DETAILED ACTION
Claims 2-21, submitted on August 4, 2023, are pending in the application and are rejected for the reasons set forth below. No claim is allowed.
The present application is being examined under the pre-AIA first-to-invent provi-sions of Leahy-Smith America Invents Act (AIA ), Public Law 112-29, 125 Stat. 284 (2011). In the event the determination of the status of the application as subject to pre-AIA 35 U.S.C. 102 and 103 (or as subject to AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from pre-AIA to AIA or vice versa) for a 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.
Use of Trademarks
The use of several trademarks used in commerce is noted throughout this applica-tion (see, e.g., specification at pp. 21-22). While the use of trademarks is permitted, they should be accompanied by the generic terminology. Furthermore they should be capitalized wherever they appear and, where appropriate, include a proper symbol indicating use in commerce such as ™ or ® following the term. The proprietary nature of the marks should be respected and every effort made to prevent their use in any manner that might adversely affect their validity as commercial marks. See MPEP1 608.01(v) (marks used in commerce and trade names).
Claim Objections
Claim 6 is object to because it appears that it should depend from claim 5 (not claim 2). Appropriate correction or clarification is suggested.
Claim Rejections – 35 USC § 112
The following is a quotation of pre-AIA 35 U.S.C. 112, second paragraph:
The specification shall conclude with one or more claims particularly point-ing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15 and 21 are rejected under pre-AIA 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
In claim 15, “the NMDA receptor antagonist” lacks antecedent basis. The examiner presumes that it was applicant’s intention that claim 15 depends from claim 14, and appro-priate correction is suggested.
Claim 21 contains several trademarks, such as ORTHENE,2 CYANOX,3 and BETASAN.4 Where a trademark (or trade name) is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the require-ments of pre-AIA 35 U.S.C. 112, second paragraph. The claim scope is uncertain because a trademark cannot be used properly to identify any particular material or product. A trade-mark is used to identify a source of goods, not the goods themselves; a trademark does not identify or describe the goods associated with the trademark. In the present case, the trade-marks are apparently used to identify or describe various chemical compounds known in commerce. See MPEP 2173.05(u) (trademarks or trade names in a claim).
Claim Rejections – 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 2, 4, 10-13, and 18-21 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Gasior (J. Pharmacol. Exp. Ther. 282, 543-53 (1997)).
Gasior (cited in applicant’s IDS5) discloses administration of increasing doses of neurosteroids, such as allopregnanolone (3α,5α-P), given in combination with a fixed, “ineffective” dose of diazepam (DZP; p. 545, “Drugs and administration regimen,” see also Table 3 and Fig. 6 at p. 549) for “protection” against convulsions and seizures that would be useful in clinical practice (see Abstract). Inasmuch as the dose of benzodiazepine is “ineffective,” the examiner concludes that it is “subtherapeutic” as recited in the instant claims. The reference also discloses dosage amounts of various neurosteroids approaching zero (Fig. 6 at p. 549), which appears to include dosage amounts so small as to be consid-ered subtherapeutic. The reference explicitly discloses combinations of both diazepam and a neurosteroid, separately administered (see, e.g., Table 3 and Fig. 6 at p. 549, as well as the discussion thereof; see also, p. 545, “Drugs and administration regimen”). When adminis-tered together, the combination provides a marked enhancement of the anti-convulsant potency of the benzodiazepine (p. 544, right column), and such combination therapy is active in different experimental models of seizures (p. 552, last paragraph). Protective dosage amounts of allopregnanolone (3α,5α-P) are about 10 mg/kg or higher (Figs. 3 and 5), which meets the limitations of claim 13. With respect to claim 19, it appears that everyone has at least some risk of being exposed to a nerve agent or a pesticide that can cause seizures (the examiner appreciates that it may be a de minimis risk, but it is nevertheless nonzero), so preventing a seizure that may be caused by any of the compounds recited in claims 20-21 is inherent the method of Gasior. See MPEP 2112.
Claim Rejections – 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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; and (4) considering objective evidence present in the application indicating obviousness or nonobviousness. See MPEP 2141 et seq.
Claims 2-4, 6, and 10-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gasior as applied above.
The disclosure of Gasior is relied upon as set forth above.
With respect to claim 3, the reference discloses separate administration, but co-administration together would have been a matter of common sense.
With respect to claim 6, it appears to be implicit in Gasior that the compounds are not heated prior to administration.
With respect to claims 14-17, although Gasior does not specifically disclose combi-nation therapy with an NMDA antagonist, such as dizocilpine (MK-801), it nevertheless would have been prima facie obvious when the reference is considered as a whole. Gasior separately teaches that dizocilpine is known to be effective in protecting against seizures (see, e.g., abstract, as well as Fig. 5 and Table 2 at p. 548). It further discloses the desirabil-ity of poly-drug therapy, which improves control of seizure symptoms and permits more favorable side-effect profiles (p. 551, right column), which provides motivation to combine dizocilpine with other anti-seizure medications. Furthermore, as a matter of law, it is prima facie obvious to combine two therapies each of which is taught by the prior art to be useful for the same purpose, in order to form a combination therapy to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06(I). One skilled in the art would therefore have viewed the use of dizocilpine together with diazepam and allopregnanolone as a combina-tion therapy for preventing seizures as being prima facie obvious because each of these three drugs is separately taught as being useful in treating seizures. Their combined use for the same purpose would have been viewed as prima facie obvious. With respect to claims 16-17, it is a matter of common sense that two or more drugs can be administered together or separately.
Claims 2-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gasior as applied above, and further in view of Morton (US 2007/0081948 A1).
The disclosure of Gasior is relied upon as set forth above. The difference between the prior art and the claims at issue is that Gasior does not specifically disclose intrapulmo-nary delivery of aerosolized particles (claims 5 and 7-8) or the claimed benzodiazepine dosage amount (claim 9).
Morton (cited in the IDS), however, discloses “dry powder pharmaceutical composi-tions comprising a benzodiazepine for administration by inhalation” (para. 0001) “for adjunctive therapy, that is, for use in combination with other medications, such as other seizure medications” (para. 0014). Morton discloses several advantages of pulmonary administration (para. 0015-17):
… with the pulmonary administration of benzodiazepines …, it is believed that a much faster time to therapeutic effect can be achieved, thereby allowing the patient to take the medication much less frequently. This is a significant advantage because benzodiazepines exhibit side effects and it is believed that with the less frequent dosing required via inhalation, these side effects can be reduced. … the further reduction in the frequency of dosing, in combination with the lower dosages, are believed to make an inhalable formulation particularly advanta-geous.
Another advantage of pulmonary administration of benzodiaze-pines for the treatment of seizure disorders is that it does not require the dose to travel through the digestive system of the patient. This is significant because, during a seizure, the diges-tive process of the patient may be disrupted. Therefore, even if a patient successfully swallows the oral medication just prior to a seizure, the seizure itself may actually prevent the medication from being digested and therefore from having its desired therapeutic effect. In contrast, as long as a patient is able to successfully inhale an inhalable benzodiazepine formulation, the drug should be absorbed systemically.
… Moreover, many seizure patients are children who may require administration of their medication whilst at school. School person-nel may be reluctant to give rectal doses or to provide injections. Even nasal administration has its disadvantages, often leading to caking within the nasal cavity and discomfort to the patient.
The reference specifically discloses taking “medication just prior to a seizure” (para.0016), i.e., preventing a seizure. It appears to be implicit in the reference that the composition is not necessarily heated within the meaning of claim 6. The average particle size of the aerosol is, for example, 2 μm (para. 0038-41), which meets the limitations of claims 7-8.
It would have been prima facie obvious at the time of invention to formulate and administer subtherapeutic amounts of allopregnanolone and a benzodiazepine as taught by Gasior using the techniques of Morton and thereby arrive at subject matter within the scope of the instant claims. One would have been motivated to do so in order to take advantage of the numerous benefits of pulmonary administration taught by Morton. One would have had a reasonable expectation of success because Morton discloses that these formulation techniques are suitable for a wide range of different drugs (see, e.g., the “primary drug” discussed at para. 0014), so surely it would be reasonable to expect that allopregnanolone or a benzodiazepine may also be formulated in this manner.
With respect to the dosage amounts recited in claim 9, differences in such parame-ters will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating they are critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable dosage ranges by routine experimentation. See MPEP 2144.05. Morton discloses a minimum benzodiazepine dosage amount of 0.25 mg (para. 0024), which, for a typical person (75 kg), would be about 3000 pg/kg, but Gasior suggests that a subtherapeutic amount, i.e., amounts even lower than taught by Morton, would be effective. It is therefore the examiner’s position that one of skill in the art would have viewed the subject matter of claim 9 as being the result of routine experimentation within the general teachings of the cited references and therefore prima facie obvious. Indeed, applicant’s own specification (p. 26, emphasis added) admits that “[a]ppropriate dosing will depend on the size and health of the patient and can be readily determined by a trained clinician” and that “[d]etermination of an effective amount for administration in a single dosage is well within the capability of those skilled in the art.”
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 appli-cation 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 Good-man, 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 applica-tions 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(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 that 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/terminaldisclaimer.
Claims 2-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over Patent No. 10,426,786 B2. Although the claims at issue are not identi-cal, they are not patentably distinct from each other. The ‘786 Patent claims a method of preventing or terminating a seizure comprising administration a benzodiazepine and allopregnanolone in a subtherapeutic dose, wherein the subject has been exposed to a nerve agent or a pesticide that can cause seizures. See claim 1 of the Patent. Dependent claim 7 is drawn to inhalational or intrapulmonary route of administration, and dependent claim 12 is drawn to co-administration with an NMDA receptor antagonist.
Claims 2-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over Patent No. 11,510,929 B2. Although the claims at issue are not identi-cal, they are not patentably distinct from each other. The ’929 Patent, of which the present application is a continuation claims a method of preventing or mitigating a seizure compris-ing: (a) determining that a subject is at risk of being exposed to a nerve agent or pesticide that can cause seizures, and (b) administering to the subject of an effective amount of a benzodiazepine and allopregnanolone, wherein each of the benzodiazepine and the allo-pregnanolone are administered in a subtherapeutic dose, and wherein the subtherapeutic dose of the benzodiazepine is in the range of 0.3 μg/kg to 3.0 μg/kg. See claim 1 of the ‘929 Patent. Dependent claim 9 is drawn to aerosolized administration, and dependent claim 13 is drawn to co-administration with an NMDA receptor antagonist.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Theodore R. Howell whose telephone number is 571-270-5993. The examiner can normally be reached Monday through Thursday, 7:00 am - 6:00 pm (Eastern Time). The examiner is generally not available on Fridays. Examiner interviews are available via telephone and video conferencing using an Office-supplied web-based collab-oration tool. To schedule an interview, applicant is encouraged to use the USPTO Auto-mated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 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 avail-able 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 or 571-272-1000.
/Theodore R. Howell/ Primary Examiner, Art Unit 1628
November 13, 2025 (revised December 2, 2025)
1 Manual of Patent Examining Procedure (MPEP), Latest Revision November 2024 [R-01.2024].
2 Ser. No. 71/518,750. For applicant’s convenience, a copy of the registration certificate for ORTHENE is included with this action.
3 Ser. No. 72/124,315. A copy of the registration certificate for CYANOX is included with this action.
4 Ser. No. 77/295,628. A copy of the registration certificate for BETASAN is included.
5 See the information disclosure statement (IDS) submitted on February 20, 2023.