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 .
Information Disclosure Statement
Two information disclosure statement (IDS) submitted: one on 02/13/2024 and one on 03/12/2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The use of the term “Eudragit L (trade name)” (as it appears on page 110 of the spec., for example), SleepSign, etc. which are trade names or marks used in commerce, has been noted in this application. All trade terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
While the Examiner has made every attempt to check the Specification for trade mark compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding trade mark use compliance.
The incorporation of essential material in the specification by reference to an unpublished U.S. application (see page 239), foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Pages 229, 231, 233, and 235 have been left blank. It is unclear if this was intentional or if information is missing from the pages.
Table 3 (page 238) appears to be missing some information – Applicant states: “as it is clear from Table 3, the test compounds of the present invention increased the wakefulness time compared to the vehicle treatment group in cynomolgus monkeys” – however, the table does not seem to show any vehicle treated monkeys for comparison (?) as all the monkeys received a dose of 3 mg/kg – see 112(a) rejection. Table 3 is shown below for convenience:
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Status of the Claims
Claims 1-17, 22-27, and 33-36 are pending in this application. Claims 28-32 and 37-45 have been cancelled by Applicant.
Allowable Subject Matter
Claims 1-17 and 22-27 are allowed.
Claim Objections
Claims 18-21 are objected to because of the following informalities:
Claims 18-21 recite the limitation "the other symbols are as defined in claim 2”. Given that claims 18-21 are presented as being dependent upon the limitations of claim 2 already, the statement "the other symbols are as defined in claim 2” is redundant and should be removed.
Appropriate correction is required.
Claims 35-36 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 33-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of the claimed conditions, does not reasonably provide enablement for prophylaxis of the same (in particular, the specification does not provide enablement for prophylaxis of Alzheimer’s disease, sepsis, bone loss, or cardiac failure). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make use of the invention commensurate in scope with these claims.
The applicant’s attention is drawn to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998), where the court set forth eight factors to considers when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the examples; and (8) the quantity of experimentation necessary.
Breadth of Claims
Claim 33 broadly encompasses a method of treatment or prophylaxis of any condition associated with orexin type 2 receptor (neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimer’s disease (AD), etc. – From Wang et al. (Front Mol Neurosci. 2018, 11: 220)), in any mammal in need thereof, comprising administration of any of the compounds of Formula I or salt thereof. Claim 34 narrows the scope of the diseases or disorders associated with orexin type 2.
The term “mammal” is defined as “(e.g., human, mouse, rat, rabbit, dog, cat, bovine, horse, swine, monkey)” in page 106 of the specification.
The term “prophylaxis” is not defined in the specification; however, The Merriem-Webster dictionary defines “prophylaxis” as measures designed to preserve health and prevent the spread of disease (Obtained from merriem-webster.com [retrieved on 04/15/2026] <URL: https://www.merriam-webster.com/dictionary/prophylaxis>). The term “prevention” is not defined in the specification. The Oxford English Dictionary defines “prevent” as to “preclude the occurrence” and thus claim 33 encompasses embodiments in which the claimed compounds can preclude the many diseases associated with orexin type 2 receptors (See definition II.9.a. Obtained from oed.com [retrieved on 2025-03-05]<URL:httos://www.oed.convdictionary/prevent_y?t=true>).
Nature of the invention/ State of the Prior Art/ Predictability in the Art
The Mayo Clinic discloses no way to prevent Alzheimer’s disease, and simply teaches there is strong evidence that healthy lifestyle habits — such as diet, exercise and not smoking — may play a role in reducing your risk of Alzheimer's disease and other types of dementia. However, more research is needed before any of these lifestyle factors can be considered a proven strategy to prevent Alzheimer's disease (Obtained from mayoclinic.org [retrieved on 04/15/2026] <URL: https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/expert-answers/alzheimers-prevention/faq-20058140>).
The CDC discloses that in order to prevent sepsis, one has to prevent infections that may lead to sepsis by practicing good hygiene, knowing the signs and symptoms, and acting fast. The CDC discloses no known prophylactics against sepsis. (Obtained from cdc.gov [retrieved on 04/15/2026] <URL: https://www.cdc.gov/sepsis/prevention/index.html>).
The Mayo Clinic discloses bone loss prevention comprises calcium-rich diet, vitamin D, staying active, reduced tobacco and alcohol consumption, and making sure other medications that are taken frequently have no detrimental effects on bone mass. The Mayo Clinic teaches no other chemotherapeutic prophylactic to prevent bone loss. (Obtained from mayoclinic.com [retrieved on 04/15/2026] <URL: https://www.mayoclinic.org/healthy-lifestyle/adult-health/in-depth/bone-health/art-20045060>).
The CDC discloses no specific chemotherapeutic methods for preventing heart disease (reding on cardiac failure), and discloses only healthy lifestyle habits and taking charge or other existing medical conditions as the main ways to reduce risks. Obtained from cdc.gov [retrieved on 04/16/2026]<URL: https://www.cdc.gov/heart-disease/prevention/index.html>).
Finally, the medical arts are also generally considered to be unpredictable making the goal of achieving prevention in this case even less likely. See Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970) (“In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involve.”).
Level of One of Ordinary Skill
The level of one of ordinary skill in the art would be high, likely an M.D. or Ph.D. in the medical arts (e.g., studying treatment of AD, sepsis, sleep disorders, etc.). See Orthopedic Equip. Co. v. All Orthopedic Appliances, Inc., 707 F.2d 1376 at 1381–82 (Fed. Cir. 1983) (Factors that may be considered in determining level of ordinary skill in the art include: … type of problems encountered in the art …”).
Guidance/Working Examples
The specification provides no working examples beyond an in vivo study of OX2R agonist activity of the instant compounds (See Tables 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, and 2-7 in pages 227-236 of the specification. Table 3 of the specification shows the wakefulness time of four monkeys treated with “test compound”, but appears to provide no comparative data of the wakefulness time for monkeys who didn’t receive treatment – see objection to the specification.
Degree of Experimentation
To practice the invention as claimed, the skilled artisan would have to screen each of the many compounds encompassed by instant Formula I in order to determine whether all the compounds meet the functional limitations of the claim for the treatment and prophylaxis/prevention of any disease or disorder associated with orexin type 2 receptors. In addition, the skilled artisan would need to determine which mammals would benefit from treatment and prevention of these diseases (human, mouse, rat, rabbit, dog, cat, bovine, horse, swine, etc.) by administering the instantly claimed compounds to a statistically significant pool of mammals from each species. Prevention/prophylaxis the aforementioned conditions (which include AD, sepsis, bone loss, and cardiac failure, etc. (which lack chemotherapeutic methods of prevention/prophylaxis in the art) would require long-term monitoring of each patient for appearance of any new disease or condition associated with orexin 2. Thus, the quantity of experimentation in this area would be extremely large, since there are a significant number of parameters that would have to be studied beyond the preliminary computational studies provided. Furthermore, the ultimate outcome of such experimentation is completely unpredictable.
In sum, taking into consideration the Wands factors outlined above, an undue amount of experimentation would be required here to make and use the full scope of the claimed invention.
Closest Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure:
Mita et al. (US 7,947,715 B2 – Pub. Date: May 24th, 2011) discloses their pesticide compounds of Formula I below (abstract). Mita does not disclose the ring to the right of the isooxazoline as a cycloalkyl or heterocycloalkyl or sulfonamides in the position corresponding to Mita’s -NR1R2. Mita provides no reason to modify their compounds to arrive at the instant invention. The closest preferred embodiments are shown below.
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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