The Board of Trustees of the Leland Stanford Junior University

Patent Trials and Appeals Board

May 15, 2020

2019006771 (P.T.A.B. May. 15, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/336,434 07/21/2014 Neta Zuckerman 48440-582001US 6978
64046 7590 05/15/2020
Mintz Levin/San Diego Office
One Financial Center
Boston, MA 02111
EXAMINER
WHALEY, PABLO S
ART UNIT PAPER NUMBER
3619
NOTIFICATION DATE DELIVERY MODE
05/15/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
IPDocketingBOS@mintz.com
IPFileroombos@mintz.com
mintzdocketing@cpaglobal.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NETA ZUCKERMAN, YAIR NOAM,
ANDREA GOLDSMITH, AND PETER P. LEE
Appeal 2019-006771
Application 14/336,434
Technology Center 1600

Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and
ELIZABETH A. LAVIER, Administrative Patent Judges.
LAVIER, Administrative Patent Judge.

DECISION ON APPEAL
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–8, 10–13, 15, and 17–19. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as The Board of
Trustees of the Leland Stanford Junior University. Appeal Br. 2.
Appeal 2019-006771
Application 14/336,434

2
CLAIMED SUBJECT MATTER
The claims are directed to methods for identifying cell type specific gene
expression data from a heterogeneous tissue sample. Claim 1, reproduced
below, is illustrative:
1. A method comprising:
determining a heterogeneous gene expression data associated
with a heterogeneous tissue sample, the heterogeneous tissue
sample having a tissue type and a composition that includes a
first plurality of cell types; obtaining, from a database, a plurality
of reference expression profiles for a second plurality of cell
types, the second plurality of cell types comprising an estimation
of the first plurality of cell types comprising the composition of
the heterogeneous tissue sample;
determining a plurality of estimated expression profiles
corresponding to the second plurality of cell types;
estimating, based at least on the plurality of estimated expression
profiles for the second plurality of cell types, a quantity of cell
types comprising the first plurality of cell types, the estimating
comprising:
determining a symmetric Kullback-Leibler divergence
between the plurality of estimated expression profiles and
the plurality of reference expression profiles; and
identifying at least one cell type comprising the actual
composition of the heterogeneous tissue sample based at
least on the at least one cell type being associated with an
estimated expression profile having a least symmetric
Kullback-Leibler divergence with respect to the plurality
of reference expression profiles;
computing a proportion of each cell type included in the first
plurality of cell types comprising the composition of the
heterogeneous tissue sample; and
separating, based at least on the quantity of cell types and the
proportion of each cell type, the heterogeneous gene expression
data associated with the heterogeneous tissue sample, the
Appeal 2019-006771
Application 14/336,434

3
heterogeneous gene expression data being separated into a
plurality of cell type specific expression profiles corresponding
to the first plurality of cell types comprising the composition of
the heterogeneous tissue sample.
Appeal Br. 23–24 (Claims Appendix).
REJECTION
Claims 1–8, 10–13, 15, and 17–19 stand rejected under 35 U.S.C.
§ 101 as being directed to subject matter ineligible for patenting. Ans. 3.
OPINION
A. The Rejection
The Examiner determined that, as method claims, Appellant’s claims
fall within one of the statutory categories of invention. See Final Action 3.
However, the Examiner rejected the claims as falling within one of the
judicially-created exceptions to eligibility, i.e., abstract ideas. See id.; see
also Ans. 3–4. More specifically, the Examiner found that the claims are
drawn to “methods for determining gene expression profiles and cell types
which rely upon a judicial exception that is an abstract idea” (Final Action
3), and nothing significantly more (see id. at 5–6), whether the limitations
are considered individually or as an ordered whole (see id. at 6).
B. Principles of Law
An invention is patent-eligible if it claims a “new and useful process,
machine, manufacture, or composition of matter.” 35 U.S.C. § 101. The
Supreme Court has long interpreted 35 U.S.C. § 101 to include implicit
exceptions, however: “[l]aws of nature, natural phenomena, and abstract
ideas” are not patentable. Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216
(2014). In determining whether a claim falls within an excluded category,
Appeal 2019-006771
Application 14/336,434

4
we are guided by the Court’s two-step framework, described in Mayo
Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012)
and Alice, 573 U.S. at 217–18 (citing Mayo, 566 U.S. at 75–77). In
accordance with that framework, we first determine what concept the claim
is “directed to.” See Alice, 573 U.S. at 219 (“On their face, the claims
before us are drawn to the concept of intermediated settlement, i.e., the use
of a third party to mitigate settlement risk.”).
Concepts determined to be abstract ideas, and thus patent ineligible,
include certain methods of organizing human activity, such as fundamental
economic practices (Alice, 573 U.S. at 219–20; Bilski v. Kappos, 561 U.S.
593, 611 (2010)); mathematical formulas (Parker v. Flook, 437 U.S. 584,
594–95 (1978)); and mental processes (Gottschalk v. Benson, 409 U.S. 63,
69 (1972)). If the claim is “directed to” an abstract idea, we turn to the
second step of the Alice and Mayo framework, where “we must examine the
elements of the claim to determine whether it contains an ‘inventive
concept’ sufficient to ‘transform’ the claimed abstract idea into a patent-
eligible application.” Alice, 573 U.S. at 221 (quotation marks omitted).
Early in 2019, the USPTO published revised guidance on the
application of § 101. USPTO, 2019 Revised Patent Subject Matter
Eligibility Guidance, 84 Fed. Reg. 50 (January 7, 2019) (“Memorandum” or
“2019 Office Guidance” or “Office Guidance”). The 2019 Office Guidance
was subsequently updated in October 2019. USPTO, October 2019 Patent
Eligibility Guidance Update, 84 Fed. Reg. 55942 (October 18, 2019)
(“October 2019 Guidance Update”).2

2 The citation provided to the Federal Register for the October 2019
Guidance Update is for the notice only. As the notice indicates, the full text
Appeal 2019-006771
Application 14/336,434

5
Following the Office Guidance, under Revised Step 2A, we first look
to whether the claim recites the following:
(1) any judicial exceptions, including certain groupings of
abstract ideas (i.e., mathematical concepts, certain methods
of organizing human activity such as a fundamental
economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into
a practical application (see MPEP § 2106.05(a)–(c), (e)–(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that
exception into a practical application, do we then look, under Step 2B of the
Office Guidance, to whether the claim:
(3) adds specific limitations beyond the judicial exception that
are not “well-understood, routine, conventional” in the field (see
MPEP § 2106.05(d)); or

(4) simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high
level of generality, to the judicial exception.
See Memorandum.
C. Analysis
1. Office Guidance—Revised Step 2A, Prong 1
We select Appellant’s claim 1 as representative of the claims subject
to this rejection. Applying Revised Step 2A, Prong 1, of the 2019 Office
Guidance, we agree with the Examiner that Appellant’s claim 1 recites
abstract ideas in a number of instances.

of the October 2019 Guidance Update, including its appendices, is available
at https://www.uspto.gov/PatentEligibility. This website also includes a link
to the 2019 Office Guidance, among other documents.
Appeal 2019-006771
Application 14/336,434

6

Representative claim 1 recites a method in which expression data
associated with a heterogeneous tissue sample are “determin[ed].” Appeal
Br. 23 (Claims Appendix). Then, at least in part using reference expression
profiles obtained from a database (and for which estimated expression
profiles are “determin[ed]”), the quantity of cell types is “estimat[ed],” the
proportion of each cell type is “comput[ed],” and the heterogeneous gene
expression data are “separat[ed], based on at least the quantity of cell types
and the proportion of each cell type . . . . into a plurality of cell type specific
expression profiles” for the cell types in the heterogeneous tissue sample.
Id. at 23–24. Because determining, estimating, computing, and separating as
recited in claim 1 involve concepts performed in the human mind, these
steps recite a judicial exception in the form of a mental process. See Office
Guidance, 84 Fed. Reg. at 52 (abstract ideas include “(c) Mental processes—
concepts performed in the human mind (including an observation,
evaluation, judgment, opinion”) (citations omitted).
Indeed, claim 1 further specifies that the step in which the quantity of
cell types is “estimat[ed]” is accomplished through, inter alia, “determining
a symmetric Kullback-Leibler divergence between the plurality of estimated
expression profiles and the plurality of reference expression profiles” and
using this result to “identify[]” at least one cell type in the tissue sample.
Appeal Br. 23 (Claims Appendix). As the Specification explains, symmetric
Kullback-Leibler divergence is “a measure used to calculate the difference
between two probability distributions” (Spec. ¶ 21), and is further defined by
mathematical equations (see id. at ¶ 28). Accordingly, we agree with the
Examiner that claim 1 recites abstract ideas. See Office Guidance (84 Fed.
Appeal 2019-006771
Application 14/336,434

7
Reg. at 52 (abstract ideas include “(a) Mathematical concepts—
mathematical relationships, mathematical formulas or equations,
mathematical calculations”)).
2. Office Guidance—Revised Step 2A, Prong 2
Having determined that Appellant’s representative claim 1 recites
abstract ideas under Revised Step 2A, Prong 1, of the 2019 Office Guidance,
we turn to Revised Step 2A, Prong 2, of the Office Guidance to determine
whether claim 1 recites additional elements that integrate the judicial
exceptions into a practical application. See Office Guidance (84 Fed. Reg. at
54–55). Appellant asserts that, in contrast to prior art methods:
the claims integrate any alleged me[n]tal process and/or
mathematical concept into a practical application for separating,
into individual cell type specific expression profiles,
heterogeneous gene expression data associated with a
heterogeneous tissue sample having multiple types of cells
without any a priori information on the quantity of cell types and
the proportion of each cell type present in the heterogeneous
tissue sample.
Appeal Br. 15. We are not persuaded. As the Examiner explains,
Appellant’s “inventive concept appears to be the algorithmic process itself,”
not a practical application thereof:
While the particular algorithmic approach to clustering gene
expression data recited in the claims may be a particular way to
achieve the separation of gene expression data associated with
cell types (without the use of a priori information), the claim
remains directed to a purportedly better form of algorithmic
analysis.
Ans. 4. Indeed, claim 1 begins with “determining a heterogeneous gene
expression data,” and ends with “separating . . . the heterogeneous gene
Appeal 2019-006771
Application 14/336,434

8
expression data.” Appeal Br. 23–24 (Claims Appendix). Thus, the input
and the output are equally abstract (as are the intermediate steps). In other
words, claim 1 does not “effect[] a transformation or reduction of a
particular article to a different state or thing” (MPEP § 2106.05(c) (citing
Bilski v. Kappos, 561 U.S. 593 (2010)), as only data are manipulated in
claim 1—nothing tangible is altered. See October 2019 Guidance Update at
13 (“[I]t is important to keep in mind that an improvement in the judicial
exception itself . . . is not an improvement in technology.”).
Thus, we agree with the Examiner that Appellant’s claim 1 does not
recite additional elements that integrate the judicial exceptions into a
practical application.
3. Office Guidance—Step 2B
For the reasons discussed above, we are persuaded that
Appellant’s representative claim 1 recites judicial exceptions (abstract ideas
in the form of mathematical concepts and mental processes) under Revised
Step 2A, Prong 1, of the 2019 Office Guidance, and does not integrate those
judicial exceptions into a practical application under Revised Step 2A, Prong
2. Accordingly, we turn to Step 2B of the Office Guidance to determine
whether (a) claim 1 recites specific limitations beyond the judicial
exceptions that are not well-understood, routine, or conventional in the field,
or (b) whether claim 1 simply appends well-understood, routine,
conventional activities previously known to the industry, specified at a high
level of generality, to the judicial exception. See Office Guidance (84 Fed.
Reg. at 56).
As discussed above, the steps of claim 1 involve the manipulation of
gene expression data, to compute the proportion of cell types in a
Appeal 2019-006771
Application 14/336,434

9
heterogeneous sample and to separate the cell type specific expression
profiles corresponding to those cell types. See Appeal Br. 23–24. Appellant
argues that “obviating the need for a priori information” is a “significant
improvement[] to conventional techniques for separating heterogeneous
gene expression data,” thus “qualify[ing] as additional elements that amount
to significantly more” than the judicial exceptions. Appeal Br. 20. But
regardless of whether it improves prior art processes, claim 1 does not recite
specific limitations beyond the abstract idea. Claim 1 begins with
“determining a heterogeneous gene expression data associated with a
heterogeneous tissue sample,” not with the tissue sample itself. Claim 1
does not sort cells; claim 1 sorts data. In other words, the improvement
described by Appellant is in the abstract idea itself. Whether considered
individually or as an ordered combination, we conclude that claim 1 does not
recite specific limitations beyond the judicial exceptions that are not well-
understood, routine, or conventional in the field.
D. Conclusion
In the present case, as discussed above, under the Mayo framework as
implemented by the 2019 Office Guidance, we are persuaded that the
preponderance of the evidence supports the Examiner’s determination that
Appellant’s claim 1 is directed to subject matter that is ineligible for
patenting. In sum, for the reasons discussed, Appellant does not persuade us
that the Examiner erred in determining that Appellant’s claim 1 is directed to
subject matter that is ineligible for patenting. We, therefore, affirm the
Examiner’s rejection of claim 1 as being ineligible for patenting. Claims 2–
8, 10–13, 15, and 17–19 are not argued separately, and fall with claim 1.
See 37 C.F.R. § 41.37(c)(1)(iv) (2016).
Appeal 2019-006771
Application 14/336,434

10
CONCLUSION
The Examiner’s rejection is affirmed.
DECISION SUMMARY
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–8, 10–13,
15, 17–19
101 Eligibility 1–8, 10–13,
15, 17–19

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED