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 of compound of example 112
PNG
media_image1.png
280
234
media_image1.png
Greyscale
in the reply filed on 06/22/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 2-3, 6-11, 14, 16, and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/invention, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
A reasonable and comprehensive search conducted by the Examiner determined that the prior art at the time of the present invention was such that it did anticipate or render obvious the elected specie
PNG
media_image1.png
280
234
media_image1.png
Greyscale
. In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected specie, i.e., the compounds of the formula (II)
PNG
media_image2.png
242
412
media_image2.png
Greyscale
and
PNG
media_image3.png
368
412
media_image3.png
Greyscale
Wherein
R1 is 5-membered heteroaryl substituted with RX
Rx is C-alkyl and H;
A is 9-membered bicyclic heeroaryl;
R3 and R4 taken together with the carbon to which they attached to from a C3-cyclolakyl;
R2 is NRgRh; and
RgRh together to which they attached to form a 9-membered heterocycle substituted with
C1-alkyl.
is CH, R6 is hydrogen atom, Z is –O-CH2-, n is 2 and R7 is optionally substitued -SO2-aryl and X is N.
The prior art search, however, are not extended to cover the full scope of the compound of the formula (I).
Priority
This application claims priority from United Stated Provisional Patent Application Number 63/462,847 that was filed on 28 April 2023.
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. U.S. Provisional Patent Application Number 63/462,847, 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 disclosure of the Provisional Application fails to provide adequate support for the compound of the formula (I)
PNG
media_image4.png
214
234
media_image4.png
Greyscale
wherein:
R1 is 5-membered heteroaryl substituted with RX
Rx is C-alkyl;
A is 9-membered bicyclic heeroaryl;
R3 and R4 taken together with the carbon to which they attached to from a C3-cyclolakyl;
R2 is NRgRh; and
RgRh together to which they attached to form a 9-membered heterocycle substituted with
C1-alkyl.
is CH, R6 is hydrogen atom, Z is –O-CH2-, n is 2 and R7 is optionally substitued -SO2-aryl and X is N, including the elected compound.
Accordingly, claims 1, 4-5, 12-13, 15, 17-18, and 21 are not entitled to the benefit of the
prior U.S. Provisional Patent Application Number 63/462,847 and they are entitled to the priority date of 04/26/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/24/2025 and 11/10/2025 has been considered by the examiner.
Claims Status
Claims 1-21 are pending. Claims 2-3, 6-11, 14, 16, and 19-20 are withdrawn. Claims 1, 4-5, 12-13, 15, 17-18, and 21 are examined in accordance to the elected spcies.
Claim Objections
Claim 1 are objected to because of the following informalities.
Claim 1 recites, in the definition of A, that is “A is a 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl, which is 9-membered bicyclic heteroaryl and 10-membered bicyclic heteroaryl is optionally substituted ….” The recitation is grammatically inconsistent because the singular verb “is” follows the identification of the two-alternative bicyclic heteroaryl groups. Appropriate correction is required, for example, “each of which is optimally substituted,” other equivalent language that accurately reflects Applicant’s intended scope.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-5, 12-13, 15, and 17-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Possession of broad genus may be demonstrated, for example, by disclosure of a sufficient number of representative species encompassing the breadth of the genus or by disclosure structural feature common the members of the genus such that one skilled in the art can visualize or recognize the members of the claimed genus. The determination is based on the disclosure as a whole and does not turn merely on the numerical relationship between the number of specifically disclosed compound and the theoretical number of compounds encompassed by the claim.
Claim 1 is directed to a compound of Formula (I), or a salt thereof, wherein Formula (I) contains multiple independently variable structural positions, including A, R1, R2, R3, and R4, together with additional nested variable associated with the substituents permitted at those positions.
In particular A encompasses either a 9-membered bicyclic heteroaryl or a 10-membered bicyclic heteroaryl, each of which may itself be optionally substituted by one of more independently selected substituents.
R1 independently encompasses, inter alia, halo, NRgRh, phenyl, benzyloxy, a 3-10-membered heteroaryl, or a 5-10-membered heteroaryl. Certain of these groups may further substituted with one or more independently selected Rx groups. Rx itself, encompasses numerous chemically distinct substituents and may be further be substituted with independently selected Ry groups. Thus, the scope associated with R1 is not limited merely to the specifically identified first-level substituent classes but additionally encompasses numerous combinations generated through successive levels of optional substitution.
R2 independently encompasses Re, -Ore, -SRe, or NRgRh, wherein the associated R groups themselves encompass additional structurally diverse alternatives.
R3 and R4 independently encompass hydrogn or C1-C6 alkyl, or alternatively may be taken together with the carbon to which they attached form a C3-C6 cycloalkyl group.
Accordingly, claim 1 encompass a genus resulting from the independent combianton of multiple structurally diverse alternatives at several poostions, including combinaitons generated by the nested substitution permtted within R1 and the additiohal alternatives incoporated though R2, R3 and R4.
Disclosure of exemplary compounds has been considered.
The Examiner has considered the substantial number of specifically prepared compounds disclosed in the specification. The specification described general synthetic procedures and provides approximately 115 compounds. The disclosed compounds are not chemically identical and demonstrate meaningful variation, particularly at the substituent corresponding to R1. The examples, include, among other structures, compounds containing thienyl, furyl, pyrazolyl, substituted pyrazolyl, pyridyl, and other heteroaryl or heterocyclic substituents. The disclosure also provided variation at other portions of Formula (I). For example, the specification demonstrates the frequently employed aminoalkyl-containing R2 embodiment and additionally provides spices containing other substituent arrangements. The disclosed species also include compounds containing the commonly exemplified H/methyl arrangement, as well as a species in which R3 and R4 together with the associated carbon from a cyclopropyl. Thus, the rejection is not based merely on the proposition that the specification disclosed numerically, nor is the rejection based on finding the specification fails to disclose Formula (I) or fails to expressly identify the individual generic substituent classes appearing in claim 1. Rather, the deficiency concerns whether the disclosed species are sufficiently representative of the structural breadth of the claimed genus as a whole.
A variable
The disclosed compounds reviewed by the Examiner are structurally concentrated with respect to the bicyclic heteroaryl group represented by A. The specifically prepared compounds are predominantly and based the presently reviewed disclosure appear essentially uniformly directed to compounds employing a quinoline-type bicyclic heteroaryl core at A. The quinoline core provides substantial support for that species and for compounds constructed around that species. However, claim 1 is not limited to quinoline. Instead, claim 1 encompasses the genus of 9-membered bicyclic heteroaryls and the genus of 10-membered bicyclic heteroaryls, optionally substituted as recited.
The specification’s generic definitions of heteroaryl identify numerous heteroaryl structures and ring systems. Such generic definition establish that Applicant contemplated various chemical groups within the terminology “heteroaryl.” However, the identification of individual heteroaryl structures in a general definition does not, without more, establish possession of the full genus of Formula (I) compounds resulting from incorporation of each such structurally distinct bicyclic heteroaryl as A in combination with the independently variable R1, R2, R3, and R4 substituents recited in the claims.
Particularly significant is the breadth encompassing 9-membered bicyclic heteroaryl A groups. The specifically prepared species reviewed do not appear to provide representative examples distributed across the branch of the claimed genus comparable to the extensive exemplification of the quinoline embodiment. Likewise, although quinoline provides a species within the 10-membered bicyclic heteroaryl genus, disclosure of numerous compounds sharing the same quinoline core doe not, by itself, provide representative species commensurate with the full structural diversity encompassed by all 10-membered bicyclic heteroaryls recited in the claims.
R1 and its nested substitution
The Examiner recognizes that the disclosure provides significant structural variation of R1. Accordingly, the rejection is not based on a finding that R1, standing alone, is wholly unsupported. Nevertheless, the scope of R1 extends materially beyond the specifically demonstrated R1 species.
Claim 1 permits multiple chemically distinct primary classes at R1 and further permits optional substitution of certain R1 groups by one or more independently selected Rx groups. Rx encompasses additional chemically diverse substituents and may itself be optional substituted by independently selected Ry. The resulting scope therefore encompasses not merely the individual heteroaryl, heterocyclic, phenyl, amino, or other R1 species, but a substantially larger genus generated through successive and independent levels of substitution.
Although the specification expressly lists these alternatives, the exemplary compounds are concentrated within particular combinations and do not provide representative species reasonably distributed throughout the full nested R1/Rx/Ry structural space encompassed by the claim.
R2 variable
The disclosure likewise provides substantial support for certain R2 embodiments, particularly exemplified aminoalkoxy-containing species. Claim 1, however, permits R2 independently to be Re, -ORe, -SRe, or -NRgRh, with the associated variables themselves encompassing further structurally distinct alternatives. The examples do not appear to provide comparable representative coverage across each of these chemically distinct R2 branches and their permitted substitutions. The Examiner does not rely upon this disparity in isolation. Rather, the R2 breadth further contributes to the structural diversity resulting from the independent combination of the claim variables.
R3 and R4 substituents
The disclosure provides substantial support for the frequently exemplified H/alkyl embodiment and additionally demonstrates at least a cyclopropyl embodiment in which R3 and R4 are taken together with their associated carbon. Accordingly, the Examiner does not rely principally upon R3/R4 as independently establishing the written description deficiency. The relevance of R3/R4 instead lies in the additional independent structural variation that the claim permits when these alternatives are combined with the substantial broader A R1, and R2 genera.
Deficiency resides in the full combinatorial genus
The written-description deficiency is therefore not that the specification fails to mention the individual chemical terms appearing in claim 1. Rather, the disclosure demonstrates possession of particular region of the claimed genus, especially compounds constructed around the repeatedly exemplified quinoline core and particular recurring combination remaining substituents. Claim 1 extends materially beyond those demonstrated regions by permitting independent selection among broad and chemically diverse A1, R1, R2, R3 and R4 alternatives, together with successive levels of optional substitutions. For example, claim 1 encompasses Formula (I) compounds simultaneously containing an unexemplified member of the 9-membered bicyclic heteroaryl genus at A, a multiply substituted heterocyclic or heteroaryl R1 containing Rx/Ry substitution, an independently selected and structurally distinct R2 branch, and an independently selected R3/R4 arrangement.
The disclosure of individual possibilities for each variable does not reasonably demonstrate that the inventors possessed the full genus generated by their unrestricted combination, particularly where the specifically prepared compounds are concentrated within a materially narrower structural region. The disclosure therefore does not provide a sufficient number or diversity of representative species commensurate with the full scope of the genus presently encompassed by claim, nor does the specification otherwise identify structural characteristics common to the members throughout the full claimed genus sufficient to demonstrate possession of the genus.
The biological data do not cure the representative-species deficiency
The Examiner has also considered the biological data provided for the disclosed compounds. The specification reports inhibition of SARS-CoV-2 papain-like protease (PLpro) using a FRET-based enzymatic assay and provides activity classification for representative compounds. Such data demonstrate that numerous specifically prepared compounds possess the tested activity. However, the biological date do not supply representative structural disclosure for the portion of the Formula (I) genus that are not otherwise adequately represented. Indeed, the tested compound remain members of the same structurally concentrated set of specifically prepared compounds discussed above. Biological characterization of numerous compounds within a particular structural region does not, with more, establish possession of structurally remote portions of the broader genus encompassed by the claim. Accordingly, the assay data have been considered but do not overcome the written description deficiency identified herein.
Generic Definitions do not alone establish possession of the claimed combinations
The Examiner has further considered the specification’s express definitions of terms such as alkyl, cycloalkyl, heterocycle, and heteroaryl and the numerous exemplary chemical groups identified within those definitions. The rejection does not rest upon an absence of literal terminology corresponding to the individual substituent alternatives. The written-description inquiry, however, is not satisfied merely because each individual substituent can be located somewhere in a generic list in the specification. The issue is whether the disclosure, viewed as a whole, reasonably conveys possession of the claimed Formula (I) genus resulting from the combinations of those alternatives. Here, the disclosure provides extensive evidence of possession of particular Formula (I) species and particular subgenera but does not provide representative species commensurate with the full structurally diversity resulting from the independent and nested combinations permitted by the claim.
Conclusion
Accordingly, although the specification demonstrates possession of numerous compounds falling within Formula (I), including a substantial number of specifically synthesized and biologically characterized species, the disclosure does not reasonably convey possession of the full genus presently encompassed by the claim. The exemplary compounds are concentrated within particular structural regions of the genus, particularly compounds employing the quinoline A core and recutting combinations of the remaining substituents, whereas the claim extends to materially broader 9- and 10-membered bicyclic heteroaryl A groups and permits extensive independent and nested variation among the remaining variables. The generic identification of individual substituent possibilities does not provide representative species commensurate with the structural diversity of the genus resulting from the claimed combinations. Therefore, the skilled artisan would not reasonably conclude from the disclosure that Applicant was in possession, as of the effective filing date, of the full scope of the presently claimed genus.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-5, 12-13, 15, 17-18, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frick et al. (US2024/0245673 A1).
Frick teaches compounds of Formula (I)
PNG
media_image5.png
353
794
media_image5.png
Greyscale
and pharmaceutically acceptable salts thereof for use in medicine and compositions, the compounds of Formula (I) may inhibit the activity of papain-like protease (PLpro) and may be useful in the treatment of viral infections, in particular viral infections associated with PLpro activity and/or expression such as coronaviruses infections. (See Abstract.) Frick further teaches a pharmaceutical composition comprising a compound of Formula (I) pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. (See claims 1 and 15. However, Frick gives particular preference in compounds
Example 252 Example 284
PNG
media_image2.png
242
412
media_image2.png
Greyscale
and
PNG
media_image3.png
368
412
media_image3.png
Greyscale
> (See paragraph [1433] and paragraph [1532].)
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.
Claims 1, 4-5, 12-13, 15, 17-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Frick et al. (US2024/0245673 A1).
Frick teaches compounds of Formula (I)
PNG
media_image5.png
353
794
media_image5.png
Greyscale
and pharmaceutically acceptable salts thereof for use in medicine and compositions, the compounds of Formula (I) may inhibit the activity of papain-like protease (PLpro) and may be useful in the treatment of viral infections, in particular viral infections associated with PLpro activity and/or expression such as coronaviruses infections, wherein R7 and R8 are each independently selected from the group consisting of H, halogen, hydroxy, C1-C6 alkyl, C1-C6 alkoxy-C1-C6 alkyl, 4-10 membered heterocycloalkyl, —C1-C6 alkyl-NR14R15, —NHR16, —N(R13)—C(═O)—R16, and —C(═O)—NR14R15, wherein any said 4-10 membered heterocycloalkyl is optionally substituted with one, two or three R10 and each R10 is independently C1-C6 alkyl. (See Abstract and claim 1.) Frick further teaches a pharmaceutical composition comprising a compound of Formula (I) pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. (See claims 1 and 15. However, Frick further exemplified compound within the disclosed genus, including compounds 252 and 284 reproduced below:
Example 252 Example 284
PNG
media_image2.png
242
412
media_image2.png
Greyscale
and
PNG
media_image3.png
368
412
media_image3.png
Greyscale
(See paragraph [1433] and paragraph [1532].)
The difference between the elected compound and compound of Example 252 of the prior art is as follow:
Elected compound Prior art compound of example 252
PNG
media_image6.png
280
234
media_image6.png
Greyscale
PNG
media_image7.png
242
413
media_image7.png
Greyscale
It would have been prima facie obvious to one of ordinary skill in the art at the time the inventioh was filed to modify the compound of Example 252 of Frick by replacing the hydrogen substituent on the nitrogen-containing bicyclic heterocycle with a methyl group and correspondingly selecting the closely related bicyclic amino substituent encompassed by Frick, thereby arriving at the elected compound. Frick expressly teaches that comound within its Formula (I), including structurally realted comopunds such as Examples 252 and 284, are usefule inhibitors of papain-like propetease )PLpro_ and for the treatment of viral infection associated with PLpro activity and/or express. Frick further expressly permits substitution of the relevant heterocycloalkyl substituent, including substitution with C1-C6 alkyl groups. Thereby teaching methyl as a permitted substituent with the same structural position.
One of ordianry skill in the art would have been motivated to make such modification because Frick itself teaches a genus of structurally related PLpro inhibitors in which substituion of the relevant nitrogen-containing heterocyclic/bicyclic moeity is permitted and identifies C1-C6 alkyl substituion as espressly contemplated variation. Methyl represents the smallest and structurally least disruptive member of the expreslly taught C1-C6 alkyl genuys. Moreover, Frick’s exemplifed compounds demonstrate structurally related introngen-containing cyclic substituents are tolerated within the same PLpro-inhibitor comound class. Thus, the proposed modification would not require changing fundamental scaffold or mechanism taught by Frick, but rather would constitute selection fo an expressly taught substituent within a position Frick identifies as variable.
One of ordinary skill in the art would also have had a reasonable expectation of scuccessfully preparing the modifed comopund and retaining the PLpro-inhibitory utility taught by Frick. Frick provides a common Formula (I) encompassing the relevant structural variation, expressly teaches C1-C6 alkyl substituion at the pertinent hetercyclic substituent, and exmplifies numerous compounds sharing the same overall pharmacophore and PLpro-inhibitor purpose, In view of these teachings, the ordianary skilled artisan would have reasoanbly expected the relatively conservative substituion of methyl for hydrogen at the indicated nitrogen-containing bicylic moeity would be chemically tolerated and woul proivde another member of Frick’s disclosed class of PLpro inhibitors. Obviousness does not require certainty of identical potent or a guarantee of success; rather, the teachings of Frick would have provided a reasoanble expectation that the modified comound could be prepared and would retain the disclosed PLpro-inhibitor activity.
Accordingly, the elected claimed compound represents no more than a predictable structural varation within the class expressly taught by Frick, obtained by selecting a substituent and heterocyclic embodiment taught Frick for the same PLpro-inhibitory purpose. Therefore, the elected species and claims 1, 4-5, 12-13, 15, 17-18, and 21 would have been obvisous to one of ordinary skill in the art over Frick.
Conclusion
Claims 1, 4-5, 12-13, 15, 17-18, and 21 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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, Amy L Clark can be reached at 571-272-1310. 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.
/JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights