DETAILED ACTION
This office action is in response to applicant’s filing dated April 10, 2026.
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 .
Status of Claims
Claims 1-20 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a compound of formula (IV) in the reply filed on April 10, 2026 is acknowledged. The traversal is on the ground(s) that the compounds are novel and requests that novelty be considered as the unifying concept. This is not found persuasive because the instant application is not a national stage application. There are no provisions for unifying concept under 37 C.F.R. 1.142 and MPEP 800. The reasons the inventions are independent and distinct and for search burden have already been provided to Applicant (see the Office Action dated February 19, 2026), and will not be repeated herein so as not to burden the record, but are herein incorporated by reference. Since Applicant has failed to demonstrate that the inventions are not distinct or that there was not a search burden, the Examiner defers to the reasons previously set forth as to why the restriction is proper.
The requirement is still deemed proper and is therefore made FINAL.
Claims 13, 14, and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on April 10, 2026.
Applicant's election with traverse of Example 3: (2S,4R)1-[(3R)-5-chloro-1-[(2,4-dimeth-d6-oxyphenyl)sulfonyl]-2,3-dihydro-3-(2-methoxy-d3-phenyl)-2-oxo-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-d6-2-pyrrolidinecarboxamide in the reply filed on April 10, 2026 is acknowledged. The traversal has been addressed above.
The requirement is still deemed proper and is therefore made FINAL.
Example 3 is a compound of formula (IV) wherein R₁, R₂, R3, R6, R₈, R9, R₁₀, R₁₁, R₁₃, R₁₅, R₁₆, R₁₇, R₁₈, R₁9, R₂₀, R₂₁ and R₂₂ are hydrogen; R12 is chlorine; and R₂₃, R24, R₂₅, R₂₆, R₂₇, R₂₈, R₂9, R30, R31, R32, R33, R34, R35, R36, and R37 are enriched in deuterium. Example 3 reads on a compound of Formula (IV) wherein the enrichment in deuterium is 47%.
Claims 1-12, 15, and 16 are presently under examination as they relate to the elected species: Example 3
Priority
The present application claims benefit US Provisional Application No. 63/513,158 filed on July 12, 2023 and claims benefit of foreign priority to EP 23185135.3 filed on July 12, 2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 12, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received on July 12, 2024. These drawings are accepted.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
In the instant case, the abstract includes phrases which can be implied “The present invention relates to…”
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 1-12, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Roux et al (US 6,730,695 B2, cited in the IDS filed January 12, 2026) in view of Oost et al (Bioorganic & Medicinal Chemistry Letters, 2011; 21:3828-3831) and Pirali et al (J Med Chem, 2019; 62(11):5276-5297, cited in the IDS filed January 12, 2026).
Regarding claims 1-12, Roux teaches a compound of formula (I) (claim 1) and a compound of formula (I) is -(2S,4R)-1-[5-Chloro-1-[2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3yl]-4-hydroxy-N ,N-dimethyl-2-pyrrolidinecarboxamide, levorotatory isomer (claim 6 and Example 1, col 46). Example 1 differs from instantly elected compound in that R₁, R₂, R3, R6, R₈, R9, R₁₀, R₁₁, R₁₃, R₁₅, R₁₆, R₁₇, R₁₈, R₁9, R₂₀, R₂₁, R₂₂, R₂₃, R24, R₂₅, R₂₆, R₂₇, R₂₈, R₂9, R30, R31, R32, R33, R34, R35, R36, and R37 are hydrogen and the compound is not enriched with deuterium. However, Roux does teach the compounds of formula (I) also comprise those in which one or more hydrogen or carbon atoms have been replaced with their radioactive isotope, for example tritium or carbon-14; such labelled compounds are useful in metabolic or pharmacokinetic research studies, in biochemical assays as receptor ligands (col 19, lines 26-31). Thus, Roux suggests isotopes of the disclosed compounds. Roux does not explicitly teach the compound of Example 1 wherein the compound is enriched with deuterium as the elected compound is enriched.
However, Oost teaches the compound SSR149415 (Figure 1):
PNG
media_image1.png
281
296
media_image1.png
Greyscale
which is the same as Example 1 taught by Roux. Moreover, Oost teaches SSR149415 exhibits a sub-optimal pharmacokinetic profile in rat; specifically, it displayed short half-life (<1 h) and high plasma clearance in rats, which is consistent with the high intrinsic clearance observed in liver microsomes, indicating extensive first-pass metabolism; in order to improve the sub-optimal pharmacokinetic profile, we sought to increase the metabolic stability of analogs from the oxindole series (page 3828, left). Thus, Oost teaches Example 1 has suboptimal pharmacokinetic profile with extensive first-pass metabolism.
Moreover, Pirali teaches deuterium is a rare, stable, nonradioactive isotope of hydrogen, which differs from protium by a single neutron (page 5276, left, 1st paragraph); the most straightforward application of deuterium substitution is to slow down drug metabolism, especially cytochrome P450 (CYP450)-mediated transformations (page 5278, left, 1st paragraph); ample literature is devoted to deuteration as a means to improve the PK profile of drugs (page 5278, right, 2nd paragraph); independent of PK parameters, deuteration of a soft-spot can be capitalized upon to reduce the formation of unwanted metabolites, as well as to increase the formation of desirable active metabolites, a phenomenon named metabolic shunting (page 5281, right, 3rd paragraph); the substitution of the acidic proton with deuterium at the chiral center of a single stereoisomer might decrease the rate of atom abstraction and afford a good strategy to stabilize chemically unstable stereoisomers (page 5283, right, 2nd paragraph); and deuteration can also be used as a means to expand knowledge, for example, to test the contribution of a metabolite to the action of a particular drug (page 5284, left, 3rd paragraph). Thus, Pirali teaches deuterium substitution is a known method utilized in drug design and known for use in improving bioavailability, drug stability, and PK profile. Moreover, Pirali teaches deutetrabenazine (figure 1); d6-tivozanib and d3-NVS-CRF38 (Figure 3); d3-ligand for GABAA-α6 (Figure 4); d3-analogue of dapagliflozin (Figure 5); d15-atazanavir and d6-dextrmethorphan (Figure 6); d9--tramadol (Figure 11); and d9-venlafaxine (Figure 18), all of which are deuterium enriched in the methoxy substituent of the compound. Pirali further teaches d9--tramadol (Figure 11) and d9-venlafaxine (Figure 18), each of which is deuterium enriched in the dimethylamide substituent of the compound. Thus, Pirali teaches it was known in the art to substitute deuterium in methoxy and dimethylamide moieties of a compound to produce deuterium enriched compounds. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to produce a deuterium enriched-SSR149415 compound wherein the methoxy moieties and the dimethylamide moieties are substituted with deuterium to arrive at the instantly elected compound with a reasonable expectation of success, since the prior art suggests formulating isotopes of structurally similar compounds including Example 1/SSR149415; Example 1/SSR149415 has suboptimal pharmacokinetic profile with extensive first-pass metabolism; deuterium substitution including deuterium substitutions in methoxy and dimethylamide moieties are known methods in drug design and known for use in improving bioavailability, drug stability, and PK profile.
Regarding claims 15 and 16, Roux teaches the compounds of formula (I) are generally administered in dosage units; the said dosage units are preferably formulated in pharmaceutical compositions in which the active principle is mixed with one or more pharmaceutical excipients (col 21, lines 10-14). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to formulate the deuterium substituted Example 1/SSR149415 suggested by the cited art in a composition comprising an pharmaceutical excipient in view of the teachings of Roux.
Taken together, all this would result in the composition of claims 1-12, 15 and 16 with a reasonable expectation of success.
Conclusion
Claims 1-12, 15, and 16 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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.
/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
Prosecution Insights