Christian Lavedan et al.

Patent Trials and Appeals BoardNov 30, 2020

2020001843 (P.T.A.B. Nov. 30, 2020)

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. 12/675,614 02/26/2010 Christian Lavedan VAND-0058-US 5491 23550 7590 11/30/2020 HOFFMAN WARNICK LLC 540 Broadway 4th Floor Albany, NY 12207 EXAMINER GOLDBERG, JEANINE ANNE ART UNIT PAPER NUMBER 1634 NOTIFICATION DATE DELIVERY MODE 11/30/2020 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): PTOCommunications@hoffmanwarnick.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte CHRISTIAN LAVEDAN, MIHAEL H. POLYMEROPOULOS, and GUNTHER BIRZNIEKS ____________ Appeal 2020-001843 Application 12/675,614 Technology Center 1600 ____________ Before JOHN G. NEW, TAWEN CHANG, and TIMOTHY G. MAJORS, Administrative Patent Judges. MAJORS, Administrative Patent Judge. DECISION ON APPEAL Appellant1 submits this appeal2 under 35 U.S.C. § 134(a) involving claims to a method for administering a compound (i.e., tasimelteon) to a selected patient suffering from a sleep disorder such as insomnia, which claims have been rejected for obviousness under 35 U.S.C. § 103. We have jurisdiction under 35 U.S.C. § 6. We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies Vanda Pharmaceuticals Inc. as the real party-in-interest. Appeal Br. 1. 2 Although not identified by Appellant under 37 C.F.R. §41.37(c)(2), this appeal is related to Appeal 2016-006278, decided November 30, 2017. Appeal 2020-001843 Application 12/675,614 2 STATEMENT OF THE CASE “Insomnia is the most common sleep disorder,” and “is both a symptom (secondary to a medical, psychiatric, circadian, or sleep disorder) and a syndrome (primary insomnia that can[]not be attributable to other conditions).” Spec. 1. “Transient insomnia refers to sleep disturbances lasting from one night to a week” and, in “chronic insomnia, symptoms are present at least three times a week for up to one month or more.” Id. at 1–2. Appellant’s “invention provides (lR-trans)-N-[[2-(2,3-dihydro-4- benzofuranyl)cyclopropyl]methyl]propanamide,” a compound also known as “tasimelteon,” for “use in the treatment of a sleep disorder or one or more symptoms of insomnia associated with another disorder in a patient having a genotype associated with efficacious response to a sleep-inducing compound.” Id. at 3–4; see Appeal Br. 3 (asserting the claims relate to an allegedly improved “method of administering tasimelteon”), 5 (claim 40). As the Specification explains, “[s]everal polymorphisms have been described in the PER3 genes, including a variable number tandem repeat (VNTR) with 2 alleles of 4 or 5 repeats,” and “[t]his VNTR has been associated with diurnal preference and delayed-sleep phase syndrome (DSPS).” Spec. 6. According to the Specification, “it was found that the PER3 VNTR polymorphisms had a significant effect on how individuals were affected by the induced transient insomnia protocol and their response to the [tasimelteon] treatment.” Id. Claims 39–46 are on appeal. Claim 39 is the only independent claim on appeal, and is illustrative: Appeal 2020-001843 Application 12/675,614 3 39. In a method of administering (lR-trans)-N-[[2-(2,3- dihydro-4-benzofuranyl)cyclopropyl]methyl]propanamide to a human patient, the improvement comprising: selecting as said patient an individual identified as having a genotype at the PER3 variable number tandem repeat (VNTR) locus that is 4/4 or 4/5. Appeal Br. 5. As a further example of the claimed subject matter, dependent claims 40 and 41 recite, respectively, “[t]he improvement of claim 39, wherein the tasimelteon[3] is administered at a daily dose of 20 mg” and “[t]he improvement of claim 39, wherein said patient is suffering from transient insomnia.” Id. Appellant seeks review of the Examiner’s rejection of claims 39–46 under 35 U.S.C. § 103 as obvious over Viola4 in view of Birznieks,5 or Viola in view of Rajaratnam.6 I. Obviousness over Viola and Birznieks The issue on appeal is whether a preponderance of the evidence supports the Examiner’s conclusion that claims 39–46 would have been obvious over Viola and Birznieks. Appellant’s arguments are addressed to the claims as a group. Accordingly, we focus our analysis on claim 39, and the other claims stand or fall with claim 39. See 37 C.F.R. § 41.37(c)(iv). 3 The term “tasimelteon” lacks express antecedent basis in claim 39, but we understand tasimelteon is the compound with the chemical name in claim 39. Appeal Br. 3. If prosecution continues, correction should be made. 4 Antoine U. Viola et al., PER3 Polymorphism Predicts Sleep Structure and Waking Performance, 17 CURRENT BIOLOGY 613–18 (2007). 5 G. Birznieks et al., Melatonin Agonist VEC-162 Improves Sleep Onset and Maintenance in a Model of Transient Insomnia, 30 SLEEP A264 (2007). 6 Rajaratnam et al., The Melatonin Agonist VEC-162 Immediately Phase- Advances the Human Circadian System, 29 SLEEP A54 (2006). Appeal 2020-001843 Application 12/675,614 4 The Examiner concludes that the combination of Viola and Birznieks renders the subject matter of claim 39 obvious. Ans. 3–5; Non-Final Act. 4– 6.7 According to the Examiner, Viola teaches an analysis of the PERIOD3 (PER3) gene and, more specifically, that a variable number tandem-repeat (VNTR) polymorphism is associated with and predictive of sleep structure. Ans. 3–4; see Viola, 613 (explaining that the VNTR is a polymorphism “in which a motif encoding 18 amino acids is repeated either four (PER34) or five times (PER35)”). The Examiner finds that Viola teaches genotyping human subjects, and having individuals with either the 5/5 genotype or 4/4 genotype undergo a sleep study. Ans. 3; see Viola, 613 (“Four hundred and four men and women were genotyped in order to select matched pairs of individuals who were homozygous for the PER34 and PER35 alleles.”). As explained by the Examiner, “Viola teaches that PER3 5/5 subjects fell asleep more readily than PER3 4/4 subjects,” that there were significant differences in sleep latency between 5/5 and 4/4 subjects, and that “PER3 4/4 patients struggle with insomnia and have a decreased propensity for sleep” versus 5/5 subjects. Ans. 3–4 (citing Viola, 614, 616). The Examiner finds that Viola does not expressly disclose selecting 4/4 subjects for treatment with tasimelteon and, thus, the Examiner turns to Birznieks. Ans. 4. According to the Examiner, Birznieks teaches “treating latency to persistent sleep with tasimelteon, also called VEC-162” and that, based on phase III trial data, Birznieks discloses that treatment with tasimelteon was safe and effective, “improv[ing] sleep onset of transient 7 This citation refers to the Examiner’s Non-Final Rejection dated March 4, 2019, and the substance of the rejection of the claims is also repeated in the Examiner’s Answer on appeal. Appeal 2020-001843 Application 12/675,614 5 insomnia.” Id.; Birznieks, A264 (teaching tasimelteon (VEC-162) “previously demonstrated improvement in sleep onset and sleep maintenance as well as the ability to immediately phase advance the human circadian system” and that, in subjects with transient insomnia, “latency-to- persistent sleep (LPS) . . . significantly improved for all VEC-162 doses,” including doses of 20, 50, and 100mg). Based on these combined teachings, the Examiner reasons that it would have been obvious for the skilled artisan “to have selected patients with the PER3 4/4 genotype as patients who have sleep latency problems and treated these patients found to be at risk or suffering from insomnia with tasimelteon.” Ans. 4. The Examiner further reasons that the skilled artisan would have been motivated to combine Viola and Birznieks in this manner, arriving at the subject matter of claim 39, in view of Viola’s teachings that subjects with the 4/4 genotype took statistically longer to fall asleep compared to 5/5 subjects, and in view of Birznieks’s teachings that “tasimelteon is a safe, well tolerated compound that reduces the latency to sleep on the first night of treatment.” Id. at 4–5. We agree with, and adopt, Examiner’s findings and reasoning supporting the determination that Appellant’s claims would have been prima facie obvious over Viola and Birznieks. See Non-Final Act. 4–6; Ans. 3–5. As the Examiner persuasively explains, Viola teaches the association between the PER3 4/4 genotype and greater susceptibility to, and propensity for, problems with sleeping and sleep loss compared to those with the 5/5 genotype—supporting a selection of subjects with the 4/4 genotype for treatment as recited in claim 39; Ans. 3–4; Viola, 614 (describing how “the two genotypes [4/4 versus 5/5] differed strikingly with respect to sleep Appeal 2020-001843 Application 12/675,614 6 propensity”), 616 (teaching that the results imply the PER3 “polymorphism may be an important marker for individual differences in sleep and susceptibility to sleep loss and circadian misalignment, which are major causes of health problems and accidents in our society”). Birznieks teaches that administration of the melatonin agonist, tasimelteon/VEC-162, was not only safe and well tolerated, but also that it improves sleep onset and maintenance in subjects with circadian rhythm disruption and insomnia— thus, providing a reason to administer that compound to sleep impaired subjects with the 4/4 genotype. We agree with the Examiner that the skilled artisan would have combined the prior art in this way, with a reasonable expectation of success in arriving at the subject matter of claim 39. Appellant’s responsive arguments are unpersuasive. We address those arguments below. Appellant argues that Viola does not teach treating any subject for any condition, using any compound. Appeal Br. 2. Further, Appellant contends, an “association between homozygous PER3 genotypes and sleep parameters, as described in Viola, is not evidence of differences in the efficacy of treating sleep disorders based on PER3 genotype.” Id. at 3 (arguing that Birznieks’s teaching of “treatment of various sleep parameters using tasimelteon does not change this, as neither describes an association of any kind to an individual’s PER3 genotype”). For at least two reasons, Appellant’s arguments are unavailing. First, that Viola may not teach treating the 4/4 or 5/5 subjects with any compound does not undermine the Examiner’s rejection. The rejection is based on the combination of teachings, with Viola providing an evidentiary basis for the Examiner’s rationale for selecting subjects with the 4/4 genotype based on Appeal 2020-001843 Application 12/675,614 7 their propensity for sleeping difficulty and impairment, and Birznieks teaching administration of tasimelteon to effectively treat various sleep parameters and insomnia. The test for obviousness is what the combined teachings as a whole would have suggested to those of ordinary skill in the art, and Appellant cannot show nonobviousness by attacking the references individually. In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Second, as pointed out by the Examiner, the claims do not recite or require “differences in efficacy.” Appeal Br. 3; Ans. 6. We agree. In Reply, Appellant contends that the Examiner has “misinterpreted the claim” by not (apparently) imposing any “differences in efficacy” requirement in the claim itself. Reply Br. 2–3 (“the reason for the ‘selecting’ step . . . is so clearly identified and described as a newly discovered difference in treatment efficacy based on the PER3 genotype”). According to Appellant, “[a]s would be apparent to one skilled in the art [reading the Specification], the reason for selecting patients with the recited genotypes is because there is a difference in treatment efficacy.” Id. (citing Spec. 7–9 about the inventors’ discoveries). We find no basis to read into claim 39 any requirement for a particular efficacy, much less different efficacies. As to the “reason” for selecting certain patients, Appellant is mistaken in overemphasizing the reason that may have motivated the inventors to select and treat subjects with the 4/4 genotype. That reason is not decisive. To the contrary, the Examiner has supplied a different reason to support combining the art’s teachings, which is detailed above. And, it is well settled that these reasons need not be the same in an obviousness analysis. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007) (“In determining whether the subject matter of a patent claim is obvious, neither Appeal 2020-001843 Application 12/675,614 8 the particular motivation nor the avowed purpose of the patentee controls.”); In re Kemps, 97 F.3d 1427, 1430 (Fed. Cir. 1996) (“[T]he motivation in the prior art to combine the references does not have to be identical to that of the applicant to establish obviousness.”); Outdry Tech. Corp. v. Geox S.P.A., 859 F.3d 1364, 1370–71 (Fed. Cir. 2017) (“Any motivation to combine references, whether articulated in the references themselves or supported by evidence of the knowledge of a skilled artisan, is sufficient to combine those references to arrive at the claimed process . . .[, which] need not be the same motivation articulated in the patent for making the claimed combination.”). Appellant’s argument that the Examiner errs in not interpreting the claims to require selecting subjects with the 4/5 genotype fares no better. Appeal Br. 3–4 (“Here, the selecting step is necessarily inclusive of those with the heterozygous 4/5 genotype.”); Reply Br. 3 (“The claims define a class of patients that is inclusive of those with 4/4 and 4/5 genotypes. These genotypes are not recited in the alternative and the Examiner cannot simply read out of this class those individuals with a 4/5 genotype.”). Under the broadest reasonable interpretation, we agree with the Examiner that claim 39 “does not require [selecting or] treating any 4/5 patient.” Ans. 6 (emphasis added). To be sure, selecting a 4/5 subject is encompassed by claim 39. But, as the Examiner points out, so is selecting a 4/4 subject. Id. (“The claims are directed to treating a patient with PER3 4/4 or 4/5.”). The language of claim 39 itself makes this plain: “selecting as said patient an individual identified as having a genotype . . . that is 4/4 or 4/5.” Appeal Br. 5 (emphasis added).8 The combined prior art teaches or suggests selecting a 8 Appellant’s interpretation that the claim requires selection of both 4/4 and 4/5 genotypes also raises more questions than it answers. It is axiomatic that Appeal 2020-001843 Application 12/675,614 9 subject with the 4/4 genotype and administering tasimelteon to said subject for the reasons already explained. Appellant’s argument that the cited art is silent on the 4/5 genotype, even if true, does not rebut the rejection of the present claims. Appeal Br. 3–4. Finally, Appellant argues that the Examiner has, for years, cited Viola in rejections, and later withdrawn those rejections. Appeal Br. 4 (asserting that Viola has been cited in several anticipation and obviousness rejections since 2012). This argument reflects Appellant’s frustration, which we hear and acknowledge, but that is not a basis for reversing the Examiner on this record.9 We are tasked with deciding the merits of the rejections now before us on appeal. As to those rejections, we do not agree that “Viola is of no subject matter that infringes a claim would, if it existed earlier, invalidate that claim. But how would claim 39 be infringed under Appellant’s interpretation? Claim 39 recites administering a compound to “a human patient” and selecting “said patient” that has a “4/4 or 4/5” genotype for that administration—in other words a single patient. Of course, the same patient cannot have both the homozygous 4/4 and heterozygous 4/5 genotype. So, does Appellant’s interpretation require selecting and administering tasimelteon to multiple patients (some of whom have a 4/4 genotype and some of whom have a 4/5 genotype) before the claim would be infringed? This makes no sense in view of the singular “a human patient” and “said patient” language recited elsewhere in claim 39 and the dependent claims. Neither are we persuaded that the alleged Jepson format of claim 39 means it requires selecting 4/4 and 4/5 subjects. The selection of 4/4 subjects from a broader patient population (including those with the 5/5 genotype), as the Examiner contends is taught or suggested by Viola, may well represent the alleged “improvement” as recited. 9 The claims have also materially changed throughout prosecution, so it is not necessarily surprising, nor can we say unreasonable, that Viola was sometimes asserted and other times not. See, e.g., Appeal 2016-006278, 3–4 (PTAB, decided Nov. 30, 2017) (listing claim 1 and rejections, none of which involved Viola). Appeal 2020-001843 Application 12/675,614 10 relevance to the patentability of the pending claims.” Appeal Br. 4. Quite the opposite, we find Viola is relevant to the claimed selection step for the reasons given by the Examiner and as explained above. For the reasons above, we determine that the preponderance of the evidence supports the Examiner’s conclusion that claim 39 (and dependent claims 40–46) would have been obvious over Viola and Birznieks. II. Obviousness over Viola and Rajaratnam The Examiner concludes that claims 39–46 would, additionally or alternatively, have been obvious over Viola and Rajaratnam. Non-Final Act. 4–6; Ans. 3–5. The Examiner relies on Viola’s aforementioned teachings, and applies Rajaratnam in much the same way as Birznieks, discussed above. Ans. 3–5. The Examiner cites, for example, Rajaratnam’s disclosure of administering tasimelteon/VEC-162 to subjects to improve overall sleep efficiency and reduce sleep latency. Ans. 4 (noting also Rajaratnam’s teachings that VEC-162 was well tolerated); Rajaratnam, A54 (disclosing that VEC-162 “improved overall sleep efficiency . . . and attenuated the reduction in REM sleep,” among other benefits, and that “VEC-162 may offer therapeutic potential for sleep-wake disorders, including individuals who for work or other reasons rapidly shift their circadian phase”). We agree with and adopt the Examiner’s findings and reasoning in support of the rejection of the claims as obvious over Viola and Rajaratnam. Non-Final Act. 4–6; Ans. 3–5. Appellant did not argue the claims or rejections separately. Appeal Br. 2–4 (making the same arguments for both obviousness rejections). Appellant’s arguments remain unpersuasive for the same reasons addressed above concerning the combination of Viola and Birznieks. Accordingly, we determine that the preponderance of the Appeal 2020-001843 Application 12/675,614 11 evidence supports the Examiner’s conclusion that claims 39–46 would have been obvious over Viola and Rajaratnam. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 39–46 103 Viola, Birznieks 39–46 39–46 103 Viola, Rajaratnam 39–46 Overall Outcome 39–46 TIME PERIOD FOR RESPONSE 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