Wallac Oy

Patent Trials and Appeals Board

Feb 1, 2021

2020003412 (P.T.A.B. Feb. 1, 2021)

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.
15/130,728 04/15/2016 Pertti Hurskainen 2010885-0010 7123
159186 7590 02/01/2021
PerkinElmer, Inc. (2010467) / Wallac Oy (2010885)
CHOATE, HALL & STEWART LLP
TWO INTERNATIONAL PLACE
BOSTON, MA 02110
EXAMINER
GROSSMAN, ANDREA S
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
02/01/2021 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):
jnease@choate.com
patentdocket@choate.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PERTTI HURSKAINEN, TEEMU KORPIMÄKI,
HEIKKI KOURU, and MIKKO SAIRANEN

Appeal 2020-003412
Application 15/130,728
Technology Center 1600
Before JENNIFER MEYER CHAGNON, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.

NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 2, 4, 6–8, and 14–16. 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. Appellant identifies the real party in interest as
Wallac Oy. Appeal Br. 2.
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STATEMENT OF THE CASE
Pre-eclampsia is a major cause of maternal and perinatal
mortality and morbidity. Pre-eclampsia is characterized by high
blood pressure and elevated levels of protein in the urine of a
pregnant individual. However, by the time these symptoms
appear, the disorder has already begun to exert deleterious
effects on the mother and fetus. If individuals at risk for pre-
eclampsia can be identified prior to symptom development,
negative outcomes may be prevented or mitigated. There is a
need for tests, systems, and methods for predicting the risk of
development of pre-eclampsia during pregnancy.
Spec. 1:5–19.
The Specification further states that the risk of both of early-onset pre-
eclampsia and severe pre-eclampsia “can be determined based at least in part
on the amount of the biochemical marker retinol binding protein 4 (RBP4) in
a biological sample taken from the pregnant individual.” Spec. 1:16–19.
According to the Specification, the invention relates to “methods, apparatus,
medical profiles and kits useful for determining the risk that a pregnant
individual has or will develop pre-eclampsia, including one or both of early-
onset pre-eclampsia and severe pre-eclampsia,” including RBP4. Id. at
1:14–16.
CLAIMED SUBJECT MATTER
The claims are directed to methods for predicting the risk of pre-
eclampsia in a pregnant individual. Claim 1 is illustrative:
1. A method for predicting risk of pre-eclampsia in a pregnant
individual, the method comprising:
measuring one or more biochemical markers including a retinol
binding protein (RBP4) biochemical marker in a blood sample
obtained from the pregnant individual during a first trimester of
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pregnancy to determine one or more biomarker levels including an
RBP4 biomarker level;
identifying, by a processor of a computing device, for each of the
one or more measured biochemical markers, a difference between the
measured biomarker level and a corresponding predetermined control
level;
responsive to the identifying, determining, by the processor, a
prediction corresponding to a relative risk of the pregnant individual
developing pre-eclampsia; and
administering to the pregnant individual medication comprising
one or more members selected from the group consisting of an
antihypertensive, a corticosteroid, an antiplatelet drug, and an
anticonvulsive.
Appeal Br. 12 (Claims App.).
REJECTION
Claims 1, 2, 4, 6–8, and 14–16 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being obvious over Nagalla and Karumanchi. Answer 4
(“Ans.”).
Name Reference Date
Karumanchi US 2006/0067937 A1 Mar. 30, 2006
Nagalla US 2010/0016173 A1 Jan. 21, 2010

OPINION
A. Issues
The Examiner concludes that the claims are drawn to methods of
predicting risk of pre-eclampsia in a pregnant individual comprising
assessing “one or more biochemical markers including a retinol binding
protein (RBP4 biochemical marker)” and administering treatment upon
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confirming a risk of pre-eclampsia, which may include “administering more
than one treatment, because the claim language is open.” Ans. 7–8.
The Examiner finds that the combination of Nagalla and Karumanchi
teaches all elements of claim 1. Id. at 4–5. In particular, the Examiner finds
that Nagalla teaches a method for predicting risk of pre-eclampsia in a
pregnant individual
comprising measuring one or more biochemical markers
including a retinol binding protein biochemical marker in a
blood sample (serum sample) obtained from the pregnant
individual during a first trimester of pregnancy (9-11 weeks) to
determine one or more biomarker levels including an RBP
biomarker level, identifying for each of the one measured
biomarkers a difference between the measured biomarker level
and a corresponding control level (comparing, measuring
relative to the level in said normal material serum) and
responsive to identifying, determining a prediction
corresponding to the relative risk of the pregnant individual
developing preeclampsia.
Id. at 4. The Examiner further finds Nagalla “teaches using software and
algorithms contained in a processor to compare and diagnose/predict”
disease and “teaches recommending treatments including anticonvulsant
therapy with magnesium sulfate and anti-hypertensives.” Id. at 4–5.
The Examiner finds “Nagalla does not teach that the control was
predetermined and does not teach administering the treatment.” Id. at 5.
The Examiner finds Karumanchi “teaches treating/preventing
preeclampsia by administering anti-hypertensives after diagnosing
preeclampsia by measuring biomarkers” and “teaches using a predetermined
normal reference value (known value).” Id. at 5.
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The Examiner concludes that it would have been “obvious at the time
the invention was made, for one of ordinary skill in the art to have used a
predetermined control value and to have administered therapy, as taught by
Karumanchi, in the method of Nagalla . . . because it is routine to use
predetermined reference values” and that “one would be motivated to
administer [therapy] in order to treat preeclampsia.” Id. The Examiner finds
the skilled artisan would have made this combination with “a reasonable
expectation of success, because treating and using known control values are
routine.” Id.
Appellant contends that the skilled artisan “would not be motivated to
take the teachings of Nagalla regarding measurements of RBP4 and make
any determination of treatment based thereon” because Nagalla teaches
away from the use of RBP4 as a biomarker for classification of pre-
eclampsia. Appeal Br. 9. Appellant further argues that the Examiner’s
proposed combination “does not teach treating/preventing preeclampsia by
administering anti-hypertensives after diagnosing preeclampsia using
biomarkers and does not teach using a predetermined normal reference value
(known value) as claimed in Appellant’s independent claim 1.” Id. Finally,
Appellant argues Karumanchi does not teach administering one of the
claimed forms of treatment to the pregnant individual with pre-eclampsia
“without primarily administering a compound that is capable of binding to
soluble endoglin” and that the skilled artisan would not have been motivated
to make the proposed combination. Id.
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 1 as representative. The issue with respect to this
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rejection is whether a preponderance of evidence supports the Examiner’s
conclusion that a skilled artisan would have had a reason to combine the
cited references to arrive at the claimed invention, with a reasonable
expectation of success.2
B. Analysis
Appellant does not separately argue the claims.3 We therefore focus
our analysis on claim 1 as representative of the remaining claims. Unless
otherwise noted, we adopt the Examiner’s findings of fact and reasoning on
scope and content of the prior art with respect to claim 1 (Final Act.4 2–6;
Advisory Action5 2–6; Ans. 3–9) and agree that claim 1 is obvious over
Nagalla and Karumanchi. We respond to Appellant’s arguments below.
Only those arguments timely made by Appellant in the briefs have been
considered; arguments not so presented are waived. See 37 C.F.R.
§ 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (“Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived.”).
Appellant contends that Nagalla’s teachings, in Tables 5a and 5b:
demonstrate no significant difference between levels of plasma
retinol-binding protein (i.e., Applicant’s claimed RBP4) in
serum samples from women in the first trimester with
preeclampsia and without pre-eclampsia (Table 5a) and no
significant difference between levels of plasma retinol-binding

2 Appellant does not present evidence of secondary considerations that,
when considered together with evidence of obviousness, shows the claims to
be nonobvious.
3 Appeal Br. 5.
4 Office Action mailed January 18, 2019.
5 Office Action mailed May 3, 2019.
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protein in serum samples from women in the first trimester with
severe pre-eclampsia compared to controls (Table 5b).
Appeal Br. 9. Appellant further argues that Nagalla illustrates that “RBP4
was a poor discriminant biomarker for classifying samples with or without
pre-eclampsia” as shown in Table 6a because “Nagalla states the area under
the curve should be between 0.5 (poor discriminant) and 1.0 (perfect
discriminant) and plasma retinal-binding protein had an area under the curve
of 0.505.” Id. As a result, Appellant argues, Nagalla teaches away from the
use of RBP4, and the skilled artisan would not have been “motivated to take
the teachings of Nagalla regarding measurements of RBP4 and make any
determination of treatment based thereon.” Id.
We are not persuaded. “Under the proper legal standard, a reference
will teach away when it suggests that the developments flowing from its
disclosures are unlikely to produce the objective of the applicant’s invention.
A statement that a particular combination is not a preferred embodiment
does not teach away absent clear discouragement of that combination.”
Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005)
(citations omitted).
We agree with Appellant that plasma retinol-binding protein is not
among the proteins that show significant protein expression level changes in
the studies summarized in Tables 5a and 5b of Nagalla. We further agree
with Appellant’s characterization of the results described in Table 6a, that
plasma retinol-binding protein is a relatively poor discriminant biomarker as
defined by Nagalla in paragraph 131. But we disagree that these disclosures
teach away from use of plasma retinol-binding protein because, as the
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Examiner states, “Nagalla teaches that the AUC6 for a biomarker should be
between 0.5-1.0 and RBP4 is within this range.” Ans. 7. Nagalla thus
discloses that plasma retinol-binding protein qualifies as a biomarker for
pre-eclampsia under its analysis parameters. Nagalla ¶¶ 132–133.
Moreover, Nagalla’s teachings regarding the usefulness of plasma
retinol-binding protein are not restricted to Tables 5a, 5b, and 6a. We agree
with the Examiner (Ans. 6–7) that “Nagalla recommends using RBP4 to
predict pre-eclampsia throughout the reference” and “even claims using it as
a biomarker.” See, e.g., Nagalla ¶¶ 17, 23, 27, 29, 31–34, 38, 112, 132,
Tables 2, 5a, 5b, 6, 8, claims 21, 30–50, 61, 64, 65, and 81. These mentions
include, e.g., disclosure of plasma retinol-binding protein as a biomarker for
use in screening for pre-eclampsia expression-level protein analysis (¶¶ 32,
33, 112, 132); results showing the fold expression change of plasma retinol-
binding protein was significant for severe pre-eclampsia (Table 2); results
showing plasma retinol-binding protein was a significant indicator for both
mild and severe pre-eclampsia in fetal gestation ages of 10–14 weeks
(Tables 4a and 4b); and claims reciting use of plasma retinol-binding protein
as a biomarker for diagnosis of pre-eclampsia in a pregnant subject in early
gestation (e.g., claims 21 and 30). None of these instances discourages use
of plasma retinol-binding protein as a biomarker. Therefore, on balance,
Nagalla does not teach away from use of plasma retinol-binding protein.

6 AUC refers to the “area under the curve” per the statistical analysis
disclosed in Table 6a. See Nagalla ¶ 132: “Table 6a summarizes the area
under the entire receiver operating characteristic curve (AUROC) and 95%
confidence intervals (CI) for the 23 potential biomarkers for classifying
samples with PE (n=73) or without PE (n=96).”
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Syntex, 407 F.3d at 1380. We are further unpersuaded by Appellant’s
argument in reply (Reply Br. 5) that some of these teachings relate to
samples taken outside of a first trimester of pregnancy, which the subject
claims recite. While that may be so, when Nagalla is considered for its
teachings as a whole, plasma retinol-binding protein is disclosed and
claimed as a biomarker for use in diagnosing pre-eclampsia at any stage of
pregnancy. “It is well settled that a prior art reference is relevant for all that
it teaches to those of ordinary skill in the art.” In re Fritch, 972 F.2d 1260,
1264 (Fed. Cir. 1992). For this same reason, we are unpersuaded by
Appellant’s argument that “Nagalla as a whole teaches detection and
diagnosis of pre-eclampsia, rather than predicting risk of pre-eclampsia, as is
claimed by Appellant.” A skilled artisan, upon reading Nagalla’s disclosure
that elevated plasma retinol-binding protein is useful for diagnosing pre-
eclampsia at any stage of pregnancy would have found it obvious to do so as
a means of predicting risk, particularly in light of the following statement
from Nagalla:
The present invention concerns, in one aspect, methods and
means for an early, reliable and non-invasive testing of pre-
eclampsia and associated complications in pregnant women by
proteomic analysis of maternal serum. The invention further
concerns, in another aspect, identification of biomarkers of pre-
eclampsia, including pre-eclampsia during early gestation, such
as in the first trimester of pregnancy, e.g., during 9 to 11 weeks,
and also during 10 to 14 weeks, using proteomics techniques.
Nagalla ¶ 62. In addition, Nagalla describes a preferred embodiment in
which “a diagnosis, prediction and/or treatment recommendation based on
the expression level in a test subject of one or more of the biomarkers herein
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is communicated to the subject” as soon as possible after determination. Id.
¶ 105 (emphasis added).
Appellant next argues that the Examiner’s proposed combination
“does not teach using a predetermined normal reference value (known value)
as claimed in Appellant's independent claim 1.” Appeal Br. 9. Appellant
argues that Karumanchi does not define “normal reference value” “as
meaning pre-determined; and, in a medical context, the word ‘normal’ is
ambiguous, as it could refer to a statistically normal distribution or a usual,
average, or typical state or condition, and neither is necessarily pre-
determined.” Id.
We are not persuaded. Karumanchi at paragraph 82 provides:
By “reference sample” is meant any sample, standard, or level
that is used for comparison purposes. A “normal reference
sample” can be a prior sample taken from the same subject, a
sample from a pregnant subject not having any pregnancy
related hypertensive disorder, such as pre-eclampsia or
eclampsia, a sample from a pregnant subject not having a
pregnancy related hypertensive disorder, such as pre-eclampsia
or eclampsia, a subject that is pregnant but the sample was
taken early in pregnancy (e.g., in the first or second trimester or
before the detection of a pregnancy related hypertensive
disorder, such as pre-eclampsia or eclampsia), a subject that is
pregnant and has no history of a pregnancy related hypertensive
disorder, such as pre-eclampsia or eclampsia, a subject that is
not pregnant, a sample of a purified reference polypeptide at a
known normal concentration (i.e., not indicative of a pregnancy
related hypertensive disorder, such as pre-eclampsia or
eclampsia) By “reference standard or level” is meant a value or
number derived from a reference sample. A normal reference
standard or level can be a value or number derived from a
normal subject that is matched to the sample subject by at least
one of the following criteria: gestational age of the fetus,
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maternal age, maternal blood pressure prior to pregnancy,
maternal blood pressure during pregnancy, BMI of the mother,
weight of the fetus, prior diagnosis of pre-eclampsia or
eclampsia, and a family history of preeclampsia or eclampsia. A
“positive reference” sample, standard or value is a sample or
value or number derived from a subject that is known to have a
pregnancy related hypertensive disorder, such as pre-eclampsia
or eclampsia, that is matched to the sample subject by at least
one of the following criteria: gestational age of the fetus,
maternal age, maternal blood pressure prior to pregnancy,
maternal blood pressure during pregnancy, BMI of the mother,
weight of the fetus, prior diagnosis of a pregnancy related
hypertensive disorder, and a family history of a pregnancy
related hypertensive disorder.
We are persuaded that this comprehensive disclosure of Karumanchi
regarding the meaning of “reference sample” as a standard or level
used for comparison purposes, in addition to its potential use as a
positive or negative control, encompasses and suggests the meaning of
“a pre-determined control level” as recited by the challenged claims.
Finally, Appellant argues that “the combination of Nagalla and
Karumanchi does not teach treating/preventing preeclampsia by
administering anti-hypertensives after diagnosing preeclampsia using
biomarkers.” Appeal Br. 9. Appellant argues that Karumanchi’s method
relates to methods for diagnosing a pregnancy-related
hypertensive disorder or a predisposition to a pregnancy related
hypertensive disorder by measuring the level or biological
activity of soluble endoglin and methods for treating a
pregnancy related hypertensive disorder, such as pre-eclampsia
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and eclampsia, using compounds that alter soluble endoglin
levels or biological activity.
Id. at 9–10. According to Appellant, Karumanchi does not disclose teaching
the treatments in Appellant’s claims “without primarily administering a
compound that is capable of binding to soluble endoglin.” Id. at 10.
We are not persuaded. Karumanchi discloses “methods for
diagnosing and treating pregnancy related hypertensive disorders, including
pre-eclampsia and eclampsia.” Karumanchi ¶ 12. Embodiments disclosed
include, after diagnosis, administering a compound to treat or prevent the
disorder, including “the step of administering to a subject an anti-
hypertensive compound (e.g., adenosine, nifedipine, minoxidil, and
magnesium sulfate).” Id. ¶ 21. We agree with Appellant that Karumanchi’s
disclosure describes, as a foundation of its method of treatment, also
employing “compounds that bind to or neutralize soluble endoglin . . . to
reduce the elevated levels of soluble endoglin.” Id. ¶ 12. However, we
agree with the Examiner (Ans. 8) that the challenged claims do not exclude
such a step because they recite the transitional phrase “comprising.” “When
a claim uses an ‘open’ transition phrase, its scope may cover devices that
employ additional, unrecited elements. . . . In contrast, ‘closed’ transition
phrases such as ‘consisting of’ are understood to exclude any elements, steps
or ingredients not specified in the claim.” AFG Industries, Inc. v. Cardinal
IG Co., Inc., 239 F.3d 1239, 1245 (Fed. Cir. 2001). Karumanchi teaches
administering an anti-hypertensive drug to treat the pregnant patient
following diagnosis, and we agree with the Examiner (Ans. 5) that the
skilled artisan would have found it obvious at the time the invention was
made to have used a predetermined control value for assessing a pregnant
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individual’s risk of pre-eclampsia in early pregnancy, and to have
administered therapy, as taught by Karumanchi, in the method of Nagalla.
For the reasons above, we affirm the Examiner’s rejection of claim 1
as obvious over Nagalla and Karumanchi. Claims 2, 4, 6–8, and 14–16,
which are not separately argued, fall with claim 1.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 4, 6–8, 14–
16
103 Nagalla,
Karumanchi
1, 2, 4, 6–
8, 14–16

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