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 .
Application and Claims Status
Claims 1-12, 17, and 19-23 were pending. In the amendment as filed on February 27, 2026, applicants have amended claims 1-5; cancelled no claims; and added no new claims. Additionally, the present specification is amended: in order to cross reference to related applications; and to amend the header on page 116 of the Specification.
Election/Restrictions
Applicant's election with traverse of Group I, drawn to compounds and composition of Formula (I), encompassed by claims 1-7, 11 in the reply filed on February 27, 2026 is acknowledged.
The traversal is on the ground(s) that all the claims share a single general inventive concept as required for unity of invention. Applicant respectfully disagrees with the Examiner’s assertion that Venkateshappa discloses or renders obvious the claimed compounds.
This is not found persuasive because:
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Where a single claim defines alternatives of a Markush group, the requirement of a technical interrelationship and the same or corresponding special technical features as defined in Rule 13.2, is considered met when the alternatives are of a similar nature. When the Markush grouping is for alternatives of chemical compounds, the alternatives are regarded as being of a similar nature where the following criteria are fulfilled:
(A) all alternatives have a common property or activity; AND
(B)(1) a common structure is present, that is, a significant structural element is shared by all of the alternatives; OR
(B)(2) in cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
The phrase “recognized class of chemical compounds” means that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention, i.e. each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
Again, the special technical feature of Group (I) can be found in PCT publication WO 2019/175897 A1, page 122, Example 8 (and other examples). Venkateshappa teaches the following PD1/PD-L1 inhibitor species 8, as well as embraces the compounds generically, both shown below:
Reference Document:
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Instant Application:
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The technical feature of the instant application does not make a contribution over the prior art. Examiner is not required to find 35 USC § 102 art that directly anticipates the instantly claimed invention in order to break unity, but rather, Examiner is required to show that when Applicant claims a Markush grouping for alternatives of chemical compounds, the alternatives are regarding as being of a similar nature where criteria (A) and (B)(1), or (B)(2) are met (vide supra). In the instant case, the compounds of instant application and Venkateshappa are all PD1/PD-L1 inhibitors, and a significant structural element is shared by all of the alternatives. Applicant’s attempt to justify that unity of inventions exists because of a pendant carboxylic acid does not fulfill the requirement that unity exists.
Accordingly, unity of invention is considered to be lacking and restriction of the invention in accordance with the rules of unity of invention is considered to be proper.
The requirement is still deemed proper and is therefore made FINAL.
Applicant further elected the species Compound 8, shown below. Examination will be limited to claims directed to the elected species, which are presently claims 1-12, 17, and 19-23, to the extent that they are readable on the elected embodiment.
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Claims 8-10, 12, 17, 19-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Therefore, claims 1-7, and 11 are presently under examination. Applicant timely traversed the restriction (election) requirement in the reply filed on February 27, 2026.
Priority
The instant application is a U.S. National Stage Application under 35 U.S.C. § 371 of
International Application No. PCT/IN2022/050381, filed April 22, 2022, designating the U.S. and
published in English as WO 2022/224278 A1 on October 27, 2022, which claims the benefits of
the Indian provisional patent application number 202141018688, filed on 22 April 2021.
However, the limitations of the instant claims are not adequately supported or enabled in the manner provided by 35. U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by IN202141018688. Claim 1 of the instant application ends with the proviso that Applicant is claiming a compound of Formula (I), except the following compounds, shown below:
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This proviso is not claimed in the priority document IN202141018688, and no support for it can be found in the specification. The earliest priority document to provide support for this limitation is the WIPO publication, WO 2022/224278, filed April 22, 2022, as written in the claims. Therefore, because the proviso first finds support in WO 2022/224278, claim 1, the instant application has been awarded the effective filling date of April 22, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) filed on October 23, 2023 and March 6, 2026 are in compliance with the provisions of 37 CFR 1.97. All references have been considered except where marked with a strikethrough. A signed copy of Form 1449 is included with this Office Action.
Specification - Abstract
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
The abstract of the disclosure is objected to because: it is currently the cover sheet of Applicant’s WIPO publication and is not in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification – Disclosure
On page 5, para 0011, in Formula (Ia) and Formula (I), the subscripts of m and n are currently not visible or legible because of substantial overlap with the molecular drawing itself. Appropriate correction is required.
On page 17, para 0073, in Formula (I), the subscripts of m and n are currently not visible or legible because of substantial overlap with the molecular drawing itself. Appropriate correction is required.
On page 21, para 0079, in Formula (II), the subscripts of m and n are currently not visible or legible because of substantial overlap with the molecular drawing itself. Appropriate correction is required.
The 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 of the errors of which applicant may become aware of in the specification.
Claim Objections – Minor Informalities
Claims 1-7 are objected to because of the following informality: the claims are not consistent with proper Markush practice. The claims should be listed in the singular, alternative format. As an example, the examiner suggests that claim 1 be rewritten to read, “A compound of Formula (I)… a stereoisomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof…’” so as to be consistent with proper Markush practice. Claims 2-7 have the same issue, and additionally, claim 7 should also be corrected to recite “…wherein the compound acts as an inhibitor for PD1/PD-L1 interaction” (emphasis added). No new matter permitted. Appropriate action is required.
Claim 2 is objected to because of the following informality: in the definition of Ring A, the term “-CRaRb-ORc” should be rewritten as “-CRaRb-ORc”. Appropriate correction is required.
Claim 6 is objected to because of the following informality: there are two periods in the claim, when there should only be a single period at the end of the claim. Currently, there is an additional period at the end of the name for compound 81, as well as a period at the end of the claim itself. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 5-6 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.
Claim 5 lists possible groups from which Ring A can be selected. For example, Applicant recites the following:
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In the above examples, it is clear that Ring A is attached to the rest of the molecule through the nitrogen atom of the heterocycle. In the following example from claim 5, however, it is unclear to where the point of attachment is to the rest of the molecule. Applicant recites:
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This is a standalone fragment with no clear connection to the rest of the molecule.
In the present instance, claim 6 recites the broad recitation “or a pharmaceutically acceptable salts thereof” and the claim also recites the “2,2,2-tirlfuoroacetate salt” of compounds 21, 22, and 74, as well as the “formate” salt of compound 80, which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claim(s) 1-5, 7, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Venkateshappa et al. (WO 2019/175897 A1, published September 19, 2019, cited on Applicant’s IDS filed on October 23, 2023)(hereinafter, “Venkateshappa”).
Venkateshappa teaches a generic group of compounds which embraces applicants’ claimed compounds (see reference Formula (I), pages 4-7) for use as pharmaceuticals and compositions (reference claims 10-11) to inhibit PD1/PD-L1 interaction (see reference page 1, para 0001)—that is, for the same uses as claimed herein. The instant claims differ from the reference by reciting a more limited genus than the reference. One of ordinary skill in the art would have been motivated to select the claimed compounds from the genus in the reference since such compounds would have been suggested by the reference as a whole. It has been held that a prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. In re Susi, 440 F.2d 442, 169 USPQ 423, 425 (CCPA 1971), followed by the Federal Circuit in Merck & Co. v. Biocraft Laboratories, 847 F.2d 804, 10 USPQ 2d 1843, 1846 (Fed. Cir. 1989).”
Reference examples 8-9, 12, 15, 35-37, 42-43, 46-47, 50-52, 59, 68-72, 77-78, 80-81, and 88 differ from instant claims only in the nature of the -CO2H substituent of R2 of Formula II (page 7, para 00011), shown below, where R2 is selected from, among other things, a “(4-10 membered heterocycloalkyl)-C1-4 alkyl-…independently optionally substituted with 1, 2, 3, or 4 Rb substituents” where Rb is selected from “…C(O)ORc”, where Rc is selected from hydrogen. This mapping arrives at reference compounds with -CO2H substituted heterocycles. The difference between the prior art and the instant claims is that the instant claims do not allow for a -CO2H substituent of Ring A of instant Formula (I), shown below.
Reference Genus: Instant Genus:
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However, Venkateshappa had specifically disclosed the modification of non-CO2H-containing species 39 and 40, shown below, although these species are disclaimed in a proviso of instant claim 1:
Reference Species 39: Reference Species 40:
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Importantly, according to reference Table 5 (para 192, para 000100), Species 39 displays biochemical PD1/PD-L1 inhibition in the B range (IC50 100-500 nM); and species 40 displays excellent biochemical PD1/PD-L1 inhibition in the A range (IC50 < 100 nM).
Venkateshappa also teaches CO2H-containing species (see earlier listing above) that otherwise read on instant claims 1-5, 7, and 11. As an example, species 46 is shown below:
Reference Species 46
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According to reference Table 5, Species 46 displays excellent biochemical PD1/PD-L1 inhibition in the A range (IC50 < 100 nM).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to substitute the A ring of instant claim 1 with the heterocycles of reference species 39 and 40 to arrive at compounds of the claimed invention because Venkateshappa had disclosed the modification of non-CO2H-containing species 39 and 40. One would have been motivated as a matter of making additional compounds to inhibit PD1/PD-L1 interaction. One would have had a reasonable expectation of success because Venkateshappa specifically disclosed that the group corresponding to Ring A of the instant claims could lack CO2H substitution. Furthermore, compounds without the CO2H substitution remained potent inhibitors of the PD1/PD-L1 interaction. One therefore could have reasonably expected that such a modification would result in compounds with similar activity to reference compounds 39 and 40.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
All claims are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUKE ALAN BORALSKY whose telephone number is (571)272-9746. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 am.
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, Jeffrey H Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.A.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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