Court Opinion

ID: 9403526
Source: CourtListenerOpinion
Date Created: 2023-06-21 15:02:34.807183+00
Date Added: 2024-06-11T17:20:07.809149
License: Public Domain

Case: 22-1489     Document: 45   Page: 1    Filed: 06/14/2023

   United States Court of Appeals
       for the Federal Circuit
                   ______________________

                IN RE: JOHN L. COUVARAS,
                           Appellant
                    ______________________

                         2022-1489
                   ______________________

     Appeal from the United States Patent and Trademark
 Office, Patent Trial and Appeal Board in No. 15/131,442.
                   ______________________

                   Decided: June 14, 2023
                   ______________________

     LAURENCE M. SANDELL, Mei & Mark LLP, Washington,
 DC, argued for appellant John L. Couvaras. Also repre-
 sented by GUANG-YU ZHU.

    MAUREEN DONOVAN QUELER, Office of the Solicitor,
 United States Patent and Trademark Office, Alexandria,
 VA, argued for appellee Katherine K. Vidal. Also repre-
 sented by KAKOLI CAPRIHAN, THOMAS W. KRAUSE, AMY J.
 NELSON, FARHEENA YASMEEN RASHEED.
                 ______________________

      Before LOURIE, DYK, and STOLL, Circuit Judges.
 LOURIE, Circuit Judge.
     John L. Couvaras appeals from a decision of the U.S.
 Patent and Trademark Office Patent Trial and Appeal
 Board (“the Board”) affirming an Examiner’s rejection of
 the pending claims of U.S. Patent Application 15/131,442
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 2                                            IN RE: COUVARAS

 as unpatentable as obvious in view of the asserted prior art.
 In re: John L. Couvaras, No. 2022-001037, 2021 WL
 6124743 (P.T.A.B. Dec. 24, 2021) (“Decision”). For the fol-
 lowing reasons, we affirm.
                        BACKGROUND
     The pending claims of the ’422 application literally re-
 cite methods of increasing prostacyclin release in the sys-
 temic blood vessels of a human with essential hypertension
 to improve vasodilation. That increased prostacyclin re-
 lease is achieved by co-administering two well-known types
 of antihypertensive agents: a GABA-a agonist and an An-
 giotensin II Receptor Blocker (“ARB”). In reality, the
 claims relate to combatting hypertension with known anti-
 hypertensive agents and claiming their previously unap-
 preciated mechanism of action.
     Representative claim 11 is presented below:
       11. A method of increasing prostacyclin re-
       lease in systemic blood vessels of a human in-
       dividual 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 com-
       bined into a deliverable form, the ARB being
       an Angiotensin II, type 1 receptor antagonist;
       delivering the composition to the human indi-
       vidual’s circulatory system by co-administer-
       ing 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
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 IN RE: COUVARAS                                            3

       prostacyclin by blockading angiotensin II in
       the human individual through the action of
       the dosage of the ARB to reduce GABA-a re-
       ceptor inhibition due to angiotensin II pres-
       ence during a period of time, and
       activating the uninhibited GABA-a receptors
       through the action of the GABA-a agonist dur-
       ing the period of time; and
       relaxing smooth muscle of the systemic blood
       vessels as a result of increased prostacyclin
       release.
 J.A. at 981–82 (emphases added). Other independent
 claims recite similar methods but state that the GABA-a
 receptors are expressed in smooth muscle and the endothe-
 lium. Id. at 984–85. Dependent claims include limitations
 drawn to dosing amounts and time-release formulations,
 and those drawn to relaxing smooth muscle through in-
 creased prostacyclin release as well as reducing blood pres-
 sure due to said relaxation. Id. at 982–87. All of the claims
 stand or fall based on the arguments presented and evalu-
 ated here.
     During prosecution, Couvaras conceded that GABA-a
 agonists and ARBs “have been known as essential hyper-
 tension treatments for many, many decades.” J.A. at 998.
 The Examiner agreed, citing ten references establishing
 that GABA-a agonists and ARBs lower blood pressure, and
 thereby treat hypertension. The Examiner also found that
 the claimed results of the compounds’ administration (i.e.,
 increased prostacyclin release, activation of uninhibited
 GABA-a receptors, and smooth muscle relaxation) were not
 patentable because they naturally flowed from the claimed
 administration of the known antihypertensive agents. Id.
 at 1011–18.
     Couvaras appealed to the Board, asserting that the
 prostacyclin increase was unexpected, and therefore
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 4                                           IN RE: COUVARAS

 should be patentable. Couvaras also asserted that objective
 indicia overcame any existing prima facie case of obvious-
 ness. Unpersuaded, the Board affirmed the rejection. De-
 cision at *9. In particular, the Board held that the claimed
 result of an increased prostacyclin release was inherent in
 the obvious administration of the two known antihyperten-
 sion agents. Id. at *3–4, *7. The Board also found that
 Couvaras’s objective indicia arguments did not overcome
 the prima facie case of obviousness, namely, because no ev-
 idence existed to support a finding of any objective indi-
 cium. Id. at *4–9.
     Couvaras appealed the Board’s decision. We have ju-
 risdiction under 28 U.S.C. § 1295(a)(4)(A) and 35 U.S.C.
 § 141(a).
                        DISCUSSION
     We review the Board’s legal determinations de novo, In
 re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), and the
 Board’s factual findings for substantial evidence, In re
 Gartside, 203 F.3d 1305, 1316 (Fed. Cir. 2000). A finding
 is supported by substantial evidence if a reasonable mind
 might accept the evidence as adequate to support the find-
 ing. Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938).
     Couvaras raises several issues on appeal. First, Cou-
 varas contends that the Board erred in affirming that a
 skilled artisan would have had a motivation to combine the
 art asserted by the Examiner. Second, Couvaras contends
 that the claimed mechanism of action was unexpected, and
 that the Board erred in discounting its patentable weight
 by deeming it simply inherent in the claimed method.
 Third, Couvaras contends that the Board erred in weighing
 objective indicia of nonobviousness. We address these
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 IN RE: COUVARAS                                           5

 arguments in turn. 1
                              I
     Couvaras contends that the Board erred in affirming
 that a skilled artisan would have had a motivation to com-
 bine the prior art as asserted by the Examiner. Couvaras
 also asserts that the Board failed to address whether or not
 a skilled artisan would have had a reasonable expectation
 of success.
      As explained by the Examiner and affirmed by the
 Board, “[i]t is prima facie obvious to combine two composi-
 tions 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.” Decision at
 *3 (quoting In re Kerkhoven, 626 F.2d 846, 850 (CCPA
 1980)). Couvaras does not challenge that the two types of
 active agents recited in the claims, GABA-a agonists and
 ARBs, were known. See, e.g., Appellant’s Br. at 9 (“The use
 of ARBs has been known for more than 30 years.”); id. at 4
 (“GABA has been known for more than 65 years”); see also
 Oral      Arg.      at     13:27–13:40,    https://oralargu-
 ments.cafc.uscourts.gov/default.aspx?fl=22-1489_0503202
 3.mp3 (referring to GABA-a agonists and ARBs as “super
 well-known compounds”). Nor does Couvaras challenge
 that GABA-a agonists and ARBs were known to be useful
 for the same purpose—alleviating hypertension. See, e.g.,
 Appellant’s Br. at 8 (conceding the “undisputed, basic prop-
 osition that GABA agonists are effective in treating hyper-
 tension in both animals and humans” and that “[t]here is
 no dispute that such uses of GABA have been known for 65

     1   Couvaras also asserted that the Board violated the
 Administrative Procedure Act by relying on an obviousness
 rationale that was disavowed by the Examiner. Couvaras
 has since withdrawn this issue on appeal; thus, we need
 not address it here. See Appellant’s Reply Br. at 4 n.2.
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 6                                            IN RE: COUVARAS

 years”); id. at 8–9 (conceding the “undisputed, basic propo-
 sition that oral administration of ARBs are known to treat
 hypertension” and that “[t]here is no dispute that ARBs
 have been known and used for such purposes for more than
 30 years”). The Board was correct that this fact alone can
 serve as a motivation to combine because “the idea of com-
 bining [these compounds] flows logically from their having
 been individually taught in the prior art.” Kerkhoven, 626
 F.2d at 850.
     Couvaras suggests that this reasoning is too generic to
 support finding a motivation to combine in the clinical con-
 text under Cardiac Pacemakers v. St. Jude Medical, 381
 F.3d 1371 (Fed. Cir. 2004). We do not agree. In Cardiac
 Pacemakers, it was undisputed that, before the work of the
 inventor, there was no device capable of treating the condi-
 tions of interest. Here, however, the opposite is true. It is
 undisputed that, before the work of Couvaras, the antihy-
 pertensive agents recited in the claims existed and were
 known to treat hypertension.
     Couvaras further concedes that the prior art teaches
 the combination of ARBs with other antihypertensive
 agents to improve treatment. Appellant’s Br. at 16. In par-
 ticular, the Board took note of the Examiner’s reliance on
 the prior art Kjeldsen 2 reference, which teaches not only
 the use of ARBs “in combination with other classes of anti-
 hypertensive agents to lower blood pressure,” but also that
 various guidelines “acknowledge the need for multiple-
 drug therapy in many patients to adequately lower blood
 pressure.” Decision at *3; J.A. at 1473. The motivation to
 combine was thus not a general motivation to cure

     2   S.E. Kjeldsen et al., Targeting the renin-angioten-
 sin system for the reduction of cardiovascular outcomes in
 hypertension: angiotensin-converting enzyme inhibitors
 and angiotensin receptor blockers, 10 EXPERT OP.
 EMERGING DRUGS, 729 (2005); J.A. at 1472–89.
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 IN RE: COUVARAS                                           7

 hypertension, but, rather, the motivation to create a par-
 ticular cure by co-administering ARBs with another class
 of known antihypertensive agents as instructed by Kjeld-
 sen.
     Couvaras further asserts that, even if there had been a
 motivation to co-administer two hypertension treatments,
 such a motivation would fail to identify a “finite number of
 identified, predictable solutions” as required by KSR Inter-
 national Co. v. Teleflex Inc., 550 U.S. 398, 402 (2007). See
 Appellant’s Br. at 29 n.12. We do not agree. First, Cou-
 varas makes this argument in a footnote, and “[a]rguments
 raised only in footnotes [] are waived.” Otsuka Pharm. Co.
 v. Sandoz, Inc., 678 F.3d 1280, 1294 (Fed. Cir. 2012). Sec-
 ond, while Couvaras argues that there was a “substantial
 number of hypertension treatment agent classes” that
 could be considered for such a combination, he does not cite
 any evidence supporting this assertion. The Board’s con-
 clusion that there was a motivation to combine, on the
 other hand, was supported by substantial evidence and
 properly aligns with the tenets of KSR.
      Finally, Couvaras asserts that the Board erred in fail-
 ing to address reasonable expectation of success. Appel-
 lant’s Br. at 25–29. But Couvaras did not present any
 arguments against the Examiner’s findings of a reasonable
 expectation of success when he appealed the Examiner’s
 Final Rejection to the Board. See J.A. at 1139–76. Absent
 exceptional circumstances, see In re DBC, 545 F.3d 1373,
 1379–80 (Fed. Cir. 2008), we generally do not consider ar-
 guments that the applicant failed to present to the Board,
 In re Watts, 354 F.3d 1362, 1367–68 (Fed. Cir. 2004). Here,
 no such exceptional circumstances exist. It was not an er-
 ror for the Board to fail to make express findings regarding
 that prong of the obviousness analysis.
                              II
     Couvaras next asserts that the Board downgraded the
 patentable weight of limitations drawn to the
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 8                                            IN RE: COUVARAS

 antihypertensive agents’ mechanism of action by deeming
 them to be merely inherent. According to Couvaras, even
 if the recited mechanism of action is, effectively, inherent
 in the claimed administration of a GABA-a agonist and an
 ARB, that mechanism, specifically the increased release of
 prostacyclin, was unexpected. Couvaras contends that be-
 cause the increased prostacyclin release was unexpected,
 under Honeywell International Inc. v. Mexichem Amanco
 Holdings S.A., it cannot be dismissed as having no patent-
 able weight due to inherency. 865 F.3d 1348, 1355 (Fed.
 Cir. 2017). But Honeywell held that “unexpected proper-
 ties may cause what may appear to be an obvious composi-
 tion to be nonobvious,” not that unexpected mechanisms of
 action must be found to make the known use of known com-
 pounds nonobvious. Id. (emphasis added).
      Here, Couvaras attempts to claim a mechanism of ac-
 tion that naturally flows from the co-administration of two
 known antihypertensive agents. See Oral Arg. at 03:18–
 03:39 (acknowledging that Appellant has not argued “spe-
 cifically against that,” i.e., that the claimed co-administra-
 tion will result in the claimed mechanism of action); id. at
 03:56–04:06 (answering a question as to whether or not Ap-
 pellant agrees that the claimed steps are “necessarily” the
 mechanism by stating “Yeah, this is the mechanism by
 which it works”). In the prostacyclin mechanism, the two
 antihypertension agents exert the same ultimate result as
 the two separate compounds were known to effect: a de-
 crease in blood pressure. We have previously held that
 “[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) (citation omitted); see also In re Huai-Hung Kao,
 639 F.3d 1057, 1070–71 (Fed. Cir. 2011) (holding that a
 “food effect” was obvious because the effect was an inherent
 property of the composition). While mechanisms of action
 may not always meet the most rigid standards for inher-
 ency, they are still simply results that naturally flow from
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 IN RE: COUVARAS                                             9

 the administration of a given compound or mixture of com-
 pounds. Reciting the mechanism for known compounds to
 yield a known result cannot overcome a prima facie case of
 obviousness, even if the nature of that mechanism is unex-
 pected.
     We therefore agree with the Board that the recitation
 of various mechanistic steps in the pending claims are in-
 sufficient to overcome the prima facie obviousness of the
 claimed methods.
                              III
     Lastly, Couvaras contends that the Board erred in
 weighing objective indicia of nonobviousness. The Board’s
 findings regarding objective indicia involve questions of
 fact that we review for substantial evidence. Gartside, 203
 F.3d at 1316.
     Couvaras contends that the Board found that the
 “main, beneficial, medical result” of the claimed invention,
 namely, an increase in prostacyclin, was “unexpected.” See
 Decision at *7 (holding, at least, that Couvaras had as-
 serted this to be the case). According to Couvaras, the
 Board erred by nonetheless giving no weight to the unex-
 pected results indicium of nonobviousness. But, as dis-
 cussed above, recitation of a mechanism of action, even an
 unexpected one, does not necessarily overcome a prima fa-
 cie case of obviousness. To establish unexpected results,
 Couvaras would have needed to show that the co-admin-
 istration of a GABA-a agonist and an ARB provided an un-
 expected benefit, such as, e.g., better control of
 hypertension, less toxicity to patients, or the ability to use
 surprisingly low dosages. We agree with the Board that no
 such benefits have been shown, and therefore no evidence
 of unexpected results exist.
     Couvaras also asserts various other errors in identify-
 ing and weighing additional indicia of nonobviousness, in-
 cluding teaching away, failure of others, and the length of
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 10                                           IN RE: COUVARAS

 time that elapsed between the initial discovery of GABA-a
 agonists and ARBs being useful in treating hypertension
 and Couvaras’s claimed method of co-administering these
 types of compounds. For example, Couvaras asserts that
 the prior art, in particular, Liu 3, teaches away from the
 combined administration recited in the claims. As ex-
 plained by Couvaras, Liu purportedly includes data that
 show a lesser reduction in blood pressure following co-ad-
 ministration of an ACE inhibitor with γ-aminobutyric acid
 (GABA), a GABA-a agonist, compared to administration of
 an ACE inhibitor alone after 24 hours. Appellant’s Br. at
 49–50 (citing J.A. at 1198, ¶7.f.ii-iii). But that is insuffi-
 cient to establish a teaching away. As the Board correctly
 noted, Liu evaluated ACE inhibitors co-administered with
 GABA in rats, not ARBs co-administered with GABA-a ag-
 onists in humans, as claimed. Even Couvaras admits that
 ACE inhibitors and ARBs “operate through different bio-
 logical mechanisms.” Appellant’s Br. at 48. The Board was
 therefore correct to find that Liu did not teach away from
 the claimed method.
     Similarly, Couvaras asserts that there was a failure of
 others to increase prostacyclin release, but the evidence
 that Couvaras cites involves merely “experimenting with
 angiotensin II levels.” Appellant’s Br. at 52. As the Board
 correctly noted, however, an investigation into the impact
 of angiotensin II is not a failure to find a solution for an
 inability to increase prostacyclin release or a failure of the
 claimed method. Decision at *8–9. The Board thus
 properly found that the purported failure to achieve pros-
 tacyclin increase through pursuing an unrelated goal did
 not establish the nonobviousness of this claimed method.

      3  C.F. Liu et al., Antihypertensive Effects of Lactoba-
 cillus-Fermented Milk Orally Administered to Spontane-
 ously Hypertensive Rats, 59 J. AGRIC. FOOD CHEM. 4537
 (2011); J.A. at 1490–96.
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 IN RE: COUVARAS                                            11

      Couvaras also asserts that the length of time between
 when the two antihypertensive classes of compounds re-
 cited in the claims were first discovered and when Cou-
 varas first thought to combine them also serves as an
 objective indicium of the claims’ nonobviousness under Leo
 Pharmaceutical Products, Ltd. v. Rea, 726 F.3d 1346 (Fed.
 Cir. 2013). We disagree. In Leo Pharmaceutical, we held
 that the “length of the intervening time between the publi-
 cation dates of the prior art and the claimed invention can
 also qualify as an objective indicator of nonobviousness.”
 Id. at 1359 (emphasis added). However, that followed from
 a finding that the record established evidence of a long-felt
 but unsolved need and failure of others.
     Here, such indicia of nonobviousness do not exist. Ra-
 ther, as the Board correctly held, there was no long-felt,
 unmet need, given the admitted availability of antihyper-
 tensive agents and a lack of evidence that the available an-
 tihypertensive treatments were somehow insufficient to
 meet patients’ needs. Decision at *5. As discussed above,
 there is also insufficient evidence to establish a failure of
 others. The Board was therefore correct to note that the
 mere length of time that the prior art knew GABA-a ago-
 nists and ARBs to be antihypertensive agents “is not per-
 suasive 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.” Decision at *4 (quoting In re Wright, 569
 F.2d 1124, 1127 (CCPA 1977)). As no such evidence of fail-
 ure exists here, the Board’s conclusion that objective indi-
 cia did not overcome the prima facie case of obviousness
 was supported by substantial evidence.
                         CONCLUSION
     We have considered Couvaras’s remaining arguments
 and do not find them persuasive. For the foregoing rea-
 sons, we affirm the Board’s final written decision.
                         AFFIRMED