B.R.A.H.M.S GmbH

Patent Trials and Appeals Board

Aug 4, 2020

2019006084 (P.T.A.B. Aug. 4, 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.
14/966,843 12/11/2015 Andreas BERGMANN 251162.000001 2731
6980 7590 08/04/2020
TROUTMAN PEPPER HAMILTON SANDERS LLP
600 PEACHTREE ST NE
STE 3000
ATLANTA, GA 30308
EXAMINER
WANG, CHANG YU
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
08/04/2020 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):
jim.schutz@troutman.com
patents@troutman.com
ryan.schneider@troutman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDREAS BERGMANN, ANDREA ERNST, and
HARALD HAMPEL1
_____________

Appeal 2019-006084
Application 14/966,843
Technology Center 1600
_____________

Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

Opinion for the Board by Administrative Patent Judge GRIMES.

Opinion Dissenting filed by Administrative Patent Judge FREDMAN.

GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for detection and diagnosis of dementia, which have been rejected as
ineligible for patenting. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as B.R.A.H.M.S GmbH.
Appeal Br. 1. We use the word Appellant to refer to “applicant” as defined in
37 C.F.R. § 1.42(a)
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STATEMENT OF THE CASE
The Specification states that “[p]rocalcitonin (PCT) is a peptide which
. . . [is] a precursor of the important hormone calcitonin.” Spec. ¶ 28. “[I]ts
proteolytic degradation . . . leads to the liberation of the mature hormone
calcitonin and other shorter peptides, including in particular so-called
katacalcin.” Id.
The Specification discloses a “method for detection . . . of dementias
. . . in which a determination of the procalcitonin immunoreactivity (PCT
immunoreactivity) is carried out in a sample of the cerebrospinal fluid (CSF)
. . . and conclusions . . . are drawn from a measured PCT immunoreactivity,
which is above a threshold value typical for healthy control persons.” Id.
¶ 16. The Specification states that “the PCT immunoreactivity in CSF can be
measured with high precision and reliability by a highly sensitive
immunoassay having a functional assay sensitivity (FAS) which is
considerably better than that of the commercial PCT immunoassays available
for sepsis diagnosis.” Id. ¶ 19.
Specifically, “[f]or the determination of the procalcitonin
immunoreactivities in serum/plasma, there exists, for example, the
commercial chemiluminescence assay LUMItest® PCT (B.R.A.H.M.S. AG),
which has a functional assay sensitivity (FAS) of 300 ng/1 and is tailored to
PCT determination in sepsis, where very high PCT concentrations can
occur.” Id. ¶ 32. “For PCT determination with a higher sensitivity, a modified
sandwich immunoassay which operates with an affinity-purified polyclonal
antibody . . . and is obtainable as LUMItest® PCTsensitiv (B.R.A.H.M.S
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AG) was recently developed. This assay has a clearly better FAS of 7 ng/1.”
Id. (citing Morgenthaler2).
Claims 14 and 16–19 are on appeal. Claim 14, reproduced below, is
illustrative:
14. A method for assisting in the detection and diagnosis
of dementias selected from the group consisting of Alzheimer’s
dementia (AD), dementia with Lewy bodies (DLB),
frontotemporal dementia (FTD) and various forms of vascular
dementia (VAD), said method comprising:
determining the level of procalcitonin (PCT) in a sample
of cerebrospinal fluid (CSF) from an adult patient who is
suffering from or, based on clinical manifestations, is suspected
of having a dementia selected from the group consisting of
Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB),
frontotemporal dementia (FTD) and various forms of vascular
dementia (VAD[)] with the aid of a highly sensitive PCT
immunoassay having a functional assay sensitivity (FAS) of 10
ng of PCT per liter (10 ng/l or 10 pg/ml) or better, said
immunoassay comprising contacting the sample of CSF from the
adult patient with a pair of antibodies, wherein one of the pair of
antibodies binds to calcitonin and the other of the pair of
antibodies binds to katacalcin, and at least one of the pair of
antibodies is an affinity-purified polyclonal antibody, wherein
an increased level of procalcitonin in said sample when
compared to levels of PCT in CSF from healthy individuals
indicates dementia.

Claims 16 and 17 are the other independent claims and, like claim 14,
require the use of an immunoassay having a functional assay sensitivity
(FAS) of 10 ng of PCT per liter (10 ng/l or 10 pg/ml) or better, said
immunoassay comprising contacting a sample of CSF from an adult patient

2 Nils G. Morgenthaler et al., “Sensitive Immunoluminometric Assay for the
Detection of Procalcitonin,” Clinical Chemistry 48:788–790 (2002).
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with a pair of antibodies, wherein one of the pair of antibodies binds to
calcitonin and the other of the pair of antibodies binds to katacalcin.
OPINION
Claims 14 and 16–19 stand rejected under 35 U.S.C. § 101 “because
the claimed invention is directed to a judicial exception (i.e., a law of nature,
a natural phenomenon, or an abstract idea) without significantly more.” Ans.
3. Specifically, the Examiner finds that the “claims recite detection and
diagnosis of dementia based on a correlation between the presence of an
increased level of procalcitonin (PCT) in CSF as compared to heathy
controls. . . . This correlation is a consequence of natural phenomenon in CSF
of patients having dementia, which is a judicial exception.” Id. The Examiner
finds that “[t]his judicial exception is not integrated into a practical
application.” Id.
The Examiner also finds that “[t]he claim(s) does/do not include
additional elements that are sufficient to amount to significantly more than
the judicial exception because the claims recite elements/steps in addition to
the judicial exception(s) that are well-understood, purely conventional or
routine in the relevant field.” Id. at 4. As evidence that the procalcitonin
immunoassay required by the claims is routine and conventional, the
Examiner cites Han,3 Morgenthaler, and Jereb.4 Id. at 9–10.

3 Yong Y. Han et al., “Cerebrospinal fluid procalcitonin and severe traumatic
brain injury in children,” Pediatric Critical Care Medicine 3:39–44 (2002).
4 M. Jereb et al., “Predictive Value of Serum and Cerebrospinal Fluid
Procalcitonin Levels for the Diagnosis of Bacterial Meningitis,” Infection
29:209–212 (2001).
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The Examiner concludes that
these additional elements or steps are mere field of use that
impose no meaningful limit on the performance of the method
and are no more than well-understood, purely conventional, and
routinely taken by others in order to apply the natural
principle. . . . Accordingly, claims 14 and 16–19 are not patent
eligible because the claimed invention is directed to a judicial
exception (i.e., a law of nature, a natural phenomenon, or an
abstract idea) without significantly more.
Id. at 12.
Appellant argues that “the methods taken as a whole employ a series of
steps that are not described by Han or Morgenthaler as being routine or
conventional.” Appeal Br. 4. Rather, Appellant argues, “Morgenthaler
discloses the highly sensitive PCT assay (with FAS of 10 ng or better) as
being new and fails to disclose . . . conducting the assay on a patient’s CSF.”
Id. at 6. Appellant reasons that “[b]ecause the assay is described as ‘new’ and
‘proposed’, the assay cannot be routine or conventional in the art. A reference
providing a first disclosure of an assay cannot suggest that such assay is
routine or conventional.” Id.
Appellant argues that “Han discloses a less sensitive older-generation
PCT assay (LUMItest-PCT) for detection of PCT in the CSF of infants for
the first time in the context of traumatic brain injury.” Id. “Han does not
disclose the assay with high sensitivity (FAS of 10 ng PCT/liter or better)
that is encompassed by the steps recited in the pending claims.” Id.
Thus, Appellant concludes,
[n]either Han nor Morgenthaler discloses or suggests that the
immunoassay, having a functional assay sensitivity (FAS) of
10 ng of PCT per liter (10 ng/1 or 10 pg/ml) or better, recited the
steps of the claims is routine or conventional.
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Accordingly, claims 14, 16 and 17 are directed to patent-eligible
subject matter under 35 U.S.C. § 101.
Id. at 7.
Principles of Law
A. Section 101
An invention is patent-eligible if it claims a “new and useful process,
machine, manufacture, or composition of matter.” 35 U.S.C. § 101. However,
the U.S. Supreme Court has long interpreted 35 U.S.C. § 101 to include
implicit exceptions: “[l]aws of nature, natural phenomena, and abstract ideas”
are not patentable. E.g., Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216
(2014).
In determining whether a claim falls within an excluded category, we
are guided by the Court’s two-part framework, described in Mayo and Alice.
Alice, 573 U.S. at 217–18 (citing Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 75–77 (2012)). 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.”); see also Bilski v. Kappos, 561 U.S. 593, 611 (2010) (“Claims 1 and 4
in petitioners’ application explain the basic concept of hedging, or protecting
against risk.”).
If the claim is “directed to” a judicial exception—a law of nature, a
natural phenomenon, or 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.”
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Alice, 573 U.S. at 221 (quotation marks omitted). “If a law of nature is not
patentable, then neither is a process reciting a law of nature, unless that process
has additional features that provide practical assurance that the process is more
than a drafting effort designed to monopolize the law of nature itself.” Mayo,
566 U.S. at 77.
B. USPTO Section 101 Guidance
In January 2019, the U.S. Patent and Trademark Office (USPTO)
published revised guidance on the application of § 101. 2019 Revised Patent
Subject Matter Eligibility Guidance, 84 Fed. Reg. 50 (Jan. 7, 2019)
(“2019 Revised Guidance”).5 “All USPTO personnel are, as a matter of
internal agency management, expected to follow the guidance.” Id. at 51; see
also October 2019 Update at 1.
Under the 2019 Revised Guidance and the October 2019 Update, we
first look to whether the claim recites:
(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) (“Step 2A, Prong One”); and
(2) additional elements that integrate the judicial exception into
a practical application (see MPEP § 2106.05(a)–(c), (e)–(h) (9th
ed. Rev. 08.2017, Jan. 2018)) (“Step 2A, Prong Two”).6

5 In response to received public comments, the Office issued further guidance
on October 17, 2019, clarifying the 2019 Revised Guidance. USPTO,
October 2019 Update: Subject Matter Eligibility (the “October 2019
Update”) (available at https://www.uspto.gov/sites/default/files/
documents/peg_oct_2019_update.pdf).
6 This evaluation is performed by (a) identifying whether there are any
additional elements recited in the claim beyond the judicial exception, and (b)
evaluating those additional elements individually and in combination to
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2019 Revised Guidance, 84 Fed. Reg. at 52–55.
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, to whether the claim:
(3) adds a specific limitation beyond the judicial exception that
is 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.
2019 Revised Guidance, 84 Fed. Reg. at 52–56.
Revised Guidance Step 2A, Prong 1
Following the Revised Guidance, we first consider whether the claims
recite a judicial exception. Independent claims 14 and 16 both recite determining
the level of procalcitonin (PCT) in a patient’s cerebrospinal fluid (CSF), “wherein
an increased level of procalcitonin in said sample when compared to levels of
PCT in CSF from healthy individuals indicates dementia.”
The Revised Guidance identifies “a law of nature, or a natural
phenomenon” as being among the judicial exceptions to patentability. 84 Fed.
Reg. at 54. We agree with the Examiner that the correlation between the level
of PCT in a patient’s CSF and dementia (of certain types) is a natural
phenomenon.
In Mayo, the Court held that “Prometheus’ patents set forth laws of
nature—namely, relationships between concentrations of certain metabolites

determine whether the claim as a whole integrates the exception into a
practical application. See 2019 Revised Guidance — Section III(A)(2), 84
Fed. Reg. at 54–55.
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9
in the blood and the likelihood that a dosage of a thiopurine drug will prove
ineffective or cause harm.” 566 U.S. at 77. Similarly here, claims 14 and 16
set forth laws of nature—namely, relationships between the level of PCT in a
patient’s CSF and the likelihood that a patient suffers from one of certain
specified types of dementia. Claims 14 and 16 therefore recite a judicial
exception to patentability.
Claim 17, however, does not state that an increased level of PCT in a
patient’s CSF, compared to healthy individuals, indicates dementia. Claim 17
is directed to
[a] method of determining the level of procalcitonin (PCT) in a
sample of cerebrospinal fluid (CSF) in an adult patient who is
suffering from or, based on clinical manifestations, is suspected
of having dementia selected from the group consisting of
Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB),
frontotemporal dementia (FTD) and various forms of vascular
dementia (VAD) with the aid of a highly sensitive PCT
immunoassay having a functional assay sensitivity (FAS) of 10
ng of PCT per liter (10 ng/l or 10 pg/ml) or better, said
immunoassay comprising contacting the sample of CSF from the
adult patient with a pair of antibodies, wherein one of the pair of
antibodies binds to calcitonin and the other of the pair of
antibodies binds to katacalcin.
Appeal Br. 10–11 (Claims Appendix).
Thus, claim 17 is directed to a method of assaying PCT in the CSF of a
patient having, or suspected of having, dementia of a specified type, using a
specific type of immunoassay. The claim does not recite a correlation
between the PCT level and a patient’s condition. Thus, claim 17 does not
recite the correlation that the Examiner points to as the judicial exception to
patentability. See Mayo, 566 U.S. at 78 (“An ‘administering’ step [and] a
‘determining’ step . . . are not themselves natural laws.”). Claim 17 is
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therefore patent eligible. See Revised Guidance, 84 Fed. Reg. at 54 (“If the
claim does not recite a judicial exception, it is not directed to a judicial
exception . . . and is eligible. This concludes the eligibility analysis.).
Revised Guidance Step 2A, Prong 2
Even though claims 14 and 16 recite a natural phenomenon, they would
still be patent-eligible if “the claim as a whole integrates the recited judicial
exception into a practical application of the exception.” Revised Guidance, 84
Fed. Reg. at 54. “A claim that integrates a recited judicial exception into a
practical application will apply, rely on, or use the judicial exception in a
manner that imposes a meaningful limit on the judicial exception, such that the
claim is more than a drafting effort designed to monopolize the judicial
exception.” Id.
The analysis of determining whether the claim integrates the judicial
exception into a practical application includes “[i]dentifying whether there
are any additional elements recited in the claim beyond the judicial
exception(s)” and “evaluating those additional elements individually and in
combination to determine whether they integrate the exception into a
practical application.” Id. at 54–55. “[R]evised Step 2A specifically excludes
consideration of whether the additional elements represent well-understood,
routine, conventional activity.” Id. at 55.
Here, claims 14 and 16 recite determining the level of PCT in a sample
of CSF using an immunoassay that has a specified functional assay
sensitivity and that uses an antibody that binds to calcitonin and an antibody
that binds to katacalcin, where at least one of those antibodies is affinity-
purified. The “examples in which a judicial exception has not been
integrated into a practical application” include “an additional element [that]
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adds insignificant extra-solution activity,” such as mere data-gathering, to the
judicial exception. Revised Guidance, 84 Fed. Reg. at 55.
In this case, performing the recited immunoassay amounts to the step
required to gather the data that is needed in order to apply the natural
phenomenon recited in claims 14 and 16. Cf. Mayo, 566 U.S. at 79:
Anyone who wants to make use of these laws must first
administer a thiopurine drug and measure the resulting
metabolite concentrations, and so the combination amounts to
nothing significantly more than an instruction to doctors to apply
the applicable laws when treating their patients.
The upshot is that the three steps simply tell doctors to gather
data from which they may draw an inference in light of the
correlations.
Similarly here, anyone who wants to make use of the natural
correlation between the PCT level in a patient’s CSF and certain types of
dementia must first measure the level of PCT in the patient’s CSF. Thus, the
immunoassay step of claims 14 and 16 is mere data gathering and does not
integrate the recited judicial exception into a practical application.
We conclude that claims 14 and 16 are directed to a natural
phenomenon.
Revised Guidance Step 2B
Finally, the Revised Guidance directs us to consider whether claims 14
and 16 include “additional elements . . . [that] provide[] ‘significantly more’
than the recited judicial exception.” 84 Fed. Reg. at 56. An additional
element that “simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high level of
generality, to the judicial exception, . . . is indicative that an inventive
concept may not be present.” Id.
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However, an additional element that “[a]dds a specific limitation or
combination of limitations that are not well-understood, routine, conventional
activity in the field, . . . is indicative that an inventive concept may be
present.” Id. The Revised Guidance also states that if, for example, an
additional element was found to be insignificant extra-solution activity under
revised Step 2A, that conclusion should be reevaluated in Step 2B: “If such
reevaluation indicates that the element is unconventional or otherwise more
than what is well-understood, routine, conventional activity in the field, this
finding may indicate that an inventive concept is present and that the claim is
thus eligible.” Id. For example, a data-gathering step might be considered
insignificant extra-solution activity under Step 2A, but if the data is gathered
in an unconventional way, it could include an “inventive concept” and render
the claim eligible under Step 2B. Id.
“The question of whether a claim element or combination of elements
is well-understood, routine and conventional to a skilled artisan in the
relevant field is a question of fact.” Berkheimer v. HP Inc., 881 F.3d 1360,
1368 (Fed. Cir. 2018). “In rejecting an application, factual determinations by
the PTO must be based on a preponderance of the evidence.” In re Oetiker,
977 F.2d 1443, 1449 (Fed. Cir. 1992) (J. Plager, concurring). In this case, the
Examiner cites Morgenthaler, Han, and Jereb as evidence that the
immunoassay required by the claims is “routine and conventional” in the art.
Ans. 9–10.7

7 The dissent cites a number of references in addition to Han, Jereb, and
Morgenthaler. Post at 22–24. Those references are not part of the record of
this application, and we will not address them further. See MPEP § 1204.04
(“[T]he Board’s review of patentability determinations is properly based on
the record of all entered . . . documents in the file.”).
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We agree with Appellant that the Examiner has not shown, by a
preponderance of the evidence, that a PCT immunoassay having a functional
assay sensitivity (FAS) of 10 ng of PCT per liter (10 ng/l or 10 pg/ml) or
better, said immunoassay comprising contacting a sample of CSF from a
patient with a pair of antibodies, wherein one of the pair of antibodies binds
to calcitonin and the other of the pair of antibodies binds to katacalcin, as
required in each of the independent claims, was well-understood, routine, and
conventional.
Han states that “PCT concentration was measured by immuno-
luminometric assay (LUMItest-PCT; Brahms Diagnostica, Berlin,
Germany).” Han 40, middle col. Similarly, Jereb states that “blood and CSF
PCT levels were determined . . . using an immunoluminometric assay
adapted from the immunoradiometric assay (LUMItest PCT, now supplied by
BRAHMS Diagnostica, Berlin, Germany).” Jereb 210, left col.
Appellant’s Specification states that “the commercial chemi-
luminescence assay LUMItest® PCT (B.R.A.H.M.S. AG) . . . has a functional
assay sensitivity (FAS) of 300 ng/1.” Spec. ¶ 32. The Examiner cites no
evidence to the contrary. See, e.g., Ans. 13 (“The claimed PCT immunoassay
is known under the tradename called ‘B.R.A.H.M.S ProCa-S®’ or
‘LUMItest® PCTsensitivity’ [sic] (supplied by BRAHMS AG), which has
functional assay sensitivity (FAS) of 7ng/l.”). Thus, Han and Jereb provide no
evidence that the immunoassay required by the claims was well-understood,
routine, and conventional.
Appellant’s Specification states that the immunoassay recited in the
claims “is described in more detail in (20).” Spec. ¶ 32. Reference “(20)” is
Morgenthaler. Spec. page 16. Morgenthaler states that the “usual two-sided
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chemiluminescence assay [immunoluminometric assay (ILMA)] for PCT has
a functional assay sensitivity (FAS) of 300 ng/L.” Morgenthaler 788, right
col. (bracketed material in original). Morgenthaler states that “[w]e
developed a new PCT assay with a >30-fold lower FAS compared with the
established ILMA.” Id. Morgenthaler “compare[d] this new assay with the
established LUMItest PCT.” Id. at 789, right col.
Thus, Morgenthaler describes the immunoassay required by the claims
as “new,” as contrasted with the “usual” or “established” immunoassay
LUMItest PCT. A “new” assay is the antithesis of an assay that is “well-
understood, routine, and conventional.” The Berkheimer court held that
[w]hether a particular technology is well-understood, routine,
and conventional goes beyond what was simply known in the
prior art. The mere fact that something is disclosed in a piece of
prior art, for example, does not mean it was well-understood,
routine, and conventional.
Berkheimer, 881 F.3d at 1369.
Mayo announced the “well-understood, routine, and conventional”
standard. Mayo, 566 U.S. at 79. The Court explained that, “[i]f a law of
nature is not patentable, then neither is a process reciting a law of nature,
unless that process has additional features that provide practical assurance
that the process is more than a drafting effort designed to monopolize the law
of nature itself.” Id. at 77. The additional features of the claims at issue in
Mayo were an “administering” step, a “determining” step, and a “wherein”
clause. Id. at 78.
As relevant here, the Court stated that “the ‘determining’ step tells the
doctor to determine the level of the relevant metabolites in the blood, through
whatever process the doctor or the laboratory wishes to use.” Id. at 79
(emphasis added). The Court also noted that “the patents state [that] methods
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for determining metabolite levels were well known in the art,” and “scientists
routinely measured metabolites as part of their investigations into the
relationships between metabolite levels and efficacy and toxicity of
thiopurine compounds.” Id.
Thus, the record in Mayo showed that (a) the claims were open to any
method of determining the relevant metabolite levels, (b) the patents
conceded that methods of measuring those levels were well known, and
(c) those skilled in the art routinely carried out such measurements. On these
facts, the Court held that the “determining” step of the claims “tells doctors to
engage in well-understood, routine, conventional activity previously engaged
in by scientists who work in the field.” Id.
The facts of the present appeal, by contrast, show a single prior art
reference announcing a new immunoassay. In no way does the evidence of
record in this appeal compare to the evidence on which the Mayo Court
found a measuring method to be well-understood, routine, and conventional.
In short, the Examiner has not provided adequate evidence to show that
the assay required by the claims on appeal was well-understood, routine, and
conventional. We therefore conclude that the specific immunoassay required
by the claims provides an inventive concept that supports patent-eligibility.
In summary, we conclude that claim 17 does not recite a judicial
exception to patentability. With regard to claims 14, 16, and dependent
claims 18 and 19, we conclude that “additional elements recited in the claims
provide[] ‘significantly more’ than the recited judicial exception (e.g.,
because the additional elements [a]re unconventional in combination).”
Revised Guidance, 84 Fed. Reg. at 56. We therefore reverse the rejection of
14 and 16–19 under 35 U.S.C. § 101.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
14, 16–
19
101 Eligibility 14, 16–19

REVERSED

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UNITED STATES PATENT AND TRADEMARK OFFICE
_____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_____________

Ex parte ANDREAS BERGMANN, ANDREA ERNST, and HARALD
HAMPEL
_____________

Appeal 2019-006084
Application 14/966,843
Technology Center 1600
_____________

Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge, dissenting.

I respectfully dissent. The Board is required to adhere to the 2019
Guidance as a matter of Office policy. 2019 Revised Guidance, 84 Fed. Reg.
at 51.
2019 Guidance Step 1
First, under “Step 1,” we consider whether the claimed subject matter
falls within the four statutory categories set forth in § 101, namely “[p]rocess,
machine, manufacture, or composition of matter.” 2019 Revised Guidance
53–54; see 35 U.S.C. § 101. Claim 14 recites a “method” and, thus, falls
within the “process” category. Consequently, I proceed to the next step of
the analysis.
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2019 Guidance Step 2A Prong 1
Second, under “Step 2A Prong 1,” we evaluate “whether the claim
recites a judicial exception, i.e., an abstract idea, a law of nature, or a natural
phenomenon.” 2019 Revised Guidance 54; see Alice Corp. v. CLS Bank
Int’l, 573 U.S. 208 (2014). The Examiner determined that the rejected claims
recite a law of nature or natural phenomenon because they “recite observing
naturally occurring biological correlations (i.e. the presence of an increased
level of PCT in CSF of patients and dementia in AD, DLB, FTD and VAD).”
Ans. 13. This determination is not disputed by Appellant. See Reply Br. 1.
2019 Guidance Step 2A Prong 2
Having determined that claim 14 recites a law of nature/natural
phenomenon, I proceed to “Step 2A Prong 2” of the 2019 Guidance, which
requires the evaluation as to whether “the claim as a whole integrates the
recited judicial exception into a practical application of the exception.” Id. at
54. “A claim that integrates a judicial exception into a practical application
will apply, rely on, or use the judicial exception in a manner that imposes a
meaningful limit on the judicial exception, such that the claim is more than a
drafting effort designed to monopolize the judicial exception.” Id.; see Mayo,
566 U.S. at 78.
The 2019 Guidance specifies that this evaluation is conducted by first
“[i]dentifying whether there are any additional elements recited in the claim
beyond the judicial exception(s),” then “evaluating those additional elements
individually and in combination to determine whether they integrate the
exception into a practical application.” 2019 Revised Guidance 54–55. The
Examiner determined claim 14 “does not integrate the mental step of
determining or the judicial exception into a practical application because the
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use of the PCT immunoassay is the same as commercially available and
provides no improvement in technology or transform the PCT immunoassay
to a different technology” (Ans. 8). This determination is not disputed by
Appellant. See Appeal Br. 4; cf. Reply Br. 1 “Appellant submits that the
claims amount to significantly more under Step 2B of the Alice/Mayo test.
(No further comments are presented herein on Step 2A.)”. Reply Br. 1.
2019 Guidance Step 2B
Having concluded that claim 14 recites judicial exceptions but does not
integrate them into a practical application—i.e., that the claim is “directed to”
those exceptions (2019 Revised Guidance 54)—we turn to whether the claim
provides an “inventive concept,” i.e., whether the additional elements beyond
the exceptions, individually and in combination, amount to “significantly
more” than the exceptions themselves. Id. at 56. According to the 2019
Guidance, “[a]dd[ing] a specific limitation or combination of limitations that
are not well-understood, routine, conventional activity in the field” may
indicate an inventive concept is present. Id. Conversely, “simply
append[ing] well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality,” typically
indicates an inventive concept is absent. Id.
The 2019 Guidance places the initial burden of demonstrating that a
limitation is well understood, routine and conventional on the Examiner. See
Revised Guidance 56, footnote 36 (“[A]n examiner’s conclusion that an
additional element (or combination of elements) is well understood, routine,
conventional activity must be supported with a factual determination.”)
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The Examiner finds that Morgenthaler8 teaches a ProCa-S PCT
immunoassay having a functional assay sensitivity of 10 ng/l or better that
comprises contacting a CSF sample with polyclonal calcitonin and
monoclonal katacalcin antibodies to determine calcitonin levels. See
Morgenthaler 788, col. 2. The Examiner finds that Morgenthaler’s “claimed
PCT immunoassay is known under the tradename called ‘B.R.A.H.M.S
ProCa-S®.’” Ans. 13. The finding that the ProCa-S assay is commercially
available is supported by the Specification, which teaches that a PCT
immunoassay “obtainable as LUMItest® PCTsensitiv (B.R.A.H.M.S AG)
was recently developed. This assay has a clearly better FAS of 7 ng/1 (20).”
Spec. ¶ 32. The Specification reference to “(20)” is directed to Morgenthaler.
See Spec. ¶ 16, reference 20.
Appellant responds that Berkheimer v. HP Inc., 881 F.3d 1360, 1369
(Fed. Cir. 2018) explains that “[w]hether a particular technology is well-
understood, routine, and conventional goes beyond what was simply known
in the prior art. The mere fact that something is disclosed in a piece of prior
art, for example, does not mean it was well-understood, routine, and
conventional.” Appeal Br. 5. Appellant asserts that because the
Morgenthaler “assay is described as ‘new’ and ‘proposed’, the assay cannot
be routine or conventional in the art. A reference providing a first disclosure
of an assay cannot suggest that such assay is routine or conventional.” Id. at
6. Appellant also asserts that “Morgenthaler does not disclose or suggest
using the new assay to assay CSF fluid in a patient.” Id. Appellant does
acknowledge that “Han describes use of the previous generation PCT-

8 Morgenthaler et al., Sensitive Immunoluminometric Assay for the Detection
of Procalcitonin, 48 Clinical Chem. 788–90 (2002).
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Lumitest assay (referred to above by Morgenthaler as established LUMI-test
PCT) to assay PCT in the CSF fluid.” Id. Appellant concludes that “the
Examiner has not made a sufficient showing that the steps recited in
independent claims 14, 16 and 17 are routine and conventional in the art.”
Id. at 7.
While I agree with Appellant and the Majority that the disclosure of a
novel assay in a single reference such as Morgenthaler is insufficient to
establish that the assay is well understood, routine, and conventional, the
Examiner also relies upon evidence showing that the assay is commercially
available from BRAHMS, as supported by the Specification. See Spec. ¶ 32.
The Examiner also established that the prior art recognized the desirability of
measuring calcitonin levels in cerebrospinal fluid. See Ans. 10, citing Han9
and Jereb.10 That the ProCa-S assay was disclosed at least three years prior
to the filing date of the application and was commercially available during
that period would, in my view, shift the burden to Appellant to demonstrate
that the assay was either not commercially available, was not advertised, or
was otherwise not routine and conventional. Appellant provides no such
evidence.
To the extent that there remains a question as to whether the ProCa-S
test was well known and in use during the period between 2000 and 2005,
there is abundant prior art demonstrating the test was available for
researchers and was used in a number of countries and laboratories during

9 Han et al., Cerebrospinal fluid procalcitonin and severe traumatic brain
injury in children, 3 Pediatric Critical Care Med. 39–44 (2002).
10 Jereb et al., Predictive Value of Serum and Cerebrospinal Fluid
Procalcitonin Levels for the Diagnosis of Bacterial Meningitis, 29 Infection
209–12 (2001).
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that period. Christ-Crain11 teaches “[a]nother ultra-sensitive assay, ProCa-S®
(BRAHMS, Hennigsdorf, Germany) is available for research use. However,
for the time being, this assay is manual and therefore, not suitable for the
routine day and night setting in an emergency or intensive care unit (ICU).”
Christ-Crain 463.
Siassi12 teaches the use of the ProCa-S assay by authors in Germany
and Denmark. See Siassi R483, footnotes 1–6, R485 (“Serum PCT levels
were determined by a specific and ultrasensitive immunoluminometric assay
(Lumitest ProCa-S®, BRAHMS-Diagnostica, Berlin, Germany.”)
Assumma13 teaches using a prototype of the ProCa-S assay in 2000,
prior to Morgenthaler, by authors in Italy. See Assumma 1583, footnotes 1–
5, 1584 (“Samples with PCT concentrations below the detection limit of the
LUMItest PCT assay were subsequently tested with the LUMItest ProCa-S
assay (BRAHMS Diagnostica), which has been developed in a prototype
format only.”)
Chaker14 teaches using the ProCa-S assay by authors in Belgium. See
Chaker 256, footnotes a–c and 257 (“Le dosage de PCT a été réalisé en

11 M. Christ-Crain & B. Muller, Procalcitonin on the Dusty Way to the Holy
Grail: A Progress Report, in 2005 Yearbook of Intensive Care and
Emergency Medicine (J.L. Vincent Ed.) 461–76 (2005).
12 Siassi et al., Mannan-binding lectin and procalcitonin measurement for
prediction of postoperative infection, 9 Critical Care R483–89 (July 19,
2005).
13 Marcello Assumma et al., Serum Procalcitonin Concentrations in Term
Delivering Mothers and Their Healthy Offspring: A Longitudinal Study, 46
Clinical Chemistry 1583–87 (2000).
14 S. Chaker et al., Measure of maternal procalcitonin in the pregnancy by an
ultrasensitive immunoluminometric assay: diagnostic and pronostic interests,
18 Immuno-analyse & Biologie spécialisée 256–59 (2003).
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double par une technique immunoluminométrique ultrasensible : PCT ProCa-
S (Brahms Diagnostica GMBH).”)
Linscheid (2003)15 and Linscheid (2004)16 teach using the ProCa-S
assay by authors in Switzerland and the United States. See Linscheid (2003)
5578, author affiliations and 5579 (“ProCT concentrations were determined
in supernatants by an ultrasensitive chemiluminometric assay with a
functional sensitivity of 6 pg/ml (ProCa-S Assay, B.R.A.H.M.S. GmbH,
Hennigsdorf-Berlin, Germany).”); cf. Linscheid (2004) 1718.
Blum,17 Seboek,18 and Puder19 teach using the ProCa-S assay by
authors in Switzerland. See Blum 3230, author affiliations and 3231 (“ProCT
was measured by an ultrasensitive immunoluminometric assay (ProCa-S;
Brahms, Hennigsdorf, Germany). The lower detection limit was 6.0
ng/liter.”); cf. Seboek 4833, author affiliations and 4835, col. 1; Puder 6014,
author affiliations and 6015, col. 2.

15 Philippe Linscheid et al., In Vitro and in Vivo Calcitonin I Gene
Expression in Parenchymal Cells: A Novel Product of Human Adipose
Tissue, 144 Endocrinology 5578–84 (2003).
16 Philippe Linscheid et al., Expression and secretion of procalcitonin and
calcitonin gene-related peptide by adherent monocytes and by macrophage-
activated adipocytes, 32 Critical Care Med. 1715–21 (2004).
17 Claudine Blum et al., Low-Grade Inflammation and Estimates of Insulin
Resistance during the Menstrual Cycle in Lean and Overweight Women, 90 J.
Clin. Endocrinology & Metabolism 3230–35 (Mar. 29, 2005).
18 Dalma Seboek et al., Somatostatin Is Expressed and Secreted by Human
Adipose Tissue upon Infection and Inflammation, 89 J. Clin. Endocrinology
& Metabolism 4833–39 (2004).
19 Jardena Puder et al., Central Fat Excess in Polycystic Ovary Syndrome:
Relation to Low-Grade Inflammation and Insulin Resistance, 90 J. Clin.
Endocrinology & Metabolism 6014–21 (August 16, 2005).
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Becker20 is a review article, with authors in the United States and
Switzerland, and discusses the use of the Morgenthaler assay. See Becker
1512, author affiliations, 1514, col. 2, citation 82.
These ten references, from different laboratories and different
countries, support the Examiner’s position21 that ProCa-S assay was well-
known, routine, and conventional by the time Appellant filed this application
in July of 2005. Applying this well-known ProCa-S assay used to sensitively
measure calcitonin to a new abstract idea, the association of calcitonin levels
with dementia, does not constitute significantly more than the abstract idea.
As the Federal Circuit noted, “[n]or is the fact that blood MPO levels
correlate with atherosclerotic CVD any less a natural law because it can only
be observed by use of certain technique.” Cleveland Clinic Foundation v.
True Health Diagnostics LLC, 760 F. App’x 1013, 1019 (Fed. Cir. 2019).
“[T]he discovery of a natural law cannot by itself provide the requisite
inventive concept.” Id. at 1021.
Thus, for the reasons explained above, I agree with the Examiner that
claim 14 “simply appends well-understood, routine, conventional activities
previously known to the industry,” and, thus, fails to present an “inventive

20 K. L. Becker et al., CLINICAL REVIEW 167 Procalcitonin and the
Calcitonin Gene Family of Peptides in Inflammation, Infection, and Sepsis: A
Journey from Calcitonin Back to Its Precursors, 89 J. Clin. Endocrinology &
Metabolism 1512–25 (2004).
21 It is unfortunate that prior to this appeal the Examiner did not apply MPEP
§ 704.10 (37 C.F.R. § 1.105(a)(2)) to request that Appellant, through the
Assignee BRAHMS, provide information regarding whether the ProCa-S
assay was commercially available for sale, if so, to how many parties was the
assay sold, what advertising, if any, was purchased and whether the
availability of the assay was shown by websites, catalogs, or other
advertising literature.
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concept” because the claim does not recite additional elements that provide
“significantly more” than the recited judicial exceptions. See 2019 Revised
Guidance 56. Therefore, I would sustain the Examiner’s rejection of claim
14 as ineligible subject matter under § 101. As a result, I would also sustain
the rejection of the other rejected claims under § 101. See 37 C.F.R.
§ 41.37(c)(1)(iv).