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 .
DETAILED ACTION
This office action is in reply to the application 18/709,395 filed on 10 May 2024, 371 of PCT/US2022/049489 filed 10 November 2022, with PRO 63/322,985 filed 23 March 2022, and PRO 63/277,902 filed 10 November 2021. Claims 3, 5, 8, 11, 17, 19-20, 24-25, 28, 34, 60-61, 67 and 69 are amended. Claims 6-7, 9-10, 12-16, 18, 21-23, 26-27, 29-33, 35-59 and 63-66 are canceled. Currently claims 1-5, 8, 11, 17, 19-20, 24-25, 28, 34, 60-62 and 67-69 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 November 2025 was filed after the mailing date of the application on 10 May 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.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because the drawing on pg. 1, fig. 1 are not clearly legible. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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 67-69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A review of the rejected claim language indicates that this claim is drawn toward “a method of treating a CNS condition or disorder in a subject in need thereof, comprising administering an effective amount of the compound of claim 1 to the subject”. In Applicant’s originally filed specification, Applicant summarizes CNS conditions under brain injury, specifying traumatic brain injury (TBI) and stroke, the resulting inflammatory response to both conditions, and associated neurodegenerative diseases that also experience an inflammatory response. However, while the Applicant discloses drug like properties of some of the compounds described in the instant specification including testing aqueous stability, plasma stability, a pharmacokinetic study of one compound 32j, and an in vivo study with rat disease model of acute TBI, it does not encompass subjects beyond rats, including animals such as dogs or monkeys, often used in toxicology studies, much less human. This leads one to conclude that the applicant was not in possession of a method of treating CNS conditions or disorders in a subject to all the disorders that are encompassed by claim 67 and are claimed in claim 69, including stroke, subarachnoid hemorrhage, traumatic brain injury, concussion, dementia, Alzheimer’s disease, epilepsy, seizure disorder, depression, and postpartum depression, to the extent that broadest reasonable interpretation requires. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structures, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. One of skill in the art would not recognize from the disclosure that the applicant was in possession of a “method of treatment” for the disease as claimed.
Additionally, it is known that there are significant challenges translating biochemical, in vitro, and in vivo studies to a clinical setting, and that not all biochemical, in vitro, and in vivo studies can be directly translated to the clinical setting. Indeed, J. M. McKim (Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo resistance, Combo. Chem. & High Throughput Scr. 2010, 13, 188-206) emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical, cell, or animal models (introduction). As the specification discloses a working example performed in vivo, one of skill in the art would not recognize that the Applicant was in possession of “a method of treatment” of the various diseases and conditions claimed in other models, much less a clinical setting.
Claims 67-69 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 treating in vivo rat model of TBI, does not reasonably provide enablement for treating CNS conditions or disorders in other patients or humans. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the Applicant. A discussion of these factors as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) Nature of invention –
The Applicant’s claims are broad. For example, claim 67 is directed to “a method for treating a CNS condition or disorder in a subject in need…”. The diseases and conditions vary with disparate etiologies, patient populations, and numerous other relevant factors while the instant specification discloses working examples only performed in vivo in the rat TBI model. As such, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is “a method of treatment” for any disease or condition claimed considering the possible breadth of what are individually diverse diseases and conditions that can arise from multiple factors, never mind considering the aggregate.
(C) The state of the prior art –
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05(a). Wang et al. (Shared risk and protective factors between Alzheimer’s disease and ischemic stroke: a population-based longitudinal study, Alzheimer’s Dement. 2021, 17, 191-204) teaches that patients suffering from Alzheimer’s and ischemic stroke develop as a result of multiple factors rather than a singular cause, that the vascular pathologies are correlated and interconnected with neurodegenerative pathologies preceding cognitive impairment. The vascular risk factors vary by age, such as middle-life factors including hypertension, high cholesterol, and obesity, compared to late-life risks (introduction). Indeed, there appears to be a very broad range of etiologies, patient populations, co-morbidities, etc. between these two diseases alone without considering the claimed aggregate. Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for the treatment of the diseases and conditions claimed.
(D) The level of one of ordinary skill in the art –
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
These hurdles render application of “a method of treatment” of the diseases and conditions claimed to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E)Existence of working examples & (F) Amount of direction or guidance by the inventor –
As previously established by Wang, both Alzheimer’s and ischemic stroke, are complex and sophisticated processes. Conversely, the specification does not demonstrate, also as previously established, a means to treat either of these conditions or others listed. Instead, the instant specification only provides in vivo results for a TBI model. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims.
(G) Quantity of experimentation needed to make or use the invention –
Taken together, the prior art demonstrates that the diseases and conditions arise from multiple factors and etiologies. This covers a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates a singular in vivo model, it does not demonstrate how “a compound” would be able to matriculate into a preclinical candidate, much less a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. Even if the compound was not being considered for human treatment, there are, as established by McKim, numerous hurdles that must be overcome for use in the broad category of a patient including the most basic of demonstrating
efficacy in vitro and in vivo, which is not a guaranteed, linear progression. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claimed invention and the unpredictability in successful application as described by claims 67-69, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in treating the diseases and conditions claimed. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of ordinary skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
Claims 1-5, 8, 11, 17, 19-20, 24-25, 28, 34 and 60-62 are allowable subject matter.
The following is a statement of reasons for the indication of allowable subject matter: the structure described by formula II is not described in a 100% embodiment in the prior art. The closest matches are structures detailed by Guthrie et al. (Progesterone analogs and uses related thereto, US 2019/0276489 A1, 2019) including structure (6) as illustrated below:
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No examples of structures containing the enamine-carbamate moiety with or without further elaboration was found. Fritzemeier et al. (Neurotherapeutic potential of water-soluble pH-responsive prodrugs of EIDD-036 in traumatic brain injury, J. Med. Chem. 2023, 66, 5397-5414; entered into the IDS on 11 November 2025) describes the compounds embodied in the claims, such as structure 13l:
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This prior art falls into the 102(b)(1)(A) exception.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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 1-5, 8, 11, 17, 19-20, 24-25, 28, 34, 60-62 and 67-69 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 3, 6, 8, 10, 14, 16-18, 21, 24, 30, 32-33, 37-38, 41, 47, 74-76 and 81-83 of co-pending Application No. 18/709,256 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-5, 8, 11, 17, 19-20, 24-25, 28, 34, 60-62 map onto claims 1, 3, 6, 8, 10, 14, 16-18, 21, 24, 30, 32-33, 37-38, 41, 47 and 74-76 of App.’256 where the same prodrug modifications utilizing the enamine-carbamate moieties are used along with the same formulation elements described in claim 62 of the instant application and 76 of the reference application. Furthermore, the products are applied to the same methods of use, i.e. as a method of treating a CNS condition or disorder, as claimed in claims 67-69 of the instant application and claims 81-83 in the reference application.
The core steroid structures are well documented, where both applications utilize known sterol core structures, the instant application utilizing known steroid cores and the reference application ‘256 utilizing saturated and unsaturated version of cholesterol-like steroids. This is documented by J. Elks (Steroid structure and steroid activity, British J. Dermatology 1976, 94, 12, 3-16) who teaches naturally occurring steroids including testosterone (20) and cholesterol (3), which represent the core structures of the instant application and the reference application, respectively:
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Even if the steroid core structures described in ‘256 are not identical to the claimed/recited steroid core structures in the instant application, it would have nonetheless been obvious to the person of ordinary skill in the art at the time of Applicant’s earliest effective filing date to follow the teachings of Elks and obtain Applicant’s claimed/recited core structures. The person of ordinary skill in the art would have had a reasonable expectation of successfully obtaining Applicant’s steroid structures in both the instant application and the reference application ‘256. A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Summary
Claims 1-5, 8, 11, 17, 19-20, 24-25, 28, 34 and 60-62 contain allowable subject matter. Claims 67-69 are rejected under 35 U.S.C. 112(a). Claims 1-5, 8, 11, 17, 19-20, 24-25, 28, 34, 60-62 and 67-69 are rejected under non-statutory double patenting.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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