Prosecution Insights
Last updated: April 19, 2026
Application No. 18/429,719

ALDOSE REDUCTASE INHIBITORS FOR TREATING SORBITOL DEHYDROGENASE DEFICIENCY

Non-Final OA §DP
Filed
Feb 01, 2024
Examiner
MCMILLIAN, KARA RENITA
Art Unit
1623
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Applied Therapeutics, Inc.
OA Round
3 (Non-Final)
30%
Grant Probability
At Risk
3-4
OA Rounds
3y 6m
To Grant
68%
With Interview

Examiner Intelligence

Grants only 30% of cases
30%
Career Allow Rate
290 granted / 953 resolved
-29.6% vs TC avg
Strong +38% interview lift
Without
With
+37.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
55 currently pending
Career history
1008
Total Applications
across all art units

Statute-Specific Performance

§101
1.6%
-38.4% vs TC avg
§103
46.0%
+6.0% vs TC avg
§102
10.8%
-29.2% vs TC avg
§112
16.9%
-23.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 953 resolved cases

Office Action

§DP
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 . Priority This application is a continuation of U.S. Application No. 18/050,627 filed on October 28, 2022, now abandoned, which is a continuation to PCT/US2021/029286 filed on April 27, 2021, which claims priority to U.S. Provisional Application No. 63/019,738 filed on May 4, 2020 and U.S. Provisional Application No. 63/019,186 filed on May 1, 2020. Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 3, 2025 has been entered. Response to Amendment By Applicant’s amendment filed on December 3, 2025, claims 29 and 56 were canceled. Claims 1-21, 24-26, 31-37 and 41-51 were previously canceled. Claims 22, 23, 27, 28, 30, 38-40 52-55, and 57-62 are currently pending and presented for examination. Response to Arguments Applicant's arguments and declaration under 37 CFR 1.132 filed on December 3, 2025 with respect to the rejection under 35 USC 103 have been fully considered and are found persuasive. Applicant’s arguments and declaration under 37 CFR 1.132 are sufficient to establish that a person of ordinary skill in the art would not have reasonably expected success by substituting the ARI of Zuchner with Compound B, due to a lack of predictability in the efficacy of ARIs as detailed in the declaration under 37 CFR 1.132 and provided for by the teachings of Iyer which screened several ARIs in worm and human fibroblast models for their ability to increase PMM2 enzymatic activity, for treating PMM2-congenital disorder of glycosylation (PMM2-CDG) and demonstrates that of the 10 ARIs tested, all inhibited the activity of aldose reductase but only epalrestat and CHCA reproducibly increased PMM2 enzymatic activity in both worms and fibroblasts. The declarant further states that it has been demonstrated that compound B produced superior results as compared to the compounds taught in Zuchner including epalrestant (see paragraphs 11-14 of the declaration). Thus, for these reasons the previous rejection under 35 USC 103 is hereby withdrawn. However, upon further search and consideration, a new double patenting rejection is detailed below. This action is non-final. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 22, 23, 27, 28, 30, 38-40 52-55, and 57-62 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 10, 21-22, 28-36 of copending Application No. 17/715,401 (U.S. Publication No. 2022/0226323 A1 Provided on IDS dated 08/15/2024) in view of Perlstein et al. WO 2020/040831 A1 (Provided on IDS dated 08/15/2024). Claims 22, 23, 27, 28, 30, 38-40 52-55, and 57-62 of the instant application claim a method of treating hereditary neuropathy associated with sorbitol-dehydrogenase (SDH) deficiency, such as Charcot-Marie Tooth (CMT) disease type 1 or 2, or distal hereditary motor neuropathy (dHMN), comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof, wherein the aldose reductase inhibitor is PNG media_image1.png 178 351 media_image1.png Greyscale or a salt thereof. The cited claims of copending ‘401 claim a method of treating PMM2-CDG, comprising administering a therapeutically effective amount of an aldose reductase inhibitor to a subject in need thereof, wherein the aldose reductase inhibitor is a compound of Formula (III): PNG media_image2.png 105 148 media_image2.png Greyscale such as PNG media_image3.png 140 246 media_image3.png Greyscale . The cited claims of the copending ‘401 do not specifically claim treating hereditary neuropathy associated with sorbitol-dehydrogenase (SDH) deficiency as claimed in the instant claims. However, Perlstein et al. teaches that congenital disorders of glycosylation (CDG) include more than 130 inborn errors of metabolism that affects N-linked, O-linked protein and lipid-linked glycosylation wherein Phosphomannomutase deficiency disease (PMM2 or PMM2-CDG) is the most common disorder of glycosylation with more than 800 patients reported worldwide [0003]. Perlstein et al. teaches that PMM2 is a rare congenital disorder of glycosylation with no cure that is an autosomal recessive disorder arising from a dysfunctional phosphomannomutase-2 gene [0004] and [0099]. Perlstein et al. teaches that the phosphomannomutase-2 enzyme is responsible for transforming mannose 6-phosphate into mannose 1-phosphate, which in turn leads to the synthesis of GDP-mannose and insufficient levels of GDP-mannose leads to under-glycosylated glycoproteins, lysosomal enzymes and serum proteins and this in turn is associated with increased proteasomal and oxidative stress [0004] and [0099]. Perlstein et al. teaches that resolving the glycosylation defect, decreasing proteasomal stress, and decreasing oxidative stress may all or singly contribute to a therapeutic effect in the disease [0004] and [0099]. Perlstein et al. teaches that PMM2-CDG patients suffer from neuromuscular abnormalities, developmental delays, failure to thrive and multiple organ system involvement from liver to kidneys [0005] and [0099]. Perlstein et al. teaches methods for increasing glycosylation in a patient in need thereof comprising administering a therapeutically effective amount of an aldose reductase inhibitor [0009]. Perlstein et al. further teaches methods for treating a condition or disorder mediated, at least in part, by phosphomannomutase-2 enzyme in a patient in need thereof comprising administering a therapeutically effective amount of an aldose reductase inhibitor [0017] and [0021]. Perlstein et al. further teaches methods for treating phosphomannomutase deficiency in a patient in need thereof comprising administering a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of an aldose reductase inhibitor [0037]. Thus Perstein et al, teaches that PMM2-CDG is a hereditary neuropathy associated with sorbitol-dehydrogenase (SDH) deficiency. Accordingly, it would have been obvious to a person of ordinary skill in the art to treat the hereditary neuropathy disorders as claimed in the instant claims that are associated with sorbitol-dehydrogenase (SDH) deficiency according to the methods of copending ‘401 which claim the treatment of PMM2-CDG, comprising administering a therapeutically effective amount of an aldose reductase inhibitor, since as taught by Perstein et al., PMM2-CDG is a hereditary neuropathy associated with sorbitol-dehydrogenase (SDH) deficiency. Thus treating the hereditary neuropathy disorders as claimed in the instant claims by the methods of copending ‘401 to arrive at the instant application is rendered obvious This is a provisional nonstatutory double patenting rejection. Conclusion Claims 22, 23, 27, 28, 30, 38-40 52-55, and 57-62 are rejected. Claims 1-21, 24-26, 29, 31-37, 41-51 and 56 are canceled. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 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, Adam C. Milligan can be reached at (571)270-7674. 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. /KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623 KRM
Read full office action

Prosecution Timeline

Feb 01, 2024
Application Filed
Sep 06, 2024
Non-Final Rejection — §DP
Mar 11, 2025
Response Filed
Jun 04, 2025
Final Rejection — §DP
Dec 03, 2025
Request for Continued Examination
Dec 03, 2025
Response after Non-Final Action
Dec 05, 2025
Response after Non-Final Action
Dec 14, 2025
Non-Final Rejection — §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
30%
Grant Probability
68%
With Interview (+37.5%)
3y 6m
Median Time to Grant
High
PTA Risk
Based on 953 resolved cases by this examiner. Grant probability derived from career allow rate.

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