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 .
Priority
The instant application is a 371 National Stage Entry of PCT/PCT/US2021/064517 filed on December 21, 2021 which claims priority to foreign application No. 63/129,130 filed on December 22, 2020.
Status of Claims
Acknowledgement is made of original (52, 64), amended (3, 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 53, 57, 60, 63), cancelled (1-2, 4-7, 9-17, 19, 21-26, 28-30, 32, 34-39, 41, 44-49, 51, 54-56, 58-59, 61-62, 65-85) claims filed December 22, 2025. Claims 3, 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 52-53, 57, 60, 63-64 are pending in instant application.
Claim Interpretation
Claim 50 recites “wherein each R8 is”. However, claim 3 does not require Z (optionally substituted with R8) to actually be present in the compound, so claim 50 is limiting R8’s identity, if at all present.
Response to Arguments
Acknowledgement is made of Applicant’s amendments and remarks filed December 22, 2025.
Specification
The amendment to the invention title has overcome the previous objection to the specification.
Previous Rejections - Withdrawn
Applicant’s amendments have overcome the following rejections:
Rejection of claims 1, 4, 14-18, 21, 31, 33, 40, 42, 43, 50 under 35 U.S.C. 102(a)(1) as being anticipated by US 2015/0236272 A1 to Park et. al.1
Rejection of claims 1, 4, 8, 14-18, 21-22 under 35 U.S.C. 102(a)(1) as being anticipated by Hay et. al. 2
Rejection of claims 1, 14-18, 21-22, 27 are under 35 U.S.C. 102(a)(1) as being anticipated by US 6,329,412 B1 to Goldstein et. al.3
Previous Rejections – Maintained/Modified
Prior Art Rejections
Applicant’s arguments regarding the prior art rejection over Dyckman (see 12/22/25 Remarks at pp. 15-16 are not persuasive. Applicant argues there is no expectation of success in the isomeric alteration of a Dyckman compound to arrive at an instant, and cites prior art. The Examiner notes the art Applicant cites is drawn to modifications in the 6- and 5- position of indole where as Dyckman and instant are drawn to 5- and 4- position of indole scaffolds. Moreover, structure-activity relationships are specific to the desired activity (aka utility) and the art Applicant cites is drawn to GPR17 agonists, not toll-like receptor inhibitors.
Even though claim 3 has been amended to more specified R1 substituents, these encompassed substituents are still taught and suggested by Dyckman (e.g. pyrimidinyl rings,
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, see Dyckman claim 1).
Absent persuasive arguments or unexpected results commensurate in scope showing the instant compounds are better toll-like receptors than their closest counter-parts in Dyckman (e.g. instant compound 52 vs Dyckman compound 257), the instant invention cannot be considered novel.
Double Patenting
Applicant’s arguments regarding the non-statutory double patenting rejection over copending Application No. 18/268,469 (see 12/22/25 Remarks at p. 17) are not persuasive. At the outset, the Examiner notes the remarks appear to have clerical error by referencing “R1 is a particular group as amended in claim 1”, which the Examiner assumes should read “claim 3”. It does not matter that instant claim 3 further limits R1, the copending claims still encompass compounds of the same structure, such as species in instant claim 52:
Instant Claim 52 p. 11
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which also reads on App’469 claim 1 Formula 1 when R is a 6-memebred monocyclic heteroaryl (2-pyridinyl) substituted with one Ra, Ra being a 6-membered monocyclic heterocyclyl (piperazinyl), R2 is C1alkyl (methyl), X1 is CR3 and R3 is H, X2 is CH, X3 is CR3 and R3 is H, Y is a 9-membered fused bicyclic heteroaryl substituted with Z and Z is C1alkyl (methyl) (8-methyl-1[1,2,4]triazolo[1,5-a]pyridine).
New Rejections
Applicant’s amendments have necessitated a new 35 USC 112 rejection of claim 3 and it’s dependent claims.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION — The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 53, 57, 60, 63-64 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 lists “NR11R11” in multiple locations (such as p. 3 “…selected from -OH, halogen, -CN, oxo, -NR11R11,…”). The newly amended claim does not define R11, but does define R11a. In addition, claims 18, 27, 31 also reference R11. It is unclear what R11 can and cannot be. Claims 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 53, 57, 60, 63-64 do not define what R11 may be and are thus included in instant rejection.
Maintained/Modified Rejections
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 3, 8, 18, 27, 31, 33, 40, 42-43, 50, 52-53, 57, 60, 63-64 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/126253 A1 to Dyckman et. al.4
Regarding compounds of Formula I and claims 3, 52, Dyckman teaches compounds of Formula I which correspond to instant Formula I when X1-X2 are CR3 and R3 is H, X3 is CH, instant Y corresponds to Dyckman A, instant R1 corresponds to Dyckman G, instant R3 corresponds to Dyckman R5 and R3 is H or halogen or alkyl, and instant R2 corresponds to Dyckman R5 (see Dyckman at claim 1).
Of note, Dyckman teaches Compound 257 (see Dyckman at p. 114).
Dyckman Formula I
Instant Formula I
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Dyckman Compound 257
Instant Claim 52 Exemplary Compound
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Regarding compositions and instant claim 53, Dyckman teaches compositions comprising compounds of Dyckman Formula I (see Dyckman at claim 9).
Regarding methods of use and claims 57, 60, 63-64, Dyckman compounds of Formula I are useful for inhibiting toll-like receptors 7, 8, or 9 for treating inflammatory diseases associated with toll-like receptor 7, 8, or 9 activity by administering to subjects (see Dyckman at p. 2 lines 21-25 and at p. 3 lines 7-10). Dyckman teaches treating diseases such as rheumatoid arthritis and Sjorgen’s syndrome (see Dyckman at claim 11).
The prior art differs from the instant claims as follows: While Dyckman teaches structurally similar compounds for the same as instant purposes, Dyckman’s structures differ in isomeric positions or by methyls.
However, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a change of positional isomers and claims 1, 52, MPEP § 2144.09(II) states position isomers are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In addition, the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. It would have been obvious to alter the positions of Dyckman group A and Dyckman group G to arrive at an anticipatory compound because it is an isomeric change and maintains the specified indole core of Dyckman Formula I.
Regarding H for Me and claim 52, the prior art suggests a C1-64 alkyl at the R1 position. It would have been obvious to substitute H for Me to arrive at ethyl in lieu of isopropyl in the Dyckman Compound 257 above as this is specifically contemplated by the reference to be a suitable alternative by maintaining the C1-C4 alkyl limitation.
Regarding H for Me and claims 18, 31, 33, 40, 42-43 and instant Y-Z, when an isomeric change of Dyckman Formula I is conducted to read on instant Formula I (see above positional isomers), and group A is pyridine optionally substituted with methylpiperazinyl, the moiety would correspond with a group wherein Y is pyridine substituted with Z
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and R8 is methyl.
Regarding claim 8 and instant R1, when an isomeric change of Dyckman Formula I is conducted to read on instant Formula I (see above positional isomers), Dyckman group G
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corresponds to instant R1
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.
In sum, one could arrive at an exemplary compound such as
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from the teachings of Dyckman in light of isomeric alterations.
Accordingly, claims 3, 8, 18, 27, 31, 33, 40, 42-43, 50, 52-53, 57, 60, 63-64 are obvious over Dyckman.
Double Patenting
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 3, 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 52-53, 57, 60, 63-64 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 4, `0, 14, 15, 16, 19, 20, 25, 31, 33, 43, 48, 52, 54, 63, 64, 65, 66, 67, 69, 73, 76, 79, 80 of copending Application No. 18/268,4695 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding compounds, the applications are drawn to overlapping or isomeric compounds for the same purpose.
Overlapping: App’469 Formula I reads on instant Formula I wherein App’469 R1 is instant Y, App’469 R2 is instant R2, App’469 X1 is instant X1, App’469 X2 is instant X2, App’469 X3 is instant X3, and App’469 Y is instant R1.
App’469 Formula I
Instant Formula I
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For example, both Formulas encompass the following exemplary structure:
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Isomeric: App’469 Formula I corresponds to instant Formula I wherein App’469 R1 is instant R1, App’469 R2 is instant R2, App’469 Y is instant Y, App’469 X1-X3 is instant X1-X3 (compare App’469 claim 63 with instant claim 52 as shown below).
App’469 Claim 63
Instant Claim 52
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Regarding methods, both applications claim compositions and methods of inhibiting toll-like receptors 7, 8, or 9 for treating inflammatory conditions such as Sjorgen’s syndrome (compare App’469 claims 69, 73, 76, 79, 80 with instant claims 53, 57, 60, 63, 64).
The copending claims differ as follows: App’469 claims compound species that are positional isomers of instant compounds.
However, it would have been obvious to one of ordinary skill in the art to arrive at the instantly claimed invention with a reasonable expectation of success in view of the copending claims for at least the following reason(s):
Regarding isomeric changes, MPEP § 2144.09(II) states position isomers are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claim 20, while included in the provisional nonstatutory double patenting rejection, appears to be free of the prior art and would be allowable if a terminal disclaimer over the copending application was filed, the 35 USC 112b issue fixed, and the claim was amended to be independent.
Conclusion
Claims 3, 8, 18, 20, 27, 31, 33, 40, 42-43, 50, 52-53, 57, 60, 63-64 64 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 SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Published August 20, 2015. Cite No. A8 in the IDS filed 1/30/24. Hereinafter Park.
2 Supplementary Information for Hay et. al. "Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains" J Am. Chem. Soc. 2014, 136, 26, 9308-9319, DOI: 10.1021/ja412434f Cite No. A91 in the IDS filed 1/30/24. Hereinafter Hay.
3 Patented December 11, 2001. Cite No. A1 in the IDS filed 1/30/24.
4 Published June 27, 2019. Cite No. A58 in the IDS filed 1/30/24. Hereinafter Dyckman.
5 371 of PCT/US2021/064516 filed December 21, 2021, claims benefit to provisional application 63/129,223 filed December 22, 2020. Hereinafter App’469.