Ex Parte Struck et alDownload PDFPatent Trials and Appeals BoardJun 13, 201912936886 - (D) (P.T.A.B. Jun. 13, 2019) Copy Citation 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 Appeal2017-004736 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"). 3 Appeal2017-004736 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 4 Appeal2017-004736 Application 12/936,886 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. 5 Appeal2017-004736 Application 12/936,886 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, 6 Appeal2017-004736 Application 12/936,886 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 7 Appeal2017-004736 Application 12/936,886 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 8 Appeal2017-004736 Application 12/936,886 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 9 Appeal2017-004736 Application 12/936,886 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. 10 Appeal2017-004736 Application 12/936,886 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 11 Appeal2017-004736 Application 12/936,886 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 12 Appeal2017-004736 Application 12/936,886 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. 13 Appeal2017-004736 Application 12/936,886 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 14 Appeal2017-004736 Application 12/936,886 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. 15 Appeal2017-004736 Application 12/936,886 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. 16 Appeal2017-004736 Application 12/936,886 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. 17 Appeal2017-004736 Application 12/936,886 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 18 Appeal2017-004736 Application 12/936,886 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. 19 Appeal2017-004736 Application 12/936,886 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 20 Appeal2017-004736 Application 12/936,886 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. 21 Appeal2017-004736 Application 12/936,886 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. 22 Appeal2017-004736 Application 12/936,886 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 23 Appeal2017-004736 Application 12/936,886 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 24 Appeal2017-004736 Application 12/936,886 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. 25 Appeal2017-004736 Application 12/936,886 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. 26 Appeal2017-004736 Application 12/936,886 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 27 Copy with citationCopy as parenthetical citation