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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/13/2026 has been entered.
Status of Claims
Claims 1-9 and 15-22 are pending.
Priority
Instant application 18/173,979, filed 02/24/2023, claims priority as follows:
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Response to Amendment/Arguments
The amendment filed 01/13/2026 has been entered. Applicant has amended claims 1 and 17.
Claims 1-3, 5, 7, 9, 17, and 22 were previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by Malamas et al. In response, applicant’s amendments have overcome the rejection. Therefore, the previous rejection under section 102 over Malamas is withdrawn.
Claim Rejections - 35 USC § 102 - New
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 17 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hamiaux et al. (Biochemical Journal, vol. 476, no. 12, June 2019, pp. 1843–56).
Hamiaux discloses the compounds 5, 7, and 8 (page 1845, Figure 1):
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Hamiaux’s compounds 5, 7, and 8 anticipate Formula I in claim 17 when X, X1, X2, and X3 are each CH; Y1 is NR5; R1 is substituted C6 aryl, substituted with a halogen substituent (Cl) and/or a methyl substituent; R2 and R3 are each H; and R5 is H.
For claim 22, Hamiaux discloses a composition comprising compound 5, 7, or 8 and a pharmaceutically acceptable carrier (page 1848, “compound stocks were prepared at 10x final concentration in 20mM Tris…”).
Therefore claims 17 and 22 are anticipated by Hamiaux.
Claims 17 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vizgunova et al. (Pharmaceutical Chemistry Journal, vol. 20, no. 9, Sept. 1986, pp. 614–17).
Vizgunova discloses the compound Va (page 614, bottom scheme):
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Vizgunova’s compound anticipates Formula I in claim 17 when X, X1, X2, and X3 are each CH; Y1 is NR5; R1 is substituted C6 aryl, substituted with OZ1; R2 is H; R3 is C3 alkyl; R5 is H; and Z1 is methyl.
For claim 22, Vizgunova discloses a composition comprising the compound and a 2% starch mucilage, and administering the composition intraperitoneally (page 616, 5th para.)
Therefore claims 17 and 22 are anticipated by Vigzunova.
Double Patenting - Maintained
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-9, and 15-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 17-18 of copending Application No. 18/247,007 (reference application) in view of Castro et al. (WO 2020243423 A1) and Liang et al. (WO 2023016562 A1)
The reference application is drawn to tetrahydroquinoline derivatives as inhibitors of YAP/TAZ-TEAD, and recites compounds having the general formula (claim 1):
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The reference application recites (claim 10) particular compounds of Table 1 which include the compound 002 having the structure:
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, compositions thereof (claim 11) and recites methods of preventing or treating YAP/TAZ-TEAD activation comprising administering a compound of the claims and further comprising administering EGFR, MEK, AXL, B-RAF, and RAS inhibitors (claims 17-18).
The only difference between the reference application’s compound 002 and instant compound 7 is the presence of an oxo group at the 4-position of the tetrahydroquinoline ring.
A prima facie case of obviousness may be made when chemical compounds have very close structural similarities (e.g. homologs, analogues, and isomers) and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See MPEP 2144.09.
In the instant case, the reference application’s compounds, such as compound 002, are analogs sharing substantial structural similarity to compounds recited by the instant claims 1, 3-9, 17, and 22. Moreover, the claims of the reference application recite administering the compounds therein to inhibit YAP/TAZ-TEAD, which is the same utility as the instantly claimed compounds.
Castro is relied upon to show that TEAD inhibitors have been disclosed before having similar structure to the compounds in the reference application. Castro discloses, for example, compounds of the Formula VIIb (page 65, [00189]):
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Further, Castro discloses compounds exhibiting TEAD inhibitory activity such as (Table 1, para. [00206]):
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;
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Despite the substitution of the 4-position in Castro’s I-68, the compound exhibited TEAD inhibitory activity (para. [00871], Table 2]). Accordingly, Castro provides a teaching that substituting the 4-position in the reference application’s compound(s) would have resulted in compounds having the same utility.
Liang is relied upon to show that TEAD inhibitors comprising a quinolinonyl motif are not new. Liang is drawn to TEAD inhibitors for use in regulating and treating diseases caused by abnormal activity of YAP/TEAD (abstract). In particular, Liang discloses compounds such as (page 12):
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Liang’s compounds comprise an oxo group at the same position of Applicant’s compound 002. Additionally, such compounds, such as T-5 and T-6, exhibited YAP-TEAD IC50 values of <1 uM according to the Table on pages 117-118. Accordingly, Liang provides evidence that s person having ordinary skill in the art would have reasonably expected that substituting the 4-position in the reference application’s compound(s) with an oxo group would have resulted in compounds having the same utility.
Therefore, in view of the foregoing, claims 1, 3-9, and 15-22 are prima facie obvious in view of the reference application, Castro, and Liang.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant argues that the combination of the cited references does not teach or suggest the presently claimed compounds. Applicant states that there is nothing in the reference application or Castro to motivate adding an oxo group at the 4-position of the tetrahydroquinoline ring. Applicant states that while Liang’s compounds have an oxo group at the 4-position, the ring also has a double bond in the quinolinone ring, which is not present in the claimed compounds.
Applicants’ arguments have been fully considered but are not found persuasive.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
As noted in the rejection, Castro demonstrates that substitution at the 4-position of the tetrahydroquinoline ring system does not preclude TEAD inhibitory activity. Further, Liang demonstrates that compounds with 4-oxo substitution possess TEAD inhibitory activity. While Liang’s compounds also possess a double bond in the ring, the reference application and Castro suggest that the double bond need not be present to achieve TEAD inhibitory activity.
Applicant additionally argues that there is nothing in US ‘007 that would motivate a person of ordinary skill in the art to specifically select compound 002 cited by the examiner for further investigation. Applicant states that compound 002 is not necessarily the “most” promising compound disclosed in the reference application.
Applicants’ arguments have been fully considered but are not found persuasive.
With respect to the argument that the reference application does not “otherwise suggest that [Compound 002] provides any benefit or special property as compared to the many other compounds within the scope of the reference’s disclosure”, please note that the reference application discloses that compound 002 possesses inhibitory activity in the sub-micromolar (i.e., nanomolar) range. See Table 3, which discloses an IC50 for compound 002 of <1 uM. A person having ordinary skill would have therefore recognized compound 002 as a potent inhibitor of YAP/TAZ-TEAD transcription activity and could have selected the compound for further investigation.
Moreover, the rejection is based on multiple compounds recited by the reference application. The rejection states “the reference application recites compounds of Table 1 which include the compound 002”. Please note that other compounds besides 002 in the reference application Table 1, including (but not limited to) compounds 001, 003, 004, 005, 006, 007, 010, 011, 012, 018, 020, etc.) possess equivalent structural similarity to compounds encompassed by the instant claims.
Applicant states that “Compound 002 is merely one of the many compounds listed as having an ‘A’ IC50 value”. Indeed, other compounds having equivalent structural similarity, such as 001, 003, 004, 005, 006, 007, 010, 011, 018, 020, are also disclosed as possessing an “A” IC50 value (reference application, Table 3). A person having ordinary skill could have selected any of these compounds for further modification according to the prior art teachings identified above in order to identify compounds having similar utility.
Compound 001 is noted in particular because it was the focus of further investigation in the reference application, and has the structure:
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Compound 001 was demonstrated to have in vitro activity in cancer cell line proliferation assays (Example 83) and in vivo anti-tumor efficacy in a human lung cancer xenograft model in mice (reference application, Example 84, Table 6, and FIG. 1).
Accordingly, should it be found that a person having ordinary skill would not have identified compounds 002, 003, 004, 005, 006, 007, 010, 011, 018, 020, etc. as suitable for further modification, the person having ordinary skill undoubtedly would have identified compound 001 as a suitable “lead compound” for further modification. The compound resulting from that modification (i.e., adding a 4-oxo substituent as taught by Liang) reads on instant claims 1, 3-7, 9, and 15-22:
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The provisional nonstatutory double patenting rejection is therefore maintained.
Allowable Subject Matter
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1, 3-9, and 15-22 are rejected. Claim 2 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621