Ex Parte Lavedan et alDownload PDFPatent Trial and Appeal BoardNov 8, 201712675614 (P.T.A.B. Nov. 8, 2017) 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. 12/675,614 02/26/2010 Christian Lavedan VAND-0058-US 5491 23550 7590 11/30/2017 HOFFMAN WARNTOK T T C EXAMINER 540 Broadway 4th Floor GOLDBERG, JEANINE ANNE ALBANY, NY 12207 ART UNIT PAPER NUMBER 1634 NOTIFICATION DATE DELIVERY MODE 11/30/2017 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 LAVED AN, MIHAEL H. POLYMEROPOULOS, and GUNTHER BIRZNIEKS1 Appeal 2016-006278 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 This is an appeal under 35U.S.C. § 134 involving claims to methods of treating a human patient suffering from transient or chronic insomnia. The Examiner rejected the claims for new matter and failure to satisfy the enablement requirement, as well as for nonstatutory double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellants identify the Real Party in Interest as Vanda Pharmaceuticals Inc. (App. Br. 1.) Appeal 2016-006278 Application 12/675,614 STATEMENT OF THE CASE The Specification explains that “[ijnsomnia 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.) According to the Specification, “[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.) Appellants’ “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; App. Br. 9 (“claim 10 recites administration of different doses of tasimelteon to a patient. . . .”).) As the Specification explains, “[sjeveral 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 10, 12, 18, 27, 29, 31, and 32 are on appeal. Claim 10 is illustrative: 2 Appeal 2016-006278 Application 12/675,614 1. A method of treating a human patient suffering from transient insomnia, the method comprising: determining, from a biological sample of the patient, the patient’s genotype at the PER3 variable number tandem repeat (VNTR) locus; in the case that the patient’s genotype at the PER3 VNTR locus is determined to be 4/4 or 4/5, administering to the patient a first effective amount of (lR-trans)-N-[[2-(2,3-dihydro-4- benzofuranyl)cyclopropyl]methyl]propanamide, wherein the first effective amount is between about 10 mg/day and about 100 mg/day; and in the case that the patient’s genotype at the PER3 VNTR locus is determined to be 5/5, treating the patient by administering to the patient a second effective amount of (1R- trans)-N-[[2-(2,3-dihydro-4-benzofiiranyl)cyclopropyl]methyl] propanamide, wherein the second effective amount is greater than would be effective for a patient whose PER3 VNTR genotype is 4/4 or 4/5. (App. Br. 12 (Claims App.).) Claim 32, the other independent claim, is similar, but recites the treatment of “chronic insomnia” and a “second effective amount” that is between about 10—300 mg/day. (Id. at 12—13.) The claims stand rejected as follows: I. Claims 10, 12, 18, 27, 29, 31, and 32 under 35 U.S.C. § 112, first paragraph (pre-AIA), for introducing new matter. II. Claims 10, 12, 18, 27, 29, 31, and 32 under 35 U.S.C. § 112, first paragraph (pre-AIA), as nonenabled. III. Claims 10, 12, 18, 27, 29, 31, and 32 for provisional nonstatutory double patenting over: claims 1 and 4—6 of US Application No. 14/511,669; claims 1 and 3 of US Application 3 Appeal 2016-006278 Application 12/675,614 No. 14/510,321 ;2 and claims 67, 70, 75, and 81 of US Application No. 14/374,257.3 Each of these double patenting rejections is based on the cited claims of the co-pending applications in view of Archer.4 IV. Claims 10, 12, 18, 27, 29, 31, and 32 for nonstatutory double patenting over claims 1, 4—8, and 15 of US 8,785,492 B2 in view of Archer. I-NEW MATTER The Examiner rejected the appealed claims as including new matter and thus failing to comply with § 112, first paragraph. (Final Act. 3.) Specifically, the Examiner finds, Appellants amended the claims (e.g., claim 10) “to require administering to the patient an effective amount of a sleep inducing agent wherein the amount is between about 10-100mg/day and [, for the 5/5 patient, the amount] is greater than would be effective for a patient whose PER3 VNTR genotype is 4/4 or 4/5.” Yet, the Examiner finds, there is insufficient descriptive support for the amendment in the Specification. (Id.) The Examiner asserts the Specification “would suggest that patients with 5/5 would be administered lower or no doses” of tasimelteon, and “[t]here is no description of an amount of tasimelteon that treats 5/5 more effectively than 4/4 or 4/5.” (Id.) Appellants make several arguments in response. (App. Br. 3—5.) Appellants contend “the specification, as filed, fully supports both the 2 This application issued as US 9,730,910 B2 on Aug. 15, 2017. 3 This application issued as US 9,549,913 B2 on Jan. 24, 2017. 4 Archer et al., WO 2004/038043 A2, published May 6, 2004. 4 Appeal 2016-006278 Application 12/675,614 recited range of 10-100 mg/day and the administration of a higher dosage to a 5/5 patient than would be administered to a 4/4 or 4/5 patient,” and Appellants cite, inter alia, the originally-filed claims as evidence. (Id. at 3.) Appellants also argue the Examiner is mistaken “in concluding that the specification suggests that a 5/5 individual should be administered a lower dose of tasimelteon.” (Id. at 4.) Rather, Appellants contend, the Specification’s disclosure of 5/5 patients that are given no drug is an alternative form of treatment. (Id. at 3 4.) Because the Specification discloses that 5/5 patients are less affected by the induced transient insomnia protocol than 4/4 or 4/5 individuals, Appellants argue that “to realize the sleep-inducing effects of tasimelteon, one would have to administer a higher dose to a 5/5 individual.” (Id. at 3.) Further, Appellants argue, the Examiner is misinterpreting the claims in purporting to require that the Specification describe distinct dosage “ranges” that are effective for the 5/5 patient, as compared to a 4/4 or 4/5 patient. (Id. at 4—5.) According to Appellants, the Specification discloses “a dosage range of 10-300 mg/day for tasimelteon [and] [t]his is the range within which all individuals may be dosed, regardless of genotype.” (Id. at 4.) Appellants contend the skilled person “would readily understand from the specification that these ranges [for treatment of the 4/4, 4/5, and 5/5 patient] may overlap” within the broader disclosed range of 10—300 mg/day, with the proviso that “a 5/5 individual be administered a higher dose than would a 4/4 or 4/5 individual, all other relevant factors (e.g., age, severity of symptoms, etc.) being equal.” (Id.) 5 Appeal 2016-006278 Application 12/675,614 For the reasons explained below, we are not persuaded the Examiner met the burden necessary to support the new matter rejection.5 The Examiner “bears the initial burden ... of presenting a prima facie case of unpatentability.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). Insofar as the written description requirement is concerned, that burden is discharged by presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims. . . . [If] the specification contains a description of the claimed invention, albeit not in ipsis verbis (in the identical words), then the examiner . . ., in order to meet the burden of proof, must provide reasons why one of ordinary skill in the art would not consider the description sufficient. In re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996) (internal quotation marks and citations omitted). “It is not necessary that the application describe the claim limitations exactly,. . . but only so clearly that persons of ordinary skill in the art will recognize from the disclosure that appellants invented processes including those limitations. In re Wertheim, 541 F.2d 257, 262, (CCPA 1976) (internal citations omitted). As argued by Appellants, the originally-filed claims — particularly claim 10 and dependent claims 11—21 — sufficiently describe the subject matter now recited in the pending amended claims. (See Spec. 16—17.) Claim 10, for instance, recites “treating a patient based on the patient’s 5 “Section 132 prohibits the introduction of new matter into the disclosure of an application. Section 112, first paragraph, requires that claim language be supported in the specification. . . . [A] rejection of an amended claim under § 132 is equivalent to a rejection under § 112, first paragraph, for lack of support.” In re Rasmussen, 650 F.2d 1212, 1214 (CCPA 1981). 6 Appeal 2016-006278 Application 12/675,614 PER3 VNTR genotype,” and claims 14 and 15 indicate the treatment is with the compound tasimelteon, and that “the effective amount is based on the patient’s PER3 VNTR genotype.” (Id.) Claim 16 and 17 recite, respectively, that the effective amount is between “about 10 mg/day and about 300 mg/day” and “about 10 mg/day and about 100 mg/day” respectively. (Id. at 17.) And claim 19 recites “the effective amount is greater for a patient whose PER3 VNTR genotype is 5/5 than a patient whose . . . genotype is 4/4 or 4/5.” (Id.) Although in haec verba support for the disputed limitation of the amended claims is lacking in any one of the original claims, when we consider the original claims together, and in the sequence presented, we are unpersuaded that the Specification lacks adequate written-descriptive support. We reverse the new matter rejection. We address the Appellants’ remaining arguments inasmuch as they are repeated with respect to and/or impact the enablement rejection (discussed further below). We agree with Appellants that the Specification’s disclosure of giving no drug to the 5/5 patient is an alternative to the method presently claimed. Claims 10 and 32 require the step of “administering a second effective amount” of the drug to the 5/5 patient. If no drug is given, the “administering” step is not carried out, nor would the skilled person interpret the absence of giving a drug as “administering a second effective amount.” As for Appellants’ contention about 5/5 patients being less affected by the induced transient insomnia protocol compared to 4/4 or 4/5 individuals, that contention appears to be supported by the Specification. (See Spec. 8.) That may explain why, in the testing described, 5/5 patients had higher overall sleep efficiency compared to non-5/5 patients despite the protocol. 7 Appeal 2016-006278 Application 12/675,614 (Id.; see also Figs, la—d.) The extent to which the protocol’s lack of effectiveness with 5/5 individuals explains the lack of effect the drug had on the 5/5 individuals is, however, less clear. (See, e.g., Spec. Fig. 3 (showing lower sleep efficiency response of 5/5 individuals treated with the drug compared to placebo); see also Lavedan Deck 1 6 (“individuals with the PER35/5 genotype . . . were also less responsive [to tasimelteon] than were those individuals with the PER35/5 genotype who were administered a placebo.”)6.) The only description in the Specification for administering greater effective amounts of drug to 5/5 patients than 4/4 or 4/5 patients is the mention of it in original claim 19 — discussed above. As to Appellants’ contentions about claim interpretation, we agree in part. We agree with Appellants that, as in claim 10, the “second effective amount” may be an amount that falls within the range of 10—100 mg/day specified for the “first effective amount.” Or it may not, and the second amount could be greater than 100 mg/day. (App. Br. 12 (claim 31, which depends from claim 10, recites that the second effective amount has an upper bound of “about 300 mg/day”).) Yet the requirement remains that the amount administered to the 5/5 patient is “greater than would be effective for a patient whose PER3 VNTR genotype is 4/4 or 4/5.” (Id.) We disagree with Appellants, however, insofar as they seek to inject words that neither appear in the claim nor find adequate support in the Specification. Appellants contend “the dose administered to a 5/5 individual is ‘greater than would be effective for [the same] patient whose PER3 VNTR genotype is 4/4 or 4/5.” (App. Br. 5 (brackets in original) (emphasis 6 Declaration of inventor Christian Lavedan, Ph.D., dated Dec. 21, 2012. 8 Appeal 2016-006278 Application 12/675,614 added).) But the claim does not recite that it is “the same” patient. To the contrary, the relevant limitation reads “a patient.” Appellants, in effect, read in an “all other relevant factors (e.g., age, severity of symptoms, etc.) being equal” limitation that is not in the claim. (App. Br. 4.) Appellants direct us to no support in the Specification that justifies including this language. The Specification, in fact, suggests all other factors are not equal. The Specification states that hundreds of “healthy male and female subjects” were tested and genotyped (Spec. 7), but the Specification provides no data or even generic results that describe the response of any particular subjects with the same age, sex, weight, severity of symptoms, etc., who differ only in their relevant genotype. Also, the claims do not limit the “administering” of either the first or second effective amounts of drug to any particular route of delivery, and the Specification suggests that many options (oral, parenteral, transdermal) are permissible. (See, e.g., Spec. 11.) We thus conclude that the patient receiving “a first effective amount” includes a patient with a 4/4 or 4/5 genotype and the patient receiving “a second effective amount” includes a patient with a 5/5 genotype — all other factors (age, sex, route of administration, etc.) need not be the same and we reject Appellants’ proposed claim interpretation. II-ENABLEMENT The Examiner rejected all the pending claims for lack of enablement. We select claim 10 as representative. 37 C.F.R. § 41.37(c)(l)(iv). The issue with respect to this rejection is: has the Examiner established by a preponderance of the evidence that the Specification does not enable the claimed invention? 9 Appeal 2016-006278 Application 12/675,614 When rejecting a claim under the enablement requirement of section 112, the PTO bears an initial burden of setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application. ... If the PTO meets this burden, the burden then shifts to the applicant to provide suitable proofs indicating that the specification is indeed enabling. In re Wright, 999 F.2d 1557, 1561—62 (Fed. Cir. 1993). “[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Id. at 1561 (citation omitted). Factors to be considered in determining whether a disclosure would require undue experimentation . . . include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). The Examiner finds that the state of the art, and unpredictability related to the invention supports a determination that the claims are nonenabled. (Final Act. 7.) According to the Examiner, “[t]he art teaches studies that demonstrate that the 5/5 genotype is not associated with efficacy of tasimelteon on sleep initiation or maintenance following sleep wake phase 10 Appeal 2016-006278 Application 12/675,614 advance.” (Id.) As evidence, the Examiner cites Rajaratnam7 and Mitkus.8 According to the Examiner, “Rajaratnam teaches that tasimelteon induced improvements were more prominent, compared to placebo, in individuals with the PER3 non 5/5 genotype.” (Id.) The Examiner finds Rajaratnam fails to evidence “that the 5/5 genotype individuals should be administered an agent in an amount greater than 10—lOOmg/day (i.e. the amount effective for 4/4 or 4/5 patients.).” (Id.) The Examiner finds Mitkus describes testing of the effect of tasimelteon (20, 50, 100 mg doses) on individuals with different PER3 genotypes, and that Mitkus shows no significant difference was observed in 5/5 individuals. (Id. at 8.) As the Examiner points out, “Mitkus specifically states that ‘there was no difference in the rate of accumulation of REM sleep for the 5/5 individuals treated with tasimelteon compared to placebo (p=.37).” (Id.; see also Mitkus (middle of second column).) Therefore, the Examiner concludes, “[i]t is unpredictable that the tasimelteon (20, 50 or 100 mg) administration would treat a [5/5] human patient suffering from a sleep disorder.” (Final Act. 8.) 7 S. M. Rajaratnam, Melatonin and melatonin receptor agonist tasimelteon for Orcadian rhythm sleep disorders: understanding inter-individual differences in efficacy, Abstract, 20th Congress of the European Sleep Research Society (Sept. 2010) (“Rajaratnam”). The Examiner states that a copy of Rajaratnam was included with the Final Rejection. Based on our review, such copy does not appear in the publicly-available record. We are including a copy of Rajaratnam and PTO Form 892 along with this Decision. 8 Shruti N. Mitkus, et al., Effect of a Period 3 (PER3) Gene Polymorphism on Response to Tasimelteon Treatment in a Phase Advance Model of Transient Insomnia, Presented at SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies (APSS), LLC (June 6—11, 2009) (“Mitkus”). 11 Appeal 2016-006278 Application 12/675,614 The Examiner also finds the Specification “provides no evidence that the broad scope of the claims are enabled across the scope of the claims.” (Id. at 8.) For example, the Examiner cites Figure 2 as illustrating “[individuals with PER3 5/5 fell asleep more quickly but wake after sleep more quickly” and “Figure 3 demonstrates that SE [sleep efficiency], EPS [latency to persistent sleep] and WASO [wake after sleep onset] responded better in non-5/5 individuals.” (Id.: see also Spec. 3 4.) The Examiner further finds “[t]he specification fails to teach how to differentially treat the genotypes” and “fails to teach whether more frequent, different agonists, more quantities are appropriate for the different genotypes.” (Final Act. 9.) The Examiner finds that undue experimentation would be required to make and use the invention’s full scope. (Id. at 9-10.) Based on the lack of guidance in the Specification and unpredictability in the art, the Examiner finds it would require “undue experimentation to determine the effective amount and whether treatment should even be provided for the 5/5 genotypes.” (Id. at 10.) The Examiner notes that “[t]he ‘higher doses’ encompassed by the claims are within the range of doses that are found to not be effective compared to control” for treating 5/5 patients. (Id. at 11.) The Examiner also points out “[t]he [Lavedan] declaration and Mitkus appears to assert that for 5/5 patients, it is not effective treatment to administer doses of 20, 50, and lOOmg of tasimlteon [sic].” (Id. at 12 (“As noted in the specification, the declaration and Mitkus, 5/5 patients who were administered these doses were less effective than a placebo.”).) The preponderance of the evidence on this record supports the Examiner’s conclusion that claim 10 is not enabled. “Patent protection is granted in return for an enabling disclosure of an invention, not for vague 12 Appeal 2016-006278 Application 12/675,614 intimations of general ideas that may or may not be workable.” Genentech Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997); cf. Brenner v. Manson, 383 U.S. 519, 536 (1966) (explaining, in context of the utility requirement, that “a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.”). Rajaratnam and Mitkus illustrate the unpredictability of treating patients having the 5/5 genotype with tasimelteon — and specifically, whether tasimelteon is effective in treating insomnia in those individuals. Mitkus, for example, repeatedly discloses that the drug (administered at 20, 50, and 100 mg) provided no significant effect to 5/5 individuals. Mitkus9 states, inter alia, “[n]o significant change in sleep efficiency was observed for PER3 5/5 individuals,” “[n]o significant difference in LPS was observed for 5/5 individuals after treatment (p=0.5),” and “[t]here was no significant difference in either rate of accumulation of total NREM sleep in PER3 5/5 individuals treated with tasimelteon or placebo (p=0.39, Table 3).” (See Mitkus cols. 1—3.)10 While Mitkus states that tasimelteon “may be beneficial, particularly to PER3 non-5/5 individuals ... in treating transient insomnia,” there is no statement or proposal of the drug effectively treating 9 Mitkus, Rajaratnam, and the Specification all appear to describe substantially the same testing of tasimelteon on PER3 genotyped individuals. For example, Mitkus and Rajaratnam both indicate that 288 healthy individuals were genotyped, 212 received tasimelteon (20, 50, and 100 mg), and that 76 individuals received placebo. The Specification also describes testing wherein “288 [individuals] were genotyped for the PER3 VNTR polymorphism” and that the individuals were given either 20, 50, and 100 mg single oral doses of tasimelteon, or a placebo. (Spec. 7.) 10 The inventor, Dr. Lavedan, also confirms that tasimelteon had less effect than placebo on 5/5 patients. (Lavedan Decl. 1 6; see also Ans. 14—15.) 13 Appeal 2016-006278 Application 12/675,614 5/5 individuals. (Mitkus col. 1; see also id. col. 4 (“tasimelteon . . . may have more opportunity to improve symptoms in treating transient insomnia in individuals who carry a PER3 non-5/5 genotype”).) The Specification also provides limited guidance, and no working examples, on effective treatment of insomnia with tasimelteon in individuals with the 5/5 genotype. Like the other evidence (e.g., Mitkus), the Specification shows no significant effect on 5/5 individuals treated with the drug. (See, e.g., Spec. Fig. 3.) Even if the Specification discloses between 10-100 mg/day (or between 10—300 mg/day) as an “effective amount,” such disclosure is, at best, bare-boned and prophetic. Genentech Inc., 108 F.3d at 1366 (Fed. Cir. 1997) (“Tossing out the mere germ of an idea does not constitute enabling disclosure.”) No data is provided to show that insomnia was effectively treated in a 4/4 individual by giving one dose and that a greater dose effectively treated insomnia in another individual with the 5/5 genotype. And, importantly, the evidence of record raises doubt about whether tasimelteon is effective in treating transient or chronic insomnia in 5/5 patients across the broad dosages claimed. In the context of determining whether sufficient utility as a drug, medicant, and the like in human therapy has been alleged, it is proper for the examiner to ask for substantiating evidence unless one with ordinary skill in the art would accept the allegations as obviously correct. . . . [WJhere there is no indication that one skilled in [[the]] art would accept without question statements [[as to the effects of the claimed drug products]] and no evidence has been presented to demonstrate that the claimed products do have those effects, an applicant has failed to demonstrate sufficient utility and therefore cannot establish enablement. 14 Appeal 2016-006278 Application 12/675,614 Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1323 (Fed. Cir. 2005) (internal citations and quotation marks omitted; text within double brackets in original).) Accordingly, given the unpredictability in the art and absence of working examples or sufficient guidance in the Specification, we agree with the Examiner that undue experimentation would be required to make and use the invention’s full scope. (Final Act. 9—12; Ans. 11—16.) Below we address Appellants’ arguments. Appellants argue Rajaratnam and Mitkus are “entirely irrelevant to analysis of the enablement of the claimed invention.” (App. Br. 6.) We disagree. At minimum, the references are relevant to the unpredictability of treating 5/5 patients with tasimelteon. Appellants contend the Examiner is misinterpreting (or confused by) the claims, and “the amount administered to a 5/5 patient need [not] be outside” the range of 10—100 mg/day as recited in claim 10. (App. Br. 6—7.) We addressed Appellants’ claim interpretation contentions above (see Section I), and we agree with Appellants that the amount administered to a 5/5 patient may be within the range of 10-100 mg/day, as long as it is greater than the first effective amount administered to the 4/4 or 4/5 patient. We also agree with the Appellants’ contention that the same individual cannot have both a 4/4 and a 5/5 genotype at the PER3 VNTR locus. (App. Br. 7.) Appellants’ contentions elide, however, the Specification’s deficiencies. In an unpredictable field, the Specification does not enable treatment of 5/5 patients with tasimelteon. Indeed, as explained above, at doses of 20, 50, and 100 mg/day, tasimelteon was less effective than placebo 15 Appeal 2016-006278 Application 12/675,614 for 5/5 patients. (Ans. \5; see also Mitkuspassim.) Appellants provide no persuasive evidence or argument to the contrary. Instead, with respect to treating insomnia in 5/5 individuals, the Specification leaves it to others to design and carry out trials of their own to investigate whether the drug is effective at any dosage. Appellants also contend “Mitkus fully supports the invention claimed.” (Id. at 8.) Appellants cite Mitkus’s teachings related to the effect of tasimelteon on non-5/5 individuals. (Id.) And, Appellants argue, “[i]f the Examiner wishes to allege the conclusions of Mitkus are unsupported, the Examiner should do so” and not “simply substitute her own conclusions for those of the authors.” (Id.) We remain unpersuaded. The issue is not whether Mitkus suggests tasimelteon may provide effective treatment of non-5/5 individuals. It does. But claim 10 is not limited to treating 4/4 or 4/5 individuals. And, it is reasonably clear the Examiner cites Mitkus as illustrating unpredictability of treating insomnia in 5/5 individuals with tasimelteon. (See, e.g., Ans. 12—13 (“It would require further unpredictable and undue experimentation to determine the effective amount and whether treatment should even be provided for the 5/5 genotypes.”) and 14—15 (“Mitkus appears to assert that for 5/5 patients, it is not effective treatment to administer doses of 20, 50 and 100 mg of tasimelteon.”).) Appellants provide insufficient persuasive argument or evidence to rebut the Examiner on this point. For the above reasons, we conclude the preponderance of the evidence supports the Examiner’s rejection of claim 10 as nonenabled. Claims 12, 18, 27, 29, 31, and 32 have not been argued separately and fall with claim 10. 16 Appeal 2016-006278 Application 12/675,614 III & IV - DOUBLE PATENTING All the double patenting rejections rely on the combination of claims (in pending applications or issued patents) with Archer.11 (App. Br. 8—9.) The Examiner cites Archer because “[n]one of the patent applications specifically teach genotyping the PER3 gene first.” (Final Act. 17.) The Examiner finds Archer “teaches one may genotype and then treat subject suffering from a sleep disorder,” and concludes “it would have been obvious to modify the methods of the patents and applications ... to determine whether the subject was homozygous for the PER3 for treatment.” (Id.) Appellants contend the extreme diurnal preference12 taught in Archer has nothing to do with the treatment of insomnia based on a patient’s PER3 genotype. (App. Br. 10.) Appellants contend, by the Examiner’s own interpretation, Archer teaches 4/4 and 5/5 (homozygotic) individuals are treated for extreme diurnal preference in the same manner, and thus Archer “teaches away from the differential treatment of 4/4 and 5/5 individuals claimed by Appellant.” (App. Br. 10—11.) We are unpersuaded the Examiner met the burden to support the double patenting rejections. The Examiner did not provide persuasive, evidence-based reasons for modifying the claims in view of Archer to provide differential treatment of insomnia based on the patient’s genotype. Neither did the Examiner provide a persuasive rebuttal to Appellants’ 11 Appellants’ contention that the “finality” of the double-patenting rejections is “improper” is a petitionable, not an appealable, matter. (App. Br. 8.) 12 Archer defines “extreme diurnal preference” as “an inclination towards an exaggerated sleep pattern.” (Archer 3:29-30.) 17 Appeal 2016-006278 Application 12/675,614 argument that Archer teaches away from differential treatment by disclosing that homozygous individuals should be treated in the same way. (Ans. 17— 18.) So, on this record, we reverse the double patenting rejections. SUMMARY We reverse the rejection for new matter. We affirm the rejection for lack of enablement. We reverse the rejections for double patenting. 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 18 Application/Control No. Applicant(s)/Patent Under Patent Notice of References Cited 12/675,614 Appeal No. 2016-006278 Administrative Patent Judge 1 Timothy G. Majors Art Unit Page 1 of 1 1600 U.S. PATENT DOCUMENTS * Document Number Country Code-Number-Kind Code Date MM-YYYY Name Classification A B C us- D us- E US- F US- G US- H US- 1 US- J US- K US- L US- M US- FOREIGN PATENT DOCUMENTS * Document Number Country Code-Number-Kind Code Date MM-YYYY Country Name Classification N O P Q R S T NON-PATENT DOCUMENTS * Include as applicable: Author, Title Date, Publisher, Edition or Volume, Pertinent Pages) U S. M. Rajaratnam, Melatonin and melatonin receptor agonist tasimelteon for Orcadian rhythm sleep disorders: understanding inter-individual differences in efficacy, Abstract, 20th Congress of the European Sleep Research Society (Sept. 2010) V w X *A copy of this reference is being furnished with the associated Board decision from this appeal.. Dates in MM-YYYY format are publication dates. Classifications may be US or foreign. U.S. Patent and Trademark Office PTO-892 (Rev. 01-2001) Notice of References Cited Part of Paper No. Abstraciverwultung Congrex Page 1 of 1 20th Congress of the European Sleep Research Society Lisbon, Portugal 14.09.2010 - 18.09,2010 Pharmacogenetics of waking and sleep: insights into basic sleep mechanisms and sleep disorders Friday, September 17, 2010. 11:00 - 13:00 Melatonin and the melatonin receptor agonist tasimelteon for Orcadian rhythm sleep disorders: understanding inter-individual differences in efficacy S.M Rajaratnam (Victoria, AU) Objectives Appropriately timed administration of melatonin or its agonists shifts the timing of endogenous circadian rhythms and facilitates sleep, in particular during the biological day when endogenous melatonin is low We evaluated the phase-shifting and sleep-promoting effects of the novel MT1/MT2 melatonin receptor agonist tasimelteon in a paradigm that simulates Circadian Rhythm Sleep Disorders (1). We have also begun to explore whether genetic factors account for individual differences in the sleep-promoting effects of tasimelteon Methods: We undertook two randomised, double-blind, placebo-controlled, parallel-group studies. In the first (inpatient) study. 39 healthy individuals were randomly assigned to tasimelteon (10, 20, 50, or 100 mg) or placebo. Individuals were exposed to a 5-h advance of sleep-wake cycle with treatment before sleep for 3 nights In the second study. 411 healthy individuals had had their sleep-wake cycle advanced by 5-h. with tasimelteon (20, 50. or 100 mg) oi placebo administered before Dedtime. We genotyped 2B8 individuals from the second study. 212 who received tasimelteon and 76 who received placebo. In a preliminary analysis, we assessed Variable Number Tandem Repeats polymorphism of the PER3 gene, a member of the Period family of clock genes. Results: Tasimelteon induced significantly larger phase-shifts in the timing of the endogenous melatonin rhythm compared to placebo. In both studies, tasimelteon improved sleep initiation (sleep latency) and maintenance (wake after sleep onset, sleep efficiency) after the advance of the sleep-wake cycle. Placebo-treated individuals with the PER3 non-5/5 genotype (4/4 and 4/5) appeared to show greater sleep disturbance following the 5-h phase advance than those in with the 5/5 genotype. Tasimeiteon-induced improvements were more prominent (compared So placebo) in individuals with the PER3 non-5/5 genotype Conclusion: Tasimelteon shifts the phase of endogenous circadian rhythms and promotes sleep when it is scheduled to occur at an adverse circadian phase. Ihus facilitating circadian adaptation to a new sleep-wake schedule. Our preliminary analysis shows that individuals with the PER3 non-5/5 genotype show greater response to tasimelteon as compared to placebo, perhaps because the agonist has more opportunity to improve sleep in such individuals due to greater sleep disturbance following the 5-h advance (1) Rajaratnam SM et al Lancet. 2009:373(9662):4B2-91. hUp://registra(ion.akrn.ch/cinsicht.php?XNABSTRACT_ID= 1 15490&XNSPRAC1 1E1D... 12/11/2013 Copy with citationCopy as parenthetical citation