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
The office acknowledges Applicants filing of the remarks and amendments on 12/29/2025 in response to the office action dated 10/01/2025. Claims 1, 9-10, 18 have been amended and claims 11, 16, and 17 cancelled. Claim 2 has been previously cancelled. Applicants arguments regarding the rejections have been fully considered. Rejections not reiterated from the previous office actions are hereby withdrawn. Arguments, which are directed to withdrawn rejections, are thus rendered moot. The arguments in regards to the reiterated rejections/references from the previous office action are addressed below. In view of Applicant's claim amendments, the following 112(1) WD rejection has been modified. The action is made Final. Claims 1, 3-10, 12-15, and 18-20 are pending and are examined based on the merits herein.
Response to Applicants Arguments
112(1) WD:
Applicants argue that the claims as amended further limit the cyclohexenone compound encompassed in the claims to be the close analogs of antroquinonol (i.e., compound 1) wherein and Y independently is oxygen or sulfur (which is in the same periodic table of oxygen sharing the similar chemical property), and R4 (the side chain of the cyclohexenone compound) to be a nonpolar group as of the side chain of Antroquinonol. It is known in the art that a group of similar compounds would possess the similar biological properties, especially if they share the same or very similar core structure, with the very similar functional groups. Here the compound encompassed in the claims share the same (X and Y independently to be oxygen) or very chemically similar (X and Y independently to be sulfur) cyclohexenone core, with the same non-polar side chain (i.e., repeating isoprene unit with nonpolar R4 group) as the exemplary compound 1, Antroquinonol. As such, these analogs of Antroquinonol possess the same or similar biological activities of compound 1. Thus, a skilled artisan could and would be able to extrapolate the effects of compound 1 as provided in the specification for treating or reducing symptoms of an RNA virus induced disease wherein the RNA virus is a coronavirus with its analogs as claims.
In response, Applicants arguments have been fully considered. However the scope of the claims are still very broad in regards to the number of compounds and to the RNA virus induced diseases (wherein the virus is coronavirus) to be treated.
Applicants claim the use of the following genus of cyclohexenone compounds in treating different RNA induced virus diseases, wherein the virus is coronavirus.
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The RNA induced virus diseases to be treated include but not limited to: respiratory Infections, SARS-CoV-2 (COVID-19), SARS-CoV, Influenza, MERS Respiratory Syncytial Virus (RSV) etc.
The structural formula in claim 1 encompasses hundreds of cyclohexenone compounds. The chemical, physical and pharmacological properties of the compounds is influenced based on the structural differences. For example the tested compound 1 and compound 28 of claim 1 has the structure of:
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As noted above there are two different substituent changes in compound 28 compared to compound 1. Further Applicants claim R4 in the formula can be ‘aryl’. Applicants have defined in [0039] of the specification that “As used herein, the term "aryl" refers to an aromatic ring wherein each of the atoms forming the ring is a carbon atom. Aryl rings are formed by five, six, seven, eight, nine, or more than nine carbon atoms”. Hence based on the aryl substituent of R4 and other substituents, R1, R2, R3 and R, the structures vary and so as their biological and pharmacological properties. As to applicants arguments in regards to analogs, the analogs may share a high degree of chemical or physical similarity such as a similar carbon backbone. However small variations in molecular structure or physical composition can lead to significant differences in their behavior, pharmacological effects, or physical properties. It is noted that even if two molecules have the same formula and connectivity (e.g. enantiomers), they can have different chemical properties. Further despite the structure similarity the compounds can have different functions. It must be recognized that the analogs are different chemical entities from the lead compound. It is not possible to retain all and exactly the same solubility and solvent partition characteristics, chemical reactivity and stability, acid or base strength, and/or in vivo metabolism properties of the lead compound. Thus, although the new analog may demonstrate pharmacological similarity to the lead compound, it is not likely to be identical to, nor will its similarities and differences always be predictable." (J. G. Cannon, Chapter Nineteen in Burger's Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume I: Principles and Practice, Wiley-lnterscience 1995, pp. 783-802, see page 784, left column, first full paragraph).
Applicants have not provided any experimental data or evidence/support to demonstrate that administration of closely related analogs of claim 1 has similar pharmacological effects in treating the claimed various RNA virus induced diseases, wherein the virus is coronavirus.
The specification provides guidance and data to the pharmacological effects to just one compound, antroquinonol (compound 1) in HBV suppression (hepatoma cell lines), anti-inflammatory, anti-viral (HBV, SARS-CoV-2, in in vitro studies), and anti-fibrosis effects. The data provided for compound 1, antroquinonol in the specification cannot be extrapolated for example in treating MERS for example and for the use of all other compounds of claim 1 in treating distinct RNA virus induced diseases, wherein the virus is coronavirus. The art of determining the in vitro/in vivo activity of a compound or set of compounds based on structural similarity to the known in vitro/in vivo activity of a compound with structural diversity is highly unpredictable. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved".
The Examiner acknowledges that an Applicant is not required to provide an explicit disclosure of every embodiment falling within the scope of a genus. However, what constitutes a "representative number" of embodiments is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. In the instant case, Applicants have provided in vitro pharmacological data for one single compound pertaining to its anti-inflammatory, anti-fibrosis effects, HBV suppression and anti-viral effects of SARS-Cov-2. A person skilled in the art would understand that applicant is not in possession of the invention as broadly claimed. The rejection is proper and thus maintained.
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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 1, 3-10, 12-15, and 18-20 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir.1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP states that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The Guidelines for Examination of Patent Applications Under 35 USC 112, "Written Description" Requirement (Federal Register, Vol. 66, No. 4, pg. ll05, column 3), in accordance with MPEP § 2163, specifically state that for each claim drawn to a genus the written description requirement may be satisfied through sufficient description of a representative number of species by a) actual reduction to practice; b) reduction to drawings or structural chemical formulas; c) disclosure of relevant, identifying characteristics (i.e. structure) by functional characteristics coupled with a known or disclosed correlation between function and structure. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention (Federal Register, Vol. 66, No. 4, p. ll05, 3rd column, 3rd paragraph). Below is such comparison.
The instant claims are directed to:
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Scope of claims: The scope of the method is broad in regards to (i) the agents to be used (ii) to the RNA induced diseases caused by coronaviruses.
Scope of disclosure and reduction to practice: The specification lists select compounds used in claim 1 (See [0076]-[0077]) and preparation of exemplary cyclohexenone compounds, in example 1.
The specification provides guidance and data to the pharmacological effects of one compound, compound 1 (Antroquinonol) in HBV suppression (hepatoma cell lines), anti-inflammatory, anti-viral (HBV, SARS-CoV-2, in in vitro studies), and anti-fibrosis effects (See examples 2-3).
Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved". See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Representative number of Examples: Applicants have provided data and evidence in regards to the effects of one agent, compound 1 (Antroquinonol) in in vitro in HBV suppression and anti-inflammatory effects towards SARS-Cov-2. There is no data that the single compound tested was in vivo.
It is not clear from the specification that how the data provided (in vitro tests) can be extrapolated in treating all RNA induced virus diseases, wherein in the virus is coronavirus. For example MERS is Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a coronavirus (MERS-CoV), and the symptoms include fever, cough and shortness of breath, commonly leading to pneumonia. According to World Health Organization, currently there is no treatment or vaccine for treating MERS (See p 1, Key Facts, https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov), Dec 2025). From the data provided for SARS-Cov-2 with compound 1, it is not predictable that the results can be applied for MERS with this compound or any other cyclohexenone compound of claim 1.
Correlation between structure and function: The structure is the compound (of claim 1) and the function is the treatment of the RNA induced virus diseases by coronavirus in a subject. The structural formula in claim 1 encompasses hundreds of cyclohexenone compounds. The chemical, physical and pharmacological properties of the compounds is influenced based on the structural differences. A correlation between structure and function in achieving the property of wherein administration of the agent(s) of claim 1 results in the treatment or prevention of various types of RNA induced virus diseases by coronavirus is less understood and is not disclosed in the prior art or in the specification. A skilled artisan would not be able to extrapolate the effects of compound 1 as provided in the specification for treating all types of coronavirus diseases in all types of subjects with the agents as claimed.
Al-Khalaifah teach that coronaviruses are responsible for a range of illnesses, which are respiratory, enteric, hepatic, and neurological. Further taught is that Avian IBV is a gamma-coronavirus in the family Coronaviridae, the order Nidovirales, and the genus Coronavirus that causes a highly contagious upper-respiratory disease in domestic chickens. Control of IBV is difficult because there is little to no cross-protection between the numerous different serotypes of the virus (See p 03, col. 1, para 3).
Al-Khalaifah teach that the “Development and production of vaccines can counter pandemics or outbreaks, but continuous mutation of the virus creates a hurdle for the vaccine developers”; One good example is IBV, which is found to have a significant mutation rate as compared to other viruses. (p 3, col. 2, last para, See Hanan Al-Khalaifah, Front Microbiol. 2022 Oct 13;13:976462, p 1-10). The reference further teach that a study conducted in China found that there was a change in four dominant genotypes. The results of the study also revealed that the Southern Chinese region had observed significant changes in the genetic diversity of the virus, which indicated that the virus mutated to come up with new strains. As a result, the previous vaccines were not effective against the mutated virus (p 4, col. 1, para 1). This teach the unpredictability of the use of vaccines or pharmaceutical agent(s) in the treatment of viral diseases.
It is not predictable from the prior art or from the specification that all viral infections as claimed are treatable with all the compounds of claim 1 at all concentrations.
In conclusion, the scope of the compounds used and RNA induced virus diseases caused by coronaviruses is large. The specification has provided limited guidance and data with just one compound 1 in regards to HBV and SARS-Cov-2 (in vitro data).
Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure species to make and possibly use of the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.”
The specification provides insufficient written description to support the genus encompassed by the claim, Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
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) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claimed subject matter and does not reasonably convey to one skilled in the relevant art that the inventors had possession of the entire scope of the claimed invention.
Conclusion
Applicant's amendment necessitated the modified ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627