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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the compound; and a Compound 4 having the structure of:
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as the elected compound species in the reply filed on July 29, 2026, is acknowledged.
Please note the elected compound 4, when construed in view of the specification (see e.g., page 44, compound 4), has a chemical name of “(S)-6-(2-aminopropyl)-7-methyl-N-(pyridin-4-ylmethyl) thieno[3,2-d][1,2,3]triazin-4-amine”.
Claims 13, 15-18, 20, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 29, 2026.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on March 13, 2025, claims 1, 3 and 21 are unchanged; claims 2, 4-6, 13-20, 22 and 24 are amended; and claims 7-12, 23 and 25 are canceled.
Claims 1-6, 13-22 and 24 are pending.
Claims 13, 15-18, 20, and 24 are withdrawn.
Claims 1-6, 14, 19 and 21-22 are under examination in accordance with the elected species.
Priority
The instant application 18/707,168 filed on May 3, 2024, is a 371 of PCT/US2022/079349 filed
on November 4, 2022, which claims priority to, and the benefits of U.S. Provisional Application No.
63/275,808 filed on November 4, 2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119€ as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/275,808, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The prior-filed application fails to disclose the compound having the structure of:
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. Therefore, to the extent that the claims are drawn to the elected compound species, the claims are not entitled to the benefit of the prior-filed application and will receive an effective filling date of November 4, 2022, which is the filling date of 371 of PCT/US2022/079349.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/25/2024, 7/30/2026 and 8/6/2026 are is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 2 and 21 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.
Regarding claim 2, the recitation of “wherein R21 is
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, wherein
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represents a single or a double bond” renders the claim indefinite, because said recitation can lead to numerous interpretations. For instance, said claim depends on independent claim 1 that clearly states “R21 is selected from the group consisting of a 6 membered aryl, 6 membered heteroaryl, and 6 membered heterocycloalkyl”; However, claim 2, when reasonably construed under the broadest reasonable interpretation, the
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of 6 membered aryl ring can each independently be a single bond to give a 6 membered cycloalkyl. In other words, it is not clear if applicant is intending to (i) redefine “6 membered aryl” to include cycloalkyl, (ii) or exclude cycloalkyl from R21. Accordingly, one skilled in art would not reasonably be apprised of the metes and bounds of the claimed R21.
Regarding claim 21, the claim directs to a table, i.e., “Table 1”, which is not present in the claim set. According to MPEP 2173.05(s), “[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’ Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)”. Therefore, the metes and bounds of claim 21 is unclear and that renders the claim indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 2, to the extent that the recitation of “
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“ includes 6-membered cycloalkyl, such as cyclohexane (i.e.,
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, wherein A1, A2, A3, A4, A5 and A6 are independently carbon and
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is single bond), said claim fails to further limit R21 set forth in claim 1. It is respectfully noted that the “R21” set forth in claim 1 can only be selected from “6 membered aryl, and 5-membered heteroaryl, and 6 membered heterocycloalkyl”, and that excludes the 6-membered cycloalkyl.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-6, 14, 19 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2021/118929 A1; referred to herein as “Zhang #2”), in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176).
Zhang #2 teaches Compound 45, 6-[(2S)-2-aminopropyl]-2-chloro-7-methyl-N-[(pyridin-4-yl)methylthieno[3,2-d]pyrimidin-4-amine (see e.g., p. 26, cpd 45), having the structure of:
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(see e.g., p. 18, Cpd 45) is an exemplary compound of Formula (I) useful for improving pre-mRNA splicing in a cell (see e.g., abstract). Zhang #2 further teaches the compound of Formula (I):
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, wherein R4 is, inter alia, hydrogen or halo (see e.g., claim 1); and the term “halo” includes chloro (see e.g., p. 39, line 25-26). Zhang #2 further teaches a pharmaceutical composition comprising an effective amount of the compound in admixture with a pharmaceutically acceptable excipient (see e.g., claims 17-19). Zhang #2 further teaches in certain aspects, the form of the compound of Formula (I) is a stereoisomer, racemate, enantiomer or diastereomer thereof (see e.g., p. 3, line 26-28).
Zhang #2 does not teach the elected compound species.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity and have been classified as either classical or nonclassical (see e.g., p. 3148-3149). Patani et al. further teaches in classical bioisosteres, trivalent substitution of -CH= with -N= is commonly used in modern drug design, for example, trivalent ring substitution of -CH= with -N= in the anti-bacterial agent norfloxacin resulted in enoxacin which is also in clinical use for its antibacterial activity shown below:
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(see e.g., p. 3159, right column, last paragraph to p. 3160, Table 29).
In this case, the difference between the compound 45 of Zhang #2 and the claimed compound is shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the Compound 45 of Zhang #2, and then modifying said compound by replacing chlorine atom with hydrogen at R4, and replacing trivalent carbon (-CH=) of six-membered fused heteroaryl ring with nitrogen (-N=) as taught by Patani et al. One would have been motivated to modify compound 45 of Zhang #2 by:
selecting hydrogen in place of chlorine at the R4 position and
replacing corresponding trivalent carbon (-CH=) of the six-membered fused heteroaryl ring with
nitrogen (-N=), thereby arriving at the ring substitution present in the elected compound 4. Zhang #2 expressly teaches that R4 of its Formula (I) compounds may be hydrogen or halo, including chloride, and identifies compound 45 is useful for improving pre-mRNA splicing in a cell. Thus, Zhang #2 itself would have suggested hydrogen as an alternative to chlorine at R4 while retaining the disclosed pre-mRNA splicing utility.
With respect to the carbon-to-nitrogen ring substitution, Patani et al. teaches that replacement of trivalent -CH= with -N= constitutes a classical biososteric replacement and that such bioisosteric substitutions are employed in medicinal chemistry for the rational modification of lead compounds to obtain structurally related compounds having similar biological activity. Accordingly, one of ordinary skill in the art seeking to arrive at additional analogs of Zhang #2’s pre-mRNA splicing compounds would have been motivated to employ the known -CH=/-N= bioisosteric replacement in the heteroaromatic ring of compound 45 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 45 as the lead compound.
One of ordinary skill in the art would also have had a reasonable expectation of success in obtaining a compound retaining the pre-mRNA splicing activity, because Zhang #2 expressly identifies hydrogen and halo as alternative R4 substituents within the formula (I) compounds are useful for improving pre-mRNA splicing. Further, Patani et al. teaches that trivalent -CH= with -N= are classical biososteres and that substitution of -CH= with -N= is a recognized medicinal-chemistry approach used to provide structurally related compounds having similar biological activity. In view of these teachings, one of ordinary skill would have reasonably expected that selecting the known -CH=/-N= bioisosteric replacement in the fused heteroaromatic ring of compound 45 of Zhang #2 would provide the corresponding triazine analog while retaining the biological activity associated with Zhang #2’s pre-mRNA splicing scaffold, thereby arriving at elected compound 4 with a reasonable expectation of success.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual 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 1-6, 14, 19 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 13-22 and 24 of copending Application No. 18/707,166, in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176).
The claims of reference application are drawn to a compound of Formula (I) or a pharmaceutically acceptable salt thereof useful for modulating splicing of a Ataxin3 pre-mRNA, including compound 1 having the structure of:
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in Table 1; and a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.
The claims of reference application do not teach the elected compound species.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity and have been classified as either classical or nonclassical (see e.g., p. 3148-3149). Patani et al. further teaches in classical bioisosteres, trivalent substitution of -CH= with -N= is commonly used in modern drug design, for example, trivalent ring substitution of -CH= with -N= in the anti-bacterial agent norfloxacin resulted in enoxacin which is also in clinical use for its antibacterial activity shown below:
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(see e.g., p. 3159, right column, last paragraph to p. 3160, Table 29).
The difference between compound 1 of reference application and the claimed compound is shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention to select the Compound 1 of reference application, and then modifying said compound by replacing trivalent carbon (-CH=) of six-membered fused heteroaryl ring with nitrogen (-N=) as taught by Patani et al. One would have been motivated to modify compound 45 of Zhang #2 by replacing corresponding trivalent carbon (-CH=) of the six-membered fused heteroaryl ring with nitrogen (-N=), thereby arriving at the ring substitution present in the elected compound 4. Patani et al. expressly teaches that replacement of trivalent -CH= with -N= constitutes a classical biososteric replacement and that such bioisosteric substitutions are employed in medicinal chemistry for the rational modification of lead compounds to obtain structurally related compounds having similar biological activity. Accordingly, one of ordinary skill in the art seeking to arrive at additional analogs of the reference compound would have been motivated to employ the known -CH=/-N= bioisosteric replacement in the heteroaromatic ring of compound 1 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 1 as the lead compound.
One of ordinary skill in the art would also have had a reasonable expectation of success in
obtaining a compound that retains the pre-mRNA splicing activity, because Patani et al. teaches that trivalent -CH= with -N= are classical biososteres and that substitution of -CH= with -N= is a recognized medicinal-chemistry approach used to provide structurally related compounds having similar biological activity. In view of these teachings, one of ordinary skill would have reasonably expected that selecting the known -CH=/-N= bioisosteric replacement in the fused heteroaromatic ring of compound 1 of reference application would provide the corresponding triazine analog while retaining the biological activity associated with reference application’s Ataxin3 pre-mRNA splicing scaffold, thereby arriving at elected compound 4 with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 14, 19 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 13-22, 24 and 26 of copending Application No. 18/707,167, in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176).
The claims of reference application is drawn to a compound of Formula (I) or a pharmaceutically acceptable slat thereof useful for modulating splicing of a Ataxin3 pre-mRNA, including compound 43 having the structure of:
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in Table 1 (referred to herein as “compound 43”); and a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier. The claims of reference application further teaches the compound of Formula (I) or a pharmaceutically acceptable slat thereof:
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, wherein R21 is selected from, inter alia, 5 membered heteroaryl (see e.g., claim 1); wherein R21 is
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, wherein
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represents a single or a double bond; each of A1, A2, A3, and A5 is independently selected from the group consisting of, inter alia, N, NH, C, CH and CH2; and A4 is selected from the group consisting of, inter alia, N, C and CH (see e.g., claim 2).
The claims of reference application do not teach the elected compound species.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical (see e.g., p. 3148-3149). Patani et al. further teaches in classical bioisosteres, trivalent substitution of -CH= with -N= is commonly used in modern drug design, for example, trivalent ring substitution of -CH= with -N= in the anti-bacterial agent norfloxacin resulted in enoxacin which is also in clinical use for its antibacterial activity shown below:
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(see e.g., p. 3159, right column, last paragraph to p. 3160, Table 29).
According to MPEP 2144.09, I, “a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.”; and MPEP 2144.09, III, further states: “[p]rior 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”.
Same logic is applicable to instant case, the compound 43 of reference application and the claimed compound have very close structural similarities and similar utilities, and the structural difference is shown below (see shaded):
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. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the compound 43 of reference application, and then modifying said compound by replacing the pyrrole ring with a pyridine ring, and replacing trivalent carbon (-CH=) of six-membered fused heteroaryl ring with nitrogen (-N=) as taught by Patani et al. One would have been motivated to modify compound 43 of reference application by:
replacing the pyrrole ring with a pyridine ring and
replacing corresponding trivalent carbon (-CH=) of the six-membered fused heteroaryl ring with
nitrogen (-N=), thereby arriving at the ring substitution present in the elected compound 4. The reference application expressly teaches that
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at R21 of its Formula (I) can contain nitrogen(s) at any position of the heteroaryl ring (i.e., at A1, A2, A3, A4, or A5), and identifies compound 43 is useful for modulating splicing of a Ataxin3 pre-mRNA. Thus, the reference application itself would have suggested that the nitrogen atom can present at any position of the heteroaryl ring while retaining the disclosed Ataxin3 pre-mRNA splicing utility.
With respect to the pyrrole to pyridine substitution, both are monocyclic heteroaryl rings that have very close structural similarities. The only structural difference between these rings was that the pyridine of the claimed compound had 5 carbon atoms and 1 nitrogen atom whereas the pyrrole of the reference compound has 4 carbon atoms and 1 nitrogen atom. Although the pyrrole and the claimed pyridine are not true homologs, the similarity between the pyrrole and pyridine is sufficiently close that one of ordinary skill in the art would have been motivated to make the substitution in searching for new compound useful for modulating splicing of a Ataxin3 pre-mRNA.
With respect to the carbon-to-nitrogen ring substitution, Patani et al. teaches that replacement of trivalent -CH= with -N= constitutes a classical biososteric replacement and that such bioisosteric substitutions are employed in medicinal chemistry for the rational modification of lead compounds to obtain structurally related compounds having similar biological activity. Accordingly, one of ordinary skill in the art seeking to arrive at additional analogs of reference compound would have been motivated to employ the known -CH=/-N= bioisosteric replacement in the heteroaromatic ring of compound 43 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 43 as the lead compound.
One of ordinary skill in the art would also have had a reasonable expectation of success in obtaining a compound that retains the activity of modulating Ataxin3 pre-mRNA splicing, because the reference application expressly identifies nitrogen present at any position of the heteroaryl ring at R21 within the formula (I) compounds are useful for modulating splicing of a Ataxin3 pre-mRNA; and one would have reasonably expect that pyrrole and pyridine have very close structural similarities that differ by one carbon atom would have expect to retain the similar properties. Further, Patani et al. teaches that trivalent -CH= with -N= are classical biososteres and that substitution of -CH= with -N= is a recognized medicinal-chemistry approach used to provide structurally related compounds having similar biological activity. In view of these teachings, one of ordinary skill would have reasonably expected that selecting the known -CH=/-N= bioisosteric replacement in the fused heteroaromatic ring of compound 43 of reference application and interchanging pyrrole with pyridine would provide the corresponding analog while retaining the biological activity associated with reference application’s Ataxin3 pre-mRNA splicing scaffold, thereby arriving at elected compound 4 with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 14, 19 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 13-22, 24 and 26 of copending Application No. 18/707,170.
The claims of reference application is drawn to a compound of Formula (I) or a pharmaceutically acceptable slat thereof useful for modulating splicing of a Ataxin3 pre-mRNA, including compound having the structure of:
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(referred to herein as “compound 2”); and a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier. The claims of the reference also teaches the compound of Formula (I) or a pharmaceutically acceptable slat thereof:
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, wherein R21 is selected from the group consisting of, inter alia, 5 membered heteroaryl (see e.g., claim 1); wherein R21 is
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, wherein
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represents a single or a double bond; each of A1, A2, A3, and A5 is independently selected from the group consisting of, inter alia, S, N, NH, C, CH and CH2; and A4 is selected from the group consisting of, inter alia, C and CH (see e.g., claim 2).
According to MPEP 2144.09, I, “a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.”; and MPEP 2144.09, III, further states: “[p]rior 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 are 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”.
Same logic is applicable to instant case, the compound 2 of reference application and the claimed compound have very close structural similarities and similar utilities, and the structural difference is shown below (see shaded):
PNG
media_image23.png
205
349
media_image23.png
Greyscale
.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the compound 2 of reference application, and then modifying said compound by replacing the sulfur atom of the thiophene ring with a nitrogen atom (i.e., pyrrole), and then replacing said pyrrole ring with a pyridine ring. One would have been motivated to modify compound 2 of reference application by:
replacing the sulfur atom of thiophene ring with a nitrogen atom and
replacing said pyrrole ring with a pyridine ring,
thereby arriving at the ring substitution present in the elected compound 4. The reference application expressly teaches that A1, A2, A3, and A5 of
PNG
media_image16.png
88
56
media_image16.png
Greyscale
at R21 of its Formula (I) may be sulfur, nitrogen or carbon, and identifies compound 2 is useful for modulating splicing of a Ataxin3 pre-mRNA. Thus, the reference application itself would have suggested that nitrogen as an alternative to sulfur and suggested that changing the position of nitrogen to A1, A2, A3 can retain the disclosed Ataxin3 pre-mRNA splicing utility.
With respect to the pyrrole to pyridine substitution, both are monocyclic heteroaryl rings that have very close structural similarities. The only structural difference between these rings was that the pyridine of the claimed compound had 5 carbon atoms and 1 nitrogen atom whereas the pyrrole of the reference compound has 4 carbon atoms and 1 nitrogen atom. Although the pyrrole and the claimed pyridine are not true homologs, the similarity between the pyrrole and pyridine is sufficiently close that one of ordinary skill in the art would have been motivated to make the substitution in searching for new compound useful for modulating splicing of a Ataxin3 pre-mRNA.
One of ordinary skill in the art would also have had a reasonable expectation of success in obtaining a compound that retains the activity of modulating Ataxin3 pre-mRNA splicing, because the reference application expressly identifies nitrogen, carbon, and sulfur as alternative A1, A2, A3, and A5 within the formula (I) compounds are useful for modulating splicing of a Ataxin3 pre-mRNA; and one would have reasonably expect that pyrrole and pyridine have very close structural similarities that differ by one carbon atom would have expect to retain the similar properties. In view of these teachings, one of ordinary skill would have reasonably expect that replacing the sulfur atom of thiophene ring with nitrogen, and interchanging pyrrole with pyridine would provide the corresponding analog while retaining the biological activity associated with reference application’s Ataxin3 pre-mRNA splicing scaffold, thereby arriving at elected compound 4 with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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