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 with traverse of Group 1, claims 1-15, in the reply filed on 04
February 2026 is acknowledged. The examiner maintains that the technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Reddy et al. (WO2018118101A1; published 28 June 2018; as cited on the IDS filed 25 July 2025) in view of the combined teaching of Concert Backgrounder (Concert Pharmaceuticals Inc., Precision Deuterium Chemistry Backgrounder, as cited on the IDS filed 23 Dec 2024), Silverman et al. (US9249149B2; patented 2 Feb 2016), and Zhu et al. (ACS Med. Chem. Lett. 2013, 4, 349-352). Since the claimed deuterated variant does not make a contribution over the prior art this technical feature is not a special technical feature and there is a lack of unity of invention amongst the different inventive groups.
Regarding the election of species requirement, Applicant’s election without traverse of Compound 1 as described in Example 1 at page 58 of the specification is acknowledged.
In addition to the elected species, the examiner has expanded the search to include species having 1-9 deuterium atoms at R6 found on the piperidine ring. The elected species combined with the expanded species read on claims 1-15.
The requirement is still deemed proper and is therefore made FINAL.
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04 Feb 2026.
Priority
Instant application claims priority as follows:
PNG
media_image1.png
104
394
media_image1.png
Greyscale
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 13 Nov 2023, 23 Dec 2024, 25 July 2025, and 30 Oct 2025 are in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Each IDS was considered. A signed copy of each form 1449 is enclosed herewith.
Claim Interpretation
Regarding the structure of the elected species, the examiner understands that the elected species corresponds to Compound 1 as described in Example 1 at page 58 of the specification, having the following structure:
PNG
media_image2.png
236
426
media_image2.png
Greyscale
That is, the elected species contains nine (9) deuterium atoms as set forth above.
Claim Rejections - 35 USC § 103
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 framework for the objective analysis for determining obviousness under 35 U.S.C. 103 is stated in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Obviousness is a question of law based on underlying factual inquiries. The factual inquiries enunciated by the Supreme Court in Graham are summarized as follows:
(A) Determining the scope and content of the prior art;
(B) Ascertaining the differences between the claimed invention and the prior art; and
(C) Resolving the level of ordinary skill in the pertinent art.
Objective evidence relevant to the issue of obviousness must be evaluated by Office personnel. Id. at 17-18, 148 USPQ at 467. The evidence may be included in the specification as filed, accompany the application on filing, or be provided in a timely manner at some other point during the prosecution. The weight to be given any objective evidence is determined on a case-by-case basis. The mere fact that an applicant has presented evidence does not mean that the evidence is dispositive of the issue of obviousness.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness
which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation (TSM) in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
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.
As discuss in the Election/Restriction section of this Office Action, the search has been expanded to include both the elected species and species having 1-9 deuterium atoms at R6 found on the piperidine ring. The following rejection applies to both the elected species and to species having 1-9 deuterium atoms at R6 found on the piperidine ring:
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Reddy et al. (WO2018118101A1; published 28 June 2018; as cited on the IDS filed 25 July 2025) in view of the combined teaching of Concert Backgrounder (Concert Pharmaceuticals Inc., Precision Deuterium Chemistry Backgrounder, as cited on the IDS filed 23 Dec 2024), Silverman et al. (US9249149B2; patented 2 Feb 2016), and Zhu et al. (ACS Med. Chem. Lett. 2013, 4, 349-352).
Regarding clams Claims 1-15, Reddy et al. teach Z944 as a compound useful for preventing and/or treating a disease or condition relating to aberrant function of a T-type calcium channel, such as epilepsy and epilepsy syndromes (e.g., absence seizures, juvenile myoclonic epilepsy, or a genetic epilepsy) and mood disorders. See pages 1. The structure of Z944 is as followings:
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Reddy et al. teach that the disclosed compounds, including Z944, may also comprise one or more isotopic substitutions. For example, hydrogen may be exchanged for deuterium, etc. See page 9.
Reddy et al. do not teach the particular deuterated compounds set forth in the instant application. In particular, claims 1-15 are drawn to compounds having the same backbone structures as Z944 taught by Reddy et al., but with one or more substitutions from hydrogen to deuterium at one of or more locations. Reddy et al. do not teach enrichment at 67.5% or 75% at each potential deuterated site.
Relevant to claims 1-11, 14 and 15, Concert Backgrounder teaches that deuterating a known pharmaceutical compound may improve the compound’s efficacy, safety, and tolerability.
Relevant to claims 1-11, 14 and 15, Zhu et al. teach a working example applied to piperidine deuteration, namely that “selective piperidine deuteration yields the targeted metabolic shunt and leads to the desired bioactivation potentiation.” See first column of page 352 and Table 2.
Relevant to claims 1-11, 14 and 15, Silverman et al. teach that deuterating a known pharmaceutical composed may improve the compound’s efficacy, safety, and tolerability. See column 2, line 5. And relevant to claims 12 and 13, Silverman et al. teaches that enrichment should be “at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation).” See column 4, line 13.
Applying KSR rationale (E) outlined above, it would have been prima facie obvious to substitute one or more deuterium atoms in place of a corresponding number of hydrogen atoms in Z944 to resulting in a deuterated compound. The motivation for doing so would be to prepare a pharmaceutical compound having improved pharmaceutical characteristic, including having improved efficacy, safety, and tolerability.
The Concert Backgrounder teaches that “deuterium is a naturally-occurring relative of hydrogen that has been used extensively in human metabolic and clinical studies. Deuterium-substituted compounds retain their molecular shape and thus have selectivity and potency comparable to their hydrogen analogs. However, since deuterium is heavier
than hydrogen, it forms significantly stronger bonds with carbon resulting in differentiated ADME (Adsorption, Distribution, Metabolism and Excretion).” This approach offers a number of potential clinical benefits and motivation to pursue them. For example, the Concert Backgrounder teaches that deuteration provides a compound with the potential for: improved safety by inhibiting the formation of toxic metabolites and reducing drug-drug interactions; better tolerability through reduction of overall dose and Cmax.; and enhanced efficacy by increasing bioavailability, AUC and Cmin with minimal impact on Cmax. Silverman et al. provide a working example of the advantages of deuteration. And Zhu et al. provide yet another working example, specifically applied to piperidine deuteration.
In the instant case, one of ordinary skill would merely be required to select from a finite number of identified, predictable solutions (location of potential deuteration substations), and as such, would have had a reasonable expectation of success. Zhu et al. and Silverman et al. both teach working examples, with the working example of Zhu et al. specifically applied to piperidine deuteration.
While it is true that the Concert Backgrounder explains that the magnitude and nature of the deuterium benefit cannot be predicted a priori, “obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” Sun Pharmaceutical Industries, Inc. v. Incyte Corp., 83 F.4th 1370, 1376 (Fed. Cir. 2023), quoting Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
In view that the one of above, the claimed invention would have been prima facie obvious at the time of filing.
Conclusion
Claims 1-20 are pending. Claims 16-20 are withdrawn. No claim is currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRADLEY S MAYHEW whose telephone number is
571-272-8428. The examiner can normally be reached Mon-Fri, 11:00 AM-7:00 PM.
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, 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.
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.
/BSM/Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights