Detailed Action
The present office action is in response to the amendments filed 12 May 2026.
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
Claims 1-10 of the pending application have been examined on the merits. Claims 11-18 and 25 remain withdrawn. Acknowledgement is made of the cancellation of claims 19-24.
Priority
Applicants identify the instant application, Serial #: 17/920,794 filed 23 Oct 2022, as a National Stage Entry of International Patent Application #: PCT/US21/28136, filed 20 Apr 2021, which claims priority from U.S. Provisional Application #: 63/016,683, filed 28 Apr 2020.
Response to Applicant Arguments
Acknowledgement is made of applicant amendments filed 12 May 2026.
The objection to claim 7 is withdrawn following applicant amendments.
The rejection of claim 5 is rendered moot following applicant amendments.
The rejection of claims 1-10 under 35 U.S.C. § 103 over WO 2021/081141 (provided in IDS 01/18/23), hereinafter ‘141, further in view of WO 2015/042397 (provided in IDS 01/18/23), hereinafter ‘397, and Chang et al. (Bioorg Med Chem, 2017, 1:381-388; provided in the office action mailed 16 Dec 2025), hereinafter Chang, is withdrawn following the clear and concise statement establishing the subject matter disclosed and the claimed invention were subject to an obligation of assignment to the same person, in the remarks filed 12 May 2026 (pgs. 9-10).
Regarding the rejection of claims 1-10 under 35 U.S.C. over WO 2016/126572 (provided in IDS 01/18/23), hereinafter ‘572 further in view of ‘397 and Chang, applicant's arguments filed 12 May 2026 have been fully considered but they are not persuasive.
Applicant argues that the instantly claimed pyridyl compounds have an unexpected improvement in brain AUC/plasma versus the same compound differing only in having a phenyl moiety instead of a pyridyl moiety. Applicant argues that this could not have been predicted by the art (pgs. 10-11).
This is not persuasive. The example applicant provides is narrower than the scope of the claims. See MPEP § 2145(VI).
Applicant further argues ‘572 does not teach or suggest swapping a phenyl ring for a pyridine ring and that ‘397 fails to cure the deficiencies of ‘572. Applicant argues that ‘397 does not differentiate compound 56 from other compounds in having glucosylceramide synthase inhibition activity (pg. 12). Applicant further argues that Chang is not directed to any particular compound or class of compounds but merely provides analysis to evaluate the change in activity based on structural changes (pg. 12). Applicant argues that Chang only provides an analysis that cannot be extrapolated to glucosylceramide synthase inhibition (pg. 13).
This is not persuasive. The rejection over ‘572, ‘397, and Chang is based on the combination of references. ‘572 teaches the core compounds, but does not teach the pyridyl moiety in place of the phenyl moiety. ‘397 teaches that the artisan would have a reasonable expectation that pyridyl moieties in place of phenyl moieties in glucosylceramide synthase inhibitors would have similar utility. Chang teaches motivation for replacing phenyl with pyridyl. Together the references render the instant claims obvious.
In light of the discussion above, the rejection of claims 1-10 under 35 U.S.C. 103, as obvious over ‘572, ‘397, and Chang is maintained for the reasons of record restated below.
Regarding the obviousness-type nonstatutory double patenting rejection of claims 1-10 over US Patent No. 10,202,340 (provided in IDS 01/18/23), hereinafter ‘340, further in view of ‘397 and Chang, applicant's arguments filed 12 May 2026 have been fully considered but they are not persuasive.
Applicant argues that the same reasons why the instant claims are novel over ‘572, ‘397, and Chang apply to the NSDP rejection over ‘340, ‘397, and Chang (pg. 14). This is not persuasive for the reasons stated above. Therefore the obviousness-type nonstatutory double-patenting rejection for claims 1-10 over ‘340, ‘397, and Chang is maintained for the reasons of record and restated below.
Regarding the obviousness-type nonstatutory double patenting rejection of claims 1-10 over US Patent No. 11,220,479 (provided in IDS 01/18/23), hereinafter ‘479, further in view of ‘397 and Chang, applicant's arguments filed 12 May 2026 have been fully considered but they are not persuasive.
Applicant argues that the same reasons why the instant claims are novel over ‘572, ‘397, and Chang apply to the NSDP rejection over ‘479, ‘397, and Chang (pg. 14). This is not persuasive for the reasons stated above. Therefore the obviousness-type nonstatutory double-patenting rejection for claims 1-10 over ‘479, ‘397, and Chang is maintained for the reasons of record and restated below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-10 is/are rejected under 35 U.S.C. 103 as being obvious over WO 2016/126572 (provided in IDS 01/18/23), hereinafter ‘572, further in view of ‘397 and Chang.
‘572 teaches compounds useful as glucosylceramide synthase inhibitors taking the form of reference Formula (I) (paragraphs [0010]-[0011]):
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‘572 teaches multiple examples where R1 and m overlap with substituents of the instant claims, including Examples 2-4, 7, 9, and 12 (paragraphs [0079]-[0091]):
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These examples are further characterized by ‘572 in paragraph [0235], reproduced below:
Example
Broken Cell IC50 (nM)
WT-MDCK IC50 (nM)
MDR1-MDCKII IC50 (nM)
Mouse liver microsome t1/2 (min)
2
48
3
15
5.5
3
54
5
27
4
4
44
5
56
7
232
4
11
37
9
123
10
17
12
56
0.87
2.5
11
‘572 further teaches a composition of a reference compound, a pharmaceutically acceptable carrier or vehicle, and a second therapeutic agent useful in the treatment of a disease or condition wherein inhibition of GCS provides a benefit, where that second therapeutic agent may be useful in the treatment of Gaucher disease (claims 10-11). However, ‘572 does not teach swapping the phenyl ring for a pyridine ring as in the instant claims.
‘397 teaches compounds useful as glucosylceramide synthase inhibitors with the same core structure, but having a pyridine ring in place of a phenyl ring as in ‘141, such as reference Compound 56 (paragraph [000539]):
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‘397 further teaches that Compound 56 has inhibits glucosylceramide synthase with an IC50 of ≤ 50 nM (paragraph [0001329]).
Chang teaches that aromatic rings are ubiquitous in pharmaceutical compounds and are often exchanged with another ring during the optimization process of drug discovery (Abstract). Chang further teaches a holistic, multiple endpoint optimization approach taking into account LogD lipophilicity, microsomal metabolism, P-gp efflux, and passive permeability (Abstract). Chang teaches that changing phenyl for 2-pyridyl creates significant changes for LogD lipophilicity, microsomal metabolism, and permeability, but no P-gp efflux (supplementary data).
By following the teachings of ‘572, ‘397, and Chang, a person of ordinary skill in the art would modify reference Examples 2-4, 7, 9, and 12, found in ‘572, by swapping the phenyl ring for a 2-pyridine ring, as taught by Chang, with a reasonable expectation of success that the pyridine ring would be active as a glucosylceramide synthase inhibitor, as taught by ‘397. The artisan would be motivated to perform this exchange to further optimize the drug and investigate the differences in LogD, permeability, microsomal metabolism, and P-gp efflux when a pyridine ring is exchanged for a phenyl ring in glucosylceramide synthase inhibitors.
The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active glucosylceramide synthase inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compound in view of the compounds taught by ‘572.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-8 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,202,340 (provided in IDS 01/18/23), hereinafter ‘340, in view of ‘397 and Chang.
‘340 claims compounds having the following structure:
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Which overlaps with the instant claims when G is -CH2-; R3 is H or F; NR2R2’ is 1-pyrrolidinyl, 3-fluoro-1-pyrrolidinyl, or 1-azetidinyl; m is 1; and R1 is halo, OC1-3 alkyl optionally substituted with one to five fluoro atoms (claim 1). ‘340 further claims a pharmaceutical composition comprising compounds of the above structure and a pharmaceutically acceptable carrier or vehicle. However, ‘340 claims a phenyl group where the instant claims require a pyridine ring.
‘397 teaches compounds useful as glucosylceramide synthase inhibitors with the same core structure, but having a pyridine ring in place of a phenyl ring as in ‘141, such as reference Compound 56 (paragraph [000539]):
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‘397 further teaches that Compound 56 has inhibits glucosylceramide synthase with an IC50 of ≤ 50 nM (paragraph [0001329]).
Chang teaches that aromatic rings are ubiquitous in pharmaceutical compounds and are often exchanged with another ring during the optimization process of drug discovery (Abstract). Chang further teaches a holistic, multiple endpoint optimization approach taking into account LogD lipophilicity, microsomal metabolism, P-gp efflux, and passive permeability (Abstract). Chang teaches that changing phenyl for 2-pyridyl creates significant changes for LogD lipophilicity, microsomal metabolism, and permeability, but no P-gp efflux (supplementary data).
By following the teachings of ‘340, ‘397, and Chang, a person of ordinary skill in the art would modify the reference claims, found in ‘340, by swapping the phenyl ring for a 2-pyridine ring, as taught by Chang, with a reasonable expectation of success that the pyridine ring would be active as a glucosylceramide synthase inhibitor, as taught by ‘397. The artisan would be motivated to perform this exchange to further optimize the drug and investigate the differences in LogD, permeability, microsomal metabolism, and P-gp efflux when a pyridine ring is exchanged for a phenyl ring in glucosylceramide synthase inhibitors.
The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active glucosylceramide synthase inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compound in view of the compounds taught by ‘340.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,220,479 (provided in IDS 01/18/23), hereinafter ‘479, in view of ‘397 and Chang.
‘479 teaches compounds of the following structure:
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which overlaps with compounds of the instant claims when R3 is H or F; R4 is H or CH3; G is CH2 or O; R6 is H, C1-3alkyl, C3-6cycloalkyl, or CD3; NR5R5’ is 1-pyrrolidinyl, 3-fluoro-1-pyrrolidinyl, or 1-azetidinyl; and R7, R8, R1, and R2 are H (claim 1). ‘479 further teaches a composition of a compound of the reference claims and a pharmaceutically acceptable carrier or vehicle (claim 13). However, ‘479 teaches a phenyl moiety where the instant claims teach a pyridine moiety.
‘397 teaches compounds useful as glucosylceramide synthase inhibitors with the same core structure, but having a pyridine ring in place of a phenyl ring as in ‘141, such as reference Compound 56 (paragraph [000539]):
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‘397 further teaches that Compound 56 has inhibits glucosylceramide synthase with an IC50 of ≤ 50 nM (paragraph [0001329]).
Chang teaches that aromatic rings are ubiquitous in pharmaceutical compounds and are often exchanged with another ring during the optimization process of drug discovery (Abstract). Chang further teaches a holistic, multiple endpoint optimization approach taking into account LogD lipophilicity, microsomal metabolism, P-gp efflux, and passive permeability (Abstract). Chang teaches that changing phenyl for 2-pyridyl creates significant changes for LogD lipophilicity, microsomal metabolism, and permeability, but no P-gp efflux (supplementary data).
By following the teachings of ‘479, ‘397, and Chang, a person of ordinary skill in the art would modify the reference claims, found in ‘479, by swapping the phenyl ring for a 2-pyridine ring, as taught by Chang, with a reasonable expectation of success that the pyridine ring would be active as a glucosylceramide synthase inhibitor, as taught by ‘397. The artisan would be motivated to perform this exchange to further optimize the drug and investigate the differences in LogD, permeability, microsomal metabolism, and P-gp efflux when a pyridine ring is exchanged for a phenyl ring in glucosylceramide synthase inhibitors.
The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active glucosylceramide synthase inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compound in view of the compounds taught by ‘479.
Conclusion
No claim is allowed. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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