA, argued for defendant-appellee.
Also represented by Steven O'Connor; Jennifer Swan,
Robert F. McCauley, Jeffrey Daniel Smyth, Lily Lim, Palo
Alto, CA; Howard Warren Levine, Washington, DC.
O'MALLEY, Reyna, and Chen, Circuit Judges.
O'MALLEY, Circuit Judge.
Board of Trustees of the Leland Stanford Junior University
("Stanford") appeals from orders of the Patent
Trial and Appeal Board ("Board") in three
interference proceedings between Stanford and the Chinese
University of Hong Kong ("CUHK"). In all of these
proceedings, the Board found that Stanford's claims were
unpatentable for lack of written description. See 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); Lo v.
Quake, No. 105, 924 (P.T.A.B. Apr. 7,
2014). Because we conclude that the Board relied
on improper evidence to support its key findings and did not
cite to other substantial evidence to support its findings,
we vacate the Board's interference decisions and remand
for further proceedings.
Technology and Patents
appeal concerns testing methods for fetal aneu-ploidies,
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). Prior to the methods developed by the inventors
involved in this appeal, physicians typically diagnosed fetal
aneuploidies using invasive amniocentesis or chorionic villus
sampling procedures. Doctors used less invasive testing
methods for identifying aneuploidies, such as ultrasonography
and biochemical marker detection, but these methods had
suboptimal diagnostic accuracy.
competing inventors in the underlying interferences on
appeal-Stanford professor Stephen Quake and CUHK professor
Dennis Lo-both developed methods for diagnosing aneuploidies
using cell-free fetal DNA ("cff-DNA") from maternal
blood samples. In 1997, Lo and a colleague discovered that
cff-DNA circulates in maternal blood in small amounts. This
discovery made possible new prenatal screening techniques for
chromosomal and other abnormalities, but researchers
developing techniques for assaying cff-DNA had to overcome
interference from maternal DNA in the maternal blood sample.
2006, Quake developed a "digital analysis" method
to detect small changes in the quantity of an aneuploid
chromosome relative to the quantity of one or more normal
chromosomes, without distinguishing between maternal and
fetal DNA. '018 patent, col. 1, 11. 46-60; col. 2, 11.
7-9; col. 7, 11. 46-61. Quake describes "a method of
differential detection of target sequences in a mixture of
maternal and fetal genetic material." Id. col.
4, 11. 43-45. The '018 specification explains that the
approach "involves the separation of the 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 multiples, 2, 3,
etc." Id. col. 1, 11. 49-52.
specification outlines the four steps in his method: (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
"[quantitative analysis of the detection of the maternal
and fetal target sequences." Id. col. 8, 1.
35-col. 9, 1. 6. The method requires a large number of
samples, as only a small amount of cff-DNA is present in a
maternal sample. The specification clarifies that the digital
PCR technique, in which a known target DNA sequence in a
reaction well is amplified by target-specific primers, is the
preferred embodiment for amplifying and detecting target
capabilities of second-generation massively parallel
sequencing ("MPS") are useful for performing
Quake's method, as this method can process large numbers
of DNA samples simultaneously. Quake's specification
discloses that second-generation MPS can be used for counting
chromosomes through DNA sequencing using the Illumina
sequencing platform. Id., col. 19, 1. 59-col. 20, 1.
3. MPS can be performed by "random" or
"targeted" methods. In the random format, all DNA
in a sample is linked to a leader sequence and amplified
using a primer complementary to the leader. Appellee Br. 10.
In the targeted format, the target sequence is specifically
amplified, and then sequenced.
claimed his method in an application filed on February 2,
2007; this application issued as U.S. Patent No. 7, 888, 017
("the '017 patent"). Quake filed continuation
application no. 12/393, 803 ("the '803
application") in February 2009. This continuation
application issued as the '018 patent at issue in this
appeal. The '017 and '018 patents share the same
original claims of Quake's '803 application
explicitly recited methods that required the detection of
"target sequences." For example, claim 1 of the
'803 application read:
1. A method of differential detection of target
sequences in a mixture of maternal and fetal genetic
material, comprising the steps of:
a) obtaining maternal tissue containing both maternal and
fetal genetic material;
b) distributing the genetic material into discrete samples,
each sample containing on average not more than about one
target sequence per sample;
c) measuring the presence of different target
sequences in the discrete samples; and
d) analyzing a number of the discrete samples sufficient to
obtain results distinguishing different target
J.A. 3253 (emphasis added).
2011, Quake cancelled all pending claims in the application
which later issued as the '018 patent, and added new
claims. A representative later-added claim from
the '018 patent states:
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 ...