DETAILED ACTION
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, 28, 36, 37, 44, 46, 115, 116, and 125 are examined herein.
Claims 2, 25, 26, 32, 74, 104, 117, 123, 124, 142, 143 and 159 are withdrawn (see restriction/election below).
Priority
This application is filed 11/01/2023 and claims the benefit of domestic priority as below:
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Information Disclosure Statements
Four references from IDS(s) received on 01/09/2024, 02/19/2024, 02/11/2025, and 03/02/2026 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant elects Group I: claims 1, 2, 25, 26, 28, 32, 36, 37, 44, 46, 74, 104, 115-117 and 123-125, drawn to products of Formula (I), without traverse in the reply field on 03/02/2026 is acknowledged.
Claims 142, 143 and 159 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected process of use, there being no allowable generic or linking claim.
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Applicant elects Compound 170 as the species, without traverse in the reply field on 03/02/2026 is acknowledged.
The applicant asserts that the claims 1, 25, 26, 32, 36, 37, 44, 46, 115, 116 and 123-125 are readable on the elected species. However, the Examiner finds that the claims 1, 2, 25, 26, 32, 36, 37, 44, 46, 115, 116, 123 and 125 read on the elected species. Claims 28, 74, 104, 117 and 124 from Group I are withdrawn from consideration because these claims do not read on the elected species.
If the elected specie is not identified in the prior arts, the elected specie would be allowable if an independent claim were drafted with that specie alone. (see MPEP 802.03)
The elected specie was not identified in the prior art. Further, the Examiner expanded the search to alternative species within the genus of Formula (I) and subsequent examination is based on alternative species expansion. (see MPEP 818) Accordingly, claims 1, 28, 36, 37, 44, 46, 115, 116, and 125 read on the alternative species, and will be examined on their merits. Claims 2, 25, 26, 32, 74, 104, 117, 123 and 124 are withdrawn from consideration because these claims do not read on the alternative species.
With respect to the expanded species, the art is rejected under Improper Markush and 35 USC 102 below.
Claim Interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard
consistent with the specification (See MPEP 2111). The “ring A2” in the claim 1 is interpreted as follows: In the specification, ring A2 is defined as an unsubstituted or a substituted monocyclic heterocyclyl (paragraph [0079]), and heterocyclyl is defined as a monocyclic, bicyclic and tricyclic ring system wherein carbon atoms together with from 1 to 5 heteroatoms constitute said ring system (paragraph [0030]). Accordingly, pyridine is properly interpreted as a monocyclic heterocyclyl within the meaning of ring A2.
Claim Rejections - Improper Markush
Claims 1, 28, 36, 37, 44, 46, 115, 116, and 125 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of spiro heterocyclic substituents is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the claimed alternatives encompass a wide variety of structurally distinct ring systems, including monocyclic heterocycles, fused heteroaryl systems, bicyclic heterocycles, and bicyclic cycloalkyl or cycloalkenyl frameworks, with substantial variation in ring size, degree of saturation, heteroatom composition (e.g., N, O, S), and fusion patterns. Although the alternatives share a spiro linkage, this feature constitutes only a limited portion of the overall molecular structure and does not represent a substantial structural feature common to all members of the group. Accordingly, the claimed alternatives do not share a “single structural similarity” as required under MPEP 2117.
In addition, the recited alternatives do not belong to a recognized class of biological chemical
activity. Acosta-Quiroga (Spirocyclic derivatives as antioxidants: a review, RSC Adv.,11, 21926, pub’d 06/21/2021) describes that spirocyclic scaffolds are widely used in medicinal chemistry and variation in ring size and/or heteroatoms are exhibited diverse bioactivities, including anticonvulsant, antibacterial, antipsychotic, antifungal, antileishmanial, antidiabetic activities, antimicrobial, antioxidants, anticancer, antiviral, antihypertensive, antimalarial, and antitumor (introduction). Acosta-Quiroga further describes that the most abundant spiro heterocycles with information about antioxidant properties are [4.5.0], followed by [4.4.0], and most of the spiro [4.4.0] compounds studied had better results than the positive controls used in the respective antioxidant assays, but other spiro compounds including [4.6.0], [5.5.0], and [5.6.0] spirocyclic system do not show the better results than the positive controls (abstract, table 3, and conclusion sections). Antioxidants and antiviral agents are fundamentally linked, with many antioxidants providing direct antiviral effects while also mitigating the oxidative stress and inflammation (e.g., cytokine storms) caused by viral infections. Furthermore, the diverse activities of N-, O-, and S- heterocyclic compounds are already well established in the medicinal chemistry field. As described in the teachings, spirocyclic derivatives and heterocyclic systems containing nitrogen, oxygen, and sulfur exhibit a broad range of structural frameworks and diverse biological activities, rather than a unified or predictable functional profile. These teachings indicate that such compounds are nor regarded in the art as a single class of functionally interchangeable compounds. Thus, spiro heterocyclic compounds represent a structurally heterogeneous category encompassing numerous distinct scaffold types rather than a well-defined, art recognized class whose members are expected to behave in a similar manner.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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, 28, 36, 37, 44, 46, 115, 116, and 125 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Shen et al (WO 2023/009187 A1, filed on 04/14/2022), which claims priority to US Provisional Application No. 63/227,206, filed on 07/29/2021.
Shen teaches spiro pyrrolidine derived antiviral agents and their use in a coronavirus infection treatment or prevention (abstract, claims 1 and 11).
With respect to claim 1, the claim recites that a compound of Formula (I), or a pharmaceutically acceptable salt thereof, defined by a Markush group. Specifically, Shen’s formula (I) includes the following features: (1) R1 is a 5 membered monocyclic heterocyclyl includes NH in the ring that is substituted with a first =O on a carbon of the ring with selected from the specific aryl (i.e., phenyl, Shen’s compound 15), monocyclic heterocyclyl (i.e., pyridine, alternative species within the genus of Formula (I)), bicyclic aryl, or bicyclic heterocyclyl at B position (page 12, lines 3-5); (2) R1, R2, R4, and R23 are hydrogen or optionally substituted -C1-C6 alkyl; (3) R3, R21, and R22 are hydrogen or optionally substituted -C1-C5 alkyl; (4) R24 is -C(O)OR25; (5) R25 is substituted -C1-C5 alkyl; (5) X is -CN (page 3-7). These features correspond to a compound encompassed within the scope of claim 1. For example, Shen’s compound 15 consists of a spiro pyrrolidine with the specific fused rings (i.e., phenyl or pyridine) attached at B position in Shen’s formula (I) (page 66). Shen further teaches that pyridine is encompassed at B position (page 12, lines 3-5). As set forth above in the claim interpretation, pyridine is a monocyclic heterocyclyl within the meaning of ring A2 in the instant claim 1. Accordingly, Shen discloses compounds encompassing the full scope of claim 1.
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Application’s Formula (I) Shen’s Formula Shen’s compound 15
With respect to claims 28, 36, and 37, the claims recite that a compound of Formula (I), wherein R2 is an unsubstituted C1-8 alkyl. As shown above, Shen teaches corresponding substituents. In particular, Shen discloses that the relevant substituents of R1 and R2 of Shen’s formula (I) (corresponding R2 of instant Formula (I)) include isobutyl. For example, Shen’s compound 15 includes an isobutyl substituent at the position corresponding to R1/R2, which is the same substituent as recited for R1/R2 in the instant claims (page 8 lines 7-9).
With respect to claim 44, the claim recites that a compound of Formula (I), wherein R4 is cyano. As shown above, Shen discloses compound 15, wherein X (corresponding R4) is -CN, which is identical to the cyano substituent recited in claim 44 (page 5 lines 10-25).
With respect to claims 46, 115, and 116, the claims recite specific substituent limitations that a compound of Formula (I), wherein R3 is
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, R8a is hydrogen and Z1 is -C(=O)-. As shown above, Shen teaches compounds meeting these limitations, which falls within the claimed scope. For example, Shen’s compound 15 (page 66) has the same substitution of
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as shown in instant claims 115 and 116, thereby disclosing a compound identical to that recited in these claims.
With respect to claim 125, the claim recites that a pharmaceutical composition comprising an
effective amount of compound of claim 1 or a pharmaceutically acceptable salt thereof, and excipient.
Shen discloses the methods of treating or preventing a coronavirus infection by administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (abstract). Shen further discloses formulation of such compounds with one or more pharmaceutically acceptable carriers or excipients (page 41 lines 26-28), as recited in claim 125.
Therefore, claims 1, 28, 36, 37, 44, 46, 115, 116, and 125 are anticipated by Shen.
Conclusion
Claims 1, 28, 36, 37, 44, 46, 115, 116, and 125 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/ Examiner, Art Unit 1621
/CLINTON A BROOKS/ Supervisory Patent Examiner, Art Unit 1621
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