Detailed Action
The present office action is in response to the remarks filed on 18 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 4, 8-9, and 11-12 of the pending application have been examined on the merits. Claims 1-3, 5-7, and 10 remain withdrawn. Acknowledgement is made of the amendments filed 18 May 2026. Acknowledgement is made of the addition of claims 11-12.
Priority
Applicants identify the instant application, Serial #: 18/005,952, filed 18 Jan 2023, as a National Stage Entry of International Patent Application #: PCT/CN2021/107774, filed 22 Jul 2021, which claims foreign priority from Foreign Application #s: CN202110364023.0, filed 03 Apr 2021, and CN202010708352.8, filed 22 Jul 2020.
Response to Applicant Arguments
Acknowledgement is made of the remarks filed 18 May 2026.
Claims 4 and 9 are rejoined as being directed to the instantly elected species following applicant amendments. The rejection of claim 8 under 35 U.S.C. § 103 is amended to include the rejoined claims. This new grounds of rejection is necessitated by applicant amendments filed 18 May 2026.
Newly added claims 11-12 are drawn to the instantly elected species and are being examined. The rejection of claim 8 under 35 U.S.C. § 103 is amended to include the newly added claims. This new grounds of rejection is necessitated by applicant amendments filed 18 May 2026.
The objection to claim 8 is rendered moot following applicant amendments.
The rejection of claim 8 under 35 U.S.C. § 112(b) is rendered moot following applicant amendments.
Regarding the rejection of claim 8 under 35 U.S.C. § 103 over US 2005/0261278 (provided in the office action mailed 17 Feb 2026), hereinafter ‘278, further in view of Hacksell et al. (Neurochem Res, 2014, 39:2008-2017; provided in the office action mailed 17 Feb 2026), hereinafter Hacksell, Patani et al. (Chem Rev, 1996, 96:3147-3176; provided in the office action mailed 17 Feb 2026), hereinafter Patani, and Brooks et al. (ACS Med Chem Lett, 2019, 10:1228-1233; provided in the office action mailed 17 Feb 2026), hereinafter Brooks, applicant arguments filed 18 May 2026 have been fully considered but are not persuasive.
Applicant argues in the remarks filed 18 May 2026 that the references fail to suggest or motivate a skilled person in the art to modify pimavanserin in any specific manner based on the genus structure of Formula (III) because the structure has near infinite numbers of substructures and species. Applicant further argues that pimavanserin has a multi-ring structure with many modification sites and there is no suggestion or guidance as to where the modification might begin (pg. 20).
This is not persuasive. MPEP § 2144.09 states that a “prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” and further that “prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).” Bioisosteric replacements are expected to have similar activity. See MPEP § 2144.09(III). ‘278 and Hacksell teach pimavanserin and Patani and Brooks teach pyridine as a known bioisostere of phenyl, and further teach the suggestion and motivation to replace phenyl with pyridine. There is therefore a prima facie case of obviousness to replace the phenyl group of pimavanserin with pyridine to form the instantly elected compound.
Applicant further argues that bioisosterism is not adequate to support obviousness without evidence of a reasonable expectation of success and that Patani and Brooks underscores the unpredictability of the art (pg. 20).
This is not persuasive. MPEP § 2144.09 states that a “prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” and further that “prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).” Bioisosteric replacements are expected to have similar activity. See MPEP § 2144.09(III).
Applicant argues that at the time of filing, substituting pyridine for phenyl in known pimavanserin-like compounds results in a loss of activity for the species and cites two compounds in WO 2019/040106 (provided in IDS 01/18/23) which teach a high activity compound with similar utility and structure as pimavanserin having a phenyl group. The reference shows that a replacement of the phenyl moiety with pyridine results in loss of activity (pg. 20-21).
This is not persuasive. The standard is a to show that the person having ordinary skill in the art would have a reasonable expectation of success and not a guaranteed expectation of success. The cited reference highlights that the pyridine replacement is within the realm of skill of the person of ordinary skill in the art. The close structural similarity of pimavanserin and the instantly elected compound is sufficient to show a prima facie case of obviousness to create the instantly elected compound from pimavanserin. See MPEP § 2144.09.
Finally, applicant argues that, compared to pimavanserin, the instantly elected compound shows significantly higher 5-HT2A antagonistic activity.
This is not persuasive. While the elected compound has higher activity against 5-HT2A than pimavanserin, no evidence is shown that this would be unexpected. Applicant arguments cannot take the place of evidence in the record. See MPEP § 2145(I).
In light of the discussion above, the rejection of claim 8 under 35 U.S.C. § 103 as obvious over ‘278, Hacksell, Patani, and Brooks is amended for the reasons of record to include claims 4, 9, and 11-12 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 4, 8-9, and 11-12 is/are rejected under 35 U.S.C. § 103 as being unpatentable over ‘278, further in view of Hacksell, Patani, and Brooks.
In the response filed 05 Nov 2025, applicant elected Group I and the following species which reads on claims 4, 8-9, and 11-12:
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Claim 9 further claims a composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.
‘278 teaches compounds of Formula (III) (paragraph [0049]):
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,
where the Ar groups can be variable with cycles or heterocycles. ‘278 also teaches a compounds of Formula (I) (paragraph [0061]):
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Which is a compound of Formula (III) when Ar1 is substituted aryl; Y2 is a bond; Y1 is methylene; Z is
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; R is methylene; n is 1; W is O; X1 is NH; X2 is methylene; and Ar2 is a substituted aryl group (paragraphs [0050]-[0059]). ‘278 further teaches a pharmaceutical composition of a compound of Formula (III) and a physiologically acceptable carrier, diluent, or excipient (paragraph [0116]). However, '278 does not teach the instantly elected compound.
Hacksell teaches that the compound of Formula (I) taught by '278 is pimavanserin, a drug with selectivity of the 5-HT2A receptor with nanomolar potency as an inverse agonist and no meaningful activity at any other G-protein coupled receptor (pg. 2008, column 1).
Patani teaches that bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safe and more clinically effective agents and the concept of bioisosterism is often considered to be qualitative and intuitive (pg. 3147, columns 1-2). Patani further teaches that substitution of benzene with pyridine is considered one of the classical bioisosteres and the replacement of -CH= with -N= is commonly used in drug design (pg. 3158, column 1; pg. 3159, column 2).
Brooks teaches that a phenyl-alkoxy group with a pyridine-alkoxy group reduced clearance and extend mean residence time for a TRPV4 inhibitor (pg. 1231, column 1). Brooks teaches that an extended mean residence time is highly desirable as it minimizes the peak to trough concentrations during a dose, improving therapeutic index and enabling a lower overall dose (pg. 1228, column 2).
MPEP 2144.08(II)(A)(4)(c) states that the “closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein).”
Based on the teachings of '278, Hacksell, Patani, and Brooks, a person having ordinary skill in the art would substitute the phenyl-alkoxy ring of the compound of Formula (I), taught by '278 and Hacksell, with a pyridinyl-alkoxy group, taught by Patani and Brooks, and arrive at the instantly elected compound. It is commonly known that benzene and pyridine are exchanged to rationally modify compounds in medicinal chemistry, as found in Patani, and the artisan would have been motivated to perform the swap of phenyl for pyridinyl in order to reduce clearance and extend the mean residence time, as taught by Brooks.
The artisan would have a reasonable expectation of success that the modified compound of Formula (III) would retain the functionality of the compound of Formula (III) because of the similarities between the compound of Formula (III) and the instantly elected compound.
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.
Conclusion
No claim is allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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