Ex Parte Bergmann et al

Patent Trials and Appeals Board

Apr 4, 2019

12921885 - (D) (P.T.A.B. Apr. 4, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/921,885 02/01/2011
23599 7590 04/08/2019
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BL VD.
SUITE 1400
ARLINGTON, VA 22201
Andreas Bergmann
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
SIMANDI-0015 6700
EXAMINER
MOSS, NATALIE M
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
04/08/2019 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):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDREAS BERGMANN, JOACHIM STRUCK, and
LEONG LOKE NG 1
Appeal2018-007120
Application 12/921,885
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREYN. FREDMAN, and
TA WEN CHANG, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for providing a prognosis for a patient having an acute coronary
syndrome, which have been rejected as obvious and as being directed to a
judicial exception to patent eligible subject matter without significantly
more. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as B.R.A.H.M.S. GMBH.
( Appeal Br. 1.)
Appeal2018-007120
Application 12/921,885
STATEMENT OF THE CASE
According to the Specification,
[p ]rocalcitonin (PCT) has become a well-established
biomarker for sepsis diagnosis: PCT reflects the severity
of bacterial infection and is in particular used to monitor
progression of infection into sepsis, severe sepsis, or septic
shock. It is possible to use PCT to measure the activity of
the systemic inflammatory response, to control success of
therapy, and to estimate prognosis.
(Spec. 2:4--7.) Further according to the Specification, PCT has been used in
"the risk stratification of patients suffering from stable coronary artery
disease (CAD). However, it is unknown so far, whether PCT has prognostic
power in acute coronary syndromes (ACS)." (Id. at 3:16-19.) The
Specification states that the "[ s ]ubject of the present invention is an in vitro
method for prognosis for a patient having an acute coronary syndrome,"
comprising determining the level of PCT. (J d. at 5: 14--19.)
Claims 1, 2, 5-11, 16-18, and 20-27 are on appeal. Claim 1 is
illustrative and reproduced below:
1. An in vitro method for prognosis for a patient having an acute
coronary syndrome for having an adverse outcome for said acute
coronary syndrome, the method comprising:
c) determining the level of procalcitonin, or a fragment of
procalcitonin consisting of amino acids 3-116 of procalcitonin,
as a prognostic marker, in a sample obtained from said patient
during hospitalization for acute coronary syndrome, wherein
said determining step comprises an procalcitonin antibody
assay having a lower limit of detection of <0.055µg/L; and
d) correlating said level of procalcitonin or fragment thereof to a
predisposition to an adverse outcome of said acute coronary
syndrome,
wherein said correlating step comprises comparing said level of
procalcitonin or fragment thereof in the patient sample to a
predetermined statistically significant threshold level correlated to a
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predisposition to an adverse outcome whereby, when said level of
procalcitonin or fragment thereof exceeds said threshold level, the
prognosis of said patient is that the patient is predisposed to said
adverse outcome, and
wherein
if said patient is thus determined to be predisposed to said
adverse outcome, monitoring of progression to an adverse outcome,
and/or therapy therefor, after hospital discharge is indicated, and
if said patient is determined to not be predisposed to said
adverse outcome, monitoring of progression to an adverse outcome,
and/or therapy therefor, after hospital discharge is not indicated.
(Appeal Br. 16 (Claims App'x).)
The Examiner rejects claims 1, 2, 5-11, 16-18, and 20-27 under 35
U.S.C. § 101 as being directed to a judicial exception (i.e., a law of nature, a
natural phenomenon, or an abstract idea) without significantly more. (Ans.
2.)
The Examiner rejects claims 1, 2, 5, 6, 9-11, 16-18, and 20-25 under
pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Remskar2 and
DiaSorin. 3 (Ans. 3.)
The Examiner rejects claims 1 and 6-8 under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Remskar, DiaSorin, and Richards. 4
(Ans. 7-8.)
2 Mojca Remskar et al., Procalcitonin in Patients with Acute Myocardial
Infarction, 114 WIEN KLIN WOCHENSCHR 205 (2002).
3 DiaSorin S.p.A., Liaison® Brahms PCT® Instructions for Use, REF
318.101 (2007).
4 A. Mark Richards, et al., Plasma N-Terminal Pro-Brain Natriuretic
Peptide and Adrenomedullin, 97 CIRCULATION 1921 (1998).
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I.
Issue
The Examiner has rejected claims 1, 2, 5-11, 16-18, and 20-27 under
35 U.S.C. § 101 as being directed to a judicial exception to patent eligible
subject matter, without significantly more. The Examiner finds that
[t]he Instant Claims recite a method for prognosis
comprising determining the level of procalcitonin (PCT)
in a patient sample, and correlating it with a predisposition
of an adverse outcome. The prognosis of a condition
based on a naturally occurring correlation of levels of a
substance produced in the body to a condition is a law of
nature. The method steps for determining prognosis are
interpreted to be the measurement of PCT, comparison of
said levels to a threshold and correlation with an adverse
outcome. As evidenced by the Art of Record below,
increased PCT levels in a patient indicate poor prognosis.
Applying it for stratification does not make the claimed
method patentable.
The relationship between PCT levels and
prognosis exists apart from any human interaction. The
"wherein" clause suggests how a patient should be treated
based on said laws of nature. Further, the steps of
determining consists of tests well known in the scientific
community that when viewed as a whole, add nothing
significantly more.
(Ans. 2-3.)
Appellants contend that the claims are not merely directed to a natural
law or principle but amount to a practical application of the natural
phenomenon. (Appeal Br. 3.) Appellants contend that "prognostic methods
have been generally recognized as not falling under the 'natural law'
umbrella." (Id. at 7.) Appellants contend that the claims do not preempt all
uses of the natural law or principle. (Id. at 3.) Appellants further contend
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that "the steps of the claimed invention are not well-understood and routine
or conventional activity." (Id. at 4.)
Appellants do not separately argue the claims. We therefore limit our
analysis to claim 1 as representative. The issue with respect to this rejection
is whether the Examiner erred in concluding that the claim 1 is directed to a
judicial exception to patent eligible subject matter without significantly
more.
Analysis
\Ve analyze this case under the framework set forth by the Supreme
Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566
U.S. 66 (2012), and applied by our reviewing court in Ariosa Diagnostics,
Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). As the Ariosa court
exp fained:
In Mayo . .. , the Supreme Court set forth a framework for
distinguishing patents that claim laws of nature, natural
phenomena, and abstract ideas from those that claim
patent-eligible applications of those concepts. First, we
determine whether the claims at issue are directed to a
patent-ineligible concept. . . . If the answer is yes, then
we next consider the elements of each claim both
individually and "as an ordered combination" to determine
whether additional elements "transform the nature of the
claim" into a patent-eligible application .... The Supreme
Court has described the second step of this analysis as a
search for an "inventive concept"-i.e., an element or
combination of elements that is "sufficient to ensure that
the patent in practice amounts to significantly more than a
patent upon the [ineligible concept] itself."
Id. at 1375.
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Jviayo Step One: vVhether Claim I Is Directed to Abstract Idea
\Ve begin with the first step of the lvf ayo test, namely whether a claim
is "directed to" a patent-ineligible concept. On January 7, 2019, the Director
of the US PTO issued the "2019 Revised Patent Subject \/fatter Eligibility
Guidance" ("Revised Guidance"), which provides further details regarding
how the Patent Office analyzes patent-eligibility questions under 35 U.S.C.
§ 101. 84 Fed. Reg. 50----57 (Jan. 7, 2019). Under the Revised Guidance, the
first step of the Jviayo test (i.e., Step 2A of the Revised Guidance) is '"a two-
pronged inquiry." Id. at 54. In prong one, we evaluate whether the claim
recites a judicial exception, such as laws of nature, natural phenomena, or
abstract ideas. Id. If the claim recites a judicial exception, the clahn is
further analyzed under prong two, which requires "evaluat[ion ofl whether
the claim recites additional elements that integrate the exception into a
practical application of that exception." id. The Revised Guidance explains
that, "[i]f the recited exception is integrated into a practical application of
the exception, then the claim is eligible at Prong Two of . .. Step 2A [ of the
Revised Guidance]." Id.
First Prong lfRevised Guidance Step 2A
\Vith respect to the first prong of Step 2A of the Revised Guidance,
we agree with the Examiner that claim 1 recites a patent-ineligible law of
nature, specifically, the "correlat[ion between ( 1) the] level of procalcitonin
or fragment thereof [in a sample obtained from [a] patient during
hospitalization for acute coronary syndrome, and (2)] a predisposition to an
adverse outcome of said acute coronary syndrome," as specifically recited in
step (d) of the claim. (Ans. 2; Appeal Br. 16 (Claims App'x).)
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In lviayo, for instance, the Supreme Comi found that a claim was
directed to a natural law, where the claim required administering a drug and
determining the levels of a metabolite following administration, where the
1evel of metabolite was indicative of a need to increase or decrease the
dosage of the drug. See l\1Jayo Collaborative Services v. Prometheus Labs.,
Inc., 566 U.S. 66, 74 (2012). Here, similarly, claim l recites correlating a
patient's '"levels of procalcitonin ... to a predisposition to an adverse
outcome of ... acute coronary syndrome," wherein if "the level of
procalcitonin ... exceeds [a "predetermined statistically significant
threshold level"] the prognosis ... is that the patient is predisposed to said
adverse outcome" and "monitoring ... and/or therapy ... is indicated."
(Appeal Br. 16 (Claims App'x).)
Second Prong of Revised Guidance Step 2A
The second prong of Step 2A asks whether the claims as a whole
integrates the judicial exception into a practical application of the exception.
Revised Guidance, 84 Fed. Reg. at 54. We find that claim 1 does not recite
additional elements that integrate the recited law of nature into a practical
application of the natural law. The only elements of claim 1 that are not a
statement of the natural law are ( 1) "detennining the level of procalcitonin,
or a fragment of procalcitonin" using "a[] procalcitonin antibody assay
having a lower limit of detection of< 0.055µg/L" and (2) a wherein clause
stating whether "monitoring ... and/or therapy ... after hospital discharge is
indicated" based on whether a "patient is ... determined to be predisposed
to [an] adverse outcome." (Appeal Br. 16 (Claims App'x).)
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As to the limitations relating to determining the level of procalcitonin,
these limitations are insignificant pre-solution activities that do not integrate
a judicial exception into a practical application. 84 Fed. Reg. at 55
( exp1aining that "insignificant extra-solution activity" does not integrate
judicial exception into practical application); lvfayo, 566 U.S. at 77
(explaining the step of "dete1mining the level of [ relevant metabolite J in [a]
subject having [an] immune-mediated gastrointestinal disorder" is
"'conventional or obvious' '[pre]-solution activity' [that] is normally not
sufficient to transform an unpatentable law of nature into a patent-eligible
application of such a law"); Athena Diagnostics, Inc. v. Afayo Collaborative
Services, LLC, 915 F.3d 743,751 (Fed. Cir. 2019) (explaining that claims to
"an ineligible discovery, together with "well-known techniques to execute
the claimed method," are directed to a natural law" and therefore patent
ineligible).
Similarly, the wherein clause relating to whether monitoring and/or
therapy is indicated for a patient merely adds an equivalent to the words
"apply if' to the law of nature and does not suffice to integrate the natural
law into a practical application. 84 Fed. Reg. at 55 (explaining that "[a]n
additional element [that] merely recites the words 'apply it' (or an
equivalent) with the judicial exception" does not integrate the judicial
exception into a practical application); },dayo, 566 U.S. at 78----79 (Wherein
clauses reciting whether increase or decrease of administered dn1g is
indicated based on measured metabolite level "simply tell a doctor about the
relevant natura11aws, at most adding a suggestion that he should take those
laws into account when treating his patients" and do not "transform
unpatentable natural c01Telations into patentable applications of those
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regularities."). Appellants admit that '"[t]he claims do not require an actual
monitoring step" and only recite whether "monitoring is indicated or not
indicated." (Appeal Br. 3.) Thus, unlike the claims in Vanda
Pharmaceuticals, and like the claims in lvfayo, claim 1 is not directed to a
method of treating disease but to a prognostic method based on a natural
relationship between the level of procalcitonin and a predisposition to an
adverse outcome of acute coronary syndrome. },dayo, 566 U.S. at 78----79;
Vanda Pharm. lnc. v. West-TVard Pharm. lnt'l Ltd., 887 F.3d 1117, 1134---
1135 (Fed. Cir. 2018).
Mayo Step Two: Whether Claim 1 Recites "Significantly More"
Having determined that claim 1 is directed to a patent-ineligible law
of nature, we next consider whether claim I recites "an element or
combination of elements that is 'sufficient to ensure that the patent in
practice amounts to significantly more than a patent upon the [ineligible
concept] itself."' Ariosa, 788 F.3d at 1375 (citation omitted). As explained
further below, we agree with the Examiner that it does not. (Ans. 2-3, 11-
14.)
Similar to the claims in Mayo, the process recited in claim 1 "tells
doctors interested in the subject about [a] correlation that ... researchers
discovered" (i.e., "correlating ... level of procalcitonin ... to a
predisposition to an adverse outcome of [an] acute coronary syndrome") and
further recites a "determining" step and a "wherein" step. Mayo, 566 U.S. at
78.
The Examiner finds, and Appellants have not persuasively disputed,
that determining the level of procalcitonin using the method recited in the
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claim (i.e., "a[] procalcitonin antibody assay having a lower limit of
detection of< 0.055 µg/L") is "well known and routine in the art as
evidenced by the prior art." (Ans. 13; see also DiaSorin (providing
instructions for using a commercially available antibody assay for the
quantitative determination of procalcitonin (PCT) in human serum and
plasma having a detection limit of< 0.032 ng/ml).) Likewise, and as
discussed above, the wherein clause in claim 1 merely "tell[ s] the relevant
audience about the laws while trusting them to use those laws appropriately
where they are relevant to their decisionmaking." Mayo, 566 U.S. at 78.
Finally, to consider the steps of the claim together as an ordered
combination "adds nothing to the laws of nature that is not already present
when the steps are considered separate." Id. at 79. Anyone who wishes to
make use of the natural law relating to correlation between procalcitonin
levels and adverse outcomes in acute coronary syndromes must first
determine the level of procalcitonin, and the claim recites no more than a
well-understood, routine, and conventional method for determining the
procalcitonin level. In short, as in Mayo, claim 1 merely "inform[ s] a
relevant audience about certain laws of nature; any additional steps consist
of well-understood, routine, conventional activity already engaged in by the
scientific community; and those steps, when viewed as a whole, add nothing
significant beyond the sum of their parts take separately." Id. at 79-80.
Accordingly, "the steps [of claim 1] are not sufficient to transform
unpatentable natural correlations into patentable applications of those
regularities." Id. at 80.
Appellants' Arguments
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Appellants argue that "the claims are not merely directed to a natural
law or principle." (Appeal Br. 3.) Appellants first contend that "prognostic
methods have been generally recognized as not falling under the 'natural
law' umbrella" and that "[i]t is certainly not naturally occurring that one
would pick the specifically claimed PCT to provide the valuable prognostic
information." (Id. at 3, 7-8.) Appellants contend that "[t]he use ... of
Myriad and Mayo ... to essentially preclude patents in [the] entire field [ of
prognosis] is not supported by these decisions and is contrary to the proper
function of the PTO." (Id. at 8-9.)
We are not persuaded. We do not hold that all claims relating to the
field of prognosis are patent ineligible. Rather, as discussed above, claim 1
as drafted is patent ineligible because it is directed to a law of nature without
significantly more. Contrary to Appellants' apparent argument, the Federal
Circuit has held similar claims to be directed to patent ineligible subject
matter. See, e.g., Cleveland Clinic Foundation v. True Health Diagnostics
LLC, 859 F.3d 1352, 1356, 1360-1361 (Fed. Cir. 2017) (holding that claims
reciting "methods for characterizing a test subject's risk for cardiovascular
disease by determining levels of [myeloperoxidase (MPO)] in a bodily
sample and comparing that with the MPO levels in persons not having
cardiovascular disease" to be directed to patent-ineligible law of nature).
Appellants next contend that, because the claimed method "include
the determination of a prognosis ... and require a specified outcome based
on that prognosis," "the method is not directed merely to assessing a state of
the patient[] but taking positive action based on such assessed state."
(Appeal Br. 3--4.) Appellants contend that "a required step of indicating that
a patient should be monitored or not monitored is clearly not a natural law or
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principle," and "[t]he claims are instead directed to a very narrowly focused
practical application of the knowledge gained by the correlation and a step
of acting on that knowledge." (Id. at 3--4.)
We are not persuaded. As Appellants admit, "[t]he claims do not
require an actual monitoring step" and only recite whether "monitoring is
indicated or not indicated." (Appeal Br. 3.) Thus, like the wherein clauses
in kfavo. which recite the level of measured metabolite that "indicates a need .,, ./
to increase [or decrease] the amount of [a] drug subsequently administered
to [a] subject," the limitations in claim l regarding whether monitoring
and/or therapy is indicated does not require "taking positive action based on
[the] assessed state [of the patient]," but "simp1y teH a doctor about the
relevant natural laws, at most adding a suggestion that he should take those
laws into account when treating his patients." 1\1ayo, 566 U.S. at 78.
Appellants also dispute the Examiner's finding that "the 'relationship
between procalcitonin levels and patient prognosis exists apart from ...
measurement," because "cited prior art fails to teach any prognosis
associated with procalcitonin levels" and "[this] practical application is only
available due to the inventors' discovery." (Id. at 4.) Appellants contend
that "the claimed invention provides a new process for an early prognosis
and early treatment" and "indicates [an] advance in the art which is eligible
for patent protection." (Id. at 8.)
We are not persuaded. As discussed above, the correlation between
procalcitonin and predisposition to an adverse outcome of an acute coronary
syndrome (i.e., the prognosis) is a law of nature, not a "practical application"
of a law of nature. Thus, it cannot impart patentability to the claims even if
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it was previously unknown. As the Supreme Court explained in the context
of mathematical algorithms,
[t]he process itself, not merely the mathematical
algorithm, must be new and useful. Indeed, the novelty of
the mathematical algorithm is not a determining factor at
all. \,Vhether the algorithm was in fact known or unknown
at the time of the claimed invention, as one of the "basic
tools of scientific and technological work," it is treated as
though it were a familiar part of the prior art.
Parker v. Flook, 437 U.S. 584, 591-592 (1978).
Appellants argue that the claims do not "preempt all or anywhere near
all uses of the natural law or principle." (Appeal Br. 3, 4, 7-8, 9.)
We are not persuaded. "While preemption may signal patent
ineligible subject matter, the absence of complete preemption does not
demonstrate patent eligibility." Ariosa, 788 F.3d at 1379. InAriosa, for
instance, our reviewing court held various dependent claims to be invalid as
directed to patent-ineligible subject matter, even though these claims are
limited to specific techniques of amplifying and detecting nucleic acid. See
id. at 1374, 1378 (finding invalid dependent claims requiring amplification
of nucleic acid bv polvrnerase chain reaction or detection of nuc1eic add via ., ~
a sequence speci fie probe because they are "focused on the use of the natural
phenomenon in combination with well-understood, routine, and
conventional activity").
Finally, Appellants contend that the claims are patent eligible under
the reasoning set forth by the Federal Circuit in Rapid Litigation
Management v. CellzDirect, 827 F.3d 1042 (Fed. Cir. 2016). (Appeal Br. 9-
10; Reply Br. 2-3.)
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We are not persuaded. As the Federal Circuit explained in Cleveland
Clinic,
In CellzDirect, the inventors developed cryo-preservation
techniques to preserve liver cells for later use. We held
that the claims were not directed to a natural law because
they were "simply not directed to the ability of [liver cells]
to survive multiple freeze-thaw cycles. Rather, the claims
of the [ asserted patent were] directed to a new and useful
laboratory technique for preserving [liver cells]." Id. at
1048. Unlike CellzDirect, the asserted claims of the
testing patents are directed to the natural existence of MPO
in a bodily sample and its correlation to cardiovascular risk
rather than to "a new and useful laboratory technique" for
detecting this relationship. Indeed, Cleveland Clinic has
not created a new laboratory technique; rather, it uses
well-known techniques to execute the claimed method.
859 F.3d at 1361. Like the claims at issue in Cleveland Clinic, claim 1 is
directed to "the natural existence of [PCT] in a bodily sample and its
correlation to [ an adverse outcome of an acute coronary syndrome] rather
than to 'a new and useful laboratory technique' for detecting this
relationship." Id. In particular, as evidenced by DiaSorin, the assay recited
in claim 1 for determining the level of procalcitonin is a well-known,
commercially available technique.
Appellants further argue that, "even if a natural phenomenon is
connected with appellants' invention, the significant details in the method
amount to a practical application of the natural phenomena rather than a
complete foreclosure of the natural phenomena." (Appeal Br. 3.)
Appellants contend that, for example, "[t]he claims require a determination
step and a correlating step where both steps are greatly specified regarding
the nature of each step and practical application of the claimed process."
(Id.)
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We are not persuaded. As discussed above, the step of "correlating
[the] level of procalcitonin ... to a predisposition to an adverse outcome of
[an] acute coronary syndrome" merely states the natural law. As also
discussed above, the "determining step" also does not add significantly more
to the natural law because it merely recites the insignificant pre-solution
activity of obtaining information (i.e., PCT level) required to make use of
the natural law using a well-understood, routine, and conventional method.
kfayo, 566 U.S. at 77; Ariosa, 788 F.3d at 1374, 1378.
Appellants contend that "[t]he failure of the prior art to identify any
correlation between PCT levels and predisposition of patients to adverse
outcomes makes clear that the steps of the claimed invention are not well-
understood and routine or conventional activity." (Appeal Br. 4--5, 8.)
We are not persuaded for reasons already discussed: The correlation
Appellants contend is not well-understood, routine, and convention is the
law of nature and thus cannot impart patentability to the claims even if it
was previously unknown. It is the claimed method, not merely the
correlation, that must be new and useful. Flook, 437 U.S. at 591-592.
Finally, Appellants contend that the claims are similar to claim 5 in
Example 29 of the May 2016 Subject Matter Eligibility Examples: Life
Sciences ("May 2016 Examples") in that they "require an affirmative
indication of monitoring or not monitoring step which is analogous to
administering vitamin D in claim 5," and "the indication step ... is clearly
'an unconventional step that is more than a mere instruction to 'apply' the
correlation ... using well-understood, routine or conventional techniques in
the field." (Appeal Br. 5-6.)
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We are not persuaded. Claim 5 in Example 29 of the May 2016
Examples affirmatively requires "administering an effective amount of
topical vitamin D" to a patient diagnosed with julitis where "at the time the
application was filed ... doctors were not commonly or routinely
administering topical vitamin D to patients withjulitis or other diseases."
(May 2016 Examples 10-11.) In contrast, Appellants' claim 1 does not
require any actual monitoring or therapy for patients predisposed to an
adverse outcome of an acute coronary syndrome (Appeal Br. 3), much less
monitoring or therapy that is not commonly or routinely provided to such
patients.
Accordingly, we affirm the Examiner's rejection of claim 1. Claims
2, 5-11, 16-18, and 20-27, which are not separately argued, fall with claim
1. 37 C.F.R. § 4I.37(c)(l)(iv).
II.
Issue
The Examiner has rejected claims 1, 2, 5, 6, 9-11, 16-18, and 20-25
as obvious over Remskar and DiaSorin. The Examiner has rejected claims 1
and 6-8 as obvious over Remskar, DiaSorin, and Richards. The same issues
are dispositive to both rejections; we therefore discuss the rejections
together.
The Examiner finds that Remskar measures plasma concentrations of
procalcitonin in patients with acute myocardial infarction, a form of acute
coronary syndrome using an immunoluminicentric assay (i.e., a
procalcitonin antibody assay). (Ans. 3.) The Examiner finds that the art
teaches normal procalcitonin value to be up to 0.5 µg/L, which the Examiner
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finds to meet the claim limitation of "a predetermined statistically significant
threshold value." (Id. at 4.) The Examiner finds Remskar teaches that,
"while procalcitonin levels 'remained normal' in patients with
uncomplicated acute myocardial infarction, ... procalcitonin levels are
increased in patients with acute myocardial infarction that is associated with
severe left heart failure and cardiac arrest," i.e., adverse outcomes. (Id. at 3.)
The Examiner therefore finds Remskar to teach "correlat[ing] the level of
procalcitonin to a predisposition to an adverse outcome of ACS." (Id. at 4.)
The Examiner finds that Remskar "does not specifically disclose the
use of a procalcitonin antibody assay having a lower limit of detection of<
0.055 µg/L." (Id.) However, the Examiner finds that DiaSorin describes
"[t]he Liaison Brahms PCT procalcitonin test," which is "an in vitro
antibody assay used for the quantitative determination of PCT in human
patient serum" and which has a lower detection limit of 0.032 µg/L. (Id.)
The Examiner concludes that "[i]t would be obvious and within the
purview of one of ordinary skill in the art to use a sensitive assay for the
detection of procalcitonin," "in order to accurately detect and correlate the
levels of procalcitonin in a patient and to predict an adverse cardiac event, as
done by Remskar." (Id.) The Examiner further concludes that "[i]t would
be obvious and routine to monitor the progression of a patient who is
predisposed to an adverse outcome." (Id. at 4--5.)
Finally, the Examiner cites to Richards for disclosing the dependent
claim limitations in claims 7 and 8, relating to "correlating levels of
procalcitonin or fragment thereof' with the additional prognostic markers of
pre-proBNP or fragments thereof ( claim 7), or the pre-proBNP fragments
NT pro-BNP or BNP (claim 8). (Id. at 8.)
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Application 12/921,885
Appellants contend that Remskar does not teach a correlation between
procalcitonin levels and predisposition to adverse outcomes of acute
coronary syndrome, because Remskar teaches findings obtained in "only a
limited number of patients" under very specific circumstances, and
"explicitly indicates that their finding preclude an analysis of the
relationship between procalcitonin concentration and severe complications."
( Appeal Br. 11.)
The issue with respect to this rejection is whether a preponderance of
the evidence of record supports the Examiner's finding that Remskar
suggests "correlating [the] level of procalcitonin or fragment thereof to a
predisposition to an adverse outcome of [an] acute coronary syndrome."
Analysis
On balance, we agree with Appellants that the Examiner has not
established a prima facie case that Remskar suggests "correlating [the] level
of procalcitonin or fragment thereof to a predisposition to an adverse
outcome of [an] acute coronary syndrome."
The Examiner asserts that Remskar teaches such a correlation
because, "while procalcitonin levels 'remained normal' in patients with
uncomplicated acute myocardial infarction, ... procalcitonin levels are
increased in patients with acute myocardial infarction that is associated with
severe left heart failure and cardiac arrest," i.e., adverse outcomes. (Ans. 3.)
We agree that Remskar teaches that "procalcitonin increases in
patients with acute myocardial infarction only if associated with severe left
heart failure, resuscitation after cardiac arrest or in the presence of bacterial
infections" and that, "in the absence of confounders such as cardiac arrest or
infection, procalcitonin increases according to the severity of left heart
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Appeal2018-007120
Application 12/921,885
failure." (Remskar Summary; id. at 208, left column.) We also recognize
that Remskar teaches that procalcitonin levels may have "the potential
function of a late prognostic indicator." (Id. at 209, left column.)
Nevertheless, Remskar concludes that the small number of patients in
its study "precludes an analysis of the relationship between procalcitonin
concentration and severe complications such as reinfarction or impending
mortality." (Id.) Remskar also teaches that there was "considerable
scattering of procalcitonin values" in the group of patients with resuscitated
cardiac arrest and again suggests that the small number of patients meeting
this criteria does not allow for addressing the reasons for the scattering. (Id.
at 208, right column.) Remskar further teaches that "[t]he issue of cut-off
values for prediction of infection or severe left heart failure, as well as
sensitivity and specificity of procalcitonin in this setting could also not be
addressed." (Id. at 209, left column.) Finally, Remskar teaches that, in light
of the above, "[t]he diagnosis of hemodynamic compromise or infection in
the setting of acute myocardial infection ... continues to be based on
traditional clinical, hemodynamic and laboratory parameters." (Id.
( emphasis added).)
In light of Remskar' s own interpretation of the results of its study, we
agree with Appellants that the Examiner has not established a prima facie
case that a skilled artisan would have had reason to use procalcitonin levels
to determine the predisposition of a patient to an adverse outcome of an
acute coronary syndrome, with a reasonable expectation of success. 5
5 We note that Remskar states that, "[i]n the absence of resuscitated cardiac
arrest or severe left heart failure, significantly increased procalcitonin values
would strongly argue for an as yet undiagnosed concomitant bacterial
infection." (Remskar 209, left column.) However, the Examiner has not
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Appeal2018-007120
Application 12/921,885
Accordingly, we reverse the Examiner's rejection of claim 1, 2, 5, 6,
9-11, 16-18, and 20-25 as obvious over Remskar and DiaSorin. The
Examiner cites Richards only for the proposition that "N-terminal pro-brain
natriuretic peptide [ (NT pro-BNP)] measure in patient plasma after
myocardial infarction predicts heart function and 2 year survival," which
relates to the dependent claim limitations in claims 6-8. (Ans. 8.) We
therefore also reverse the Examiner's rejection of claims 1 and 6-8 as
obvious over Remskar, DiaSorin, and Richards for the same reasons already
discussed.
SUMMARY
For the reasons above, we affirm the Examiner's rejection of claims 1,
2, 5-11, 16-18, and 20-27 as being directed to a judicial exception to patent
eligibility without significantly more. We reverse the Examiner's rejections
of claims 1, 2, 5, 6, 9-11, 16-18, and 20-25 as obvious over Remskar and
DiaSorin and claims 1 and 6-8 as obvious over Remskar, DiaSorin, and
Richards.
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).
AFFIRMED
argued or shown that concomitant bacterial infection would be encompassed
within the construction of the phrase "adverse outcome of acute coronary
syndrome."
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