Julio A. ChirinosDownload PDFPatent Trials and Appeals BoardDec 5, 201914765583 - (D) (P.T.A.B. Dec. 5, 2019) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/765,583 08/04/2015 Julio A. CHIRINOS 46483-6090-00-US.604682 2007 10872 7590 12/05/2019 Riverside Law LLP Glenhardie Corporate Center, Glenhardie Two 1285 Drummers Lane, Suite 202 Wayne, PA 19087 EXAMINER ARNOLD, ERNST V ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 12/05/2019 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): dcoccia@riversidelaw.com dockets@riversidelaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte JULIO A. CHIRINOS __________ Appeal 2018-006907 Application 14/765,583 Technology Center 1600 __________ Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and MICHAEL A. VALEK, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1, 3–7, 9, 11, 12, 24, 26, and 27. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as The Trustees of The University of Pennsylvania. Appeal Br. 3. Appeal 2018-006907 Application 14/765,583 2 STATEMENT OF THE CASE The sole rejection before us for review is the Examiner’s rejection of claims 1, 3–7, 9, 11, 12, 24, 26, and 27, under 35 U.5.C. § 103(a) as being unpatentable over Lundberg,2 Kapil,3 Udelson,4 and Elkayam5 (Final Act. 3–11 (entered May 11, 2017)). Claim 1 is representative and reads as follows: 1. A method of treating heart failure with preserved ejection fraction (HFpEF) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising at least one selected from the group consisting of inorganic nitrate or inorganic nitrite. Appeal Br. 19. OBVIOUSNESS The Examiner’s Prima Facie Case The Examiner cited Lundberg as disclosing the use of inorganic nitrates and nitrites for treating congestive heart disease. See Final Act. 4. The Examiner also noted Lundberg’s teaching that inorganic nitrates and nitrites could be used in combination with sildenafil. Id. at 5. The Examiner cited Kapil as disclosing that beetroot juice, which contains significant amounts of nitrate, lowers blood pressure and also 2 US 2010/0092441 A1 (published Apr. 15, 2010). 3 Vikas Kapil et al., Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans[:] Role for Nitrite-Derived NO, 56 HYPERTENSION 274–281 (2010). 4 James E. Udelson, MD, Heart Failure with Preserved Ejection Fraction, 124 CIRCULATION e540–e543 (2011). 5 Uri Elkayam et al., The Role of Organic Nitrates in the Treatment of Heart Failure, 41 PROGRESS IN CARDIOVASCULAR DISEASES 255–264 (1999). Appeal 2018-006907 Application 14/765,583 3 increases plasma nitrate and nitrite. Id. The Examiner noted in particular that Kapil “suggest[s] the thesis that dietary (inorganic) nitrate is a potential preventative measure or treatment for cardiovascular disease (page 280, perspectives).” Id. at 6. The Examiner cited Udelson as teaching that approximately half of heart failure patients have heart failure with preserved ejection fraction (HFpEF), the treated condition recited in Appellant’s claims. Id. The Examiner particularly noted Udelson’s teaching that favorable results were obtained in a study in which HFpEF was treated with sildenafil. Id. The Examiner cited Elkayam as teaching that organic nitrates (as opposed to the inorganic nitrates recited in Appellant’s claims) were associated with a number of positive effects in patients with chronic congestive heart failure. Id. at 6–7. The Examiner found that Lundberg differed from Appellant’s claims in that Lundberg did not “expressly teach that the patient has heart failure with preserved ejection fraction in the method resulting in improved exercise tolerance, reduction of large artery stiffness, reducing arterial wave reflections, improving vasodilator response to exercise, increasing blood flow during exercise and increasing muscle oxidative capacity.” Id. at 7. The Examiner determined, however, that “[t]his deficiency in Lundberg et al. is cured by the teachings of Kapil et al., Elkayam et al., and Udelson.” Id. Specifically, the Examiner concluded that it would have been obvious to perform the method of Lundberg et al. on a patient that has heart failure with preserved ejection fraction, as suggested by of Kapil et al. and Udelson, resulting in improved exercise Appeal 2018-006907 Application 14/765,583 4 tolerance, reduction of large artery stiffness, reducing arterial wave reflections, improving vasodilator response to exercise, increasing blood flow during exercise and increasing muscle oxidative capacity, as suggested by Elkayam et al., and produce the instant invention. Id. at 9. The Examiner reasoned that a skilled artisan would have been motivated to administer inorganic nitrates and/or nitrites to patients with HFpEF as recited in Appellant’s claims because “administration of nitrites and nitrates, whether organic or inorganic, to treat patients with heart failure, such as congestive heart disease, is already extremely well known in the art as taught by Lundberg et al. and Udelson teaches that 50% of those patients had preserved ejection fraction.” Id. The Examiner also reasoned that it would have been obvious to administer inorganic nitrates and/or nitrites to HFpEF patients “because Udelson teaches that the best treatment of those patients has been with sildenafil and Lundberg et al. teach combining nitrites and nitrates, with beetroot as a source of nitrate, with sildenafil to treat heart disease.” Id. at 10. Analysis As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden . . . of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. Appeal 2018-006907 Application 14/765,583 5 We select claim 1 as representative of the rejected claims. See 37 C.F.R. § 41.37(c)(1)(iv). Having carefully considered the arguments and evidence advanced by Appellant and the Examiner, Appellant does not persuade us that the preponderance of the evidence fails to support the Examiner’s conclusion of obviousness as to claim 1. Lundberg discloses administering inorganic nitrites and/or nitrates, the active agents recited in Appellant’s claim 1, in order “to decrease oxygen consumption.” Lundberg ¶ 6. Lundberg includes “congestive heart disease” among disorders treatable with inorganic nitrites and/or nitrates. Id. ¶¶ 11, 98. Lundberg discloses an experiment in which ingesting beetroot juice, which contains inorganic nitrates, significantly reduced blood pressure in a hypertensive individual. Id. ¶¶ 129–130. Lundberg discloses that inorganic nitrites and/or nitrates can be combined with a variety of additional drugs, including “cardiovascular drugs (statins, ACE inhibitors, beta-receptor antagonists, diuretics, angiotensin 2 receptor antagonists, organic nitrates, calcium channel blockers)” as well as “drugs for treatment of pulmonary hypertension including prostacyclin analogues, endothelin receptor antagonists and sildenafil.” Id. ¶ 58. Although Lundberg describes treating “congestive heart disease” with inorganic nitrites and/or nitrates (id. ¶ 11, 98), Lundberg does not expressly describe using inorganic nitrites and/or nitrates to treat patients with HFpEF, the treated disorder recited in Appellant’s claim 1. As the Examiner noted, however, Udelson discloses that it was “well established that among patients with the clinical syndrome of heart failure (HF), approximately half have preserved systolic function, known most Appeal 2018-006907 Application 14/765,583 6 commonly as heart failure with preserved ejection fraction (HFpEF).” Udelson e540. Udelson discloses that hypertension is among conditions associated with HF hospitalization. See id. (“Several factors were associated with an increased risk of incident HF hospitalization or HF death, including older age, hypertension, and diabetes mellitus, whereas randomization to trandolapril reduced risk.”) (Emphasis added). Udelson notes in particular that “[p]redictors of HFpEF include[] increased systolic blood pressure, atrial fibrillation, and female sex, whereas HF with reduced EF was associated with prior myocardial infarction and left bundle-branch block QRS morphology.” Id. (Emphasis added). Udelson, noting that studies of therapeutic agents in HFpEF patients “have generally shown neutral results,” discloses that one study involved “controlled blood pressure.” Id. at e542. Udelson notes that when administered sildenafil, “[f]avorable results were . . . seen in a small study involving an important subgroup of HFpEF patients, those with pulmonary hypertension.” Id. Thus, although Udelson (like Lundberg) does not describe treating HFpEF patients with inorganic nitrites and/or nitrates, Udelson informed the skilled artisan that hypertension is among the risk factors for HF in general, and HFpEF in particular. And, as noted above, in addition to its generic teaching of treating congestive heart disease with inorganic nitrites and/or nitrates, Udelson teaches that inorganic nitrates reduce blood pressure. Lundberg ¶¶ 129–130. Accordingly, to summarize, Udelson teaches that hypertension is among the risk factors for HFpEF, and Lundberg teaches that inorganic Appeal 2018-006907 Application 14/765,583 7 nitrates reduce blood pressure. Appellant does not persuade us, therefore, that the Examiner erred in determining that a skilled artisan, viewing Lundberg’s generic teaching of treating congestive heart disease with inorganic nitrites and/or nitrates, had motivation and a reasonable expectation of success in treating HFpEF patients with inorganic nitrites and/or nitrates. Indeed, the Kapil article cited by the Examiner bolsters the Examiner’s position. Specifically, as the Examiner found, Kapil discloses a study “demonstrat[ing] dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation” including in the form of beetroot juice. Kapil 274 (abstract). And, as the Examiner also found, Kapil suggests administering inorganic nitrates to treat cardiovascular disease. See id. at 280 (“Although we acknowledge that our studies represent the responses of a healthy volunteer population, our evidence suggests that a dietary nitrate approach to CVD [cardiovascular disease] may have therapeutic use.”). Given Udelson’s teaching that hypertension is among the risk factors for HFpEF, and given the teachings in Lundberg and Kapil that inorganic nitrates reduce blood pressure in a manner suggesting their use in treating congestive heart and cardio vascular diseases, we are not persuaded that the Examiner erred in finding that a skilled artisan had motivation and a reasonable expectation of success in treating HFpEF patients with inorganic nitrites and/or nitrates, as recited in Appellant’s claim 1. Elkayam, the last reference cited by the Examiner, further bolsters the Examiner’s conclusion of obviousness. Elkayam discloses that “[a]lthough Appeal 2018-006907 Application 14/765,583 8 not approved by the FDA for the treatment of chronic congestive heart failure (CHF), organic nitrates are widely used in patients with CHF.” Elkayam 255 (citations omitted). Elkayam notes that, among other desirable effects of organic nitrates, one desirable result of administering organic nitrates to CHF patients is a “substantial reduction in . . . systemic blood pressure.” Id. Thus, although Elkayam does not specifically describe treating HFpEF patients as recited in Appellant’s claim 1, Elkayam nonetheless discloses more generally that it was desirable to treat congestive heart failure with nitrate-containing compounds that reduce blood pressure. Accordingly, to summarize, Udelson discloses that hypertension was a known risk factor for HFpEF, and Lundberg and Kapil teach that inorganic nitrates, like the organic nitrates used in Elkayam, reduce blood pressure in a manner suggesting their use in treating congestive heart and cardio vascular diseases. We are not persuaded, therefore, that the Examiner erred in finding that the cited references would have provided a skilled artisan with motivation for and a reasonable expectation of success in treating HFpEF patients with inorganic nitrites and/or nitrates, as recited in Appellant’s claim 1. Turning to Appellant’s arguments, Appellant cites twelve documents, among them three declarations, as evidence that the Examiner erred in determining that a skilled artisan would have considered it obvious to administer inorganic nitrites and/or nitrates, as recited in Appellant’s claim 1, to treat HFpEF patients. See Appeal Br. 10 (citing Appendices A–C (entered on March 2, 2017), Exhibits G, I, N, and O (entered on February 23, 2016), Exhibits S and T (entered on August 15, 2016), the Declaration of Appeal 2018-006907 Application 14/765,583 9 Dr. Chirinos (entered on August 15, 2016), and the Declarations of Drs. Sweitzer and Shah (entered on March 2, 2017)). In particular, Appellant contends, the Declarations of Drs. Chirinos,6 Sweitzer,7 and Shah8 establish that a skilled artisan would not have considered organic nitrites/nitrates to be equivalent to inorganic nitrites/nitrates in relation to treating HFpEF, and that a skilled artisan therefore would not have had a reasonable expectation of success in, or motivation for, treating HFpEF patients with inorganic nitrates, as recited in Appellant’s claim 1. See Appeal Br. 11–13. Moreover, Appellant contends, HFpEF is specific disease with a distinct physiology and response to treatment, such that a skilled artisan would not have been motivated to apply teachings regarding other types of heart failure to HFpEF. See id. at 14–16. We do not find Appellant’s arguments persuasive. We first note that “[o]bviousness, and expectation of success, are evaluated from the perspective of a person having ordinary skill in the art at the time of invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 974 (Fed. Cir. 2014) (quoting Velander v. Garner, 348 F.3d 1359, 1377 (Fed. Cir. 2003)). Thus, in Bristol-Myers Squibb v. Teva the court determined that, based on prior art teachings, selection of a particular lead compound would have been obvious, despite the fact that post-invention disclosures 6 Declaration of Julio A. Chirinos, M.D., Ph.D., pursuant to 37 C.F.R. § 1.132 (declaration signed August 12, 2016). 7 Declaration of Nancy K. Sweitzer, M.D., Ph.D., pursuant to 37 C.F.R. § 1.132 (declaration signed January 17, 2017). 8 Declaration of Sanjiv Shah, M.D., pursuant to 37 C.F.R. § 1.132 (declaration signed January 27, 2017). Appeal 2018-006907 Application 14/765,583 10 established that the compound later was found to be toxic. See Bristol- Myers Squibb v. Teva, 752 F.3d at 974 (“As the district court points out, in October 1990 [(the time of the invention)], 2′–CDG was not yet known to have high toxicity, and BMS’s expert, Dr. Schneller, agreed that researchers at the time treated 2′–CDG as a promising compound.”) (Internal quotations omitted). In the present case, Appellant’s earliest claimed priority date is February 7, 2013. See Spec. 1 (as amended August 4, 2015). In contrast, each of Appendices A9 and B,10 as well as Exhibits G,11 I,12 S,13 and T,14 has a publication date after Appellant’s earliest priority date, that is, after Appellant’s invention. 9 Payman Zamani et al., Isosorbide Dinitrate, With or Without Hydralazin, Does Not Reduce Wave Reflections, Left Ventricular Hypertrophy, or Myocardial Fibrosis in Patients with Heart Failure With Preserved Ejection Fraction, 6 J. AM. HEART. ASSOC. 1–16 (2017) (Appendix A). The copy of Appendix A in the record appears to be an uncorrected proof, as evidenced by markings on each page. 10 Payman Zamani et al., Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure with Preserved Ejection Fraction, 120 CIRC. RES. 1–11 (2016) (Appendix B). 11 Payman Zamani et al., Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure with Preserved Ejection Fraction, 131 CIRCULATION 371–380 (2014) (Exhibit G). 12 Margaret M. Redfield, M.D., et al., Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction, 373 N. ENGL. J. MED. 2314–2324 (2015) (Exhibit I). 13 Joel Eggebeen, MS, et al., One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction, 4 JACC: HEART FAILURE 428–437 (2016) (Exhibit S). 14 Clyde W. Yancy, MD, MSc, FACC, FARA, et al. (Writing Committee Members), 2013 ACCF/AHA Guideline for the Management of Heart Appeal 2018-006907 Application 14/765,583 11 As to Exhibit T, each of Drs. Sweitzer and Shah declares that the information therein is “representative of expert opinion and best practice at the time of the invention.” Sweitzer Decl. ¶ 3; see also Shah Decl. ¶ 3 (same statement). Appellant, however, advances no evidence suggesting that, despite their post-invention publication dates, a skilled artisan would have been aware of the teachings in Appendices A and B, or Exhibits G, I, and S, such that the artisan would have been able to consider the information in those documents when evaluating whether it would have been obvious to treat HFpEF patients with inorganic nitrates, as recited in Appellant’s claim 1. Appendix C, cited in each of the Declarations of Drs. Chirinos, Sweitzer, and Shah (Chirinos Decl. ¶ 13; Sweitzer Decl. ¶ 4; Shah Decl. ¶ 4), includes no indicia that the document was ever published, such that a skilled artisan would have been aware of the teachings therein at the time of Appellant’s invention. See Appendix C generally (document entered March 2, 2017). Indeed, it is unclear who performed the study described in Appendix C, or when the study was performed. See id. generally. Accordingly, to the extent Appellant’s arguments, and the opinions of Drs. Chirinos, Sweitzer, and Shah rely on the teachings in Appendices A–C, and Exhibits G, I, and S, as undermining the motivation for, and the reasonable expectation of success in, treating HFpEF patients with inorganic nitrites and/or nitrates, we do not find those arguments persuasive. See Bristol-Myers Squibb v. Teva, 752 F.3d at 974 (“Obviousness, and Failure, 128 CIRCULATION e240–e327 (2013) (Exhibit T or “the Guideline”). The even numbered pages of Exhibit T provide an October 15, 2013 publication date. Appeal 2018-006907 Application 14/765,583 12 expectation of success, are evaluated from the perspective of a person having ordinary skill in the art at the time of invention.”). As noted above, despite the post-invention publication date of Appellant’s Exhibit T (the 2013 ACCF/AHA Guideline for the Management of Heart Failure or “the Guideline”), both Dr. Sweitzer and Dr. Shah testify that the information therein is “representative of expert opinion and best practice at the time of the invention.” Sweitzer Decl. ¶ 3; see also Shah Decl. ¶ 3 (same statement). Rather than undermining the Examiner’s conclusion of obviousness, however, we find that the Guideline bolsters the Examiner’s conclusion of obviousness. Contrary to Appellant’s contention that HFpEF and HFrEF (heart failure with reduced ejection fraction) are entirely distinct conditions requiring entirely distinct therapeutic treatment agents, the Guideline teaches that one shared treatable symptom of HFpEF and HFrEF is hypertension: Elevated blood pressure is a major risk factor for the development of both HFpEF and HFrEF, a risk that extends across all age ranges. Long-term treatment of both systolic and diastolic hypertension has been shown to reduce the risk of incident HF by approximately 50%. Treatment of hypertension is particularly beneficial in older patients. . . . Given the robust outcomes with blood pressure reduction, clinicians should lower both systolic and diastolic blood pressure in accordance with published guidelines. Exhibit T e260 (emphasis added; citations omitted). And, as to HFpEF, the treated condition recited in Appellant’s claims, the Guideline expressly teaches that it is desirable to administer blood pressure reducing agents: Blood pressure control concordant with existing hypertension guidelines remains the most important recommendation in patients with HFpEF. Evidence from an Appeal 2018-006907 Application 14/765,583 13 RCT [randomized controlled trial] has shown that improved blood pressure control reduces hospitalization for HF, decreases cardiovascular events, and reduces HF mortality in patients without prevalent HF. In hypertensive patients with HFpEF, aggressive treatment (often with several drugs with complementary mechanisms of action) is recommended. ACE inhibitors and/or ARBs are often considered as first-line agents. Specific blood pressure targets in HFpEF have not been firmly established; thus, the recommended targets are those used for general hypertensive populations. Id. at e274 (citations omitted). Thus, consistent with the Udelson article’s identification of hypertension as a primary risk factor for HFpEF, the Guideline identifies reducing blood pressure as a primary therapeutic objective in HFpEF patients. And as noted above, both Lundberg and Kapil disclose that inorganic nitrates are effective blood pressure reducing agents. See Lundberg ¶¶ 129–130; Kapil 274, 280. Accordingly, to summarize, the Guideline teaches that blood pressure reducing agents were known to be useful for treating HFpEF, and Lundberg and Kapil teach that inorganic nitrates were known to be effective blood pressure reducing agents. Appellant does not persuade us, therefore, that the Guideline establishes that a skilled artisan, at the time of the invention, lacked either motivation for, or a reasonable expectation of success in, using inorganic nitrates to treat HFpEF, as recited in Appellant’s claim 1. To the contrary, given the Guideline’s teaching that blood pressure reducing agents were useful for treating HFpEF, viewed alongside the teachings in Lundberg and Kapil that inorganic nitrates were known to be effective blood pressure reducing agents, we find that the Guideline actually supports the Examiner’s conclusion of obviousness. Appeal 2018-006907 Application 14/765,583 14 We acknowledge the disclosure in Exhibit N15 that “[i]f HFpEF and HFrEF were part of the same HF disease spectrum, they would be expected to respond similarly to treatment. However, medications that have been shown to produce unequivocal improvements in HFrEP have not produced similar beneficial effects in HFpEF (Figure 2).” Exhibit N 2007 (citations omitted). We acknowledge the disclosure in Exhibit O16 that β-blockers produced inconsistent results in HFrEF and HFpEF patients: Large clinical trials have convincingly shown that β-blocker therapy reduces mortality and improves LV function in [HFrEF] patients. In [HFpEF] patients, favourable effects of β–blocker therapy on mortality and LV function have not been convincingly demonstrated. After hospital discharge, [HFpEF] patients had improved survival when using β-blockers and in a community-based registry, carvedilol use was accompanied by similar 1 year mortality in [HFpEF] and [HFrEF] patients but less reduction in hospitalizations in [HFpEF] patients. In the SWEDIC trial, carvedilol had no effect on mortality or hospitalizations, but ameliorated E/A ratio of [HFpEF] patients. In a similar study, however, 6 months of atenolol use had no effect on diastolic LV function of [HFpEF] patients with unchanged pulmonary capillary wedge pressure. Because of these inconsistent results, the use of β-blockers in [HFpEF] patients is further evaluated in clinical trials, such as the Japanese DHF study. Exhibit O 1864 (citations omitted). 15 Barry A. Borlaug, MD & Margaret M. Redfield, MD, Are Systolic and Diastolic Heart Failure Overlapping or Distinct Phenotypes Within the Heart Failure Spectrum ?, 123 CIRCULATION 2006-2014 (2011) (Exhibit N). 16 Nazha Hamdani et al., Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction, 30 EUR. HEART J. 2314–2324 (2015) (Exhibit O). Appeal 2018-006907 Application 14/765,583 15 As noted above, however, the Guideline expressly states that “[b]lood pressure control concordant with existing hypertension guidelines remains the most important recommendation in patients with HFpEF.” Exhibit T e274 (emphasis added). And as also discussed above, inorganic nitrates were known in the art to be effective blood pressure reducing agents. See Lundberg ¶¶ 129–130; Kapil 274, 280. Accordingly, the fact that certain therapeutic agents might not have been expected to treat HFpEF patients does not negate the fact that blood pressure reducing agents were known to be useful for treating HFpEF, the condition treated in Appellant’s claim 1. And, inorganic nitrates, treatment agents recited in Appellant’s claim 1, were known to be useful for reducing blood pressure. In sum, for the reasons discussed, Appellant does not persuade us that, when viewed as a whole, the prior art of record fails to support the Examiner’s conclusion that a skilled artisan would have considered it prima facie obvious to administer inorganic nitrates to treat HFpEF, as recited in Appellant’s claim 1. Appellant does not advance any specific objective evidence of nonobviousness to rebut the prior art evidence of obviousness discussed above. Because a preponderance of the evidence, therefore, supports the Examiner’s conclusion of obviousness as to Appellant’s claim 1, we affirm the Examiner’s rejection of claim 1. As to the Examiner’s rejection of claims 3–7, 9, 11, 12, and 24, Appellant relies on the arguments discussed above in relation to claim 1. See Appeal Br. 16. Therefore, for the reasons discussed above as to claim 1, we also affirm the Examiner’s rejection of claims 3–7, 9, 11, 12, and 24. Appeal 2018-006907 Application 14/765,583 16 As to the Examiner’s rejection of claims 26 and 27, Appellant relies on the arguments discussed above in relation to claim 1, and also includes a brief summary reiterating the arguments presented in traversing the rejection of claim 1. See Appeal Br. 16–17. Therefore, for the reasons discussed above as to claim 1, we also affirm the Examiner’s rejection of claims 26 and 27. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 3–7, 9, 11, 12, 24, 26, 27 103(a) Lundberg, Kapil, Udelson, Elkayam 1, 3–7, 9, 11, 12, 24, 26, 27 TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED Copy with citationCopy as parenthetical citation