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 .
DETAILED ACTION
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on July 27, 2026.
Claim 21 is amended to exclude Enamine catalog Compound No. 1324012946 (CAS# 2419701-18-9). Thus, rejections of claims 21, 24, 27-28 and 31-32 anticipated by Compound No. 1324012946 under 35 U.S.C. 102(a)(1) is withdrawn.
Election/Restrictions
Applicant elected , with traverse, Group I, subgenus compound of Formula (Ia-2) and species, N-(4- Chlorophenyl)-4-hydroxy-3- {8- [4-(trifluoromethoxy)phenyl]-2,8-diazaspiro[5.5]undecan-2-yl}butanamide (Example 10), having following structure, in the reply filed on 10/23/2025.
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The Restriction Requirement is still deemed proper and made Final in last office action mailed on 01/27/2026.
Claims 35 and 36 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The elected species is a compound of Formula I, wherein
R1, R2, R4, R5 is H;
R3 is OCF3;
R6 is CH2OH;
X is -CONH-, R7 is a phenyl group substituted with halogen (Cl);
Hy is spiroheterocyclic group
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,
The elected species read on claims 21, 24, 27-28, 31-32 and 34.
Claims 22-23, 25,-26, 29 and 33 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
The elected species, Example 10 (CAS# 2759854-20-9, entered STN database on February 18, 2022) is found free of anticipatory 102 prior art. The search and examination was expanded to non-elected species of claim 34:
N-(4-Chlorophenyl)-5-hydroxy-3- {4- [4-(trifluoromethoxy)phenyl]piperazin-1-yl}pentanamide having following structure:
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4-Chloro-N-(3-hydroxy-2- {4- [4-(trifluoromethoxy)phenyl]piperazin-1-yl }propyl)benzamide having following structure:
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The non-elected species were rejected under 35 USC §103 in previous office action mailed on 01/27/2026. Other non-elected species remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Claim 34 still recites the rejected non-elected species. Thus, claims 21, 24, 27-28, 31-32 and 34 remain rejected and the action made final.
Status of Claims
Claims 21-29 and 31-34 are pending in the present Application
Claims 22-23, 25,-26, 29 and 33 remain withdrawn.
Claims 21, 24, 27-28, 31-32 and 34 are currently under examination.
Priority
This instant application 18/040,040 filed 01/31/2023, is a 371 of PCT/EP2020/087097 filed 12/18/2020, which claims benefit of EP 20189036.5 filed 07/31/2020. The certified copy of EP 20189036.5 is filed on 01/31/2023.
Information Disclosure Statement
The information disclosure statement dated 03/25/2026 is being considered by the Examiner.
Action Summary/ Response to Arguments
Applicant's remarks filed 07/27/2026 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s persuasive arguments .The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office action.
Claim 21 is amended to exclude Enamine catalog Compound No. 1324012946 (CAS# 2419701-18-9). Thus, rejections of claims 21, 24, 27-28 and 31-32 anticipated by Compound No. 1324012946 under 35 USC 102(a)(1) is withdrawn.
Please see response to arguments in following maintained/reapplied rejections under 35 USC § 112 and 103.
Claim Rejections - 35 USC § 112 – Improper Markush Group
Claims 21, 24 and 27-28 remain rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature (maintained).
A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
In the present case, claims 21, 24 and 27-28 are drawn to a compound of formula I comprising combination of Hy alternatives and XR7 that are in different recognized classes, thus the Markush grouping embraces different chemical compounds that do not share significant structural similarity between the species.
The Markush grouping for compounds of Formula I recites vast variety of moieties Hy, XR7 in combination with different R groups, etc. that are not within the same class. For example, claim 21 recites limitations of R7 selected from groups a) to h), wherein the aryl group, pyrrolidinyl group, NHCONH2 and C1-3 alkyl belong to different chemical class.
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Hy moiety comprising variety of heterocyclic ring comprising N, O , S atoms belong to different class. Instant specification does not disclose any Hy moiety comprising S atoms.
There is only minimal structure moiety in common, phenyl ring substituted with R1-R5 among the alterative compounds claimed in Formula I, which is a minimal part of the structures compared with other varieties of Hy and XR7 Markush groups. The phenyl ring connected with Hy shared among the species do not necessarily share a common use of VDAC inhibition flows from the phenyl ring in combination with Hy moiety.
Each of these findings demonstrates that not all members recited in this Markush group belong to the same recognized chemical class, i.e., the species fail to share a substantial structural feature and/or a common use associated with the phenyl ring.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Applicant argues the claimed compounds “are inhibitors of VDAC1 for treating prediabetes and diabetes, prevent diabetes disease progression (deterioration) and prevent progression of prediabetes to diabetes." Spec. 1. Therefore, the claimed compounds share a common use.
RESPONSE: Applicant's arguments have been fully considered, but NOT persuasive. Instant Spec discloses about 44 compound species, wherein the structures of Compounds 11-28 and 29-44 are disclosed in Spec (See PGPub US 2023/0348464 A1 [0155], [0245] and [0249]). The structures of Compounds 1-10 are not explicitly disclosed with corresponding chemical names. Instant Spec discloses VDAC1 affinity assay wherein Compounds 1 -10 showed various VDAC1 affinity (See Table 2). Instant Spec does NOT disclose VDAC1 activity for Compounds 11-44. Instant Spec does NOT disclose any assay related to diabetes disease or prediabetes. In absence of sufficient activity data, instant claimed compound genus of Formula I comprising vast variety of Hy, XR7 moiety and R groups are not fully established as VDAC1 inhibitors and do NOT share a common use.
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.
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.
Claims 21, 24, 27-28, 31-32 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Shoshan-Barmatz et al. (US 20180118700 A1, hereafter Shoshan-Barmatz’ 700, family member of WO 2017/046794, Applicant’s IDS dated 01/31/2023)(maintained and reapplied as necessitated by amendment).
Shoshan-Barmatz’ 700 teaches piperazine and piperidine derivatives, compound of Formula I, Ia, Ib, Id, as inhibitor of Voltage- Dependent Anion Channel ( VDAC) oligomerization, associated with apoptosis induction or the treatment of diseases associated with enhanced apoptosis, e.g. e.g. Alzheimer's disease (See abstract, [0001], [0053], [0066], [0068], Table 1, Examples 1- claims 1-32 ).
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It’s noted Shoshan-Barmatz’ 700 embodiment comprising R3 heteroalkyl in combination with piperidine(A is C) is considered as read on instantly claimed bi-heterocyclic Hy wherein first and second heterocyclic ring connected with a bond . Although the attached/connecting position to phenyl ring might be different, the bi-heterocyclic moiety in a whole is considered as obvious to a skilled artisan.
Shoshan-Barmatz’ 700 teaches variety of compound species, e. g, compound of Formula 1 (See [0087], Table 1, Example 2),
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In searching for more VDAC inhibitor, it would have been obvious to one of ordinary skilled in the art to further explore different Hy moiety and R groups based on the collective teachings of Shoshan-Barmatz’ 700 and general knowledge of structure similarity and bioisosteric modification. According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities 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). Whether the heterocyclic moiety is mono-heterocyclic or bi-heterocyclic, the Hy moiety in a whole is considered as obvious over Shoshan-Barmatz’ 700 to a skilled artisan, in the absence of evidence to the contrary.
For example, Formula 1 of Shoshan-Barmatz’ 700 could be modified and arrive at instant non-elected species of claim 34 which are considered as homologs, CH2OH vs CH2CH2OH.
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As stated in MPEP 2144 .09 III : “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) (Claimed and prior art compounds were both directed to heterocyclic carbamoyloximino compounds having pesticidal activity. The only structural difference between the claimed and prior art compounds was that the ring structures of the claimed compounds had two carbon atoms between two sulfur atoms whereas the prior art ring structures had either one or three carbon atoms between two sulfur atoms. The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.)”.
Formula 1 of Shoshan-Barmatz’ 700 is also the reverse amide of instant non-elected compound species of claim 34, 4-Chloro-N-(3-hydroxy-2- {4- [4-(trifluoromethoxy)phenyl]piperazin-1-yl }propyl)benzamide having following structure:
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One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of structure similarity and bioisosteric modification of SAR study . Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant argues the Office Action relies on an alleged close structural similarity and similar utility to support the conclusion of obviousness and “ the compounds disclosed in Shoshan-Barmatz are used to treat Alzheimer's disease. The Applicant's compounds, on the other hand, are used to treat prediabetes and diabetes.
RESPONSE: Applicant's arguments have been fully considered, but NOT persuasive. Shoshan-Barmatz’ 700 discloses compound of formula I that is very similar to instant claimed non-elected species. A skilled artisan would be motivated to modify compound of formula I and reasonably expect the homolog or reverse amide of formula I exhibit similar VDAC activity in absence of evidence to the contrary.
Regarding the alleged use of instant compounds to treat prediabetes and diabetes, instant Spec does NOT disclose VDAC activity for Compounds 11- 44 and does NOT disclose any assay related to prediabetes and diabetes with instant claimed compounds. Thus, the alleged use to treat prediabetes and diabetes is NOT supported by instant Spec. Further, instant claims are drawn to compounds wherein the biological activity is the property of compound and the intended use does not necessarily further contribute to the structural limitation of compounds.
Conclusion
NO claims are 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.
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/L.M./ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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