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 .
Claim Status
Claims 1-10,13-15, 18, 22, 27-28, and 32-34 are pending. Claims 27-28 and 32-34 are withdrawn as directed to a non-elected invention. Claims 2-5, 7, 9-10, 13-15, 18, and 22 are withdrawn as directed to non-elected species. Claims 1, 6 and 8 are presently considered.
Election/Restriction
Applicant’s election without traverse of Group I (original claims 1-10, 13-15, 18, and 22, directed to products) and the species, shown below, in the reply filed on 4/20/2026 is acknowledged.
The originally elected species is understood to be
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The elected species is understood to satisfy the requirements of Formula (I) at claim 1, which has the following structure:
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,
wherein R3 is understood to be the substituted cycloalkyl1 of 4-N-methyl-piperazinyl (
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); wherein R2 is a benzyl group, which is a C1 alkyl further substituted with a phenyl moiety (i.e., a benzyl group is an alkyl substituted with an aryl;
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); wherein R1 is an aryl and specifically a pyridinyl moiety (
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); and wherein A is
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and R16 is a C2 alkyl. Applicant failed to identify where in the originally filed disclosure the elected species was actually disclosed (i.e., by page, Example, or Figure number), and it the corresponding CAS Registration number is unknown. It is presently assumed Applicant made a proper species election by electing a single, disclosed species as required by the requirement, and that Applicant did not introduce new matter by electing a non-disclosed species.
Although Applicant identified that the originally elected species read upon instant claims 1, 6-8, and 18 (see, e.g., Reply filed 4/20/2026 at 2), this is incorrect because the species does not read upon claim 7 since it lacks an R3 that is either a “benzyloxy 4-N-methyl-piperazinyl” or otherwise a benzyloxycarbonyl moiety. Furthermore, no concentration was identified on record in connection to the originally elected species corresponding to “an effective amount to inhibit a cysteine protease” (i.e., it is unclear the originally elected species was tested at all, and it does not appear at Table 1), and, therefore, the elected species does not read upon claim 18. Accordingly, the originally elected species is understood to read upon instant claims 1, 6, and 8.
Following extensive search and examination, the originally elected species has been deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to a non-elected species of CAS Reg No: 438045-12-6
and CAS Reg. No: 438045-12-6. Following extensive search and examination, the non-elected species was deemed anticipated in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 27-28 and 32-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/20/2026.
Claims 2-5, 7, 9-10, 13-15, 18, and 22 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. Election was made without traverse in the reply filed on 4/20/2026.
Accordingly, claims 1, 6, and 8 are presently considered.
Priority
The priority claim to US Provisional 63/156198 (filed 03/03/2021) and US Provisional 63/156211 (filed 3/03/2021) are acknowledged.
Information Disclosure Statement
The IDS filed 9/05/2023; 10/28/2024; 10/28/2024; and 10/28/2024 are each acknowledged and presently considered.
Applicant should note that one or more documents disclosed on the IDS form submitted on 10/28/2024 were not considered since they did not conform to 37 CFR 1.98(b) by providing a proper date, as 37 CFR 1.98(b) requires that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. See MPEP 609.04(a). Here, the earliest priority claim is US Provisional 63/156198, filed 03/03/2021); therefore, all documents published in 2020 or later must be accompanied by both month and date of publication.
References that were not considered have been indicated by strike-though on the attached IDS forms. Although not considered, these documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01 (see, e.g., Spec. filed 9/05/2023 at p. 103, showing links at citation (2) and (8)-(9); id. at 155 at 1st full ¶).
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Drawings
The drawings are objected to because:
The images contain illegible text or images of such low resolution that details are obscured. Specifically, Figure 10(a), 16, 18, 20, 22A, 23C, and 25A contain illegible aspects.
The Figures do not show colors (see, e.g., Spec. filed 2023-09-05 at page 7 and 128, referring to “blue” and “red” at Figs. 25A-25B; see id. at 7 referring to Fig. 22A-22C showing “green” and “colored dashed lines”).
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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections
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.
[Rejection 01]
Claims 1, 6, and 8 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by WO2002/48097 (attached with appended CAS substance table, 10 pages).
Regarding instant claims 1, 6, and 8, WO’097 teaches and discloses compounds within the instant claim scope (see, e.g., WO’097 at claims 1, 7, 13, 33, and 35-38), including at least the following two compounds:
1.N-(N-(4-methylpiperazinylcarbonyl)phenylalanyl) tyrosinal (i.e., [4-metylpiperazine]-C(=O)-[Phenylalanine-[Tyrosinal], wherein Tryrosinal is Tyr-H where the carboxylic acid (COOH) is reduced to an aldehyde (CHO)) (see, e.g., WO’097 at claim 13 at page 82). This claimed compound corresponds to substance “47” and CAS No. 438045-11-5 in the Substance Table, which identifies that the compound may alternatively be called 1-Piperazinecarboxamide, N-[(1S)-2-[[(1S)-1-formyl-2-(4-hydroxyphenyl)ethyl]amino]-2-oxo-1-(phenylmethyl)ethyl]-4-methyl-N-(N-(4-methylpiperazinylcarbonyl)phenylalanyl)tyrosinal, and that the compound has the chemical structure of
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This chemical structure satisfies the requirements of instant claims 1, 6, and 8 wherein R1 is a substituted aryl, R2 is a benzyl moiety (an aryl substituted C1 alkyl), A is
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, and R3 is a 4N-alkyl-piperazinyl moiety (see, e.g., WO’097 at Substance Table at Compound 47, claim 13).
(S)-2-(N-(4-methylpiperazinylcarbonyl)phenylalanyl)amino-4-phenylbutanal, (i.e., ) (see, e.g., WO’097 at claim 13 at page 82). This compound corresponds to Substance Table Compound “48” and CAS NO: 438045-12-6 in the Appended Substance Table, which identifies that the compound may alternatively be called 1-Piperazinecarboxamide, N-[(1S)-2-[[(1S)-1-formyl-3-phenylpropyl]amino]-2-oxo-1-(phenylmethyl)ethyl]-4-methyl-(S)-2-(N-(4-methylpiperazinylcarbonyl)phenylalanyl)amino-4-phenylbutanal (see, e.g., WO’097 at Substance Table at Compound 48, claim 13), and the compound has the chemical structure of
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This chemical structure satisfies the requirements of instant claims 1, 6, and 8 wherein R1 is a aryl-substituted alkyl, R2 is a benzyl moiety (an aryl substituted C1 alkyl), A is
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, and R3 is a 4N-alkyl-piperazinyl moiety (see, e.g., WO’097 at Substance Table at Compound 48, claim 13).
Furthermore, formulations and applications of such compounds were known and claimed in the prior art (see, e.g., WO’097 at claims 1, 7, 13, 33, and 35-38).
Accordingly, claims 1, 6, and 8 are clearly anticipated by the prior art.
[Rejection 02]
Claims 1, 6, and 8 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Lee et al.2.
Regarding instant claims 1, 6, and 8, Lee discloses the compound of “4-Methylpiperazinyl-CO-Phe-hPhe-al”, wherein “al” is understood to be aldehyde (-CHO), as Compound 9052 (see, e.g., Lee at Table 1 on 3811). This compound is understood to have the following chemical structure3:
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(see, e.g., Lee at Table 1 on 3811). This structure satisfies the requirements of instant claims 1, 6, and 8, wherein R1 is a aryl-substituted alkyl, R2 is a benzyl moiety (an aryl substituted C1 alkyl), A is
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, and R3 is a 4N-alkyl-piperazinyl moiety (compare Compound 9052 at Lee at Table 1 on 3811 with instant claims 1, 6, and 8). In addition, in view of Table 1, an artisan would readily appreciate that the tested compounds were necessarily and inherently utilized in purified form in pharmaceutical assays requiring pharmaceutical compositions wherein the compound was present in an amount effective for obtaining an IC50 value.
Accordingly, claims 1, 6, and 8 are anticipated by the prior art.
[Rejection 03]
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by SCHEMBL11863658 (published in 2015; cited in IDS filed 9/05/2023 as cite No. 3).
Regarding instant claim 1, SCHEMBL11863658 discloses the compound of
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, (see, e.g., SCHEMBL11863658 at 1-8), which satisfy the requirements of instant claim 1, wherein R3 is substituted alkyl (-CH2NH2), R1 is aryl; R2 is hydrogen; and A is -C(O)H (see, e.g., SCHEMBL11863658 at 1-8).
Accordingly, claim 1 is anticipated by the prior art.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US20230301988 (corresponding to abandoned Application 18/023,661; Notice of abandonment mailed 4/27/2026) pertains to highly similar compounds to those presently claimed. The prosecution history and art therein is relevant to the instant application.
Examiner Notes
To facilitate compact prosecution, if Applicant amends the claims to recite the originally elected species directly, Applicant should clearly identify all supporting disclosure(s) to such species present in the originally filed disclosure and priority documents.
Examiner assumes the species election was properly performed by Applicant (i.e., that a single, disclosed species was properly elected as required by the Requirement mailed 2/18/2026). However, following review, the Examiner was unable to find unambiguous support in the original disclosure for this exact species. In the absence of clear support, Applicant is advised that in the absence of identification, a subsequent amendment attempting to specifically claim this exact species may necessitate a rejection under 35 USC §112 and/or alter the applicable priority.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 The 4-N-methyl-piperazinyl was identified in the Response to Requirement filed 4/20/2026 as a heteroaryl of 4-N-methyl-piperazinyl, which is understood to be an error, as this substituent is understood to be a substituted cycloalkyl, wherein “substitutions” include substitutions of carbons with nitrogen (see, e.g., Spec. filed 9/05/2023 at 16 at 2nd and 3rd full ¶¶, 16-17 at bridging ¶, 17 at 1st full ¶ to 18 at 1st partial ¶, 20 at 1st full ¶, dependent claim 6).
2 Lee et al, 2003. Antimalarial Activities of Novel Synthetic Cysteine Protease Inhibitors. Antimicrob Agents Chemother 47, https://doi.org/10.1128/aac.47.12.3810-3814.2003; hereafter “Lee”.
3 Examiner notes that this corresponds to the attached Search notes identifying references associated with CAS NO: 438045-12-6.
Prosecution Insights