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 filed 17 June 2022. Claims 3-9, 12, 15, 17-29, 32-40, 48-50, 53-59, 61-69, 72-76, 78-79, 83-94, 99-113, 115, and 117 are amended. Claims 10-11, 13-14, 16, 30-31, 41-47, 60, 77, 80-82, 95-98, 114, 118-124, 126-128, and 130-149 are canceled. Claims 116, 125 and 129 are withdrawn. Currently, claims 1-9, 12, 15, 17-29, 32-40, 48-59, 61-76, 78-79, 83-94, 99-113, 115-117, 125 and 129 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12 May 2023 and 26 June 2025 was filed after the mailing date of the application on 17 June 2022. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I claims, drawn to compounds of formula (I) or formula (II) which reads upon claims 1-9, 12, 15, 17-29, 32-40, 48-59, 61-76, 78-79, 83-94, 99-113, 115, and 117 in the reply filed on 11 November 2025 is acknowledged. Applicant’s election without traverse of the compound from claim 1 (see below) in the reply filed on 11 November 2025 is also acknowledged.
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The elected species was searched and found to be free of the prior art.
The search was expanded to the full scope of the claims. The closest match is a structure described by Jin et al. (Terpinoid derivatives and uses thereof, WO2020/068689A1, filing date 23 September 2019, entered in the IDS on 12 May 2023), described as compound intermediate 2, as illustrated below:
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No examples of eligible structures, before the effective filing date, beyond C17-CH2-NH-C=O-R were identified.
Claims 1-4, 12, 15, 17-26, 32-35, 48-49, 53-54, 67-68, 72-73, 112 and 117 encompass the elected species and will be examined.
Claims 5-9, 27-29, 36-40, 50-52, 55-66, 69-71, 74-76, 78-79, 83-94, 99-111, 113 and 115 do not encompass the elected species and are withdrawn in the interest of compact patent prosecution.
Claims 125 and 129, previously withdrawn from consideration as a result of a restriction requirement, requires all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions (Groups I and III), as set forth in the Office action mailed on 11 September 2025, is hereby withdrawn and claims 125 and 129 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
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 125 and 129 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 language of the rejected claims indicates that these claims are drawn towards “a method of treating or preventing a disease or disorder in a patient in need thereof comprising administering to the patient a pharmaceutically effective amount of a compound of claim 1 or a pharmaceutically composition according to claim 117” and “the method of claim 125, wherein the patient is a human”. A description of the term “a method of treating or preventing a disease or disorder…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984). Accordingly, claiming “a method of treating or preventing a disease or disorder…” in the absence of knowledge as to what the Applicant regards as “a method of treating or preventing a disease or disorder…” is not a description of “a method of treating or preventing a disease or disorder…”. In Applicant’s originally filed specification, Section III “Diseases associated with inflammation and/or oxidative stress”, starting pg. 55, expounds upon known diseases and disorders associated with dysregulated inflammation and oxidative stress including a variety of genera including cancer, autoimmune diseases, and inflammatory diseases such as inflammatory skin diseases. However, the applicant only demonstrates species application to in vitro inhibition of Nitric Oxide, CYP3A4, and CellTiterGlo assay of the AREc32 EC2x reporter cell line. Applicant does not demonstrate that the product is capable of claimed method of “treating or preventing a disease or disorder…” to the breadth and scope of which broadest reasonable interpretation requires and merely provides hypothetical corollaries. Indeed, the Applicant asserts, on pg. 58, that the antioxidant/anti-inflammatory properties of the compounds disclosed are responsible for the activation of the Keap1/Nrf2/ARE pathway, without being bound by theory. As per MPEP 2163, 1, II, 3, i): “Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is 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 structure, 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 treating or preventing a disease or disorder…” as claimed.
It is also known that there are significant challenges translating in vitro studies to both in vivo and all biological subjects in a clinical setting and that not all in vitro and in vivo studies can be directly translated to the clinical setting. As claim 129 is dependent on claim 125, and that the specification discloses working examples only performed in vitro, one of skill in the art would not recognize that the Applicant was in possession of “a method of treating or preventing a disease or disorder in a patient that is human” and can be used to treat and prevent the possible breadth of diseases and disorders.
Claims 125 and 129 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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 – Claims 125 and 129 are directed to “a method of treating or preventing a disease or disorder in a patient in need thereof comprising administering to the patient a pharmaceutically effective amount of a compound of claim 1 or a pharmaceutically composition according to claim 117” and “the method of claim 125, wherein the patient is a human”. While the Applicant discloses the potential application of the product in inhibiting pathways associated with inflammation and oxidation, which are implicated processes for a wide breadth of diseases and disorders, they are not unto themselves demonstrative single agent means of treating diseases and disorders. The Applicant hypothesizes about corollary diseases and disorders, such as cancers, autoimmune diseases, inflammatory diseases, eye diseases, degenerative conditions, acute organ failure, infectious diseases, complications with of diabetes, allergies, myocardial infarction, renal failure, tissue damage, organ failure, autism, etc., of which the product may potentially play a role in the treatment of, but discloses only in vitro working examples to show inhibition of nitric oxide, CYP3A4 and CellTiterGlo assay of the AREc32 EC2x reporter cell line. Consequently, it is reasonable to conclude that the claim of diseases and disorder, to what is known to one of ordinary skill in the art, is incredibly broad and encompasses numerous possibilities that are differentiated by target, types and subtypes, patient populations, etiologies, etc. Cancer alone is a broad class of heterogenous diseases for which there exists no general treatment or prevention. Hanahan et al. (The hallmarks of cancer, Cell, 2000, 100, 1, 57-70) teaches that “there are more than 100 distinct types of cancer and subtypes of tumors can be found within specific organs”. It is also known that there are significant challenges translating in vitro studies to both in vivo and all biological subjects in a clinical setting and that not all in vitro and in vivo studies can be directly translated to the clinical setting. As claim 129 is dependent on claim 125, and that the specification discloses working examples only performed in vitro, one of skill in the art would not recognize that the Applicant was in possession of “a method of treating or preventing a disease or disorder in a patient that is human” and can be used to treat and prevent the possible breadth of diseases and disorders.
(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). To the best knowledge of the examiner, there is no general pharmacological agent and/or pharmaceutical composition containing pharmacological agents capable of preventing myocardial infarction or cardiovascular disease. Rallidis et al. (Causes, angiographic characteristics, and management of premature myocardial infarction, JACC 2022, 79, 24, 2431-2449) teaches that there are no dedicated guidelines on the management or treatment for individuals with acute myocardial infarction and medications such as dual-antiplatelet therapy, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins are prescribed. Similarly, as previously stated, there is no general pharmacological agent and/or pharmaceutical composition containing pharmacological agents for cancer prevention or cancer treatment. The American Association for Cancer Research (CancerProgressReport, AACR, 2022) teaches that life style changes geared toward prevention and early screening are the most efficacious in regards to cancer prevention. Prominent cancer treatments unveiled in 2022 included molecularly targeted therapies including cell-signaling inhibitors such as asciminib toward a type of leukemia, and immunotherapies including ciltacabtagene autoleucel targeting multiple myeloma. 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 treating and/or preventing diseases and disorders as 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 treating or preventing a disease or disorder in a patient in need thereof comprising administering to the patient a pharmaceutically effective amount of a compound of claim 1 or a pharmaceutically composition according to claim 117” and “the method of claim 125, wherein the patient is a human” 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 – The prior art, such as the American Association for Cancer Research report of 2022, teaches several cancer treatments approved by the FDA in 2022. Conversely, the specification does not provide direction or guidance to a person of ordinary skill in the art, to be able to make use of the elected species as means of treating or preventing diseases and disorders in patients including humans. Rather, the medicinally relevant properties of triterpenoids are inferred in reference to numerous diseases and disorders without establishing a direct use case. 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 fields relevant to all possible diseases and disorders, is incredibly expansive and covers a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates selective activity on specific biological mechanisms or on one specific cell line, it does not demonstrate how the elected species or the genus of the elected species would be able to matriculate into preclinical candidate, much less a new investigational drug. 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 125 and 129, 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 application in the method of use in treating or preventing diseases and disorders. 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 claims, 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 skill in the art would be forced into undue experimentation to practice the claimed invention.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 12, 15, 17-26, and 32-35 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Jin et al. (Terpinoid derivatives and uses thereof, WO2020/068689A1, filing date 23 September 2019, entered in the IDS on 12 May 2023).
Jin teaches intermediate 2 (pg . 94, Scheme - intermediate 2) as a Boc protected amino precursor substrate, synthesized from starting material 2A in 7 steps. The structural difference between the elected species and intermediate 2, are 2,2-difluoromethyl amide compared to a tert-butoxy carbamate substitution pattern. Claims 1-4, 12, 15, 17-26 and 32-35 encompass intermediate 2 within the claim limitations and therefore are anticipated by the prior art.
Claim Rejections - 35 USC § 103
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.
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.
Claim 117 is rejected under 35 U.S.C. 103 as being unpatentable over Jin et al. (Terpinoid derivatives and uses thereof, WO2020/068689A1, filing date 23 September 2019, entered in the IDS on 12 May 2023) in view of Rowe et al. (Handbook of pharmaceutical excipients 6th edition, Pharmaceutical Press, 2009).
Jin teaches intermediate 2 (pg . 94, Scheme - intermediate 2) as a Boc protected amino precursor substrate, synthesized from starting material 2A in 7 steps. Jin does not, however, teach a pharmaceutical composition comprising a compound of claim 1 and an excipient.
This deficiency is rectified by Rowe who extensively covers many topics within the field of drug formulation, including, but not limited to, typical properties of select excipients, incompatibilities, safety, related substances, among others. As such, it would have been prima facie obvious, to a person of ordinary skill in the art, to explore well known and documented excipients to develop a pharmaceutical composition appropriate for a compound of claim 1 utilizing well established literature that is exemplified by Rowe.
Claims 125 and 129 are rejected under 35 U.S.C. 103 as being unpatentable over Jin et al. (Terpinoid derivatives and uses thereof, WO 2020/068689A1, filing date 23 September 2019, entered in the IDS on 12 May 2023) in view of McGovern-Gooch et al. (Synthetic triterpenoid inhibition of human ghrelin o-acyltransferase: the involvement of a functionally required cysteine provides mechanistic insight into ghrelin acylation, Biochemistry 2017, 56, 919-931).
Jin teaches intermediate 2 (pg . 94, Scheme - intermediate 2) as a Boc protected amino precursor substrate, synthesized from starting material 2A in 7 steps. Jin does not, however, teach a method of treating or preventing a disease or disorder in a patient in need, where the patient is human, comprising administering to the patient a pharmaceutically effective amount of a compound of formula I or a pharmaceutical composition.
This dearth is overcome by McGovern-Gooch who teaches the use of a class of synthetic triterpenoids that selectively inhibit the human isoform of ghrelin O-acyltransferase, which catalyzes an essential octanoylation step in ghrelin maturation. The inhibitors are characterized as reversible covalent inhibitors and are described as a foundational step towards developing a new set of therapeutics targeting diabetes and obesity, a subset of diseases and disorders that afflicts the American population, with 26 million adults and children suffering from diabetes in 2011 and 382 million people worldwide in 2013 (abstract, pg. 1). As such, it would prima facie obvious, to a person of ordinary skill in the art, to consider the use of terpenoid derivatives, such as that of the elected species, as a possible therapeutic component to help address the incredibly broad set of human diseases and disorders in existence.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: elected species T62, as recited in claims 48-49, 53-54, 67-68, 72-73, and 112 were not taught in the prior art in a 100% embodiment.
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The closest match is a structure described by Jin et al. (Terpinoid derivatives and uses thereof, WO2020/068689A1, filing date 23 September 2019, entered in the IDS on 12 May 2023), described as compound intermediate 2, as seen below:
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No examples of eligible structures beyond C17-CH2-NH-C=O-R were identified.
Summary
Claims 48-49, 53-54, 67-68, 72-73, and 112 are allowed.
Claims 5-9, 27-29, 36-40, 50-52, 55-66, 69-71, 74-76, 78-79, 83-94, 99-111, 113 and 115 are withdrawn.
Claims 1-4, 12, 15, 17-26, 32-35, 117, 125 and 129 are not allowed.
Conclusion
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