DETAILED ACTION
The amendment submitted on January 21, 2026 has been entered. Claims 27-32 are pending in the application and are rejected for the reasons set forth below. No claim is allowed.
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 . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the 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.
Election/Restrictions
Applicant’s election without traverse of Group II, drawn to a method of providing respir-atory stimulation, in the reply filed on January 21, 2026 is acknowledged. All of the pending claims correspond to the election invention, with claims drawn to the other invention having been cancelled by amendment.
Claim Objections
Claims 27-28 are objected to because of the following informality: “to a subject in need thereof” should be inserted after the word “administering.” Appropriate correction is required.
Claim Rejections – 35 USC § 112
The following is a quotation 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.
Claims 27-32 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for “Compound A,” does not reasonably provide enablement for all compounds of Formula (I). 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 and use the invention commensurate in scope with these claims.
The claims are in the pharmaceutical arts and are directed to a method of providing respiratory stimulation comprising a compound of Formula (I), which is a generic formula that embraces millions of possible compounds. On the other hand, applicant has only presented evidence of a working example for one such compound, referred to as “Compound A.” See applicant’s specification at p. 50 et seq. In order to practice the invention commensurate in scope with the claimed subject matter, one of skill in the art would need to first devise a method of making the compounds and then testing them to validate whether or not they are actually useful for the stated purpose. To this end, the prior art recognizes the following challenges that would burden one of skill in the art:
Research and development (R&D) challenges
High costs and long timelines: One of the most significant challenges in drug production is the high cost and extended timeline required for research and development. On average, it takes 10-15 years and over a billion dollars to bring a new drug to market. The process includes initial discovery, preclinical testing, clinical trials, and regulatory approval. The substantial financial and time investments pose a risk to pharmaceutical companies, especially when the success rate for new drug candidates is relatively low.
Scientific and technical hurdles: Drug discovery involves identifying and validating targets, such as proteins or genes, that play a role in disease. However, understanding complex biological systems and identifying suitable targets can be challenging. Additionally, once a target is identified, finding a compound that effectively interacts with it without causing adverse effects is another significant hurdle. Advances in genomics, proteomics, and bioinformatics have improved target identification and validation, but these processes are still fraught with uncertainties.
Clinical trial difficulties: Clinical trials are essential for demonstrating the safety and efficacy of new drugs. However, designing and conducting these trials is complex and time-consuming. Recruiting and retaining participants, ensuring adherence to protocols, and managing data are all significant challenges. Moreover, the need for large, diverse populations to achieve statistically significant results can further complicate the process. The stringent requirements and the high costs associated with clinical trials contribute to the overall difficulty of drug development.
Manufacturing challenges
Scaling up production: Transitioning from small-scale laboratory production to large-scale manufacturing is a major challenge in drug production. The processes that work in a controlled lab environment may not be directly scalable to industrial production. This scale-up requires significant adjustments to ensure consistency, purity and potency of the drug. Additionally, the development of robust and reproducible manufacturing processes is essential to meet regulatory standards.
Quality control and assurance: Maintaining high quality and consistency in drug production is critical. Variability in raw materials, changes in production conditions, and human error can all impact the final product. Implementing stringent quality control measures, including regular testing and validation, is necessary to ensure that every batch meets the required specifications.
Arham, “The Complexities and Challenges of Drug Production,” Anna. Clin. Trai. Vacci. Res 2024;14(4),264-65. The evidence therefore establishes that the claimed invention is broad, but applicant has presented one working example (Compound A), and this technology area is known as being fraught with numerous technical challenges.
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. The amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. The scope of the required enablement varies inversely with the degree of predictability involved. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required from an applicant. See MPEP 2164.03.
In order to practice the invention as claimed, one would need to make numerous different chemical compounds and test them to determine whether they actually work according to the claims. Even though one of skill in the art is generally quite sophisticated, the level of technical problems that exist in order to make and use the invention commensurate in scope with the claims would present a burden of undue experimentation.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0142647 A1 by Dax et al.
Dax discloses compounds of Formula (I) (para. 0009-18) and pharmaceutical composi-tions thereof (para. 0165-82) for nasal administration (para. 0194). These compounds “are respiratory stimulants and useful in the treatment of breathing control disorders or diseases” (para. 0071), including respiratory depression (para. 0039). The compositions “comprise between 0.1% and 100% (w/w) active ingredient” (para. 0168), which overlaps with the some-what narrower concentration range recited in claims 27-28. In situations like this, “where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obvi-ousness exists.” See MPEP1 2144.05(I) (overlapping, approaching, and similar ranges, amounts, and proportions). Dax also discloses treating opioid-induced respiratory depression (see Example 95 at para. 0481-83), which meets the limitations of claim 29. The reference further discloses treating abnormal respiration associated with “anesthetics, sedatives, anxiolytics, hypnotics, alcohol,” and other non-opioid drugs (para. 0005 and 0163), which meets the limitations of claim 30.
Claims 27-32 are rejected under 35 U.S.C. 103 as being unpatentable over Dax as applied to claims 27-30 above, and further in view of US 2005/0053659 A1 by Pace et al.
The disclosure of Dax is relied upon as set forth above. The difference between the prior art and the claims at issue is that Dax does not specifically disclose treating respiratory depression caused by inflammation or infection. Pace, however, discloses that it was known in the prior art that “[r]espiratory illnesses with increased susceptibility to opiate-induced respiratory depres-sion and/or cessation include infectious or inflammatory conditions” (para. 0005). It is the natu-ral motivated of the skilled artisan to use existing pharmaceutical compositions in accordance with their known or expected properties and thereby arrive at predictable outcomes. See, e.g., MPEP 2144.07 (art recognized suitability for an intended purpose). Apprised of the utility in Dax that the compounds of Formula (I) are useful for treating respiratory depression, it would have been apparent to the skilled artisan that they would also be useful for the types of respiratory depression described in Pace. One would have had a reasonable expectation of success because the implicit disclosure of Dax is that the compounds therein are broadly useful for treating a wide range of respiratory disorders, so it would be a reasonable presumption that they would also be useful for treating the disorders described in Pace.
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 possi-ble 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 provi-sions 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 accompa-nied 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 27-28 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,138,267 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 1 of the ‘267 Patent is directed to a method of treating respiratory depression caused by a non-opioid agent comprising administering, to a patient in need thereof, an effective amount of a particular compound within the scope of Formula (I). The patent also discloses intranasal administration (col. 20, l. 66). As explained in more detail above, the concentration limitations of instant claims 27-28 would have been prima facie obvious over the general teachings of the cited Patent (see, e.g., col. 40, ll. 25-35). The examiner therefore concludes that instant claims 27-28 and 30 are drawn to subject matter that it prima facie obvious over the corresponding claims of the ‘267 Patent.
Claims 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,544,369 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 1 of the ‘369 Patent is drawn to a method of treating opioid overdose comprising administering various compounds of Formula (I). Claim 2 of the ‘369 Patent is directed to opioid overdose accompanied by respiratory depression. The Patent also discloses intranasal administration (col. 3, l. 66). The concentration limitations of the instant claims are prima facie obvious over the teachings of the cited Patent for substantially the same reasons discussed above.
Claims 27-28 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of copending Application No. 18/213,451 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘451 Application claims a method of treating neurological ventila-tory insufficiency comprising administering a compound of Formula (I). See claim 1 of the ‘451 Application. Dependent claim 12 is directed to nasal administration. Dependent claim 8 is drawn to a patient not having an opioid-induced respiratory depression, such suggests the subject matter of instant claim 30. The accompanying written description (see, e.g., pp. 61-62) generally discloses the concentration limitations of the instant claims, so the examiner concludes that the subject matter of instant claims 27-28 and 30 is prima facie obvious over the claims of the ’451 Application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-28 and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 69, and 71 of copending Application No. 18/795,777 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 1 of the ’777 Application is directed to a method of treating respiratory depression modulated by a non-opioid agent comprising administering a compound of Formula (I). The concentration limitations of the instant claims are prima facie obvious for substantially the same reasons discussed above. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-29 and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 33 of copending Application No. 18/866,742 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Claims 1 and 16 of the ‘742 Application are directed to a method of treating respiratory depression comprising administering a compound of Formula (I). Dependent claim 2 of the ‘742 Application is drawn to respiratory depression in a patient experi-encing a bacterial or viral infection. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-16, 18-19, 26-27, and 68 of copending Application No. 18/909,393 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Claims 1-3 and 9 of the ‘393 Application are directed to a method of treating respiratory depression by administering a compound of Formula (I). Claims 6-8 of the ‘393 Application are drawn to opioids, which suggests the subject matter of instant claim 29. Claim 26 of the ‘393 Application is drawn to non-opioid agents, which suggests the subject matter of instant claim 30. Claim 27 of the ‘393 Application includes nasal administration. As explained above, the concentration limitations of the instant claims are prima facie obvious over the general teachings of the written description of the ‘393 Application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 - Thursday, 8:00 am - 7:00 pm (Eastern Time). 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, Amy L. Clark can be reached at (571)272-1310. The fax phone number for the organ-ization where this application or proceeding is assigned is 571-273-8300.
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THEODORE R. HOWELL
Primary Examiner
Art Unit 1628
/THEODORE R. HOWELL/ Primary Examiner, Art Unit 1628
February 20, 2026 (revised March 15, 2026)
1 Manual of Patent Examining Procedure (MPEP), Latest Revision November 2024 [R-01.2024]