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
Election/Restriction
Acknowledgement is made of Applicant’s election with traverse of 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 traversal is based on that “ Office Action provides no evidence demonstrating that these technical features lack inventive step over the cited prior art. Specifically, merely suggesting that the compounds wherein Hy represents a first and second mono-heterocyclic ring connected by any linker are not generally exemplified to exhibit the desired biological activity does not constitute a valid reason to conclude that such compounds lack inventive step. On the contrary, inventive step should be recognized for those embodiments wherein Hy represents a first and second monoheterocyclic ring connected by a linker. Accordingly, the claimed formula satisfies the requirements of inventive step over the compounds disclosed in WO 2017/046794”.
Applicant’s argument is fully considered, but NOT persuasive. Please note Restriction Requirement is NOT full examination. Although instant claimed compound of Formula I shared a minimal structure of
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connected with variety of Hy moiety, the shared structure is not inventive since WO 2017/046794 disclosed general formula (Ia) and compound species that are similar to the shared structure.
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Instant claim 21 recites definition for Hy: c) a first and a second mono-heterocyclic ring connected by a linker, wherein each mono-heterocyclic ring is independently selected from a monoheterocyclic ring having 4-7 ring atoms, wherein 1-3 ring atoms are N, 0-1 ring atoms is O and 0-1 ring atoms is S…. There is no definition for the linker connecting the first and the second mono-heterocyclic ring in c) element. The linker could be a bond or any group. Whether the heterocyclic moiety is mono-heterocyclic or bi-heterocyclic, the Hy moiety as a whole is considered as obvious over WO 2017/046794, thus, the Restriction Requirement is still deemed proper and made Final.
Claims 35 and 36 are 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 are 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 Feb 18, 2022) is found free of anticipatory 102 prior art. The examiner has expanded the search to non-elected species of claim 34:
N-(4-Chlorophenyl)-5-hydroxy-3- {4- [4-(trifluoromethoxy)phenyl]piperazin-1-yl}pentanamide,
.
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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 are rejected under 35 USC 103 in following section. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. The absence of other citations of prior art should not be interpreted as an indication that other subgenera within Formula (Ia-2) are free of prior art. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be 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 are 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 01/31/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Claim Objections
Claims 21, 28, 31-32 are objected to because of the following informalities:
Claim 21 recites X-R7 taking together is CONR’R’’, ring atoms are missing for “1-2 is selected from nitrogen”, “0-2 from oxygens” “1-4 is selected from nitrogen”.
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Claim 21 recites Hy wherein ring atoms are plural which should be followed by “are” instead of is. For example, “0-2 ring atoms” are are
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Claim 28 recites h) a C12 alkyl substituted with … C2 alken should be C2 alkene.
Claim 31 recites “wherein 1-2 is N, 0-1 is O and the remaining ring atoms are carbon” , ring atom(s) should follow “1-2” and “0-1” .
Claim 32 recites “ 0-1 ring atoms is O”, ring atoms are plural followed by “is”.
Specification
35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are: the definition of compound of formula I regarding R1 to R7 and Hy. Please note following are only exemplary typo errors. Applicant is required to correct any errors of which applicant may become aware in the specification.
Page 4 and page 7, X-R7 taking together is CONR’R’’, ring atoms are missing for “1-2 is selected from nitrogen”, “0-2 from oxygens” and “1-4 is selected from nitrogen”.
Page 5, para1; page 8 and 9, wherein ring atoms are plural which should be followed by “are”. For example, “0-2 ring atoms” are are
Page 17, ring atoms ” are missing:
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Page 18, first para, “wherein 2 are N”, ring atoms are missing from the number 2.
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Page 43, Table 2 is shaded.
Drawings
The drawings are objected to because there is no legend in Figure 1 to illustrate what’s the claimed subject matter. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112 – Improper Markush Group
Claims 21, 24 and 27-28 are 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.
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, and NHCONH2 and 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 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).
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 21, 24, 27-28 and 31-32 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 21 recites various Hy, R groups that are indefinite.
R1-R5: “quaternary ammonium” is vague and indefinite. It’s not clear what groups were attached to the “quaternary ammonium”.
R7: “tertiary ammonium” which is vague and indefinite. It’s not clear what groups were attached to the “tertiary ammonium”. ‘tertiary ammonium” could also be a ring with nitrogen atom.
Hy: a) bi-heterocyclic group ; b) spiroheterocyclic group
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It’ not clear how many N, O, or S atom are in the first or second heterocyclic ring and what’s the difference of the first heterocyclic ring attached to phenyl ring from second heterocyclic ring attached to the carbon atom.
Hy c) wherein a first and a second mono-heterocyclic ring connected by a linker, wherein each mono-heterocyclic ring is independently selected from a monoheterocyclic ring having 4-7 ring atoms, wherein 1-3 ring atoms are N, 0-1 ring atoms is O and 0-1 ring atoms is S…”. There is no definition for the linker connecting the first and the second mono-heterocyclic ring in c) elements. An ordinary skilled in the art would not know what linker is between the two heterocyclic rings, alkyl, amide, ester or other group? As such, the Hy as recited in claim 21 is indefinite.
Claims 24, 27-28 are rejected due to dependency on claim 21.
Claim 24 recites “quaternary ammonium” which is vague and indefinite. It’s not clear what groups were attached to the “quaternary ammonium”.
Claim 31 recites “wherein Hy is a non-aromatic cyclic system selected from a) wherein the biheterocyclic group has from 8 to 11 ring atoms wherein 1-2 is N, 0-1 is O and the remaining ring atoms are carbon”. It’s not clear wherein the N atoms and/or O atoms are located in the bi-heterocyclic ring system.
Claim 32 recites “wherein Hy is a non-aromatic cyclic system selected from b) wherein the spiroheterocyclic group has from 8 to 11 ring atoms wherein 2-3 ring atoms are N, 0-1 ring atoms is O, and the remaining ring atoms are carbon”. It’s not clear wherein the N atoms and/or O atoms are located in the spiroheterocyclic ring system.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 21, 24, 27-28 and 31-32 are rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention.
Compound No. 1324012946 (CAS# 2419701-18-9) is public available/on sale from Enamine Advanced HTS collection catalog (See "Accession No. 1234012946", Enamine Advanced HTS Collection Catalog, May 27, 2020, Applicant’s IDS dated 01/31/2023).
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Compound No. 1324012946 (CAS# 2419701-18-9) 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 pyrrolidinyl substituted with CONH2.
Hy is spiroheterocyclic group,
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As such, compound No. 1324012946 (CAS# 2419701-18-9) anticipates instant invention.
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),
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 linker (alkyl). 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.
Conclusion
NO claims are allowed.
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/L.M./ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628