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 a compound of Formula (I), or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound; and a Compound 35 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 35, when construed in view of the specification (see e.g., page 62, compound 35), has a chemical name of “6-[(2S)-2-aminopropyl]-7-bromo-N-[(thiophen-2-yl)methyl]thieno[3,2-c]pyridazin-4-amine”.
Claims 13, 15, 17-20, 24 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.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 November 25, 2024, wherein claims 1-3 and 21 are unchanged; claims 4-6, 13-20, 22, and 24 are amended; claim 26 is newly added; claims 7-12, 23 and 25 are canceled.
Claims 1-6, 13-22, 24 and 26 are pending.
Claims 13, 15, 17-20, 24 and 26 are withdrawn.
Claims 1-6, 14, 16, and 21-22 are under examination in accordance with the elected species.
Priority
The instant application 18/707,167 filed on May 3, 2024 is a 371 of PCT/US2022/079347 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(e) 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. 18/707,167, 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 not entitled to the benefit of the prior-filed applications and will receive an effective filling date of November 4, 2022, which is the filling date of 371 of PCT/US2022/079347.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/25/2024, 7/30/2026, and 8/6/2026 are 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.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that the specification contains a nucleic acid sequence, see for example, Table 4 of the specification, as originally filed. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
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 “
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” 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 5 membered heteroaryl, and 5 membered heterocycloalkyl”; However, claim 2, when reasonably construed under the broadest reasonable interpretation, the A1, A2, A3, A4, and A5 of said 5 membered heteroaryl or heterocycloalkyl can each independently be carbon, and
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can selected from a single bond or a double bond to give a 5 membered aryl or a 5 membered cycloalkyl. In other words, it is not clear if applicant is intending to (i) redefine “5 membered heteroaryl” and “5 membered heterocycloalkyl” to include aryl and cycloalkyl, (ii) or exclude aryl and 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, the recitation of “
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“, includes 5-membered cycloalkyl such as cyclopentane (i.e.,
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, wherein A1, A2, A3 and A5 are independently carbon and
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is single bond) that 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 “5 membered heteroaryl, and 5-membered heterocycloalkyl”, and that excludes the 5-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, 16, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2020/167628 A1; cited in the IDS filed on October 25, 2024), in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176; cited in the IDS filed on July 30, 2026).
Zhang et al. teaches Compound 53, 2-[(2S)-2-aminopropyl]-3-bromo-5-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-b]pyridin-7-amine (see e.g., p. 31, Cpd 53), having the structure of:
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(see e.g., p. 19, Compound 53) is an exemplary compound of Formula (I) useful for improving pre-mRNA splicing in a cell (see e.g., abstract). Zhang et al. further teaches the compound of Formula (I):
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, wherein R1 is, inter alia, phenyl or heteroaryl; R5 is, inter alia, hydrogen or halo (see e.g., p. 2, line 20 to p. 30, line 34); and the term “halo” includes chloro and the term “heteroaryl” includes thiophenyl, and the term thiophenyl may also be referred to as thienyl (see e.g., p. 46, line 22 to p. 47, line 1; p. 48, line 20-21). Zhang et al. further teaches a pharmaceutical composition comprising an effective amount of the compound in admixture with a pharmaceutically acceptable excipient (see e.g., claims 12-13). Zhang et al. 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. 50, line 13-14).
Zhang et al. does not teach the elected species of compound of Formula (I).
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 53 of Zhang et al. 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 53 of Zhang et al., and then modifying said compound by replacing chlorine atom with hydrogen at R5, changing the position of sulfur atom in the thienyl, 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 53 of Zhang et al. by:
selecting hydrogen in place of chlorine at the R5 position
changing the position of sulfur atom in the thienyl 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 35. Zhang et al. expressly teaches that R5 of its Formula (I) compounds may be hydrogen or halo, including chloride, and R1 of its Formula (I) compounds may be heteroaryl, including thienyl, and identifies compound 53 is useful for improving pre-mRNA splicing in a cell. Thus, Zhang et al. itself would have suggested hydrogen as an alternative to chlorine at R5 and attach thienyl at any suitable attachment point 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 et al.’s pre-mRNA splicing compounds would have been motivated to employ the known -CH=/-N= bioisosteric replacement in the heteroaromatic ring of compound 53 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 53 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 et al. expressly identifies hydrogen and halo as alternative R5 substituents and thienyl as R1 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 53 of et al. would provide the corresponding triazine analog while retaining the biological activity associated with Zhang et al.’s pre-mRNA splicing scaffold, thereby arriving at elected compound 35 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.
Claims 1-6, 14, 16, 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”).
Zhang#2 teaches Compound 82, 6-[(25)-2-ami nopropyl]-7-bromo-2-chloro-N-[(thiophen-2-yl)methyl]thieno[3,2-d]pyrimidin-4-amine (see e.g., p. 28, Cpd 82), having the structure of:
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(see e.g., p. 21, Compound 82) 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 R1 is, inter alia, phenyl or heteroaryl; R4 is, inter alia, hydrogen or halo (see e.g., claim 1); and the term “halo” includes chloro and the term “heteroaryl” includes thiophenyl, and the term thiophenyl may also be referred to as thienyl (see e.g., p. 39, line 25-26; p. 37, line 34 to p. 38, line14). 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).
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. ‘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)”; and according to MPEP 2144.09, II, “[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In reWilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977)”.
Same logic is applicable to instant case, the compound 82 of Zhang#2 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 82 of Zhang #2, and then modifying
said compound by replacing chlorine atom with hydrogen at R4, changing the position of sulfur atom in the thienyl ring, and then changing the position of the nitrogen atom in the diazine fused ring. One would have been motivated to do so, because Zhang #2 expressly teaches that R4 of its Formula (I) compounds may be hydrogen or halo, including chloride, and identifies compound 82 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 changing the position of sulfur atom in the thienyl ring, and the position of the nitrogen atom in the diazine fused ring, position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
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 the reference application expressly identifies hydrogen and halo as alternative R4 substituents within the formula (I) compounds are useful for improving pre-mRNA splicing; and position isomers have very close structural similarities and similar utilities. In view of these teachings, one of ordinary skill would have reasonably expected that changing the position of sulfur atom in the thienyl ring, and changing the position of the nitrogen atom in the diazine fused ring would provide the corresponding position isomers while retaining the biological activity associated with Zhang #2’s pre-mRNA splicing scaffold, thereby arriving at elected compound 35 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, 16, 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.
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 20 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 is also drawn to the compound of Formula (I) or pharmaceutically acceptable salt thereof
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, wherein R21 is hteroaryl; R21 is
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, wherein
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represents a single or double bond; each of A1, A2, A3, A5, and A6 is independently selected from the group consisting of S, N, C, CH; and A4 is selected from the group consisting of N, C, CH, and CR1A (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 20 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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241
439
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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 20 of reference application, and then modifying said compound by replacing the nitrogen atom of the pyridyl ring with a sulfur (i.e., thiopyrylium), and then replacing said thiopyrylium ring with a thiophene ring. One would have been motivated to modify compound 20 of reference application by:
replacing the nitrogen atom of pyridyl ring with a sulfur atom and
replacing said thiopyrylium ring with a thiophene ring,
thereby arriving at the ring substitution present in the elected compound 35. The reference application expressly teaches that A1, A2, A3, A5, and A6 of
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87
55
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at R21 of its Formula (I) may be sulfur, nitrogen or carbon, and identifies compound 20 is useful for modulating splicing of a Ataxin3 pre-mRNA. Thus, the reference application itself would have suggested that sulfur as an alternative to nitrogen and suggested that changing the position of sulfur to A1, A2, A3, A5, and A6 can retain the disclosed Ataxin3 pre-mRNA splicing utility.
With respect to the thiopyrylium to thiophene substitution, both are monocyclic heteroaryl rings that have very close structural similarities. The only structural difference between these rings was that the thiophene of the claimed compound had 4 carbon atoms and 1 sulfur atom whereas the thiopyrylium of the reference compound has 5 carbon atoms and 1 sulfur atom. Although the thiopyrylium and the claimed thiophene are not true homologs, the similarity between the thiopyrylium and thiophene 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, A5, and A6 within the formula (I) compounds are useful for modulating splicing of a Ataxin3 pre-mRNA; and one would have reasonably expect that thiopyrylium and thiophene 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 nitrogen atom of pyridyl ring with sulfur, and interchanging thiopyrylium with thiophene 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 35 with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 14, 16, 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. 18/707,168, in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176; cited in the IDS filed on July 30, 2026).
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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154
165
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in Table 1 (referred to herein as “compound 4”); 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 is also drawn to the compound of Formula (I) or pharmaceutically acceptable salt thereof
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239
211
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, wherein X4 is selected from the group consisting of N, and CR24; R24 is selected from the group consisting of, inter alia, H, halo, or C1-6 alkyl (see e.g., claim 1); and that can be CBr (see e.g., claim 16); or CCH3 (see e.g., claim 19); wherein R21 is
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, wherein
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15
45
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represents a single or a double bond; each of A1, A2, A3, A5 and A6 is independently selected from the group consisting of, inter alia, S, N, NH, C, CH, CR1A, CH2 (see e.g., claim 2).
The claims of the reference application do not expressly teach the elected compound species of Formula (I).
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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157
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101
389
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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 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 4 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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243
394
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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 4 of reference application, and then modifying said compound by replacing CCH3 with CBr at X4, replacing the nitrogen atom of the pyridyl ring with a sulfur (i.e., thiopyrylium), then replacing said thiopyrylium ring with a thiophene ring, and then replacing trivalent nitrogen (-N=) of six-membered fused heteroaryl ring with carbon (-CH=) as taught by Patani et al. One would have been motivated to modify compound 4 of reference application by:
selecting CBr in place of CCH3 at the X4 position,
replacing the nitrogen atom of pyridyl ring with a sulfur atom,
replacing said thiopyrylium ring with a thiophene ring, and
replacing corresponding trivalent replacing trivalent nitrogen (-N=) of six-membered fused heteroaryl ring with carbon (-CH=),
thereby arriving at the ring substitution present in the elected compound 35. The reference application expressly teaches that X4 of its Formula (I) may be CCH3 or CBr, and further teaches A1, A2, A3, A5, and A6 of
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55
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at R21 of its Formula (I) may be sulfur, nitrogen or carbon, and identifies compound 4 is useful for modulating splicing of a Ataxin3 pre-mRNA. Thus, the reference application itself would have suggested that CBr as an alternative to CCH3 at X4; sulfur as an alternative to nitrogen to arrive at
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86
58
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, and suggested that changing the position of sulfur to A1, A2, A3, A5, and A6 can retain the disclosed Ataxin3 pre-mRNA splicing utility.
With respect to the thiopyrylium to thiophene substitution, both are monocyclic heteroaryl rings that have very close structural similarities. The only structural difference between these rings was that the thiophene of the claimed compound had 4 carbon atoms and 1 sulfur atom whereas the thiopyrylium of the reference compound has 5 carbon atoms and 1 sulfur atom. Although the thiopyrylium and the claimed thiophene are not true homologs, the similarity between the thiopyrylium and thiophene 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 nitrogen-to-carbon ring substitution, Patani et al. teaches that replacement of trivalent -N= with -CH= 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 4 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 4 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 CBr as an alternative to CCH3 at X4, identifies nitrogen, carbon, and sulfur as alternative A1, A2, A3, A5, and A6 within the formula (I) compounds are useful for modulating splicing of a Ataxin3 pre-mRNA; and one would have reasonably expect that thiopyrylium and thiophene 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 expect that selecting the known -CH=/-N= bioisosteric replacement in the fused heteroaromatic ring of compound 4 of reference application, replacing CCH3 with CBr at X4, replacing the nitrogen atom of pyridyl ring with sulfur, and interchanging thiopyrylium with thiophene 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 35 with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 14, 16, 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, in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176; cited in the IDS filed on July 30, 2026).
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 8”); 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 application do not expressly teach the elected compound species of Formula (I).
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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103
157
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Greyscale
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101
389
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(see e.g., p. 3159, right column, last paragraph to p. 3160, Table 29).
The difference between compound 8 of reference application and the claimed compound is shown below (see shaded):
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241
439
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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 8 of the reference application, and then modifying said compound by replacing trivalent nitrogen (-N=) of six-membered fused heteroaryl ring with carbon (-CH=) as taught by Patani et al. One would have been motivated to modify the compound 8 of the reference application by replacing trivalent nitrogen (-N=) of six-membered fused heteroaryl ring with carbon (-CH=), because the reference application discloses compound 8 as one of the preferred embodiments useful for modulating splicing of a Ataxin3 pre-mRNA; and Patani et al. teaches that replacement of trivalent -N= with -CH= 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 8 because such a modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biosocial activity of compound 8 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 activity of modulating Ataxin3 pre-mRNA splicing, because one would have reasonably expected that selecting the known -CH=/-N= bioisosteric replacement in the fused heteroaromatic ring of compound 8 of reference application would provide the corresponding triazine analog while retaining the biological activity associated with reference application’s Ataxin3pre-mRNA splicing scaffold, thereby arriving at elected compound 35 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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