KIM, Sung K. et al.

Patent Trials and Appeals Board

Sep 26, 2019

14311070 - (D) (P.T.A.B. Sep. 26, 2019)

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.
14/311,070 06/20/2014 Sung K. KIM 4213.0020001 5858
155954 7590 09/26/2019
STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
(Illumina)
1100 New York Avenue, NW
Washington, DC 20005
EXAMINER
BRUSCA, JOHN S
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
09/26/2019 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):
e-office@sternekessler.com
illuminadocket@illumina.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte SUNG K. KIM, GREGORY HANNUM,
JENNIFER GEIS, and COSMIN DECIU
____________

Appeal 2019-0037921
Application 14/311,070
Technology Center 1600
____________

Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and
RYAN H. FLAX, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
The claims in this appeal are directed to a computer-implemented,
fetal gender-independent, fetal ploidy independent, and fetal polymorphism-
independent method for determining a fraction of fetal nucleic acid in a test
sample from the blood of a pregnant female. The Examiner rejected the
claims under 35 U.S.C. § 101 as reciting patent ineligible subject matter.
Pursuant to 35 U.S.C. § 134, Appellants appeal the Examiner’s
determination that the claims are unpatentable. We have jurisdiction for the
appeal under 35 U.S.C. § 6(b). The Examiner’s decision is reversed.

1 The Appeal Brief (“Appeal Br.” entered Dec. 21, 2018) identifies
Sequenom, Inc. and Illumina, Inc. as the real-parties-in-interest. Appeal Br.
3.
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STATEMENT OF THE CASE
The Examiner finally rejected claims 1–6 and 13–26 under 35 U.S.C.
§ 101 because the claimed invention is directed to a judicial exception to
patent eligibility. Final Act. 3; Ans. 3.
Claim 1, the only independent claim on appeal, is reproduced below:
1. A computer-implemented, fetal gender-independent,
fetal ploidy independent and fetal polymorphism-
independent method for determining a fraction of fetal
nucleic acid in a test sample from sequenced test sample
nucleic acid, comprising:
(a) receiving onto a memory counts of sequence reads
of sequenced test sample nucleic acid that are mapped to
corresponding portions of a reference genome, which test
sample nucleic acid comprises circulating cell-free (CCF)
nucleic acid from blood of a pregnant female bearing a
fetus;
(b) receiving onto a memory a set of weighting factors
that have been calculated for each portion of the
reference genome from a fitted relation between (i) a
fraction of fetal nucleic acid for each of multiple training
samples, and (ii) counts of sequence reads mapped to
each portion of the multiple training samples, wherein at
least one weighting factor corresponds to the each
portion and is indicative of the fraction of fetal nucleic
acid of the each portion;
(c) assigning, using a microprocessor, the set of
weighting factors to the portions of the reference
genome, wherein each of the portions is independently
associated with a corresponding weighting factor;
(d) generating, using a microprocessor, portion-
specific fetal fraction calculations for the portions
according to (i) the count of the sequence reads of the
sequenced test sample nucleic acid mapped to the portion
of the reference genome for the each portion of the
sequenced test sample, and (ii) the assigned weighting
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factors for the each portion of the sequenced test sample;
and
(e) determining, using a microprocessor, a fraction of
fetal nucleic acid for the test sample based on the
portion-specific fetal fraction calculations.

SECTION 101 REJECTION
The Examiner rejected claims 1–6 and 13–26 under 35 U.S.C. § 101
as directed to a judicial exception to patent eligibility. Final Act. 3; Ans. 3.
The Examiner found that the claims are directed to an abstract idea and law
of nature. Final Act. 7; Ans. 3, 8.
Under 35 U.S.C. § 101, an invention is patent-eligible if it claims a
“new and useful process, machine, manufacture, or composition of matter.”
However, not every discovery is eligible for patent protection. Diamond v.
Diehr, 450 U.S. 175, 185 (1981). “Excluded from such patent protection are
laws of nature, natural phenomena, and abstract ideas.” Id. The Supreme
Court articulated a two-step analysis to determine whether a claim falls
within an excluded category of invention. Alice Corp. Pty. Ltd. v. CLS Bank
Int’l, 573 U.S. 208, 216 (2014); Mayo Collaborative Servs. v. Prometheus
Labs, Inc., 566 U.S. 66, 75–77 (2012).
In the first step, it is determined “whether the claims at issue are
directed to one of those patent-ineligible concepts.” Alice, 573 U.S. at 217.
If it is determined that the claims are directed to an ineligible concept, then
the second step of the two-part analysis is applied in which it is asked
“‘[w]hat else is there in the claims before us?’” Id. The Court explained
that this step involves
a search for an “ ‘inventive concept’ ” – i.e., an element or
combination of elements that is “sufficient to ensure that the
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patent in practice amounts to significantly more than a patent
upon the [ineligible concept] itself.”
Alice, 573 U.S. at 217–18 (citing from Mayo, 566 U.S. at 75–77).
Alice, relying on the analysis in Mayo of a claim directed to a law of
nature, stated that in the second part of the analysis “the elements of each
claim both individually and ‘as an ordered combination’” must be
considered “to determine whether the additional elements ‘transform the
nature of the claim’ into a patent-eligible application.” Alice, 573 U.S. at
217.
The PTO recently published revised guidance on the application of 35
U.S.C. § 101. USPTO’s January 7, 2019 Memorandum, 2019 Revised
Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50, 51–57 (2019)
(“2019 Eligibility Guidance”). This guidance provides direction on how to
implement the two-part analysis of Mayo and Alice.
Step 2A, Prong One, of the 2019 Guidelines, looks at the specific
limitations in the claim to determine whether the claim recites a judicial
exception to patent eligibility. In Step 2A, Prong Two, the claims are
examined to identify whether there are additional elements in the claims that
integrate the exception in a practical application, namely, is there a
“meaningful limit on the judicial exception, such that the claim is more than
a drafting effort designed to monopolize the judicial exception.” 84 Fed.
Reg. 54 (2. Prong Two).
If the exception is not integrated into a practical application, then as in
the Mayo/Alice framework, Step 2B of the 2019 Guidelines asks whether
there is an inventive concept to ensure that the patent is significantly more
than a patent on the ineligible concept, itself. 84 Fed. Reg. 56. In making
this determination, it must be considered whether there are specific
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limitations or elements recited in the claim “that are not well-understood,
routine, conventional activity in the field, which is indicative that an
inventive concept may be present” or whether the claim “simply appends
well-understood, routine, conventional activities previously known to the
industry, specified at a high level of generality, to the judicial exception,
indicative that an inventive concept may not be present.” 84 Fed. Reg. 56
(footnote omitted).
With these guiding principles, we proceed to determine whether the
claimed subject matter in this appeal is eligible for patent protection under
35 U.S.C. § 101. As explained in more detail below, we conclude that the
claims are directed to patent-eligible subject matter.

Step 2A, Prong One
In Step 2A, Prong One, of the 2019 Guidelines, the specific
limitations in the claim are examined to determine whether the claim recites
a judicial exception to patent eligibility, namely whether the claim recites an
abstract idea, law of nature, or natural phenomenon. The 2019 Guidelines
lists three groupings of abstract ideas:
(a) Mathematical concepts—mathematical relationships,
mathematical formulas or equations, mathematical
calculations[]
(b) Certain methods of organizing human activity . . .
(c) Mental processes--concepts performed in the human
mind (including an observation, evaluation, judgment, opinion).
84 Fed. Reg. 52.
The Examiner found that the claims recite a judicial exception. Final
Act. 3. The Examiner described the judicial exception as being a law of
nature. Id. The Examiner also found that the judicial exception recited in
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the claims is an “abstract idea of” the “analysis of abstract data.” Id. at 4.
The Examiner also referred to the claims as reciting the abstract idea of a
mental process and mathematical concept. Ans. 3.
We begin the analysis with determining whether the claims recite a
judicial exception to patent eligibility under 35 U.S.C. § 101.
The preamble of claim 1 recites that the method is a “method for
determining a fraction of fetal nucleic acid in a test sample from sequenced
test sample nucleic acid.” The test sample “comprises circulating cell-free
(CCF) nucleic acid from blood of a pregnant female bearing a fetus.”
The Specification defines “fraction of fetal nucleic acid.”
In certain embodiments, the amount of fetal nucleic acid in a
sample is referred to as “fetal fraction[.]” In some
embodiments “fetal fraction” refers to the fraction of fetal
nucleic acid in circulating cell-free nucleic acid in a sample
(e.g., a blood sample, a serum sample, a plasma sample)
obtained from a pregnant female.
Spec. 118:4–8.
Appellants explain that “[d]etermining the fetal fraction is important
because this information allows the provider of the test to understand the
extent to which a given sample is representative of the fetus’s DNA, which
in turn reduces the likelihood that the test will generate a false positive.”
Appeal Br. 3–4. Consistently, the last step of claim 1 recites “(e)
determining, using a microprocessor, a fraction of fetal nucleic acid for the
test sample based on the portion-specific fetal fraction calculations.”
The preamble and last step of the claimed method recite a law of
nature or natural phenomenon because the amount of fetal nucleic acid
which occurs naturally in the blood of a pregnant female bearing a fetus is
determined and the detected fetal nucleic acid is, itself, a natural product.
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As explained in Ariosa Diagnostics, Inc. v. Sequenom, Inc. 788 F.3d 1371,
1376 (Fed. Cir. 2015), if “[t]he method . . . begins and ends with a natural
phenomenon,” as it does here, it recites “matter that is naturally occurring.”
We next proceed to the other steps in the claim to determine whether
other judicial exceptions to patent eligibility are recited in the claims.
Step (a) of the claim recites a step of receiving data, where the data
comprises nucleic “sequence reads of sequenced test sample nucleic acid.”
Step (a) is therefore a data collection step and does not recite a judicial
exception to patent eligibility.
Step (b) of the claim recites “receiving onto a memory a set of
weighting factors.” The claim recites how the weighting factors have been
calculated, but the claim does recite a step in which the calculation is
performed. Step (b), like step (a), is therefore also a data collection step and
does not recite a judicial exception.
In step (c) of claim 1, the weighting factors are assigned “using a
microprocessor” to “portions of the reference.” The Examiner found that
this step is a mental process. Ans. 3. Appellants identify specific disclosure
in the Specification where the assigning function is described. Appeal Br. 5.
We have reviewed these disclosures at 4:4–29, 87:13–30, 129:10–29, and
190:25–28 of the Specification, and none of the descriptions provide any
detail that would exclude the assignment from being performed in the human
mind. Thus, we agree with the Examiner that step (c) of claim 1 recites a
mental process.
Step (d) of the claim is “generating . . . portion-specific fetal fraction
calculations for the portions [of the reference genome]. The claim recites
that the calculations are generated “according to” (i) sequence reads and (ii)
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the assigned weighting factors, but does not disclose a formula for how the
calculation is performed. Appellants identify sections of the Specification as
written description support for this step (Appeal Br. 5) which disclose
generally how the calculation is performed, although no specific formula is
used (Spec. 128:13–27, 129:10–29, 134:17–135:2, and 140:6–23). For
example, the Specification discloses:
In some embodiments portion-specific fetal fraction estimates
are determined based in part on portion-specific parameters
and their relation to fetal fraction. Portion-specific parameters
can be any suitable parameter that is reflective of (e.g.,
correlates with) the amount or proportion of reads from CCF
fragment lengths of a particular size (e.g., size range) in a
portion. A portion-specific parameter can be an average, mean
or median of portion-specific parameters determined for
multiple samples. Any suitable portion-specific parameter can
be used.
Spec. 128: 13–18 (emphasis added).
Thus, one of ordinary skill in the art reading these disclosure in the
Specification would understand the recited “generating” and “calculations”
are defined in the Specification as mathematical concepts.
Step (d) of the claim comprises “generating . . . portion-specific fetal
calculations” according to (i) sequence reads and (ii) the weighting factors.
While no specific formula for performing the calculation is recited in the
claim, the step is an abstract idea because the claim recites a mathematical
relationship between the portion-specific fetal calculations and (i) the
sequence read counts and (ii) assigned weighting factors. 84 Fed. Reg. 52
(“[M]athematical concepts” are “mathematical relationships” and
“mathematical calculations.”). Appellants’ contention that the recited step is
not an abstract idea does not address the step in the claim of “generating . . .
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calculations” or the express recited mathematical relationship. Appeal Br.
22–23; Reply Br. 6.
In sum, we agree with the Examiner’s determination that claim recites
judicial exceptions to patent eligibility. We thus proceed to the next step of
the analysis to determine whether these exceptions are integrated into a
practical application, and if not, whether there is an inventive concept to
ensure that the patent is significantly more than a patent on the ineligible
concepts.
Step 2A, Prong Two
Prong Two of Step 2A under the 2019 Guidance asks whether there
are additional elements that integrate the exception into a practical
application. As in the Mayo/Alice framework, we must look at the claim
elements individually and “as an ordered combination” to determine whether
the additional elements integrate the recited abstract idea into a practical
application.
Appellants contend that, even if the claims are found to recite patent-
ineligible steps, their use “as part of an overall method for determining how
much of the nucleic acid in a physical blood sample comes from a fetus
instead of the pregnant female herself is absolutely a practical application.”
Reply Br. 9. Appellants argue that the claimed method is technological
improvement to determining the fetal fraction in “a real, physical blood
sample” and “is a real-world, practical application of any mathematical
concept or mental step that may be recited in the claims.” Id. at 10.
Appellants also argue “the claims are a practical application because they
sufficiently limit the use of the alleged abstract idea to determining the fetal
fraction as specifically claimed.” Id. at 12.
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We find Appellants’ arguments to be persuasive.
As discussed in the 2019 Guidance, “[a] claim that integrates a
judicial exception in a practical application will apply, rely on, or use the
judicial exception in a manner that places a meaningful limit on the judicial
exception, such that the claim is more than a drafting effort designed to
monopolize the judicial exception. 84 Fed. Reg. 54. Integration into a
practical application is evaluated by identifying whether there are additional
element individually, and in combination, which go beyond the judicial
exception. Id. at 54–55.
In this case, the additional steps of claim 1 place a meaningful limit on
the claimed method of determining a fraction of nucleic acid in the test
sample. Specifically, the recited “set of weighting factors” received into
memory in step (b) of the claim is an integral part of the claim and improves
the method of detecting the fetal fraction “beyond generally linking the use
of the judicial exception to a particular technological environment.” 84 Fed.
Reg. 55.
The Specification explains that a weighting factor is “a coefficient or
constant that, in part, describes and/or defines a relation between a fetal
fraction (e.g., a fetal fraction determined from multiple samples) and a
portion-specific parameter for multiple samples (e.g., a training set).” Spec.
129:17–19. In step (b), the weighting factors are received into a memory, in
step (c) they are assigned to portions of a reference genome, and in step (d)
they are used to generate portion-specific fetal calculations. In the last step
of the claim, step (e), “a fraction of fetal nucleic acid for the test sample
based on the portion-specific fetal fraction calculations” is determined.
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Therefore, the weighting factors recited in step (b) of claim 1 are used
in a specific way to improve detecting the fetal nucleic acid fraction. Unlike
in Ariosa, 788 F.3d at 1374, where the claims recited a general steps of
amplifying a paternally inherited nucleic acid and detecting it or subjecting it
to a test, the rejected claims in this appeal recite a specific and detailed
method in which a series of steps are accomplished that results in
“determining, using a microprocessor, a fraction of fetal nucleic acid for the
test sample based on the portion-specific fetal fraction calculations. The
appealed claims are also distinguishable from the claims in Mayo, where the
uniqueness of the claimed method was not the drug administration or the
determination of the levels of the drug in the subject, but instead the
discovery of the relationship between the drugs levels and the need to adjust
the amount of drug administered to the subject. Mayo, 566 U.S. at 74–75.
Thus, the natural relationship or law of nature was the bulwark of the Mayo
claim. Here, in contrast, the core of rejected claim 1 is the method steps
which enable the detection of the fraction of nucleic acid in the sample
which is fetal.
The improvement embodied in claim 1 is to the process of detecting
the fraction of fetal nucleic acid and not solely to the mathematical concepts
utilized to accomplish the detection. As held in Flook, 437 U.S. at 591,
“[t]he process itself, not merely the mathematical algorithm, must be new
and useful.” Id. at 591.
In Flook, 437 U.S. at 594–95, claims to updating alarm limits were
found to be ineligible for patent, despite providing “a new and presumably
better method for calculating alarm limit values.” The claim at issue in
Flook was directed to a “method for updating the value of at least one alarm
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limit on at least one process variable involved in a process comprising the
catalytic chemical conversion of hydrocarbons.” Flook, 437 U.S. at 596–97
(Appendix to Opinion of the Court). The steps comprised determining a
new alarm base using a mathematical algorithm, using the alarm base to
update an alarm limit, and then adjusting the alarm limit to the updated
value. Id. The Court found the claim to be a judicial exception to subject
matter eligibility
In contrast, the claims in Diamond v. Diehr, 450 U.S. 175 (1981) were
found to be patent-eligible, although a mathematical equation was recited in
the claim. In Diehr, the claims were directed to a method of operating a
rubber-molding press to mold a compound by curing it in a mold cavity.
Application of Diehr, 602 F.2d 982, 983–84 (CCPA 1979). The temperature
in the mold during the rubber-molding process was constantly determined
and provided to a digital computer. Id. The computer calculated the
Arrhenius equation for the reaction time during the cure to determine when
the compound was cured and to then automatically open the press. Id.
Although the claim recited a mathematical formula, the Arrhenius equation,
the Court held that the claim was eligible for a patent.
[W]hen a claim containing a mathematical formula implements
or applies that formula in a structure or process which, when
considered as a whole, is performing a function which the
patent laws were designed to protect (e.g., transforming or
reducing an article to a different state or thing), then the claim
satisfies the requirements of § 101.
Diehr, 450 U.S. at 192–93.
In this case, the weighting factors recited in claim 1, step (b), are used
to determine the fraction of fetal nucleic acid in the blood of pregnant
female. The claimed method, using such factors in steps (c) through (e),
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reduces the probability of false positives, require fewer steps (Kim Decl.2
¶ 3), improves accuracy of the detection (Reply Br. 9), and is less expensive
and faster than the prior art (Reply Br. 10; Kim Decl. ¶ 7). The Examiner
found the improvement is to an “abstract idea” (Ans. 7), but the
determination of a fraction of fetal nucleic acid in a test sample is not
“abstract,” but rather is an improvement to a process in which fetal nucleic
acid is detected.
Our conclusion is consistent with McRO, Inc. v. Bandai Namco
Games Am. Inc., 837 F.3d 1299, 1313 (Fed. Cir. 2016). The McRO claims
involved the manipulation of data, e.g., generating morph weight sets to
animate lip and facial expressions of three dimensional characters similar to
the weighting factors recited in the claims. The court in McRO found that
the “claimed process uses a combined order of specific rules that renders
information into a specific format that is then used and applied to create
desired results: a sequence of synchronized, animated characters.” McRO,
837 F.3d at 1313. Here, the order of the specific rules in the claim utilizing
weighting factors is used to create the desired result of determining the fetal
nucleic fraction which improves the corresponding technological process.
The claim as a whole, unlike the claims in Flook and in Ariosa, is an
“application of the principle.” Flook, 437 U.S. at 594.
Rapid Litigation Management Ltd. v. CellzDirect, Inc., 827 F.3d 1042
(Fed. Cir. 2016) is also consistent with the conclusion reached here. In
CellzDirect, 827 F.2d at 1048, the court found that claims comprising steps
of isolating and freezing naturally-occurring hepatocytes were patent-

2 Sung Kyun Kim, Ph.D. (filed February 12, 2018, hereinafter “Kim Decl.”).
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eligible, despite being based on the discovery that cells could survive freeze-
thaw cycles, because the end result was “not simply an observation or
detection of the ability of hepatocytes to survive multiple freeze-thaw
cycles.” Rather, the court found “the claims are directed to a new and useful
method of preserving hepatocyte cells.” Id. The court observed that the
inventors did not stop at “their discovery,” but employed it “to create a new
and improved way of preserving hepatocyte cells for later use.” Id. Here,
the inventors did not simply perform mathematical operations and make an
observation about the relationship of weighting factors and nucleic acid in a
sample, but instead employed the recited abstract ideas in a useful way to
determine the fraction of nucleic acid in a sample. Accordingly, we find
that claim as a whole integrates the abstract ideas into a practical application.
Thus, the claim is eligible for a patent under 35 U.S.C. § 101 because it is
not directed to a judicial exception, and it is unnecessary for us to proceed to
Step 2B.

Summary
For the foregoing reasons, we conclude that the Examiner erred in
rejecting claim 1, and dependent claim 2–6 and 13–26, as ineligible for a
patent under 35 U.S.C. § 101.

REVERSED