Ex Parte Struck et al

Patent Trials and Appeals Board

Jun 13, 2019

12936886 - (D) (P.T.A.B. Jun. 13, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/936,886 12/28/2010
23599 7590 06/17/2019
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BL VD.
SUITE 1400
ARLINGTON, VA 22201
Joachim Struck
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.
VOSS-0065 7544
EXAMINER
FOSTER, CHRISTINE E
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
06/17/2019 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 JOACHIM STRUCK, NILS MORGENTHALER,
ANDREAS BERGMANN, and CHRISTIAN MULLER
Appeal2017-004736
Application 12/936,886
Technology Center 1600
Before ERIC B. GRIMES, DEBORAH KATZ, and J. JOHN LEE,
Administrative Patent Judges.
LEE, Administrative Patent Judge.
DECISION ON APPEAL
Appellants1 appeal under 35 U.S.C. § 134 from the Final Rejection of
claims 1, 3, 5, 9, 10, 12, 14, 17, and 19-21, which are all the claims pending
in the present application. We have jurisdiction over the appeal under
35 U.S.C. § 6(b ).
We AFFIRM.
1 Appellants identify B.R.A.H.M.S. GmbH as the real party in interest.
(App. Br. 1.)
Appeal2017-004736
Application 12/936,886
CLAIMED SUBJECT MATTER
The present invention relates generally to a method for "the prediction
of impaired peak oxygen consumption (V02) for a subject not having a heart
failure." Spec. 1. Independent claim 1 is illustrative of the claims on appeal
and recites:
1. An in vitro method for the measurement of peak oxygen
consumption (V02) in a subject who does not have heart failure,
wherein said measurement is made when the subject is in a
resting state, comprising:
(a) detecting and quantitating in a sample of blood
serum or plasma from the subject the level of a
polypeptide marker C-terminal proendothelin-1 (CT-
proET-1 ),
wherein said detection and quantitation comprises an
immunoassay which comprises
(i) contacting said sample with an antibody
which specifically binds to said CT-proET-1 to
form an antibody:CT-proET-1 complex, and
(ii) quantitating the antibody:CT-proET-1
complex,
thereby determining the level of the CT-proET-1 in the
sample; and
(b) comparing the thus-determined level of CT-proET-
1 in the subject to a calculated threshold value previously
determined by statistical analysis of CT-proET-1 values in
a reference population having exercise intolerance and not
having heart failure, which distinguishes between subjects
having impaired peak V02 of <14 ml/kg/min and subjects
not having impaired peak V02 of <14 ml/kg/min;
wherein a level of CT-proET-1 in the sample exceeding the
calculated threshold value indicates that the subject has impaired
peak V02 of <14 ml/kg/min.
2
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Application 12/936,886
REJECTIONS ON APPEAL
Claims 1, 3, 5, 9, 10, 12, 14, 17, and 19-21 stand rejected under
35 U.S.C. § 101.
Claims 1, 3, 5, 9, 10, 12, 14, 17, and 19-21 stand rejected under
35 U.S.C. § 112, first paragraph.2
Claims 1, 3, 5, 9, 10, 12, 14, 17, and 19-21 stand rejected under
35 U.S.C. § 112, second paragraph.
Claims 1, 3, 5, 9, 12, 14, 17, and 19-21 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable in view of Krum, 3 Kinugawa,4 Williams,5 Festa,6
Papassotiriou,7 Buechler,8 and Allard. 9
2 We apply the pre-AIA version of§ 112 because the instant application was
filed before September 16, 2012. See Leahy-Smith America Invents Act,
Pub. L. No. 112-29, § 4(c), (e), 125 Stat. 284,296 (2011). Similarly, we
apply the pre-AIA version of§ 103 because the instant application was filed
before March 16, 2013. See id. § 3(c), (n)(l).
3 H. Krum et al., Role of Endothelin in the Exercise Intolerance of Chronic
Heart Failure, 75 AM. J. CARDIOLOGY 1282 (1995).
4 T. Kinugawa et al., Plasma Endothelin-1 Levels and Clinical Correlates in
Patients With Chronic Heart Failure, 9 J. CARDIAC FAILURE 318 (2003).
5 S. G. Williams et al., Complementary roles of simple variables, NYHA and
N-BNP, in indicating aerobic capacity and severity of heart failure, I 02
INT'L J. CARDIOLOGY 279 (2005).
6 P. Festa et al., Amino-Terminal Fragment of Pro-Brain Natriuretic
Hormone Identifies Functional Impairment and Right Ventricular Overload
in Operated Tetralogy of Fallot Patients, 28 PEDIATRIC CARDIOLOGY 339
(2007).
7 J. Papassotiriou et al., Immunoluminometric Assay for Measurement of the
C-Terminal Endothelin-1 Precursor Fragment in Human Plasma, 52
CLINICAL CHEM. 1144 (2006).
8 U.S. Patent No. 5,939,272, issued Aug. 17, 1999 ("Buechler").
9 U.S. Patent No. 5,928,878, issued July 27, 1999 ("Allard").
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Application 12/936,886
Claim 10 stands rejected under 35 U.S.C. § 103(a) as unpatentable in
view of Krum, Kinugawa, Williams, Festa, Papassotiriou, Buechler, Allard,
and Colpitts. 10
ANALYSIS
A. Rejection Under§ 1 OJ for Patent-Ineligible Subject Matter
Appellants appeal the Examiner's rejection of claims 1, 3, 5, 9, 10, 12,
14, 17, and 19-21 as ineligible subject matter under§ 101. App. Br. 4-8.
All of the rejected claims are argued together as a group. See id. As such,
we select claim 1 as representative of the rejected claims, and we decide the
appeal of the rejection of all of the rejected claims on the basis of claim 1.
See 37 C.F.R. § 41.37(c)(l)(iv).
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 Supreme Court has held that § 101 includes implicit
exceptions-laws of nature, natural phenomena, and abstract ideas-which
are not patent-eligible. See Alice Corp. v. CLS Bank Int'!, 573 U.S. 208,216
(2014). Earlier this year, the Office issued the 2019 Revised Patent Subject
Matter Eligibility Guidance, 84 Fed. Reg. 50 (Jan. 7, 2019) ("2019
Guidance"), which addresses the manner in which § 101 case law is to be
applied by the Office. The Board is required to adhere to the 2019 Guidance
as a matter of Office policy. Id. at 51. 11 The 2019 Guidance sets forth a
10 U.S. Patent Application No. 2007/0178504 Al, published Aug. 2, 2007
("Colpitts").
11 Although the Office Action at issue, as well as all the briefing for this
appeal, was completed before the 2019 Guidance was issued, the 2019
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four-part analysis for determining whether a claim is eligible subject matter
under § 101; the four parts are denominated Step 1, Step 2A Prong 1, Step
2A Prong 2, and Step 2B. See id. at 53-56.
1. 2019 Guidance Step 1
First, under "Step l ," 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
Guidance 53-54; see 35 U.S.C. § 101. Claim 1 recites a "method" and, thus,
falls within the "process" category. Consequently, we proceed to the next
step of the analysis.
2. 2019 Guidance Step 2A Prong 1
Second, under "Step 2A Prong l," we evaluate "whether the claim
recites a judicial exception, i.e., an abstract idea, a law of nature, or a natural
phenomenon." 2019 Guidance 54; see Alice Corp. v. CLS Banklnt'l, 134 S.
Ct. 2347, 2354 (2014). The Examiner determined that the rejected claims
recite a law of nature or natural phenomenon because they recite "the
naturally occurring correlation between levels of CT-proETl and peak
V02," specifically in the limitation, "wherein a level of CT-proET-1 in the
sample exceeding the calculated threshold value indicates that the subject
has impaired peak V02 of <14 ml/kg/min." Final Act. 4. Additionally, the
Examiner determined that the rejected claims recite "mental activity
performed solely in a practitioner's head" (i.e., a mental process),
specifically in the limitation, "comparing the thus-determined level of CT-
Guidance "applies to all applications ... filed before, on, or after January 7,
2019." 2019 Guidance 50.
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proET-1 in the subject to a calculated threshold value." Id. at 4-5. We
agree with these conclusions, and Appellants' arguments to the contrary are
unpersuasive for the following reasons.
Appellants argue that "[p Jeak oxygen consumption (V02) is not a law
of nature/natural phenomenon" because it "is a man-made value." App.
Br. 4. According to Appellants, V02 "is not a direct measure of oxygen
consumption by the patient but merely an estimate of oxygen consumption
used as a way to estimate exercise capacity." Id. Further, Appellants
contend "[t]he claimed invention is directed to a biomarker" that "does not
directly assess any natural phenomenon," but rather "is a surrogate for
another value and [that] other value, peak oxygen consumption (V02), itself,
is a man-made value providing merely an estimate of a physiological state,
i.e., exercise capacity." Id. Appellants' argument, however, is undermined
by their own Specification. The Specification states, "V02 max or peak V02
... is the maximum capacity of an individual's body to transport and utilize
oxygen during incremental exercise." Spec. 3. Further, the Specification
provides a mathematical formula for V02 max (V02 max= Q (Ca02 -
Cv02)), which is based solely on "the cardiac output of the heart [Q]," "the
arterial oxygen content [Ca02]," and "the venous oxygen content [Cv02]."
Id. These parameters are indisputably natural phenomena, namely the
natural properties of a human patient's body during exercise.
Claim 1 is similar to the claim held to recite a law of nature in
Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859 F.3d
1352 (Fed. Cir. 2017). In that case, the Federal Circuit examined a claim to
a method wherein the amount of "myeloperoxidase [ (MPO)] in a bodily
sample" is determined and compared to MPO levels in control subjects,
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which indicates "the extent of the test subject's risk of having atherosclerotic
cardiovascular disease." Id. at 1356. Similarly, claim 1 recites, "detecting
and quantitating in a sample of blood serum or plasma from the subject the
level of [CT-proET-1 ]," and comparing that value to "a calculated threshold
value previously determined by statistical analysis of CT-proET-1 values in
a reference population," which indicates whether the subject has "impaired
peak V02." Just as the Federal Circuit determined the claims in Cleveland
Clinic to be directed to a natural law (i.e., the correlation between MPO and
heart disease), we determine claim 1 here to recite a natural law, namely the
correlation between CT-proET-1 and the various cardiovascular properties
represented by peak V02. See Cleveland Clinic, 859 F.3d at 1361.
Although Appellants argue that the present invention is "an in vitro test"
(App. Br. 5), the claim in Cleveland Clinic also was an in vitro test
performed using a sample. See Cleveland Clinic, 859 F.3d at 1356.
We also agree with the Examiner that claim 1 recites an abstract idea.
Specifically, as the Examiner found, claim 1 recites, "comparing the thus-
determined level of CT-proET-1 in the subject to a calculated threshold
value previously determined by statistical analysis of CT-proET-1 values in
a reference population," which is a comparison that could be performed
entirely in a practitioner's mind. Final Act. 4-5. As such, claim 1 recites a
mental process, which is one of the three groupings of subject matter that the
2019 Guidance designates as meeting the abstract idea exception. 2019
Guidance 52. Appellants do not address this aspect of the rejection.
3. 2019 Guidance Step 2A Prong 2
Having determined that claim 1 recites a law of nature/natural
phenomenon and an abstract idea, we proceed to "Step 2A Prong 2" of the
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2019 Guidance, which requires that we evaluate 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 Collaborative Servs. v. Prometheus Labs., Inc.,
566 U.S. 66, 78 (2012).
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 Guidance 54-55. The
Examiner determined that, aside from the recited judicial exceptions, claim 1
amounted "only to general instructions to apply or use the ... naturally
occurring correlation." Final Act. 4. Specifically, the Examiner noted that,
in addition to the judicial exceptions, the claim only recites measuring the
levels of CT-proET-1 levels in a sample from a subject not having heart
failure while the subject is in a resting state, the measurement being
performed with an immunoassay using an antibody. Id. at 6. According to
the Examiner, measuring CT-proET-1 levels with such an immunoassay was
an established, common technique. Id. at 6-7. Further, the Examiner
determined that, "the patient population [ specified in claim 1] does not
impact or represent a technical advance or improvement in the assay,"
because no indication is given that the immunoassay would be performed
any differently than normal. Id. at 7. The Examiner also noted the claim
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does not require any action be taken based on the recited comparison of CT-
proET-1 values or determination of impaired peak V02. Id. at 4-5. Based
on the above, the Examiner concluded that the claim does not integrate the
recited judicial exceptions into a practical application. Id. We agree even
considering Appellants' arguments, as explained further below.
Step 2A Prong 2 of the 2019 Guidance is a change from prior
guidance from the Office regarding § 101 that was in effect at the time
Appellants submitted their briefing in this appeal. See 2019 Guidance 54
("Prong Two represents a change from prior guidance."). Nonetheless, as
the 2019 Guidance applies to applications filed before it was issued (id. at
50), we consider arguments presented by Appellants addressing issues
relevant to Step 2A Prong 2. First, Appellants argue the Examiner erred by
failing to consider the "combination of elements" recited in claim 1, rather
than elements individually. App. Br. 6-7; Reply Br. 3-4. Second,
Appellants contend that claim 1 "clearly does not preclude all or anywhere
near all uses of the natural phenomenon." App. Br. 7-8.
We first disagree that the Examiner failed to consider the relevant
elements of claim 1 in combination. Step 2A Prong 2 requires that only
"any additional elements recited in the claim beyond the judicial
exception(s)" be considered. 2019 Guidance 54-55 (emphasis added). As
discussed above, the recited comparison of CT-proET-1 levels to a
calculated threshold value and correlation of CT-proET-1 levels with
impaired peak V02 are subject matter falling under judicial exceptions to
§ 101. Thus, the only remaining elements recited in claim 1 are "detecting
and quantitating" CT-proET-1 levels in a sample using an immunoassay, the
sample coming from a subject without heart failure in a resting state. The
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Examiner expressly considered these elements, individually and in
combination. Final Act. 6-7.
Appellants point to the combination of "the specific C-terminal CT-
proET -1, to select the patient class as claimed, to use a specific manner of
immunoassay by forming complexes with antibodies to determine the CT-
proET-1 and using the CT-proET-1 as a surrogate marker for assessing
whether the patient has a certain peak oxygen consumption (V02) threshold
level." As an initial matter, using CT-proET-1 as a marker for assessing
peak V02 (i.e., the recited correlation) is not an additional element because
it recites a natural law, as discussed above. See Ans. 35. Further, the
Examiner found that determining CT-proET-1 levels using the specific
immunoassay recited in claim 1 (including forming complexes with
antibodies) was an established technique, citing specific prior art literature as
evidence. 12 Final Act. 6-7. Additionally, the Examiner found no indication
that the recited immunoassay would be applied differently to the specific
patient class recited, and cited prior art literature involving detection of CT-
proET-1 levels with immunoassays in patients with similar characteristics.
Id. Thus, the Examiner considered the combination of elements Appellants
rely on, and Appellants do not explain why these findings are inadequate.
12 Appellants dispute that all immunoassays involve antibodies binding to an
antigen to form a complex, contending that the Examiner failed to cite
evidence for such a proposition. Reply Br. 4. This argument is conclusory,
and regardless of whether that proposition is true, the Examiner cited
evidence that the immunoassay recited in claim 1 (including forming
complexes with antibodies) was an established practice in the art. Final Act.
6-7. Appellants do not dispute that finding or the cited evidence.
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Moreover, we note that "add[ing] insignificant extra-solution activity
to the judicial exception" is insufficient to integrate the exception into a
practical application (2019 Guidance 55). Data gathering steps typically
constitute such insignificant extra-solution activity. See Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79 (2012) (concluding that
additional element of measuring metabolites of a drug administered to a
patient was insignificant extra-solution activity); OIP Techs., Inc. v.
Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015) (holding that mere
data gathering is insufficient to confer patent eligibility). Here, the
"detecting and quantitating" steps, including the recited immunoassay,
gather the data (i.e., determine CT-proET-1 levels) necessary to conduct the
recited comparing and correlating (i.e., the judicial exceptions).
Appellants' preclusion argument also is unpersuasive. Even assuming
that Appellants are correct that claim 1 does not preclude or preempt all uses
of the correlation between CT-proET-1 and peak V02, "the absence of
complete preemption does not demonstrate patent eligibility." Ariosa
Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir. 2015).
Moreover, "generally link[ing] the use of a judicial exception to a particular
technological environment or field of use" is insufficient to integrate a
judicial exception into a practical application. 2019 Guidance 55. Thus,
contrary to Appellants' arguments (App. Br. 7), limiting claim 1 to specific
types of patients and assessing specific molecules using an otherwise more
broadly applicable technique (e.g., immunoassays) is insufficient. See
Mayo, 566 U.S. at 78 (concluding that the limitation of administering a drug
to a particular patient population merely limited the use of a judicial
exception to a particular technological environment); Parker v. Flook, 437
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U.S. 584, 595 (1978) (determining that limiting an ineligible alarm limit
calculation to specific process variables in a chemical process was
insufficient for patent eligibility).
In addition, we note that Appellants did not demonstrate error in the
Examiner's conclusion that claim 1 does not involve a "technical advance or
improvement" in the recited immunoassay. Nor did Appellants argue, much
less demonstrate, that claim 1 "uses a judicial exception to effect a particular
treatment or prophylaxis for a disease or medical condition," implements or
uses a judicial exception with "a particular machine or manufacture that is
integral to the claim," or "effects a transformation or reduction of a
particular article to a different state or thing." 2019 Guidance 55; see MPEP
2106.05(a)-(c), (e).
For the above reasons, Appellants have not shown that the Examiner
erred in concluding that claim 1 does not integrate the recited judicial
exceptions into a practical application.
4. 2019 Guidance Step 2B
Having concluded that claim 1 recites judicial exceptions but does not
integrate them into a practical application-i.e., that the claim is "directed
to" those exceptions (2019 Guidance 54)-we finally tum 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
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known to the industry, specified at a high level of generality," typically
indicates an inventive concept is absent. Id.
As discussed above, the Examiner correctly determined that the only
"additional" elements recited in claim 1 are measuring the levels of CT-
proET-1 levels in a sample from a subject not having heart failure while the
subject is in a resting state, the measurement being performed with an
immunoassay using an antibody. Final Act. 6. The Examiner further found
that these elements are "well-understood, routine and conventional activities
previously known to the industry." Id. Specifically, the Examiner found
that determining levels of CT-proET-1 in a sample from a subject not having
heart failure was "well-understood and conventional" and "does not go
beyond conventional activity previously engaged in by others," citing prior
art literature as supporting evidence. Id. at 6-7.
In addition, the Examiner found that the claimed method "do[ es] not
add any feature that is more than well-understood, purely conventional, or
routine in the field of diagnotistics and biochemical assay methodologies,"
specifically finding that "[i]t is not the case that the CT-proET-1 assay
would be performed differently on patients without heart failure and who are
in a resting state." Id. at 7. The Examiner also notes in her Answer that the
claim does not recite a "meaningful limitation, such as a particular or
unconventional antibody, for example, in [the immunoassay step] that
distinguishes it from well-understood, routine and conventional data
gathering activity ... e.g., the routine and conventional techniques of
detecting a protein using an antibody to that protein." Ans. 36. We agree
and find Appellants' arguments unpersuasive, as explained below.
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First, as discussed above, Appellants argue the Examiner failed to
consider the combination of all the elements of the claim. See App. Br. 6-7;
Reply Br. 3-4. This is unpersuasive for similar reasons as for Step 2A
Prong 2. Nor do we find persuasive Appellants' contention that the record
does not provide a basis for the Examiner's findings. App. Br. 6. As noted
above, the Examiner cited specific evidence to support her findings that the
additional elements of claim 1 were well-understood, routine and
conventional. See Final Act. 6-7. Moreover, we note the Specification
itself states that a "particular preferred embodiment" (that is also recited in
dependent claim 9) uses a "sandwich assay, which is a noncompetitive
immunoassay, wherein the molecule to be detected and/or quantified is
bound to a first antibody and a second antibody." Spec. 6. According to the
Specification, "[t]he general composition and procedures involved with
'sandwich assays' are well-established and known to the skilled person," and
prior art references to that effect are incorporated by reference. Id.; see also
id. at 5 ( citing a prior art reference disclosing a sandwich immunoassay
measuring CT-proET-1 levels). The Specification, thus, supports the
Examiner's finding that the recited detection and quantitation of CT-proET-
1 via immunoassay was well-understood, routine and conventional.
Finally, Appellants contend that the lack of an anticipatory prior art
reference demonstrates that the additional elements of claim 1, when viewed
in combination, are not well-understood, routine and conventional. App. Br.
5-6; Reply Br. 3-4. Novelty, however, is a different requirement for
patentability, and the lack of anticipation does not confer patent eligibility.
See Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709, 716 (Fed. Cir. 2014) (the
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fact that a method was "not previously employed in this art is not enough-
standing alone-to confer patent eligibility upon the claims").
Thus, for the reasons explained above, we agree with the Examiner
that claim 1 "simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high level of
generality," and, thus, fails to present an "inventive concept" because the
claim does not recite additional elements that provide "significantly more"
than the recited judicial exceptions. See 2019 Guidance 56. Therefore, we
sustain the Examiner's rejection of claim 1 as ineligible subject matter under
§ 101. As a result, we also sustain the rejection of claims 3, 5, 9, 10, 12, 14,
17, and 19-21 under§ 101. See 37 C.F.R. § 41.37(c)(l)(iv).
B. Rejection Under§ 112 for Lack of Written Description
Appellants appeal the rejection of claims 1, 3, 5, 9, 10, 12, 14, 17, and
19-21 under 35 U.S.C. § 112, first paragraph, for lack of adequate written
description support. 13 App. Br. 8-12. As explained below, we do not
sustain this rejection.
1. Claims 1, 3, 9, 12, 14, 17, 19, and 20
With respect to claim 1, the Examiner concluded that insufficient
written description existed to support the limitation, "a calculated threshold
value previously determined by statistical analysis of CT-proET-1 values in
a reference population having exercise intolerance and not having heart
13 Although the Examiner also rejects claims for improperly reciting new
matter, the basis for the rejection is inadequate written description support.
See Final Act. 9-12. Thus, we consider together all the grounds given for
rejecting the claims under§ 112, first paragraph.
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failure, which distinguishes between subjects having impaired peak V02 of
<14 ml/kg/min and subjects not having impaired peak V02 of <14
ml/kg/min." Final Act. 9, 13-15. In particular, the Examiner determined
that the written description did not support the recited "reference population
having exercise intolerance and not having heart failure" ( emphasis added),
or the full range for the recited "calculated threshold value ... which
distinguishes between subjects having impaired peak V02 of <14 ml/kg/min
and subjects not having impaired peak V02 of <14 ml/kg/min." Id. We
disagree with the Examiner's conclusions.
More specifically, the Examiner first determined that the written
description describes a reference population having exercise intolerance, but
that it does not support requiring the population also to not have heart
failure. See id. at 9 ( citing Spec. 13). According to the Examiner, the only
disclosure of a reference population included patients with heart failure, i.e.,
individuals with "NYHA heart failure stages I-IV." Ans. 38 (citing Spec.
13, Table 1). Appellants note, however, that the cited table in the
Specification makes clear that NYHA I-IV refers to "Dyspnea functional
class," i.e., the degree of shortness of breath, not heart failure. Reply Br. 1.
Further, Appellants assert the Specification explicitly states that patients
without heart failure are the focus of the invention, which informs a person
of ordinary skill that the recited threshold value should be drawn from a
population that similarly does not have heart failure. See App. Br. 9;
Spec. 1, 2. We agree with Appellants that the Examiner did not adequately
demonstrate that the written description fails to sufficiently support the
recited reference population.
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Next, the Examiner concluded the recited threshold value actually
claims a "genus of threshold values possessing the functional characteristic
of distinguishing" between patients with impaired peak V02 and those
without, finding that different statistical analyses and variability among
individuals (e.g., in age) could yield different values. Final Act. 13; Ans. 42.
The Examiner then determined that the written description does not support
the entire range of that purported genus of threshold values. Final Act. 13.
We agree with Appellants, however, that the Examiner did not explain
sufficiently why the description of the calculated threshold-i.e., that it has
the functional characteristic of distinguishing between impaired peak V02
(<14 ml/kg/min) and non-impaired peak V02 in patients-fails to reasonably
convey possession of the invention. The Examiner's reasoning that testing
would be required (Ans. 42) fails to establish that a person of ordinary skill
would not glean the full scope of the claim from the written description. 14
For example, the Examiner's analysis does not adequately address
Appellants' contention that it was well within the ordinary skill in the art to
conduct a statistical analysis to calculate a threshold value that achieves the
recited functional result. See App. Br. 9-10.
For the above reasons, we do not sustain the rejection of claim 1 under
§ 112, first paragraph. The Examiner does not provide any further basis for
rejecting dependent claims 3, 9, 12, 14, 17, 19, and 20 as lacking sufficient
written description support. Thus, we also do not sustain the rejection of
those claims under§ 112, first paragraph.
14 The Examiner did not reject the claims for failing to enable a person of
ordinary skill to practice the invention without undue experimentation,
including calculating the recited threshold value.
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2. Claims 5, 10, and 21
In addition to the reasoning discussed above with respect to
independent claim 1, the Examiner provided further analysis to support the
rejection of claims 5, 10, and 21 for lack of written description. For claim 5,
the Examiner concluded that the recited calculated threshold value for BNP
(B-type natriuretic peptide) or NT-proBNP (N-terminal pro-BNP) levels is
insufficiently supported for similar reasons as for the calculated threshold
values for CT-proET-1 levels in claim 1. See Final Act. 15; Ans. 43.
Consequently, the Examiner's reasoning for the BNP/NT-proBNP threshold
is deficient for similar reasons.
In addition, the Examiner asserted that the written description does
not support the recitation in claim 5 that NT-proBNP may be used as a
"surrogate marker" for BNP in a sample. Final Act. 10 ("[T]he specification
does not contain any suggestion that one could measure the level of BNP by
measuring instead NT-proBNP."). We disagree.
As Appellants assert (App. Br. 10), the Specification indicates that the
levels of both BNP and NT-proBNP are (similar to CT-proET-1) indicative
of impaired peak V02. Spec. 4. Although the Examiner is correct that this
disclosure describes them as alternatives (Ans. 39), i.e., alternative markers
for impaired peak V02, the Specification explains both BNP and NT-
proBNP are indicators for impaired peak V02 because they are fragments of
proBNP, which also is an indicator for impaired peak V02. Id. ProBNP, a
larger precursor polypeptide, "can be proteolytically cleaved into BNP and
[NT-proBNP]"-i.e., proBNP can be split into a BNP fragment and an NT-
proBNP fragment. Spec. 1. We are persuaded that these disclosures provide
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sufficient written description support for the recited use of NT-proBNP as a
surrogate marker for BNP in claim 5.
The rejection of claim 10 for lack of written description is based in
part on similar reasoning as for claim 1 regarding calculating a threshold
value to distinguish between impaired and non-impaired peak V02 (Final
Act. 12, 15), and for claim 5 regarding the use ofNT-proBNP as a surrogate
marker (id. at 9-10). We are persuaded the Examiner erred in these aspects
of the rejection for essentially the same reasons as discussed above. In
addition, the Examiner found that the written description did not support
"measuring values of," and calculating a "threshold value" for, the
additional marker "presence of diabetes," as recited in claim 10. Id. at 12.
We agree with Appellants, however, that one of ordinary skill in the art
would understand clearly that measuring the presence of diabetes refers to
assessment of whether diabetes is present or not, and calculating a threshold
value similarly refers to a binary value indicating whether diabetes is
present. App. Br. 12; Reply Br. 5.
Finally, for claim 21, the Examiner found that the recited value of
35.9 pg/mL was supported only as a threshold for BNP levels, not NT-
proBNP levels. Final Act. 10-11. In her Answer, the Examiner
acknowledged an amendment to claim 21 that requires that BNP be
measured directly (i.e., that the recited value refers only to BNP, not NT-
proBNP as a surrogate), and indicated the rejection should be withdrawn.
Ans. 41. Thus, we do not sustain this rejection of claim 21.
For the reasons explained above, we do not sustain the rejection of
claims 5, 10, and 21 under § 112, first paragraph, for lack of adequate
written description.
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B. Rejection Under§ 112 for Indefiniteness
Appellants appeal the rejection of claims 1, 3, 5, 9, 10, 12, 14, 17, and
19-21 under 35 U.S.C. § 112, second paragraph. App. Br. 8-12. As
explained below, we sustain this rejection only as to claim 10.
1. Claims 1, 3, 5, 9, 12, 14, 17, and 19-21
Regarding claims 1 and 5, the Examiner concluded that the
"calculated threshold value" recited in each claim is indefinite. Final Act.
16-1 7. The Examiner's reasoning is similar to reasoning given for the
rejection of those claims for lack of written description, i.e., that the recited
threshold value actually encompasses a range of values due to variations in
statistical analyses and reference populations. See id. at 1 7. According to
the Examiner, "it cannot be determined based on the specification what
values would fall within the scope of the claims" because basing the
calculations on "parameters that may vary ... renders the metes and bounds
of the claims unclear." Id. We are persuaded, however, that the Examiner
erred in this determination for similar reasons as for the written description
rejection with respect to the same claim terms.
More specifically, the Examiner did not explain adequately why the
requirement that the calculated threshold value "distinguishes between
subjects having impaired peak V02 of <14 ml/kg/min and subjects not
having impaired peak V02 of <14 ml/kg/min" fails to provide sufficient
boundaries to each claim's scope. We are persuaded by Appellants, who
assert essentially the same argument as for written description regarding this
limitation-i.e., that an artisan would have understood sufficiently from the
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claims how to calculate a threshold value that achieves the recited functional
result by applying an ordinary level of skill. 15 See App. Br. 9-10, 12-13.
Therefore, we do not sustain the Examiner's rejection of claims 1 and
5 as indefinite. Further, the Examiner does not provide any further basis for
rejecting dependent claims 3, 9, 12, 14, 17, and 19-21 as indefinite. Thus,
we also do not sustain the indefiniteness rejection of these claims.
2. Claim 10
The Examiner determined that claim 10 is indefinite because inter alia
it recites the term "value" or "values" several times, but some instances of
these terms are insufficiently clear and cause an unreasonable degree of
ambiguity in the claim. We agree.
For example, claim 10 first recites, "measuring values of at least one
additional marker having a correlation to peak V02." Next, the claim
recites, "assigning a value of 1 or O to each marker, when the result obtained
for said marker is indicative of an increased probability of severely impaired
peak oxygen consumption for said subject or not, respectively." The next
recited step is "comparing the thus determined values for each marker ... to
a calculated threshold value," and specifies how that value is calculated.
The next clause of the claim recites, "wherein the additional marker(s)
and their respective value(s) indicative of an increased probability of
severely impaired peak oxygen consumption for said subject, and to which a
value of 1 is assigned, are selected from ... ," and recites a group of specific
markers and associated threshold values (e.g., "BNP>35.9 pg/mL"). As the
15 We note that claims 19 and 21 recite specific numerical values for the
calculated threshold values in question. Thus, the Examiner's rejection of
these claims is even more clearly erroneous.
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Examiner explained (id. at 18-19), it is unclear what the "respective
value(s)" refers to, particularly in light of the "calculated threshold value"
limitation. Appellants assert that the term refers to the recited group of
specific threshold values. App. Br. 14.
If that is the case, however, the claim certainly would be disjointed
and unclear. On the one hand, the claim as interpreted by Appellants would
recite measuring values of additional markers and comparing them to
calculated threshold values. On the other hand, the claim also would recite
simply selecting a threshold value from the recited group of specific
threshold values (without an explicitly recited comparison to the measured
values). The Examiner correctly observed that it is insufficiently clear how
then the claimed method assigns the "value of 1 or O" to indicate "an
increased probability of severely impaired peak oxygen consumption for
said subject"-e.g., using the calculated threshold or the selected threshold.
See Final Act. 18-19; Ans. 44.
Appellants' interpretation also leads to further ambiguities. If, as
Appellants contend, the "additional marker(s) and their respective value(s)"
are simply selected from the recited group of options, the claim seemingly
indicates these are all markers "to which a value of 1 is assigned." The
claim, however, also recites, "wherein a score is calculated from the sum of
the values addressed to each of said markers," and indicates the score may
be "predictive of a higher probability of severely impaired peak oxygen
consumption." If all additional markers are assigned a value of 1, the recited
score would seem to always yield the same answer. Thus, we agree with the
Examiner that the "score" limitation is unclear as a result. See Ans. 44.
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For the above reasons, we conclude that Appellants have not
demonstrated that the Examiner erred in determining that claim 10 is
indefinite because, even when applying Appellants' own interpretation of
the claim, the claim language is insufficiently clear to reasonably apprise a
skilled artisan of its meaning. Thus, we sustain the rejection of claim 10 as
indefinite under§ 112, second paragraph.
C. Rejection Under§ 103(a)for Obviousness
The Examiner rejected claims 1, 3, 5, 9, 12, 14, 17, and 19-21 as
obvious in view of Krum, Kinugawa, Williams, Festa, Papassotiriou,
Buechler, and Allard. Final Act. 20-32. Appellants argue all of these
claims together and do not address them individually. See App. Br. 14-19.
The Examiner rejected claim 10 as obvious in view of the same combination
of references in further view of Colpitts. Id. at 32-34. As explained below,
we are not persuaded the Examiner erred.
Appellants first argue that the Examiner did not present sufficient
motivation to combine the teachings of the asserted references to arrive at
the claimed invention. App. Br. 15-16; Reply Br. 6. We disagree. In fact,
some of the asserted references were cited specifically because they
demonstrate a motivation to combine.
The Examiner found that Krum teaches measuring plasma levels of
endothelin-1 (ET-1) in both subjects with, and subjects without, heart
failure. Final Act. 21. Further, the Examiner found that Krum indicates that
plasma ET-1, measured during exercise, is "significantly inversely
correlated" with peak V02 in both groups of test subjects. Id.; see Krum
1283, Fig. 1. The Examiner acknowledged, however, that Krum does not
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teach (1) measuring CT-proET-1 (rather than ET-1) as a marker for peak
V02, and (2) testing subjects in a resting state. Final Act. 21-22.
For the first of these elements, the Examiner found that Papassotiriou
teaches measuring CT-proET-1 as a surrogate marker for ET-1, including
with a sandwich immunoassay. Id. at 24-25. As the Examiner found,
Papassotiriou itself indicates that CT-proET-1 is preferable to ET-1 as a
biomarker because no extraction step is needed, and ET-1 levels are difficult
to quantify due to its instability and rapid binding to receptors, thereby
providing a motivation to combine its teachings with Krum. Id. at 23, 25.
For the second element, the Examiner found that Kinugawa teaches
measuring ET-1 in subjects in a resting state because ET-1 levels were
essentially unaffected by exercise. Id. at 25. As the Examiner found,
Kinugawa found a correlation between ET-1 levels and peak V02 in resting
patients, although Kinugawa only studied patients with heart failure and not
those without heart failure (unlike Krum, which studied both). Id. at 22.
The Examiner also cited Williams, finding that it teaches measuring a
biomarker correlated with peak V02, namely NT-proBNP, in patients in a
resting state. Id. at 22-23. In particular, the Examiner noted teachings in
Williams that highlighted the benefits of testing subjects at rest-e.g.,
exercise testing requires sophisticated testing facilities whereas testing blood
samples of resting patients does not-thereby providing a motivation to
combine teachings regarding measuring peak V02 biomarkers in subjects in
a resting state with the teachings of Krum. Id. at 23-24.
In sum, the Examiner found that Krum teaches measuring ET-1 levels
as a marker for peak V02 in subjects without heart failure, as recited in the
present claims, albeit during exercise. The Examiner then found that a
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person of ordinary skill would have modified the method in Krum to test the
subjects in a resting state, as recited in the present claims, based on the
teachings of Kinugawa (peak V02 is correlated with ET-1 in subjects at rest)
and Williams (measuring subjects at rest is easier than during exercise).
Further, the Examiner found that a skilled artisan would have been
motivated to substitute CT-proET-1 for ET-1, as recited in the present
claims, based on Papassotiriou, which teaches that CT-proET-1 is a
preferable substitute because it is easier to measure than ET-1. We agree
with these findings, and we disagree that the Examiner failed to show
adequate motivation to combine these references. 16
Most of Appellants' remaining arguments involve attacking the cited
references individually, which is unpersuasive because the Examiner relies
on the combination of the cited references. For example, Appellants argue
that Krum only studied patients during exercise. App. Br. 16. As discussed
above, however, the Examiner cited Kinugawa and Williams for testing
subjects in a resting state. Appellants argue Krum, Kinugawa, Williams, and
Festa do not teach using CT-proET-1 as a marker for peak V02, because
those references involved ET-1 or NT-proBNP instead. Id. at 16-17. As
discussed above, however, the Examiner cited Papassotiriou for its teaching
that CT-proET-1 can be used as a surrogate marker in place ofET-1, and
Krum for its teaching that ET-1 is a marker for peak V02. Appellants'
argument that Kinugawa and other cited prior art do not teach testing
subjects without heart failure is similarly unpersuasive (App. Br. 17-18); the
16 Appellants also allege an insufficient motivation was shown as to Festa.
App. Br. 17-18. This argument also is unpersuasive because the Examiner
cited Festa for substantially similar teachings as Williams. See Final Act. 24.
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Examiner found, and we agree, that Krum studied both subjects with and
without heart failure, teaching that "[p ]lasma levels of [ET-1] ... were
significantly inversely correlated with maximum oxygen consumption (V02
max) in both groups studied" (Krum 1283, Fig. 1; Final. Act. 21 ).
To the extent Appellants are arguing that the cited references teach
away from the claimed invention (see App. Br. 18-19; Reply Br. 6-7),
Appellants fail to identify any specific evidence indicating that any of the
references criticizes, discredits, or otherwise discourages testing subjects
without heart failure, or any other aspect of the claimed invention. Thus,
Appellants have not established that the references teach away from the
claimed invention. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Moreover, as discussed above, we agree with Examiner's finding that Krum
affirmatively teaches testing subjects without heart failure.
For the reasons explained above, we adopt the Examiner's findings
and sustain the rejection of claims 1, 3, 5, 9, 12, 14, 17, and 19-21 as
obvious in view of Krum, Kinugawa, Williams, Festa, Papassotiriou,
Buechler, and Allard. Appellants rely on the same arguments for claim 10,
additionally arguing only that adding Colpitts to the asserted prior art
combination does not make up for the alleged deficiencies of the other prior
art references. App. Br. 19. Thus, we also sustain the rejection of claim 10
as obvious in view of Krum, Kinugawa, Williams, Festa, Papassotiriou,
Buechler, Allard, and Colpitts.
DECISION
WeAFFIRMtheExaminer'srejectionofclaims 1, 3, 5, 9, 10, 12, 14,
17, and 19-21 under 35 U.S.C. § 101.
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We REVERSE the Examiner's rejection of claims 1, 3, 5, 9, 10, 12,
14, 17, and 19-21 under 35 U.S.C. § 112, first paragraph.
We REVERSE the Examiner's rejection of claims 1, 3, 5, 9, 12, 14,
17, and 19-21 under 35 U.S.C. § 112, second paragraph.
We AFFIRM the Examiner's rejection of claim 10 under 35 U.S.C.
§ 112, second paragraph.
We AFFIRM the Examiner's rejection of claims 1, 3, 5, 9, 10, 12, 14,
17, and 19-21 under 35 U.S.C. § 103(a).
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l .136(a). See 37 C.F.R.
§ l.136(a)(l )(iv).
AFFIRMED
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