Prosecution Insights
Last updated: April 19, 2026
Application No. 18/303,789

N-PALMITOYLETHANOLAMIDE AND MELATONIN FOR USE IN THE TREATMENT OF AUTISM SPECTRUM DISORDER AND OTHER NEUROBEHAVIORAL DISORDERS SIMILARLY ACCOMPANIED BY RESTLESSNESS, IRRITABILITY, SLEEP DISORDERS, AND POTENTIALLY STEREOTYPIES

Final Rejection §103§112
Filed
Apr 20, 2023
Examiner
TRAN, SUSAN T
Art Unit
1615
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Epitech Group S P A
OA Round
2 (Final)
63%
Grant Probability
Moderate
3-4
OA Rounds
3y 4m
To Grant
98%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allow Rate
632 granted / 1009 resolved
+2.6% vs TC avg
Strong +36% interview lift
Without
With
+35.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
52 currently pending
Career history
1061
Total Applications
across all art units

Statute-Specific Performance

§101
0.3%
-39.7% vs TC avg
§103
39.1%
-0.9% vs TC avg
§102
22.7%
-17.3% vs TC avg
§112
21.5%
-18.5% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1009 resolved cases

Office Action

§103 §112
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 . Claim Rejections - 35 USC § 112 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 1, 3 and 10-16 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. Regarding claim 1, the phrase “such as” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 1 recited that phrase “comprising or consisting of administering palmitoylethanolamide (PEA) in combination with a compound selected from melatonin, tryptophan triptophan (TRP) and 5-hydroxytryptophan triptophan (5H-TRP), in which said palmitoylethanolamide and said compound are administered separately, in combination or simultaneously.” If Markush language is intended, the proper Markush phrasing should read: selected from the group consisting of. 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. Claims 1, 10, 11 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Eyal et al. (WO 2021033149) in view of Carley et al. WO 2007047577 A2, further in view of Jacobsen et al. (US Patent 9468627), Mellar et al. “The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review”, and Smith et al. “Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomized Trial in Older Malnourished People in Primary Care”. Eyal et al. (WO 2021033149) (hereinafter Eyal et al.) disclose methods of treating a condition which includes autism spectrum disorder by administering a composition comprising N-palmitoylethanolamide (PEA) (para 0074) as a modulator for treating a condition that is inclusive of autism spectrum disorder (para 0058 and 0076, 00115-00117, 00120-00121, 00130, claims 1, 13, 15.). The formulations can contain from 0.1 to 100 mg modulator (para 0025). The composition is suitable for oral administration (para 00106). Eyal et al. does not disclose administration in combination with 5-hydroxy tryptophan (5H-TRP). However, combination of tryptophan and any cannabimimetic agents such as palmitoylethanolamide is known in the art. See for example the teaching Carley. More specifically, Jacobsen et al. (US Patent 9468627) (hereinafter Jacobsen et al.) disclose 5-HTP formulations useful for treatment of a psychiatric disorder/serotonergic neurotransmission dysregulation disorder where the disorder include autism (col. 1, lines 18-21, col. 2, lines 16-30, col. 8, lines 60-col. 9, line 23). The daily dose of 5-HTP includes 0.05-10 g (50-10000 mg) (co. 6, lines 19-26). Jacobsen et al. discloses that serotonin enhancer refers to any compound that increases, directly or indirectly, the availability of serotonin in the central nervous system for binding to serotonin receptors (col. 12, lines 34-44). Palmitoylethanolamide is an indirect serotonin enhancer as the reference to Mellar et al. teaches it increases serotonergic neurotransmission through serotonin receptor 5HT1 and downregulates 5HT2A/C receptors. Eyal et al. disclose 0.1-100 mg modulator and Jacobsen et al. disclose 50-10000 mg of the 5-HTP. Taken together this allows for ratios that would overlap with claim 10. Claim 10 recites there may be 5 times more PEA or includes ratio where there is 10 times more 5H-TRP which is a wide range and no evidence of criticality. Both Eyal et al. and Jacobsen recognize for treatment of autism disorders. While Eyal et al. does not teach the 5H-TRP (a.k.a 5HTP) , Jacobsen et al. teaches this for treatment that encompasses the same condition (autism). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to include 5HTP of Jacobsen et al. in the compositions for treatment of autism as taught by Eyal et al. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). Eyal et al. disclose the compositions are formulated for oral administration but does not explicitly state it is “dietary compositions” or “food supplements”. Smith et al. “Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomized Trial in Older Malnourished People in Primary Care” (hereinafter Smith et al.) disclose that oral nutritional supplements are acceptable and make a difference to patients and significantly improve intake. Therefore, it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have the oral compositions of Eyal et al. be formulated such that they are nutritional compositions. One would have been motivated to do so because these have shown to make a difference to patients and improve intake. Formulation into the forms as claimed in claim 16 would be readily apparent to one of ordinary skill in the art. 7. Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Eyal et al. (WO 2021033149) in view of Carley et al. WO 2007047577 A2, further in view of Jacobsen et al. (US Patent 9468627), Mellar et al. “The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review”, and Smith et al. “Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomized Trial in Older Malnourished People in Primary Care” as applied to claims 1, 10, 11 and 14-17 above, and further in view of Rajendra et al. (WO 2021048871). The modified Eyal et al. has been discussed supra and does not disclose micronized form of palmitoylethanolamide and having mode between 6 and 10 microns. (WO 2021048871) (hereinafter Rajendra et al.) disclose due to the lipophilic nature and large particle size in the native state, molecules of PEA have limitations in terms of solubility and bioavailability (age 14, lines 25-26). The micronization technique is used in the pharmaceutical field to enhance the dissolution rate of drug and thereby reduce variability of drug absorption when orally administered. The PEA can be used in various forms including micronized and having particle sizes from 2 µm-10 µm (see bottom of page 14- page 15, line 7). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to include the PEA in micronized form having particle sizes ranged from 2-10 µm. One would have been motivated to do so to enhance the dissolution rate of the drug and thereby reduce variability of drug absorption when orally administered. 8. Claims 1, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Eyal et al. (WO 2021033149) in view of Carley et al. WO 2007047577 A2, further in view of Jacobsen et al. (US Patent 9468627), Mellar et al. “The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review”, and Smith et al. “Ready-Made Oral Nutritional Supplements Improve Nutritional Outcomes and Reduce Health Care Use-A Randomized Trial in Older Malnourished People in Primary Care” as applied to claims 1, 10, 11 and 14-17 above, and further in view of CutCliffe “Could fish oil help autism symptoms in toddlers born prematurely?”. The modified Eyal et al. has been discussed supra and does not disclose palmitoylethanolamide administered with docoshexaenoic acid (DEA). CutCliffe “Could fish oil help autism symptoms in toddlers born prematurely?” disclose that toddlers given a supplement containing EPA, DHA and GLA showed greater reduction in symptoms of autism spectrum disorder than those give a placebo. The dosages included 225 mg DHA (less than 500 mg). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to further add DHA supplements (Omega 3 oils) to the compositions of Eyal et al. One would have been motivated to do so because supplementation showed a greater reduction in symptoms of autism spectrum disorder compared to those given a placebo. Thus, it treating autism spectrum disorder it would be beneficial to add the omgega-3 oils of CutCliffe where the DHA dose is 225 mg. Response to Arguments Applicant’s arguments filed 12/10/2025 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. To place the claims in condition for allowance, it is suggested to amend the claims to include palmitoylethanolamide and trypophan in one single unit dosage form for administration of both compounds concurrently. Conclusion Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSAN T TRAN whose telephone number is (571)272-0606. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 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, ROBERT A. WAX can be reached at 571-272-0623. 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. /SUSAN T TRAN/Primary Examiner, Art Unit 1615
Read full office action

Prosecution Timeline

Apr 20, 2023
Application Filed
Sep 06, 2025
Non-Final Rejection — §103, §112
Dec 10, 2025
Response Filed
Mar 21, 2026
Final Rejection — §103, §112 (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
63%
Grant Probability
98%
With Interview (+35.9%)
3y 4m
Median Time to Grant
Moderate
PTA Risk
Based on 1009 resolved cases by this examiner. Grant probability derived from career allow rate.

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