John CouvarasDownload PDFPatent Trials and Appeals BoardDec 24, 20212022001037 (P.T.A.B. Dec. 24, 2021) 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. 15/131,442 04/18/2016 John L. Couvaras 82044.0002-00 7130 85944 7590 12/24/2021 Lei Mei Mei & Mark LLP P.O. Box 65981 Washington, DC 20035-5981 EXAMINER SZNAIDMAN, MARCOS L ART UNIT PAPER NUMBER 1628 MAIL DATE DELIVERY MODE 12/24/2021 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte JOHN L. COUVARAS __________ Appeal 2022-001037 Application 15/131,442 Technology Center 1600 __________ Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to a method of increasing prostacyclin release in systemic blood vessels to improve vasodilation. The Examiner rejected the claims as obvious. 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 inventor, John L. Couvaras (see Appeal Br. 3). We have considered the Specification of Apr. 18, 2016 (“Spec.”); Non-Final Office Action of Apr. 14, 2021 (“Non-Final Action”); Appeal Brief of July 23, 2021 (“Appeal Br.”); Examiner’s Answer of Oct. 19, 2021 (“Ans.”); and Reply Brief of Dec. 7, 2021 (“Reply Br.”). Appeal 2022-001037 Application 15/131,442 2 “Hypertension . . . can be due to various causes, such as constriction of the blood vessels. Angiotensin II is a potent vasoconstrictor in the human body” (Spec. 1:21 to 2:1). “Angiotensin II receptor blockers (ARBs) are substances that block the action of angiotensin II by preventing angiotensin II from binding to angiotensin II receptors on blood vessels. As a result, the blood vessels are less constricted and blood pressure is reduced” (id. at 2:11–16). “GABA receptors are activated through the action of the GABA or GABA-a analog during the period of time to promote production and release of smooth muscle relaxing substances by the activation of the GABA-a receptors” (id. at 5:11–15). “[S]ince the GABA-a receptors were found to be present in substantially any smooth muscle and endothelium, the composition of the present invention can be used to effect any of the various vascular circuits such as pulmonary, coronary, cutaneous, splanchnic and the like” (id. at 11:16–20). The Specification teaches: The present invention is a combination of an existing class of anti-hypertensive drugs, Angiotensin Converting Enzyme Inhibitors (ACE-I) and/or Angiotensin Receptor Blockers (ARBs), with the amino acid GABA or GABA-a analog, to improve the smooth muscle relaxation response, improved vasodilation and improved blood pressure reducing response, or reducing the dose of current ACE inhibitor and/or ARBs with GABA or GABA-a analogue and achieve the same response. (Spec. 6:3–10). Appeal 2022-001037 Application 15/131,442 3 Claims 11, 12, 15, 16, 24, 25, 27, 29, 30, and 32 are on appeal.2 Claim 11 is an independent claim, is representative and reads as follows: 11. A method of increasing prostacyclin release in systemic blood vessels of a human individual with essential hypertension to improve vasodilation, the method comprising the steps of: providing a human individual expressing GABA-a receptors in systemic blood vessels due to essential hypertension; providing a composition of a dosage of a GABA-a agonist and a dosage of an ARB combined into a deliverable form, the ARB being an Angiotensin II, type 1 receptor antagonist; delivering the composition to the human individual’s circulatory system by co-administering the dosage of a GABA-a agonist and the dosage of the ARB to the human individual orally or via IV; synergistically promoting increased release of prostacyclin by blockading angiotensin II in the human individual through the action of the dosage of the ARB to reduce GABA-a receptor inhibition due to angiotensin II presence during a period of time, and activating the uninhibited GABA-a receptors through the action of the GABA-a agonist during the period of time; and relaxing smooth muscle of the systemic blood vessels as a result of increased prostacyclin release. The Examiner rejected claims 11, 12, 15, 16, 24, 25, 27, 29, 30, and 32 under 35 U.S.C. § 103(a) as obvious over Thomson,3 Cheng,4 Kaufman,5 2 The Examiner withdrew claims 17, 18, 21–23, 26, 28, 31, and 33 from consideration (see Non-Final Act. 3). 3 Thomson et al., US 2010/0104728 A1, published Apr. 29, 2010. 4 Cheng et al., US 2012/0164120 A1, published June 28, 2012. 5 Kaufman et al., US 2013/0251671 A1, published Sept. 26, 2013. Appeal 2022-001037 Application 15/131,442 4 Kimura,6 Hayakawa,7 Elliot,8 Inoue,9 See,10 Kjeldsen,11 and Emala12 (Non- Final Act. 4–15). The Examiner finds that Thomson, Cheng, Kaufman, Kimura, Hayakawa, Elliott, and Inoue evidence that “GABA agonists are effective in treating hypertension in both animals and humans” (Non-Final Act. 5). The Examiner finds that Hayakawa teaches a “single oral dose of GABA (0.05 mg/kg or 0.5 mg/kg or 5.0 mg/kg . . . significantly decreases blood pressure from 4 to 8 hours after administration” (Non-Final Act. 6). The Examiner also finds “See and [Kjeldsen] teach that the oral administration of ARBs are known to treat hypertension” (Non-Final Act. 7). The Examiner finds it would have been obvious 6 Kimura et al., Involvement of -Aminobutyric Acid (GABA) B Receptors in the Hypotensive Effect of Systemically Administered GABA in Spontaneously Hypertensive Rats, 89 Japanese J. Pharmacol. 388–94 (2002). 7 Hayakawa et al., Effect of a -aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar- Kyoto rats, 92 British J. Nutrition 411–7 (2004). 8 Elliott et al., GAMMA AMINOBUTYRIC ACID: CIRCULATORY AND RESPIRATORY EFFECTS IN DIFFERENT SPECIES; RE- INVESTIGATION OF THE ANTI-STRYCHNINE ACTION IN MICE, 146 J. Physiology 70–84 (1959). 9 Inoue et al., Blood-pressure-lowering effect of a novel fermented milk containing -aminobutyric acid (GABA) in mild hypertensives, 57 European J. Clinical Nutrition 490–5 (2003). 10 See, S., Angiotensin II receptor blockers for the treatment of hypertension, 2 Expert Opinion Pharmacol. 1795–1804 (2001). 11 Kjeldsen et al., Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, 10 Expert Opinion Pharmacol. 729–45 (2005). 12 Emala, SR., US 2010/0048732 A1, published Feb. 25, 2010. Appeal 2022-001037 Application 15/131,442 5 to treat hypertension in a human suffering from hypertension comprising the orally or i.v. co-administration of a composition comprising a dosage of GABA or a GABA agonist and a dosage of ARB, each of which is taught by the prior art to be useful for the same purpose (treating hypertension), in order to form a third composition to be used for the very same purpose. (Non-Final Act. 7). The Examiner finds “[d]ose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Optimization of parameters is a routine practice” (id. at 13). Appellant responds objected indicia of non-obviousness both compel and confirm that the claimed invention is not obvious. First, the fact that the prior art in the old, crowded, and lucrative art of hypertension treatment never referenced, taught, or suggested the co- administration of a GABA-a agonist (or any GABA-related compound) and an ARB strongly suggests non-obviousness. Second, despite the Examiner’s touting that some effective treatments for hypertension exist, the treatment of essential hypertension remains a long felt, but unresolved need. Third, the prior art taught away from the claimed co-administration by (a) suggesting that GABA is unrelated to the release of vasodilators (like PGI2) and (b) by indicating that combining GABA with an ACE Inhibitor (with a known effect similar to, but distinct from, ARBs) yielded less of a blood pressure decrease that an ACE Inhibitor alone. Fourth, as confirmed by the silence in the prior art and the Inventor’s laboratory data, the resulting synergistic release of PGI2 was an unexpected result. Fifth, the claimed invention directly flows from the Inventor’s recognition of a problem, namely “the conflicting paradigm that ARBs lower blood pressure in eHTN humans despite that many eHTN humans have negligible to low normal levels of Angiotensin II in circulation.” Finally, failure of others is shown by at least the prior art previously cited by the Examiner. Appeal 2022-001037 Application 15/131,442 6 (Appeal Br. 13–14). We find the Examiner has the better position and address Appellant’s arguments in turn. Appellant first argues that “despite their decades-long separate prevalence in the prior art relating to hypertension treatment, the prior art has no record of a GABA-related compound and an ARB being coadministered or otherwise combined” (Appeal Br. 13). The Examiner’s cited art is not limited to showing that antihypertensive agents should be administered singly, but rather Kjeldsen teaches “[u]se of ARBs alone or in combination with other classes of antihypertensive agents to lower blood pressure . . . reduces risk of cardiovascular disease outcomes” (Kjeldsen 729, abstract). Kjeldsen also notes guidelines that “acknowledge the need for multiple-drug therapy in many patients to adequately lower blood pressure” (Kjeldsen 729). Therefore, the prior art itself provided a direct suggestion to combine different known antihypertensive agents, a teaching that ARBs and GABA are known hypertensive agents, and a reason to combine different hypertensive agents because “[m]ost patients require multiple-drug therapy to reach blood pressure goals. Blood pressure treatment guidelines recognise the desirability of initiating treatment with multiple-drug therapy” (Kjeldsen 738, col. 2). See In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980) (“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.”) Appellant next contends the “law prohibits reliance on inherency in obviousness for unknown properties . . . . The use of inherency in obvious[ness] is clearly not appropriate here because, as the Examiner Appeal 2022-001037 Application 15/131,442 7 repeatedly admitted, ‘the prior art was not aware of’ ‘increasing prostacyclin release in systemic blood vessels of a human individual’” (Appeal Br. 22). We find this argument unpersuasive because the Federal Circuit has “recognized that inherency may supply a missing claim limitation in an obviousness analysis.” PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1194–5 (Fed. Cir. 2014). The court’s “early precedent, and that of [its] predecessor court, established that the concept of inherency must be limited when applied to obviousness, and is present only when the limitation at issue is the ‘natural result’ of the combination of prior art elements.” Id. at 1195. As applied to the current facts, the natural result of treating a patient with the obvious combination of an ARB and a GABA agonist at optimized dosages would have necessarily resulted in increasing prostacyclin release in the absence of rebuttal evidence. As the Examiner noted, “[n]ewly discovered results of known processes directed to the same purpose are not patentable because such results are inherent.” In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2012); cf. Ans. 9–11. This is also analogous to Kao, where a limitation to a “food effect” was found obvious because the effect was an inherent property of the composition being used for treatment itself. In re Huai-Hung Kao, 639 F.3d 1057, 1071 (Fed. Cir. 2011). We are not persuaded by Appellant’s contention that “the Examiner may be relying (or may rely) on the similar obviousness rationale of ‘[c]ombining prior art elements according to known methods to yield predictable results’” (Appeal Br. 22) because to the extent that the Examiner relies on this as a secondary rationale, the Examiner notes that the prior art and legal precedent would have suggested combining different Appeal 2022-001037 Application 15/131,442 8 antihypertensive compounds such as GABA and ARBs for the benefit of treating hypertension (see Ans. 13). The Examiner finds the reason to combine in treating hypertension, not in “increasing prostacyclin release in systemic blood vessels of a human individual” (see id.). The Examiner finds that result inherent in the obvious combination of GABA and an ARB used for hypertension treatment. Appellant contends the objective indicia of (i) length of intervening time between the prior art and invention; (ii) long felt, but unresolved needs; (iii) teaching away by others; (iv) unexpected results; (v) recognition of a problem; and (v[i]) failure of others all forcefully counsel towards reversal of the obviousness rejection. There is a nexus between all of these objective indicia and claim 11 because, as discussed below, each secondary condition directly corresponds to the claimed (i) co- administration of compounds and/or (ii) subsequent steps taken to arrive at the desired result. (Appeal Br. 25). Length of time Appellant first argues that “the ‘components’ at issue here have been known as essential hypertension treatments for many, many decades . . . Nonetheless, there was no teaching or suggestion in the prior art to co- administer or combine these ‘components’” (Appeal Br. 26). Appellant cites Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1358 (Fed. Cir. 2013) for the proposition that “the substantial ‘elapsed time between the prior art and the [the patent application’s] filing date evinces that the . . . claimed invention was not obvious to try” (id. at 27 (citing Leo Pharm., 726 F.3d at 1356.)). We find this argument unpersuasive because the panel decision in Leo Pharm. cannot overrule the en banc CCPA precedent that the “mere age of Appeal 2022-001037 Application 15/131,442 9 the references is not persuasive of the unobviousness of the combination of their teachings, absent evidence that, notwithstanding knowledge of the references, the art tried and failed to solve the problem.” In re Wright, 569 F.2d 1124, 1127 (CCPA 1977). Appellants have provided no evidence that the prior art tried to combine GABA and ARBs and failed to obtain an anti- hypertensive composition. We also note the Examiner pointed out that “Leo Pharm. presented several medical research articles discouraging the combination” while here “there is nothing in the prior art teaching away from mixing GABA a agonists with ARBs” (Ans. 15). Long-felt need Appellant next argues that: The treatment of essential hypertension is a “long felt, but unresolved need.” It affects millions of Americans; the pharmaceutical industry generates billions of dollars annually through related treatments-and the industry spends billions of dollars in new treatment development. (Affidavit ¶5.) The claimed invention is squarely directed at this long felt, but unresolved need. (Appeal Br. 28; citing Declaration of Dr. John Couvaras ¶5, dated Apr. 30, 2020). We are not persuaded. To establish a long-felt need, three elements must be proven: First, the need must have been a persistent one that was recognized by ordinarily skilled artisans. In re Gershon, 372 F.2d 535, 538 (CCPA 1967). Second, the long-felt need must not have been satisfied by another before Appellant’s invention. See Newell Companies, Inc. v. Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988) (“[O]nce another supplied the key element, there was no long-felt need or, indeed, a problem Appeal 2022-001037 Application 15/131,442 10 to be solved . . . .”). Third, the invention must, in fact, satisfy the long-felt need. In re Cavanagh, 436 F.2d 491, 496 (CCPA 1971). In this case, Appellant has provided no evidence supporting the first two of these three elements. While Dr. Couvaras states “there is a long-felt, but unresolved need,” Dr. Couvaras’ own statements support a finding that there was no long-felt need as currently available marketed ARBs were selling billions of dollars of compound to patients (Couvaras Decl. ¶5). That the ARBs are selling very well does not suggest a need, but rather the absence of a need. And while Dr. Couvaras states that pharmaceutical companies “are incentivized to and expend substantial resources toward new and improved eHTN treatments,” no evidence is presented of expenditures by a pharmaceutical company on hypertensive treatments after the 2005 publication dates of See and Kjeldsen (Couvaras Decl. ¶5). Even if such expenditures were demonstrated, there is no evidence that the current compounds are insufficient. The Examiner pointed out, regarding long-felt need, that it may be that “there were already so many drugs and combinations of drugs for the efficacious treatment of hypertension that there might have been no need to find or explore a new combination that will require substantial financial commitment” (Ans. 17). And we agree with the Couvaras Declaration that “[v]arious eHTN treatments have been used for many, many decades. For example, GABA has been known about for over 65 years, and the use of ARB’s has been known over 30 years” (Couvaras Decl. ¶5). The Examiner also finds “there are already several solutions for the treatment of hypertension” (Ans. 18). Appellant provides no persuasive evidence that the current antihypertensive compounds were unsatisfactory or that there was a need or problem with Appeal 2022-001037 Application 15/131,442 11 these current compounds that was then solved by the combination of GABA and ARBs. Teaching away Appellant argues the prior art teaches away, specifically noting that Liu,13 a reference previously identified in prosecution, “discloses co- administering both GABA-related and Angiotensin II-related compound— and more specifically, GABA and an ACE Inhibitor (as opposed to an ARB). Liu, however, ultimately found that this combination of yielded less of a blood pressure decrease that an ACE Inhibitor alone” (Appeal Br. 30). Appellant also argues that the Examiner’s apparent proposition that a valid teach-away must be so narrow and precise as to substantially disclose the claimed invention makes no sense. If a reference taught the claimed invention, it would anticipate the claims—even if the invention was simultaneously denigrated. Accordingly, this novel dismissal or [sic] a teach away has no merit. The co- administration of similar compounds in Liu—and their failure—is unquestionably relevant. (id. at 32). In Medichem, the court explained that “[w]here the prior art contains ‘apparently conflicting’ teachings (i.e., where some references teach the combination and others teach away from it) each reference must be considered ‘for its power to suggest solutions to an artisan of ordinary skill . . . consider[ing] the degree to which one reference might accurately discredit 13 Liu et al., Antihypertensive Effects of Lactobacillus-Fermented Milk Orally Administered to Spontaneously Hypertensive Rats, 59 J. Agricultural Food Chem. 4537–43 (2011). Appeal 2022-001037 Application 15/131,442 12 another.’” Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006). Appellant’s argument that the Examiner’s test would limit teaching away to anticipation situations is incorrect, as teachings in the instant case that the ARB or GABA compounds were toxic, were unable to function in combination with other anti-hypertensive agents, or were previously incapable of synthesis represent examples of the types of teachings that might cause an ordinary artisan to “be discouraged from following the path set out in the reference, or . . . be led in a direction divergent from the path that was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). However, no such teaching has been presented on these facts.14 The asserted teaching away, that an entirely different chemical entity of ACE inhibitor compounds does not show improved anti-hypertensive effect when combined with GABA compounds, is not a teaching away from the obvious combination of ARBs and GABA compounds “because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). This is particularly the case when the cited prior art teaches “[u]se of ARBs alone or in combination with other classes of antihypertensive agents to lower blood pressure . . . reduces risk of cardiovascular disease outcomes” (Kjeldsen 729, abstract). Kjeldsen also notes guidelines that “acknowledge 14 Indeed, arguably Liu’s teaching does not even teach away from the combination of ACE inhibitor compounds and GABA compounds because an “obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” Gurley, 27 F.3d at 553. Appeal 2022-001037 Application 15/131,442 13 the need for multiple-drug therapy in many patients to adequately lower blood pressure” (Kjeldsen 729). Kjeldsen teaches “[m]ost patients require multiple-drug therapy to reach blood pressure goals. Blood pressure treatment guidelines recognise the desirability of initiating treatment with multiple-drug therapy” (Kjeldsen 738, col. 2). Thus, to the extent that Liu provides a suggestion regarding combinations with ACE inhibitor compounds, Kjeldsen directly teaches that ARBs, one of the claimed antihypertensive class of compounds, should be combined with other classes of antihypertensive agents as discussed above. Therefore, the closer evidence of Kjeldsen better evidences a desire and teaching to combine ARBs with other antihypertensive agents in treatment of humans than the more remote evidence in Liu that a combination of unclaimed ACE inhibitor compounds with GABA did not clearly improve hypertension in a tested animal model. Unexpected results Appellant contends: It was unexpected that systemic vessels released prostacyclin- and further was unexpected that such release occurs only when ATI receptor was blocked and GABA-a receptor was stimulated. (Affidavit ¶9.b.) And, it was unexpected that release of prostacyclin due to a combined/cooperative action of GABA-a and Ang II would be highly dependent on the vascular circuit (and vascular compartment)-and claim 11 recites “GABA-a receptors in systemic blood vessels.” (Appeal Br. 33). Appellant further contends “the trend of scientific thinking for treatment of essential Hypertension has moved towards Nitric Oxide (EDRF) promotion and away from promotion of ‘release of prostacyclin’” (id. at 34). Appeal 2022-001037 Application 15/131,442 14 We do not find any showing of unexpected results here. That is, Appellant does not demonstrate that the combination of ARBs with GABA results in unexpectedly better control of hypertension, less toxicity to patients, the ability to use reduced dosages, or some other unexpected advantage. Instead, Dr. Couvaras has established that the “main, beneficial medical result of my claimed invention- ‘increasing prostacyclin release in systemic blood vessels of a human individual with essential hypertension’-is unexpected” (Couvaras Decl. ¶9). However, “increased prostacyclin release” is simply a recitation of an inherent, but unknown, property of an otherwise obvious formulation and “an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations.” Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012). That is, identifying an inherent result of the combination of GABA and ARB compounds does not constitute an patentable invention unless there is also a showing that the newly discovered inherent result also provides an unexpected benefit of some sort. See also In re Kao, 639 F.3d 1057, 1070 (Fed. Cir. 2011) (The prior art’s “express teachings render the claimed . . . formulation obvious, and the claimed ‘food effect’ adds nothing of patentable consequence.”). Appellant states that this may allow reduced dosages in the Specification (see Spec. 10:4–10), but no evidence is adduced to show this benefit. It is well settled that unexpected results must be established by factual evidence. “Mere argument or conclusory statements in the specification does not suffice.” In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1994). Here, neither the Specification nor the Couvaras Declaration Appeal 2022-001037 Application 15/131,442 15 demonstrate that reduced dosages of ARBs or GABA treat hypertension when these compounds are combined and used in patients or animal models. Recognition of a problem Appellant contends the “claimed invention stems from the Inventor’s recognition of a problem, namely ‘the conflicting paradigm that ARBs lower blood pressure in eHTN humans despite that many eHTN humans have negligible to low normal levels of Angiotensin II in circulation’ and the breakthrough scientific discoveries made pursuant to such recognition” (Appeal Br. 35). We are not persuaded. “The discovery of the cause of a problem . . . does not always result in a patentable invention” In re Wiseman, 596 F.2d 1019 (CCPA 1979). Appellants . . . are, in effect, arguing that a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable to them because it also possesses an inherent, but hitherto unknown, function which they claim to have discovered. This is not the law. A patent on such a structure would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. Id. at 1023. Applying Wiseman to the instant facts, we do agree with Appellant that Dr. Couvaras appears to have identified a receptor complex that may be involved in hypertension (see, e.g., Couvaras ¶9), but what is missing from that recognition is any nonobvious impact on treatment using anti- hypertensive agents. Simply identifying an inherent result of an obvious combination is not a persuasive secondary consideration. Santarus, 694 F.3d at 1354. Appeal 2022-001037 Application 15/131,442 16 Failure of others Appellant contends the “pharmaceutical industry has failed to solve the large, continuing, and growing problem of essential hypertension”; that “the closest prior art of record, Liu, was a failure”; and that “Bird and Magness, tried and failed to increase the release of PGI2 in systemic vessels by experimenting with Angiotensin II levels” (Appeal Br. 36). To show a failure of others, the evidence must establish that others skilled in the art tried and failed to find a solution for the problem solved by the applicant. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1540 (Fed. Cir. 1983). One must also show that the others who failed had knowledge of the critical prior art. In re Caveney, 386 F.2d 917, 923 (CCPA 1967). In this case, Appellant does not show that others tried to use the inventive product, a combination of an ARB and GABA, and failed to treat hypertension. Conclusion of Law Appellant has not provided evidence of secondary considerations that, when considered as a whole with the evidence supporting the prima facie case, supports a finding of non-obviousness. Appeal 2022-001037 Application 15/131,442 17 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § References/Basis Affirmed Reversed 11, 12, 15, 16, 24, 25, 27, 29, 30, 32 103 Thomson, Cheng, Kaufman, Kimura, Hayakawa, Elliot, Inoue, See, Kjeldsen, Emala 11, 12, 15, 16, 24, 25, 27, 29, 30, 32 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED Copy with citationCopy as parenthetical citation