University of Washington through its Center of Commercialization et al.

Patent Trials and Appeals Board

Apr 14, 2021

2020006271 (P.T.A.B. Apr. 14, 2021)

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. 15/188,239 06/21/2016 Alexander Cherkassky NEN-25103/16 5290 37742 7590 04/14/2021 DINSMORE & SHOHL LLP 900 Wilshire Drive Suite 300 TROY, MI 48084 EXAMINER PYLA, PAUL D ART UNIT PAPER NUMBER 1653 NOTIFICATION DATE DELIVERY MODE 04/14/2021 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): MichiganPatTM@dinsmore.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte ALEXANDER CHERKASSKY, JASON COUMOYER, and MICHAEL GELB ____________ Appeal 2020-006271 Application 15/188,239 Technology Center 1600 ____________ Before DONALD E. ADAMS, FRANCISCO C. PRATS, and TAWEN CHANG, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 1, 3, and 5-13 (Appeal Br. 3).2 We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 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 PerkinsElmer Life Sciences, Inc., and the University of Washington through its Center for Commercialization” (Appellant’s April 4, 2020, Appeal Brief (“Appeal Br.”) 3). 2 Pending claims 14-18 stand withdrawn from consideration (Appeal Br. 3). Appeal 2020-006271 Application 15/188,239 2 STATEMENT OF THE CASE Appellant’s disclosure “relates to analytical reagents for detecting enzymatic activity for detecting lysosomal enzyme activity” (Spec.3 ¶ 2). Claim 1 is reproduced below: 1. A method for detecting enzymatic activity, comprising: contacting a sample containing a target enzyme with a composition comprising a first substrate and a second substrate, under conditions wherein the target enzyme is capable of acting on the first substrate or the second substrate to produce an enzymatic product; and detecting said enzymatic product; the first substrate having the formula: where A is a galactose linked to O by a glycosidic bond; B1 is selected from the group consisting of: a C1-C20 alkyl; a heteroatom containing C1-C20 alkyl; C2-C20 alkenyl; a heteroatom containing C2-C20 alkenyl; and a substituted or unsubstituted C6-C20 aryl; B2 is selected from the group consisting of: a C2-C7 urethane; a C2-C7 amido; a C2-C7 ester; a C2-C7 uriedo; a C2-C7 carbamato; a C2-C7 carbonyl; a C1-C7 alkyl; a heteroatom containing C1-C7 alkyl; a C1-C7 alkyl having a substituent of N, O, or S; a C2-C7 alkenyl; a heteroatom containing C2-C7 alkenyl; and a C2-C7 alkenyl having a substituent of N, O, or S; and B3 is selected from the group consisting of: a C1-C20 alkyl; a heteroatom containing C1-C20 alkyl; C1-C20 alkyl having a substituent of N, O, or S; C4-C20 ether; C1-C20 ester; C1-C20 alkenyl; a heteroatom containing C1-C20 alkenyl; 3 Appellant’s June 21, 2016, Specification. Appeal 2020-006271 Application 15/188,239 3 C2-C20 alkenyl having a substituent of N, O, or S; C1-C20 alkynl; a heteroatom containing C1-C20 alkynl; C2-C20 alkynl having a substituent of N, O, or S; C6-C20 aryl; and a C6-C20 heterocyclic containing a heteroatom of N, O or S; and the second substrate having the formula: . (Appeal Br. 16-17 (emphasis added).) Claims 1, 3, and 5-13 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Zhang,4 as evidenced by Ogawa.5 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Zhang discloses “a series of assay mixtures that can be used to determine enzyme activity in an individual. The assay mixtures of the invention include a substrate for the enzyme activity to be tested, an internal standard, detergent, and a buffer” (Zhang ¶ 5; see Ans.6 3, 15 (Examiner finds that Zhang discloses methods of determining the activity of, inter alia, galactocerebroside β-galactosidase and β-glucocerebrosidase); Ans. 9-10 (Examiner finds that Zhang discloses methods, wherein first and second substrates are combined within [its] assay.”)). 4 Zhang et al., US 2008/0248512 A1, published Oct. 9, 2008. 5 Ogawa et al., Synthesis of Potent β-D-Glucocerebrosidase Inhibitors: N- Alkyl-β-Valienamines, 6 BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 929-932 (1996). 6 Examiner’s July 7, 2020, Answer. Appeal 2020-006271 Application 15/188,239 4 FF 2. Examiner finds that Zhang’s method of determining enzyme activity comprising a first substrate, C8 galactosyl ceramide, and a second substrate C12 glucosyl ceramide (see Ans. 4 and 6 (citing Zhang ¶¶ 20, 27, 59, Figs. 1B, 1E)). FF 3. Examiner finds that Zhang’s method differs from Appellant’s claimed method, wherein Zhang’s first substrate, C8 galactosyl ceramide, contains a C8 amido at the B2 position of Appellant’s Formula I instead of “a C2-C7 amido” (Ans. 5). FF 4. Examiner finds that Zhang’s method differs from Appellant’s claimed invention, wherein Zhang’s second substrate, C12 glucosyl ceramide, contains a C12 amido instead of a C5 amido (Ans. 7). FF 5. Zhang discloses that substrates used in [its] activity assays can be the [enzyme’s] natural substrates . . . or can be a modified version of the natural substrate, or a synthetic substrate . . ., [wherein] the substrate[s] . . . are [preferably] synthetic sphingolipids containing N-linked fatty acyl chains that are shorter than the typical natural substrates. (Zhang ¶ 71; see Ans. 13, 15.) FF 6. Examiner finds that Ogawa disclosed the synthesis of β-D- glucocerebrosidase inhibitors, n-alkyl-β-valienamines, that differ with respect to the length of their alkyl chain (see Ans. 17; see generally Ogawa, Title, Abstr.). FF 7. Examiner finds that Ogawa established the alkyl chain length of n- alkyl-β-valienamines define “a pocket of inhibitory activity,” with “an eventual ‘peak’ of activity,” wherein inhibitory activity of n-alkyl-β- valienamines increased as the alkyl chain length increased from, e.g., butyl to decyl, wherein the highest activity was achieved with a decyl chain length Appeal 2020-006271 Application 15/188,239 5 and, thereafter, activity decreased as the alkyl chain length was further increased beyond decyl to tetradecyl (Ans. 17-18 (citing Ogawa 931, Table 1). FF 8. Examiner finds that Ogawa provides teachings that it was known in the art to test for optimal activity via testing different chain lengths across an activity profile, and by changing the chain length, an optimal activity profile can be produced as to what size chain length would have the best activities against the enzyme. (Ans. 18.) FF 9. Appellant discloses “[i]t was unexpected that the short alkyl chain length of particular B2 structures (length of C2-C7) would allow recognition by the desired enzyme with sufficient affinity and turnover rate to be operable” (Spec. ¶ 49; see id. ¶ 113 (Appellant discloses that its second substrate, which contains a C5 amido, provides “a 2-fold improvement in product detection over a similar compound” having a C12 amido.)). ANALYSIS Based on Zhang, as evidenced by Ogawa, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious to “utilize other galactosyl ceramide and glucosyl ceramide substrates similar in structure to the ones above from Zhang,” including those that fall within the scope of Appellant’s claimed invention (Ans. 9). In this regard, Examiner finds that those of ordinary skill in this art would have found it prima facie obvious to optimize substrates utilized in Zhang’s method, by varying the chain length of the substrate’s fatty acid (see Ans. 16-19). As Appellant explains however, Zhang discloses a “C12 glucosylceramide as a substrate used in a method of determining acid Appeal 2020-006271 Application 15/188,239 6 glucocerebrosidase activity” and “reveals that the only reason the glucosylceramide alkyl group chain length was shortened was to ensure that the synthetic substrate was different from the physiological substrate” (Appeal Br. 8-9; see id. at 8 (Appellant contends that Zhang fails to guide one of ordinary skill in this art to the size of a shorted alkyl group chain length and provides “no basis to predict [whether a shortened] . . . substrate would retain binding and functional activity.”); see FF 2, 4, 5). We agree. Zhang directs those of ordinary skill in this art to utilize “synthetic sphingolipids containing N-linked fatty acyl chains that are shorter than the typical natural substrates” and, at best, suggests that a shorter substrate would perform equally as well as the longer natural substrate (see generally FF 5). In contrast, Appellant discloses that it was not only unexpected that short alkyl chain length structures would allow recognition by the desired enzyme with sufficient affinity and turnover rate to be operable, but it was also unexpected that Appellant’s second substrate, which contains a C5 amido, provides “a 2-fold improvement in product detection over a similar compound” having a C12 amido. (FF 9; see also FF 2-4). As Examiner appreciates, Ogawa discloses that the inhibitory activity of n-alkyl-β- valienamines decreased as the alkyl chain length was reduced from, e.g., a decyl to a butyl alkyl chain length (see FF 7; see also Appeal Br. 9-10 (Appellant explains that Ogawa’s “results show that reducing the chain length significantly reduces the ability of the inhibitors to bind . . . [the enzyme] and compete with the natural substrate.”); Appeal Br. 13 (Appellant contends that “Ogawa actually further supports the argument that the claimed C5 glucosylceramide is unexpectedly active for use as a substrate for Appeal 2020-006271 Application 15/188,239 7 the enzyme”); Appeal Br. 12 (Appellant contends that Osiecki-Newman7 provides similar results to Ogawa, wherein shortening a C8- glucosylceramide to a C1-glucosylceramide resulted in a 13-fold decrease in the Vmax of the enzyme assay); Reply Br.8 6). In sum, we agree with Appellant’s contention that “[b]oth Ogawa and Osiecki-Newman demonstrate that [a] skilled person would expect a C5 glucosylceramide to be a functionally inferior substrate . . . relative to [the] C12 substrate taught in Zhang” (Appeal Br. 13). Thus, even if a person of ordinary skill in this art would have been motivated to modify the alkyl chain length of Zhang’s C12 substrate, the evidence on this record supports a finding that a skilled artisan would expect shortening the alkyl chain length to that required by Appellant’s claimed invention would have resulted in a less effective substrate, and would have found Appellant’s “2-fold improvement in product detection [using Appellant’s C5 amido compound] over a similar compound” having a C12 amido unexpected on this record (see FF 6-9; Reply Br. 5 (Appellant contends that it “unexpectedly found that shortening the fatty acid portion of the ceramides by over seven carbons (out of only 12 taught in Zhang for a glucosylceramide, resulted in dramatically improved ability of the substrate to function leading to over two-fold greater activity relative to the Zhang substrate” and that its “claims explicitly recite and require this specific substrate such that the claims are narrowly drawn to the unexpected results exemplified in the specification”)). 7 Osiecki-Newman et al., Human acid β-glucosidase: use of inhibitors, alternative substrates and amphiphiles to investigate the properties of the normal and Gaucher disease active sites, 915 BIOCHEMICA ET BIOPHYSICA ACTA 87-100 (1987). 8 Appellant’s September 4, 2020, Reply Brief. Appeal 2020-006271 Application 15/188,239 8 For the foregoing reasons, we are not persuaded by Examiner’s assertion that “[t]he structures are so similar in the art to that of the instant claims that a person of ordinary skill in the art would test fatty acid chain lengths from C12 down to C4 to find the optimal chain length needed to maximize the enzymatic activity” (Ans. 21). For the same reasons, we are not persuaded by Examiner’s assertion that “Appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art” (id. at 13). CONCLUSION The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness. The rejection of claims 1, 3, and 5-13 under 35 U.S.C. § 103(a) as unpatentable over Zhang, as evidenced by Ogawa, is reversed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 3, 5-13 103 Zhang, Ogawa 1, 3, 5-13 REVERSED