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 .
Claims 1-3 and 113-119 have undergone amendments. Claims 7-12, 21-25, 35, and 36 have been cancelled. Thus, Claims 1-3, 5, 6, 13, 30, 33, 34, and 113-119, submitted on 15 May 2026, represent all claims currently under consideration.
Election/Restrictions
A complete search for Claim 1 was performed, with no prior art retrieved (See STN Search, Search Notes). The election of species requirement is hereby withdrawn. A complete search for Claim 114 was performed with prior art retrieved (See STN Search, Search Notes). Thus, Claims 1-3, 5-6, 13, 17-19, 29, 30, 32-34, 40, 42, 44, 46, 50, 52, 54, and 113-119, submitted on 15 May 2026, represent all claims currently under consideration.
Response to Amendment
The objection to Claim 1 is withdrawn. Applicant has amended Claim 1 to require only one proviso, rendering the objection moot.
The objection to Claims 116-119 is withdrawn. Applicant has amended Claim 116 to define TTR as transthyretin.
The 35 U.S.C. § 112(b) rejections of Claims 1-3, 5, 6, 13, 30, 33-35, and 114-119 are withdrawn. Applicant has amended Claims 1-3 and 114 to remove the parentheticals.
The 35 U.S.C. § 102(a)(2) rejection of Claims 1-3, 5, 6, 13, 30, 33-35, and 113-119 over Prasad is withdrawn. Applicant has amended Claims 1 and 114 to require that R5 is selected from specific heteroaryl groups, with Claim 113 amended to compounds which contain these specific heteroaryl groups at the corresponding R5 position. Prasad does not teach, suggest, or provide motivation for compounds which contain these specific heteroaryl groups at this position.
The 35 U.S.C. § 103 rejection of Claims 1-3, 5, 6, 13, 30, 33-35, and 113-119 over Prasad in view of Thornber is withdrawn. As described previously, Applicant has amended the claims to require specific heteroaryl groups at the variable R5 position, which are not taught, suggested, nor is there any motivation provided, by Prasad.
The provisional non-statutory patenting rejection of Claims 1-3, 5, 6, 13, 30, 33-35, and 113-119 over claims 1, 142, and 144-149 of co-pending application No. 18/419,081 is maintained as it is not the only rejection remaining.
Claim Rejections - 35 USC § 102- NEW GROUNDS OF REJECTION
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.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2348087-82-9 (Entered STN: 28 June 2019).
STN SRN 234087-82-9
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94
264
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has Ar1 as phenyl substituted with alkyl, variable X-1- as NH, n as 1, R1-R4 each as H, X2 as bond, and R5 as imidazolyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2347882-11-3 (Entered STN: 28 June 2019).
STN RN 2347882-11-3
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80
224
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has Ar1 as furanyl, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as 4-pyridinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2347681-15-4 (Entered STN: 28 June 2019).
STN RN 2347681-15-4
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93
262
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Ar1 as pyridinyl, variable X-1- as NCH2CH3, R1-R4 each as H, n as 1, X2 as bond, and R5 as 4-pyridinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2347380-03-2 (Entered STN: 27 June 2019).
STN RN 2347380-03-2
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89
267
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has Ar1 as furanyl, variable X-1- as NH, R1-R4 each as H, n as 2, X2 as bond, and R5 as imidazolyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2347161-77-5 (Entered STN: 27 June 2019).
STN RN 2347161-77-5
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82
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has Ar1 as thienyl, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as 4-pyridinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2346568-39-4 (Entered STN: 26 June 2019).
STN RN 2346568-39-4
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111
269
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has Ar1 as phenyl substituted with OCH3, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as 3-pyridinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 2345261-16-5 (Entered STN: 25 June 2019).
STN RN 2345261-16-5
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76
270
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has Ar1 as phenyl substituted with Cl, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as 4-pyridinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 1691557-25-1 (Entered STN: 26 April 2015).
STN RN 1691557-25-1
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has Ar1 as pyrimidinyl, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as 5-pyrimidinyl.
Claim 114 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN RN 1497623-28-5 (Entered STN: 18 December 2013).
STN RN 1497623-28-5
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has Ar1 as phenyl substituted with fluorine, variable X-1- as NH, R1-R2 each as H, n as 0, X2 as bond, and R5 as oxazolyl.
Double Patenting- REJECTIONS 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, 5-6, 13, 17-19, 29, 30, 32-34, 40, 42, 44, 46, 50, 52, 54, and 113-119 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 142, and 144-149 of copending Application No. 18/419,081 (Amended claims of 3 May 2024) (‘081).
Claim 1 of ‘081 is directed to a compound of formula I
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wherein A is
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; X1 is O or NR5; X2 is H, halo, heteroaryl, CN, OR6, or NR7R*; n is an integer from 0-3, p is an integer from 0-3; Ar1 is an optionally substituted aryl or heteroaryl; R1-R8 are selected from (i)-(viii):
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1025
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530
1018
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; R9 is H, haloalkyl, alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl (all optionally substituted); and R10 and R11 are H, halogen, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl, aryl, heteroaryl, aralkyl, heteroarlkyl (all optionally substituted) or OR9. Claim 142 claims the compound of claim 1 wherein the compound of formula I has the structure
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. Claim 144 claims several specific compounds which meet the limitations of the examined application, such as Compound 35
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, Compound 49
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, and compound 54
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.
Claim 145 claims a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. Claim 146 claims a method of inhibiting or preventing TTR aggregation and/or amyloid formation in the eye or CNS of a subject comprising administering a compound of Claim 1. Claim 147 claims a method of inhibiting or preventing TTR aggregation and/or amyloid formation in peripheral nerves or cardiac tissue of a subject comprising administering a compound of claim 1. Claim 148 claims a method of treating a subject having peripheral TTR amyloidosis or ocular or cerebral amyloid angiopathy comprising administering a compound of claim 1. Claim 149 claims aa method of treating a subject having familial amyloid polyneuropathy, familial amyloid cardiomyopathy, TTR oculoleptomeningeal amyloidosis or senile systemic amyloidosis comprising administering a compound of Claim 1.
Regarding Claim 113, several of the claimed compounds are obvious variations of what is disclosed by ‘081. Compound 89 of the examined application
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differs from Compound 35 of ‘081
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by increasing the length of the alkyl chain connecting the heteroaromatic ring system to the ester, and altering the location of the attachment point on the heteroaromatic ring. The artisan would not expect these compounds to have significantly different properties due to the close chemical structure (See MPEP § 2144.09 I).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 5-6, 13, 17-19, 29, 30, 32-34, 40, 42, 44, 46, 50, 52, 54, and 113-119 are rejected.
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 PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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