2021000348 (P.T.A.B. Sep. 8, 2021)

Vidasym, Inc.

Patent Trials and Appeals BoardSep 8, 2021

2021000348 (P.T.A.B. Sep. 8, 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. 15/948,359 04/09/2018 Megumi Kawai 0412.01PCT-USC 7817 25871 7590 09/08/2021 ADSERO IP LLC 8210 SOUTHPARK TERRACE LITTLETON, CO 80120 EXAMINER BADIO, BARBARA P ART UNIT PAPER NUMBER 1628 NOTIFICATION DATE DELIVERY MODE 09/08/2021 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): efspatents@sbiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte MEGUMI KAWAI Appeal 2021-000348 Application 15/948,359 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, RYAN H. FLAX, and DAVID COTTA, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL The Examiner rejected claims 1, 2, 4, and 6–18 under 35 U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject the claims. 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 Vidasym, Inc. Appeal Br. 3. Appeal 2021-000348 Application 15/948,359 2 STATEMENT OF THE CASE The Examiner rejected claims 1, 2, 4, and 6–18 in the Final Action under pre-AIA 35 U.S.C. 103(a) as obvious in view of Von Geldern et al. (US 8,377,913 B2, issued Feb. 19, 2013) (“Von Geldern”). Final Act. 2. Claim 1, the only independent claim on appeal, is directed to a compound of Formula (I). The complete structure is in the appendix to this Decision (from the Claims Appendix in the Appeal Brief; annotated to show positions C2, C10, C20 of the Formula (I) compound). The Formula (I) compound is a vitamin D3 derivative and is described in the Specification as a vitamin D receptor (VDR) agonist. Spec. ¶¶ 2, 5, 6. The endogenous VDR agonist is 1,25-dihydroxyvitamin D3, also known as calcitriol. Id. at ¶ 2. Calcitriol functions by activating VDR. Id. “The activated VDR recruits cofactors to form a complex that binds to vitamin D response elements in the promoter region of target genes to regulate gene transcription.” Id. This appeal is related to Appeal 2017-003708 in Application Serial No. 13/264,280 (“the ’280 application”). A decision in that appeal was entered Oct. 31, 2017, in which the Examiner was affirmed-in-part. DISCUSSION Claim 1 is directed to a compound of Formula (I). The structural features of the compound focused on in this appeal comprise =CH2 (methylene) (the R1 group) at position C2, the “unnatural” bond orientation at the C20 position, and oxygen (–O–) at the X-position in the side chain attached to C20. The C20 position of the compound is a stereo center in which the side chain directly connected to it can be in two orientations. The Appeal 2021-000348 Application 15/948,359 3 two orientations are referred to as “the natural isomer” and “the unnatural isomer.” All the compounds within the scope of claim 1 are the unnatural isomer. Appeal Br. 10 (also called “epimer”). The Examiner found that Von Geldern describes a genus of compounds that encompass a compound with =CH2 at R1, the “unnatural” C20 epimer, and oxygen (–O–) at the X-position of the C20 side-chain, making it obvious to make a compound with each of these features. Ans. 3– 5; Final Act. 5. Appellant argues that it would not have been obvious to make an unnatural epimer with an –O– in the side chain because no predictable results can be derived from Von Geldern. Appeal Br. 12, 16. Appellant asserts that its compounds “possess consistent, unexpectedly superior potency in activating VDR.” Id. at 12. In making its argument, Appellant cites to the Manual of Patent Examining Procedure (“MPEP”) where obviousness is discussed. Appeal Br. 13–15. Specifically, Appellant reproduces statements in the MPEP that “combining known prior art elements is not sufficient to render the claimed invention obvious if the results would not have been predictable to one of ordinary skill in the art,” the requirement to establish a “reasonable expectation of success” in combining references to achieve the claimed invention, and “whether the proposed modification or combination of the prior art has a reasonable expectation of success is determined at the time the invention was made.” Appeal Br. 14–15 (emphasis omitted). Appellant does not clearly identify what the “reasonable expectation of success” and “predictability” relate to, but in view of their arguments about the predictability of the activity of the compounds in Von Geldern in activating Appeal 2021-000348 Application 15/948,359 4 the vitamin D receptor (“VDR”), we understand their argument to be that it would be unpredictable that its unnatural C20 epimers with an –O– group in the side-chain would possess improved VDR affinity. See Appeal Br. 18. As explained in the MPEP, when “there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success.” MPEP 2143.02 (citing In re Merck & Co., 800 F.2d 1091 (Fed. Cir. 1986) (Ninth Edition, Revision 10.219, Last Revised June 2020). The Examiner found a reason to make a compound in the scope of Formula (1) because Von Geldern describes a genus which encompasses the claimed compound, making it obvious to select any of the species of the genus. Final Act. 5. The Examiner found that Von Geldern further teaches that its compounds include both stereoisomers when asymmetric or chiral centers are present. Final Act. 14 (citing Von Geldern 16:14–39). The C20 position of Formula (I) is one such center. The Examiner also found that Von Geldern describes an example in which the C20 unnatural epimer retains activity and is, in some cases, superior to calcitrol. Final Act. 5. The Examiner thus concluded that “the skilled artisan would have the reasonable expectation that both isomers would be useful.” Final Act. 5. Appellant did not identify a defect in the Examiner’s reasoning for finding it obvious to have made the structure of a Formula (I) with the C20 unnatural epimer and the –O– in the C20 side-chain. Appellant’s principal arguments have to do with the unpredictability of such a compound’s activity and the lack of reason to make it. Appeal 2021-000348 Application 15/948,359 5 To begin, we find that the Examiner provided sufficient reason to make C20 epimers, namely because of the statement in Von Geldern that its compounds “may exist as stereoisomers wherein asymmetric or chiral centers are present” (Von Geldern 16:14–15) and Example 3, the disclosure of a compound2 having the unnatural epimer at C20 (id. 36:25–40). Because Von Geldern provides a reason to have made the unnatural epimer, we look for some teaching away from making an unnatural epimer at C20, evidence that such an unnatural epimer would not have had activity, and/or evidence of unexpected results. In making this determination, we note that claim 1 does not require the Formula (I) compound to possess an activity of a certain type or have a specific amount of activity. As indicated by Appellant, Von Geldern only makes one unnatural epimer that is described in Example 3. This compound has a =CH2 group at C2 and an –O– in the side chain attached to the C20 of the unnatural C20 epimer. Von Geldern 36:35–45. This compound has activity as shown in Tables 1, 2, and 3 reproduced below: 2 We refer to the compounds made in Von Geldern by their example number, such as Example 1, Example 2, Example 3, etc. Appeal 2021-000348 Application 15/948,359 6 Table 1 shows binding of compounds to VDR, the vitamin D receptor. Von Geldern 82:21–24. Table 2 shows the ability of compounds to activate the vitamin D response element (VDRE). Von Geldern 83:10–25. Binding of the compound to VDR causes the receptor to form a complex that binds to VDRE and regulate gene transcription. Von Geldern 1:30–39 (see Fig. 1). Table 3 shows the activity of compounds to elicit differentiation of HL-60 cells which involves the signaling pathways affected by vitamin D receptor activators/agonists. Von Geldern 21:39–43, 54–55. As indicated by Tables 1–3, although Example 3 has less activity than the natural epimer of Example 1 in the three different assays, it is more potent that the control calcitriol in activating VDRE (compare 0.9 to 5.9 in Table 2) and in eliciting HL-60 differentiation (compare 3.9 to 7 in Table 3). It is less potent than calcitriol when direct binding to the receptor is measured (compare 1334.5 to 0.03 in Table 1). Calcitriol is the active hormone 1,25-dihydroxyvitam D3 which binds the nuclear VDR. Von Geldern 1:30–39. Example 3 is also more potent than the natural epimer Example 2 in the two assays described in Tables 2 and 3 (compare 0.9 to Appeal 2021-000348 Application 15/948,359 7 52.7 in Table 2 and 3.9 to 162.0 in Table 3). All the assays require the compound to bind to VDR, but only the first assay summarized in Table 1 measured direct binding to the receptor. While these assays show that different vitamin D analogs have different activity, the unnatural epimer still possessed activity in all three assays, and even had more activity than the natural epimer in some cases. Thus, one of ordinary skill in the art would not have been dissuaded from making an unnatural epimer based on this evidence alone. Appellant’s argument that the activity of Example 3 does not show a “consistent trend” in the various assays is not persuasive because it is active in all assays and the claim does not require any specific level of activity. The ordinary artisan would reasonably expected based on the evidence from Tables 1–3 that an unnatural epimer with a C20 side-chain comprising –O– would have VDR activity.3 Appellant’s argument about lack of predictability addresses only the specific level of activity and the claim has no requirement of a specific amount of activity as long as the compound is active. In an attempt to show “unpredictability,” Appellant points to further evidence that: (1) unnatural C20 epimers with –O– have less activity than the natural epimers (Appeal Br. 20); (2) modifying the position of the methylene group =CH2 had an unpredictable impact on activity in the VDR reporter gene assay (Appeal Br. 16–17); and (3) a natural epimer with =CH2 and –O– compounds is less potent and even inactive as compared to the unnatural epimer and calcitriol (Appeal Br. 17–18). 3 By VDR activity, we mean any activity that begins with binding to VDR, including measurements made by direct binding to the receptor and the downstream effects of binding, such as VDRE activation, HL-60 differentiation, gene expression, etc. Appeal 2021-000348 Application 15/948,359 8 With respect to the activity of unnatural epimers (argument (1) above), Appellant cited data from the Yamada4 and Shimizu5 publications that “when the natural and unnatural epimers at the C20 position with –O– in the side chain are compared, . . . the unnatural epimers at the C20 position with –O– in the side chain exhibit inferior potency ranging from a few fold to ~100-fold weaker activities.” Appeal Br. 20. For this reason, Appellant contends that there would be no reason to make the unnatural epimer. This argument does not persuade us that the Examiner erred. The activity of natural and unnatural C20 epimers from Yamada/Shimizu is summarized in Table 1 of the Appeal Brief. Appeal Br. 20. Appellant did not provide evidence establishing which of these compounds, if any, fall within the scope of claim 1. For example, the compound of Formula (1) comprises R1 is =CH2 or cyclopropyl at C2. The structures provided by Appellant of the compounds listed in Table 1 of the Appeal Brief appear to have a different R1 group than the R1 group of the claimed compounds. See Response of Dec. 21, 2018 at 25 showing the structures of the compounds listed in Table 1; referenced in Appeal Br. 20. This difference is significant because Shimizu discloses that its experiments evaluated the “structure- activity relationships” of the side chain structure of various vitamin D analogs by varying them. Shimizu, Abstract. In other words, the combination of the specific R1 group side chain and –O– substituent of the unnatural epimer in Yamada/Shimizu may have had less activity than a compound with the same side chains, but in the natural epimer 4 Yamada et al., EP 1 559 708 A1, published Aug. 3, 2005. 5 Masato Shimizu et al., Synthesis and biological activities of new lrt,25- dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain, 14 Bioorganic & Medicinal Chemistry 4277–94 (2006). Appeal 2021-000348 Application 15/948,359 9 configuration, this pattern of activity might not be representative of the structures encompassed by Formula (I), particularly where R1 at C2 is =CH2. Indeed, as discussed below, the evidence provided by Appellant shows an advantage of a =CH2 group at R1. Appellant has given no reason as to why a person of ordinary skill in the art would have relied upon a different structure of a vitamin D analog as predictive of the activity of the claimed Formula (I) compounds. In addition to this, to the extent that the unnatural epimers are less active than the natural epimers, we have not been pointed to a teaching in either Von Geldern, Yamada, or Shimizu that unnatural epimers lack activity. “[A] known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). A “finding that the prior art as a whole suggests the desirability of a particular combination need not be supported by a finding that the prior art suggests that the combination claimed by the patent applicant is the preferred, or most desirable, combination.” In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004). Thus, even if the unnatural epimer is not preferred and has no advantage over the natural epimer, the teaching by Von Geldern that its compounds can be stereoisomers, and the manufacture of an active unnatural C20 epimer (Example 3), provides a reason to have made other unnatural epimers. Both Von Geldern and Yamada show that such epimers are active and therefore “operable” compounds. “[A] reference may teach away from a use when that use would render the result inoperable.” In re ICON Health and Fitness, Inc., 496 F.3d 1374, 1381 (Fed. Cir. 2007). Appeal 2021-000348 Application 15/948,359 10 In its second argument, Appellant argues that modifying the position of the methylene group =CH2 had an unpredictable impact on activity in the VDR reporter gene assay (Appeal Br. 16–17). Appellant specifically cites the data in Von Geldern reporting the effect of a compound, the VDR reporter gene. Table 2 is reproduced below: The table reproduced above shows that Example 7 has higher activity than Example 9 (compare 12.2 to >10,000). The table also shows that Example 10 has similar activity to Example 11 (compare 149.2 to 181.8). Appellant states that the structures of Examples 7 and 9 only differ by the =CH2. In Example 7, the =CH2 group is on the C2 position, while it is absent in Example 9. Appeal Br. 16–17. Appellant states that structures of Examples 10 and 11 only differ by the =CH2 group, where the =CH2 in Example 10 is on the same ring as in Example 7, but at different position, C10, and in Example 11 the =CH2 is absent at C10. Id. Appellant argues that “[t]he removal of the methylene group from the A-ring of Example 7 to Appeal 2021-000348 Application 15/948,359 11 make Example 9 changed the activity in the VDR reporter gene assay from 12.2 nM to >10,000 nM (a change of~ 1,000-fold), while a similar modification on the A-ring of Example 10 to make Example 11 (resulting in a A-ring identical to that in Example 9) did not have any significant impact (149.8 nM vs. 181.8 nM).” Id. First, none of these compounds have an –O– at the same position as the claimed compounds and none are the unnatural epimer. The Examiner also pointed to additional structural differences between the compounds. Ans. 7. Second, Examples 7 and 9 show that placement of the =CH2 at C2 (the same position and group covered by the claimed Formula (I) compound) had a beneficial effect on activity (compare 12.2 to >10,000), providing a reason to have selected it to have arrived at a compound within the scope of claim 1. In fact, the Examiner identified a compound having a =CH2 group at this position as the closest prior art. Ans. 8. Appellant’s comparison of the effect of =CH2 group position in Examples 7 and 9 as compared to Examples 10 and 11 has little weight because such compounds are significantly different in structure from each other and from the claimed compounds. In particular, the =CH2 group is at different positions in Examples 7/9 and 10/11, the claimed –O– in the C20 side-chain is not present in any of Examples 7, 9, 10, and 11, and none of Examples 7, 9, 10, and 11 are the unnatural epimer. All Appellant has shown by this comparison is that varying the structure of a compound affects binding to the VDR and provides evidence of the relationship between structure and function, a well-established principle in medicinal chemistry as illustrated by Shimizu. Appellant seeks to use a comparison from the data Appeal 2021-000348 Application 15/948,359 12 from Examples 7 and 9 to data from Examples 10 and 11, but ignores their significant structural differences. We next address Appellant’s third argument that the evidence shows unpredictably because a natural epimer with =CH2 and the –O– side chain is less potent and even inactive as compared to the unnatural epimer and calcitriol. The argument is based on Example 12 of Von Geldern. Von Geldern’s Example 12 is a natural C20 epimer having an –O– in the side chain attached to C20 and =CH2 at the C2 position. Von Geldern describes Example 12 as being less potent than calcitriol in the VDR reporter gene assay (compare 16.9 to 5.9), more potent in eliciting HL=60 differentiation (compare 0.2 to 7), and more potent in a renin mRNA assay (compare 0.2 to 1.6). Appellant, however, provides data in the Specification and the Wu-Wong Declaration6 using Vida-36, which they state is the same compound as Example 12, that Vida-36/Example 12, is 1,000-fold less potent in their own assay and the assay performed in the Wu-Wong declaration. Appeal Br. 17. First, none of the data from their own Specification and the Wu-Wong declaration are prior art, and thus do not bear on the issue of the expectation of success of whether an unnatural C20 epimer having –O– in the side chain attached to C20 and =CH2 at the C2 position would be active. Second, to the extent there is discrepancy in the data, Appellant has not provided evidence that it would undermine or discredit the rest of the data reported in Von Geldern. While Appellant made such an argument in the appeal relating to 6 Declaration under 37 C.F.R. § 1.132 by Jinshyun Ruth Wu-Wong (dated Dec. 4, 2018). Dr. Wu-Wong is a co-inventor of Von Geldern and an employee of the real party in interest of the instant application. Appeal 2021-000348 Application 15/948,359 13 the ’280 application, such argument has not been made here. Thus, we do not see the relevance of this so-called “Data discrepancy” 7 to the obviousness of the claimed subject matter.8 Appellant also argues that Von Geldern shows that making the unnatural epimer involves tedious separation steps, “which adds another level of difficulty (vs. making the natural epimer).” Appeal Br. 19. Appellant also argues that this points in the opposite direction to making the unnatural epimer, given that there is no advantage to it. As to the asserted difficulty in making the unnatural epimer, Von Geldern describes making compounds with asymmetric or chiral centers, and discloses that separation can be accomplished “by preparation of racemic mixtures followed by resolution well-known to those of ordinary skill in the art.” Von Geldern 16:27–29. Appellant did not provide evidence that preparing a compound within the scope of the claim is difficult, that it required undue experimentation, or there were repeated failures before it worked. Cf. Forest Laboratories, Inc. v. Ivax Pharmaceuticals, Inc., 501 F.3d 1263 (Fed. Cir. 2007) (nonobviousness of a purified enantiomer shown by evidence of failure to resolve the compound and unexpected results). This argument is therefore unavailing. 7 Dr. Wu-Wong is a co-inventor of Von Geldern, but doesn’t explain the discrepancy between the Von Geldern data and her own data in the declaration. 8 Dr. Wu-Wong obtained the results using a CHO-K1 and a GAL4-VDR chimeric receptor containing the VDR ligand binding domain and the (UAS)4-alkaline phosphatase gene. Wu-Wong Decl. ¶ 4. The reporter gene assay described in Von Geldern uses a different cell line (HEK) and vitamin D response element linked to the reporter gene. Von Geldern 83:10–17. The experiments are therefore not comparable. Dr. Wu-Wong also performed a cell differentiation assay using HL-60 cells. Appeal 2021-000348 Application 15/948,359 14 Appellant contends that its data shows that “the claimed compositions possess consistent, unexpectedly superior potency.” Appeal Br. 12. As evidence, Appellant points to the data in Example 83, Table 3 and Example 85, Table 4 of the Specification, and the data in the Wu-Wong Declaration. Appeal Br. 21. Table 3 of the Specification shows the results of an experiment in which the ability of a compound to induce gene expression in HL-60 cells was tested. Spec. ¶ 311. The genes measured were CYP24A1 and CD14. Spec. ¶ 312. The measurements were made by using PCR to quantitate the mRNA expressed from these genes. Spec. ¶ 313. The results in Table 3 are described in the Specification as showing “that the test compounds activate VDR, leading to the modulation of VDR target genes such as CYP24Al.” Spec. ¶ 314. Table 4 shows the results of an experiment using human coronary artery smooth muscle cells to test the potency of compounds in inducing the expression of CYP24A1 and VDR. Spec. ¶¶ 319, 320. Gene expression was quantitated using PCR. Spec. ¶ 323. A summary of the results of four compounds is shown. Spec. ¶ 324. The Specification comments on only one of the compounds, Vida-5, which is one of the compounds in the scope of Formula (I) (see claim 12): The results show that Vida-5 is potent in inducing CYP24Al expression with an EC50 at 2.9 nM. Fig. 5B shows the result from a typical VDR expression study. The results show that Vida-5 is potent in inducing VDR expression with an EC50 at 1.3 nM. Spec. ¶ 323. “One way for a patent applicant to rebut a prima facie case of obviousness is to make a showing of ‘unexpected results,’ i.e., to show that Appeal 2021-000348 Application 15/948,359 15 the claimed invention exhibits some superior property or advantage that a person of ordinary skill in the relevant art would have found surprising or unexpected.” In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). Soni further explained “when an applicant demonstrates substantially improved results . . . and states that the results were unexpected, this should suffice to establish unexpected results in the absence of evidence to the contrary.” Soni, 54 F.3d at 751. In this case, Appellant has not provided a statement by the inventors or one of ordinary skill in the art that the results are “unexpected” or even superior. Appellant does not guide us to a statement in the Specification or Wu-Wong declaration that the results are a substantial improvement and unexpected. Dr. Wu-Wong states in the declaration that “the compounds claimed in the current application exhibit potency better than or similar to the positive control, calcitriol” with respect to the VDR transcriptional assay, but does not describe the results as unexpected. Wu-Wong Decl. ¶ 3. While Appellant made such a statement in the Appeal Brief, it is not sufficient: An applicant cannot prove unexpected results with attorney argument and bare statements without objective evidentiary support. See In re Lindner, 59 C.C.P.A. 920, 457 F.2d 506, 508 (CCPA 1972); In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (“attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness”); In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995) (“It is well settled that unexpected results must be established by factual evidence. Mere argument or conclusory statements ... [do] not suffice.”) (quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)). CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003). Thus, under CFMT, the unexpected results are legally insufficient. Appeal 2021-000348 Application 15/948,359 16 The results are also insufficient because they have not been compared to the closest prior art. “[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). Appellant reports data in the Specification for unnatural epimers, as discussed above, but it has not been explained whether any of the compounds tested are representative of Von Geldern. Similarly, the data in Dr. Wu-Wong’s declaration is compared to calcitriol, but it does not appear that any of the Von Geldern compounds were tested. The reason this comparison is necessary is because the compounds must be substantially better than the prior art to demonstrate that their activity is not predictable. Without this comparison, it cannot be determined whether the asserted improvement in activity is any better than the activity of the prior art. In Dr. Wu-Wong’s declaration, all the compounds in the table are stated to be “compounds claimed in the current application,” and not any are said to be part of the prior art. Wu-Wong Decl. ¶ 3. Unexpected results must also be “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005). Here, we have not been guided to evidence that the compounds tested are representative of the genus which is claimed, or even of a smaller genus of claimed compounds. Testing several species in the scope of claim 1 (Wu-Wong Decl. ¶ 3), does not necessarily establish that all the compounds in the claims genus would have the same activity. As indicated by Shimizu, it is known that varying the structure of a compound can change its activity. Therefore, when the claim encompasses a genus of compounds as it does here, with different side chains, Appellant Appeal 2021-000348 Application 15/948,359 17 has the burden to show that they all possess the activity asserted to be unexpected and superior.9 As this was not demonstrated, we find the results are not commensurate with the scope of the claim. For the foregoing reasons, the rejection of claim 1 is affirmed. Claims 2, 4, and 6–18 were not argued separately and fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv), CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 2, 4, 6–18 103 Von Geldern 1, 2, 4, 6–18 TIME PERIOD 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 9 This analysis is different when demonstrating the obviousness of the genus because a claim is unpatentable under § 103 if any compound within the genus would have been obvious to the person of ordinary skill in the art at the time of the invention. See In re Klein, 987 F.2d 1569, 1570 (Fed. Cir. 1993); In re Muchmore, 433 F.2d 824, 826 (CCPA 1970).