DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 2, 4, 6, and 12-23 are pending in this application. Claims 1, 3, 5, and 7-11 have been cancelled by Applicant.
Claim Objections
Claim 2 is objected to because of the following informalities: the structure
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is blurry and difficult to read.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 2, 4, 6, 12-19, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2020/147798 A1 – Int. Filing Date: Jan. 16th, 2020 – cited in IDS – previously cited) (“Wang”).
Regarding instant claims 2, 4, 12-19, and 22-23, Wang discloses their compounds of Formula A as BTK inhibitors (page 1 of translated doc.; and Abstract) – which is the same intended use as the instant application. Wang’s compounds read on the instant claims when A-B fused ring system is
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(page 3, lines 8-9); and wherein L-1-Cyc1-L2-Cyc2 is
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or
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(page 2, lines 25 and 30), as in their preferred embodiments of Formula B and C below, which read on instant X being
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. Also, embodiments where instant X is
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and
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are obvious, since compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09.
Furthermore, Wang specifically discloses their
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in Formulae B and C can be
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(page 4, lines 6-10). Wang also teaches their R12-15 can be H, halogen, substituted or unsubstituted C1-C6 alkyl, etc. (page 2, bottom, of translated doc.).
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(B)
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(C)
Wang specifically discloses their preferred embodiment 30 below (page 60), which reads on the instant compounds when n = 1; X is -O-; R6 is H; and R8 is F, -OMe, and H. While Wang’s preferred embodiment differs in the arrangement of the nitrogens of the bicyclic core, Wang specifically discloses their A-B fused core can be
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(page 3, lines 8-9), which corresponds to the core of the instant compounds when R1 is amino and R2 is H.
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(30)
Regarding claim 2, while the instant compounds require m to be 1 or 2 – Applicant is advised that the courts have found that Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). Therefore, the instant compounds are still obvious for embodiments where m = 1.
Therefore, regarding claims 2, 4, 12-19, and 22-23, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Wang’s disclosed formulae and preferred embodiments; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of BTK inhibitor compounds disclosed by Wang. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Further regarding claim 4, at least the compound below, is still obvious in view of Wang’s disclosure.
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Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding claim 6, Wang discloses pharmaceutical compositions comprising their compounds and an acceptable carrier (page 7, line 9 of translated doc.).
Claims 2, 4, 6, and 12-23 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2020/147798 A1 – Int. Filing Date: Jan. 16th, 2020 – previously cited) (“Wang”); as applied to claims 2, 4, 6, 12-19, and 22-23; in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591 – previously cited) (“Meanwell”).
The teachings of Wang are disclosed above and incorporated herein.
While Wang does not teach their compounds wherein R9 and R13 are H; the teachings of Meanwell are relied upon for these disclosures.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell teaches -O- and -CH2- as classical divalent bioisosteres (Table 1).
Therefore, regarding claims 2, 4, and 12-23, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Wang’s disclosed formulae and preferred embodiments in view of Meanwell. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of BTK inhibitor compounds disclosed by Wang; in view of Meanwell’s teachings that the design of bioisosteres leads to optimization of lipophilicity, potency, etc. in lead compounds and drugs. Accordingly, one having ordinary skill in the art would have been motivated to replace the -O- in Wang’s compounds for
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, wherein R9 and R13 are H to arrive at the instant invention.
Further regarding claim 4, the compound below, for example, is still particularly obvious in view of Wang’s disclosure, since their R12-13 (corresponding to instant R8) can be H.
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Regarding claim 6, Wang discloses pharmaceutical compositions comprising their compounds and an acceptable carrier (page 7, line 9 of translated doc.). Therefore, it would have been obvious to one of ordinary skill to prepare pharmaceutical compositions comprising the instant compounds in which X is
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.
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Applicant has failed to acknowledge the objection to claim 2, therefore, the claim objection is maintained herein.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 07/20/2026 have been fully considered but they are not persuasive.
Applicant argues amendments to claim 2 requires instant compounds to be bridged, which is not a feature disclosed by Wang or Meanwell. Applicant states bridged structures can lead to different properties and that one of ordinary skill would not have been motivated to make the modifications required to arrive at the instant compounds and that ‘existing technologies lack a reasonable expectation of success.’ Applicant cites case law and highlights the following:
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Applicant further argues the instant compounds have been demonstrated to have ‘particularly good BTK kinase inhibitory effects’. Applicant points to results from the spec to say that compounds from claim 4 have particularly advantageous BTK inhibitory activity – see results for compounds 5 and 106 below, for example, taken from the spec. (Table 15, page 115).
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wherein A means ≤ 5 nM activities.
Wang discloses their compound 30, which was cited in the rejections herein, has the following activities: (see page 66 of Wang).
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As can be seen from this data, Wang’s compound has similar activities of ≤ 5 nM. Therefore, Applicant’s arguments regarding unexpected results are not persuasive.
Regarding Applicant’s arguments that ‘bridged structures can lead to different properties’. Applicant needs to demonstrate this with more than mere statements. Wang’s data shows similar properties as the instant compounds regardless of bridge moiety. Furthermore, Applicant is reminded, the courts have found that Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Wang discloses their compounds of Formula A as BTK inhibitors (page 1 of translated doc.; and Abstract) – which is the same intended use as the instant application. Wang’s compounds read on the instant claims when A-B fused ring system is
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(page 3, lines 8-9); and wherein L-1-Cyc1-L2-Cyc2 is
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or
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(page 2, lines 25 and 30), as in their preferred embodiments of Formula B and C below, which read on instant X being
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and
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are obvious, since compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Furthermore, Wang specifically discloses their
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in Formulae B and C can be
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(page 4, lines 6-10). Wang also teaches their R12-15 can be H, halogen, substituted or unsubstituted C1-C6 alkyl, etc. (page 2, bottom, of translated doc.).
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(B)
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(C)
Wang specifically discloses their preferred embodiment 30 below (page 60), which reads on the instant compounds when n = 1; X is -O-; R6 is H; and R8 is F, -OMe, and H. While Wang’s preferred embodiment differs in the arrangement of the nitrogens of the bicyclic core, Wang specifically discloses their A-B fused core can be
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(page 3, lines 8-9), which corresponds to the core of the instant compounds when R1 is amino and R2 is H.
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(30)
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Wang’s disclosed formulae and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of BTK inhibitor compounds disclosed by Wang. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Therefore, Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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