DETAILED ACTION
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 . 1
Status of Claims
Claims 1-26 are pending. Claims 1-3 and 7-19 read on the elected species, and under examination. Claims 4-6 and 20-26 are withdrawn. Applicant’s elected species (without traverse) is SARS-CoV-2 infection aka COVID-19. The claimed methods disclose 23-O-Acetylalisol B (identified Alisol B in this action). See SciFinder search.2
Claim Interpretation
Amended Claim 1 recites a prophylactic (emphasis added) method or responsive treatment of a human corona virus infection (COVID19) of a respiratory system or a symptom thereof in a subject, comprising an effective amount of Alisol 23 B of Formula (I) “as the only active agent,” to the subject, or a pharmaceutically acceptable salt, derivative, or prodrug thereof (emphasis added).
Initially, it is noted the term “active agent” is not recited in the specification, while there is reference to a formulation containing a therapeutically effective amount of the “active ingredient” noted to be Alisol B. See page 8 of the specification. Note that neither “derivative” or “prodrug” are defined in the specification.
The contradictory limitations of Alisol B as the only active, while simultaneously claiming pharmaceutically acceptable salts, derivatives or prodrugs there also being permissible, on its face, renders the scope of claim 1 unclear, see below indefinite rejection.
Accordingly, due to the lack of definitions in the specification, a broad and reasonable interpretation of the claim permits the inclusion of additional compounds, see below prior art rejections according a broad interpretation of the terms, especially the term “derivative.”.
Further, the recitation of prophylactic treatment of human coronavirus infection of a respiratory system or symptom thereof in a subject is interpreted to a human subject is identified as not having a human coronavirus infection, where Alisol B can be administered as prophylaxis, or an alternative agent can be given. See page 14 last paragraph.
Claim 3 has been amended to include the Omicron variants of SARS-Cov2 (COVID-19) infections. It is noted that such variants were not discovered until November 2021, well past the earliest claimed priority to provisional Application 63/261759 of Sept 28 2021. Therefore claim 3, only has the earliest priority to Sept 28 2022, the filing of this non-provisional application3, where the Omicron variant is cited. The Omicron variant is not disclosed in the Sept 2021 provisional but only in this non-provisional application filed Sept 2022.
Response to Arguments
Applicant’s arguments and amendments with respect to claim(s) 1-3, 7, 8 and 13-19 being rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fan et al. Chinese Traditional and Herbal Drugs; (24): 2297-2306, 2020 (abstract only), have been fully considered and are persuasive. The rejection of claim(s) 1-3, 7, 8 and 13-19 has been withdrawn.
Applicant’s arguments and amendments with respect to claim(s) 1-3 and 7-19 being rejected under 35 USC 103 as being obvious over Fan et al. in view of Zhao et al. Phytomedicine 85 (2021) 153315, Sept 9 2020, have been fully considered, where the amendments to the claims have necessitated the below new rejections, 35 USC 112(b) and 35 US 103, as detailed below.
New Claim Rejections Necessitated by Amendment - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3 and 7-19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 has been amended to recite the method comprising an effective amount of Alisol B of Formula (I) “as the only active agent,” to the subject, or a pharmaceutically acceptable salt, derivative, or prodrug thereof (emphasis added). Claim 1 indicates the exclusion of any active agent other than Alisol B of Formula (I) by the language “as the sole active agent”, but indicates a salt, derivative, or prodrug of Formula (I) is permitted. Examiner notes that the term “active agent” is not defined, or even used, in the instant specification. A skilled artisan would not be apprised of the metes and bounds of the instant claims because the claims do not clearly set forth which compounds, including derivatives and prodrugs, are permitted and excluded, particularly given the lack of definitions for terms such as “derivative” and “active agent”.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-2, 7-8, 10 and 13-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al. Analysis on material basis and efficacy network of Huopo Xialing Decoction in treating damp pathogen stagnation of lung syndrome of early COVID-19 Chinese Traditional and Herbal Drugs; (24): 2297-2306, 2020 (abstract only). Fan was cited by the Examiner on the PTO-892 form previously.
Claim 1 recites a method for prophylactic (emphasis added) or responsive treatment of a human coronavirus infection (SARS-CoV-2 virus as per claim 2)of a respiratory system or a symptom thereof in a subject, said method comprising administering an effective amount of 23-O-Acetylalisol B of Formula (I) as the only active agent, or a pharmaceutically acceptable salt, derivative, or prodrug (emphasis added) thereof to the subject. As detailed above, in terms claim interpretation, a broad and reasonable interpretation of claim 1 allows for other compounds, not just Alisol B as the only active agent, to be administered to the subject in need.
Regarding claims 1-2 and method claimed, Fan discloses that the claimed compound, Alisol B, 23-acetate, Alisol B, plays a role in the treatment of COVID-19, where it is taught that its role is by blocking the protein synthesis of SARS-CoV-2 virus, preventing the virus from entering the host cells, regulating the IL signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, T cell receptor signaling pathway, C-type lectin receptor signaling pathway and inhibiting the expression of related inflammatory factors. See abstract.
While Fan teaches the treatment of COVID-19 with Alisol B as claimed, it does not teach an embodiment where Alisol B is the only active ingredient. However, it is noted that a broad and reasonable interpretation of claim 1 allows for embodiments inclusive of other compounds, as per Fan. See above Claim Interpretation and 35 USC 112(b) rejections. Further, while Fan does not specify the respiratory system of a subject, it would be obvious for a PHOSITA to treat it because the known impact SARS-CoV2 (COVID-19) infection has on the respiratory system of a subject.
Prior to the filing of the present patent application, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of the primary reference Fan to look at any of the 12 compounds of Fan, including Alisol B, to investigate its activity against COVID-19 infections known to affect the respiratory system.
The PHOSITA would have has a reasonable expectation of success because due to the limited number of compounds taught by Fan, including Alisol B, it would be obvious to try treating COVID-19 with these compounds, in combination or individually, affecting a subject’s respiratory system.
Regarding claim 7, human subject infected with a corona virus at time of administration, Fan discloses that the Huopu Xialing Decoction (comprising the claimed compound 23-Alisosol-B) was used to treat humans of the early coronavirus pneumonia. See Methods and Results section of abstract.
Regarding claim 8 and the limitation of a human subject that previously had the coronavirus infection at the time of administering, wherein the past coronavirus infection includes the human subject having contracted a coronavirus infection one or more times in the past, the claim is broadly and reasonably interpreted to include recently infected humans (overlapping with the patient population of claim 7), and as the patient population of claim 7 is obvious, previously infected humans having contracted the infection one or more times in the past would also be obvious to treat.
Regarding claim 10, Fan discloses that the claimed compound, Alisol B,23-acetate, Alisol B, plays a role in the treatment of COVID-19, where it is taught that its role is by blocking the protein synthesis of SARS-CoV-2 virus, preventing the virus from entering the host cells, where prevention of virus from entering host cells would render the prophylaxis aspect of claim 10, see abstract.
Claim 13 limits the invention to where the claimed 23-O-Acetylalisol B, has properties of reducing viral replication, by reducing the number of viral gene copies by about 4-logs and the viral titer by about 2.5 times in lung tissues of hamster infected by SARS-Co V-2, Fan discloses such property noting 23-acetate Alisol B plays a role by blocking the protein synthesis of SARS-CoV-2 virus, preventing the virus from entering the host cells, regulating the IL signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, T cell receptor signaling pathway, C-type lectin receptor signaling pathway and inhibiting the expression of related inflammatory factors. See abstract.
Claims 14-19 recite the functionally descriptive limitations of where the claimed compound
inhibits the infiltrations of CD11b-positive macrophages by about 3 times and CD3-positive T cells by about 3.5 times in the lung tissues of hamster infected by SARS-CoV-2 (claim 14)
decreases reactive oxygen species (ROS) by about 1.4 times and reactive nitrogen species (RNS) by about two times in the lung tissues of hamster infected by SARS-Co V-2 (claim 15)
increases the proliferation and differentiation of human B cells in the lung tissues of hamster infected by SARS-CoV-2. (claim 16)
increases BB220+ cell populations by about 1.28, 1.55, and 3.47 times after 48 hours treatment with 4μM, 8μM, and l 6μM, respectively (claim 17)
inhibits the proliferation of human T lymphocytes and macrophages (claim 18)
reduces the amount of IL-17, IFN-y, IL6 and IP10 (CXCL10) (claim 19).
It is pointed out that Fan addresses some of these properties noting 23-acetate Alisol B plays a role by blocking the protein synthesis of SARS-CoV-2 virus, preventing the virus from entering the host cells, regulating the IL signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, T cell receptor signaling pathway, C-type lectin receptor signaling pathway and inhibiting the expression of related inflammatory factors. See abstract.
With regard to any of these properties of claims 13-19 not expressly disclosed by Fan, such properties would be necessarily present in its claimed method, whether expressly taught or not.
For example, with regard to the properties of 23-O-Acetylalisol B to inhibit the proliferations of human T-lymphocytes and macrophages, as well as reduce the amount of interleukins as per claims 18-19, because the method of claim 1 is taught by Fan, the limitations of claims 18-19 are necessarily present in the prior art. Therefore, the properties of 23-O-Acetylalisol B claims 18-19 are present in the cited prior art.
Claims 1-2 and 7-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al. Analysis on material basis and efficacy network of Huopo Xialing Decoction in treating damp pathogen stagnation of lung syndrome of early COVID-19 Chinese Traditional and Herbal Drugs; (24): 2297-2306, 2020 (abstract only), in view of Zhao et al. Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19 Phytomedicine 85 (2021) 153315, Available online Sept 9 2020. Fan and Zhao were cited by the Examiner on the PTO-892 form previously.
It is noted that Fan teaches the limitations of claims 1-2, 7-8, 10 and 13-19 as detailed above.
However, it is noted that certain embodiments of the method of claim 1 are not necessarily disclosed by the teachings of Fan, in particular those embodiments represented by claims 9 and 11-12.
Claims 9 and 11-12 disclose (biological samples, prophylaxis treatment and oral dosing etc.). To address this, those embodiments of claim 1, as detailed by claims 9 and 11-12, are rendered prima facie obvious as a PHOSITA following the teachings of Fan and Zhao to treat COVID19 would modify these teachings to treat those embodiments of claims 9-(biological sampling (claim 9) and oral dosing of drugs (claims 11-12)). The PHOSITA would have had a reasonable expectation of success because it would be obvious to try to take biological samples, treat prophylactically and orally dose drugs as claimed.
Regarding claim 9 and the identification of a coronavirus infection in a subject via a biological sample, affecting a respiratory system, Fan teaches the treatment of patients identified to be suffering from COVID-19, see abstract. With regard to the limitation of a biological sampling of the patient, Zhao teaches the collection of COVID-19 related disease genes and agents, see page 2, column 2, first paragraph, to be treated with the traditional Chinese medicine (TCM) formula Qing-Fei-Pai-Du decoction (QFPDD), taught to comprise 23-O-Alisol B , see abstract. Further, Zhao teaches identification of COVID-19 by various methods involving biological samples, including coagulation dysfunction and inflammatory cytokine storm, see page 2 column 1, first paragraph. A PHOSITA would have a rationale to treat coronavirus respiratory infections as COVID-19 is known to affect respiratory systems.
Regarding claims 11-12 and orally dosing 23-O-Alisol-B, Zhao teaches the traditional Chinese medicine (formula Qing-Fei-Pai-Du decoction (QFPDD) comprising 23-O-alisol B is taken orally, see page 2, column 1 about middle of page.
The rationale to support a finding of obviousness are prior art elements (treating COVID-19 with 23-O-Alisol-B as per Fan) combined with known methods (prophylaxis treatment, as well as oral dosing of 23-O-Alisol-B as per Zhao) to predictably arrive at the claimed invention.
Claims 1-3 and 7-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al. Analysis on material basis and efficacy network of Huopo Xialing Decoction in treating damp pathogen stagnation of lung syndrome of early COVID-19 Chinese Traditional and Herbal Drugs; (24): 2297-2306, 2020 (abstract only), in view of Zhao et al. Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of Qing-Fei-Pai-Du decoction in the treatment of COVID-19 Phytomedicine 85 (2021) 153315, Available online Sept 9 2020 in further view of Duong Alpha, Beta, Delta, Gamma: What’s important to know about SARS-CoV-2 variants of concern? CMAJ 2021 July 12; 193:31059-60 and/or Karim and Karim Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic The Lancet Comment Volume 398, Issue 10317p2126-2128 December 11, 2021. Duong 2021 and Karim Dec 2021 are cited on the PTO-892 form.
Fan and Zhao were cited by the Examiner on the PTO-892 form previously.
As detailed above, claim 3 is only afforded priority to Sept 28 2022.
As detailed above, the teachings of Fan and Zhao render claims 1-2 and 7-19 obvious. However, these references do not necessarily recite the species of amended claim 3 reciting an Omicron variant or Omicron BA 5.2 variant.
With regard to claim 3 and the alpha and delta variants of SARS-CoV2, these are taught by Duong 2021. See title and first and second pages. Regarding the omicron variant of claim 3 Karim 2021 teaches omicron COVID19 variants. See abstract and pages 1-3.
Prior to the filing of this application it would have been prima facie obvious for a PHOSITA to modify the teachings of Fan and Zhao to treat COVID-19, so as to treat the alpha, delta and omicron variants claimed, per Duong and Karim. The PHOSITA would have had a reasonable expectation of success because knowing the method of claim 1 is obvious over Fan and Zhao, it would obvious to try and treat the alpha, delta and omicron variants.
RESPONSE TO ATTORNEY ARGUMENTS:
The Sept 2025 Attorney response states Fan lists 12 potentially active components including claimed compound Alisol B that play a role blocking protein synthesis of SARS-CoV2, to prevent the virus from entering the host cells, regulating IL, MAPK, PI3K-Akt, T-cell, C-leptin signaling pathways, and inhibiting related inflammatory factor expression. See also Shen Declaration, paragraphs 2-3, only made available to the Examiner as of October 2025).
The Attorney response states Zhao fails to provide information regarding the activity of 12 potentially active compounds in the respiratory system (only the nervous, sensory, circulatory and digestive systems). Id at Shen Declaration.
The Attorney response states its experiments indicate that the network pharmacology data could not represent real antiviral or ACE2 inhibitory activities against SARS-CoV2 (Figures 1-3, Table 1), where Zhao’s network data could not be applied to the respiratory system (i.e., computational binding scores do not predict functional outcomes). See also a reference to Fig 4 demonstrating viral titer of DMSO carrier compared to baicalin and stigmasterol. Id at Shen Declaration.
The Attorney response concludes that claim 1 includes the respiratory system and is allegedly limited to Alisol B as the only active ingredient, which it argues Zhao fails to provide information regarding the activity of 12 active compounds in the respiratory system.
In response, as detailed above, the data from the Shen Declaration and reference by the Sept 2025 response are in support, and emphasize a claimed method focused solely on Alisol B for the treatment of COVID-19 (aka SARS-CoV2 infections) known to be associated with a subject’s respiratory system.
As detailed above in the rejections, the indefinite nature of the claimed method with regard to active ingredients and that it would be obvious to try to treat the claimed subject in need’s respiratory system due to the nature of SAR-CoV2 infections (COVID-19), the claims remain prima facie obvious as detailed above.
With regard to the Shen Declaration and evidence presented, while they do purport to be supportive of only using Alisol B as the sole active ingredient to treat COVID-19 (SARS-CoV2 infections) known to
Conclusion
In summary, no claims are allowed. Applicant's amendment necessitated the new 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application claims priority to 63/261,759 filed 09/28/2021.
2 CAS Registry Number: 26575-95-1
(8α,9β,11β,14β,23S,24R)-23-(Acetyloxy)-24,25-epoxy-11-hydroxydammar-13(17)-en-3-one (ACI)
8α,9β,14β-Dammar-13(17)-en-3-one, 24,25-epoxy-11β,23-dihydroxy-, 23-acetate, (23S,24R)- (8CI)
23-Acetylalismol B
23-O-Acetylalisol B
Alisol B 23-acetate
Alisol B 23-monoacetate
Alisol B monoacetate
3 See pages 2, 4 (FIGS. 1E, 1F, 1K, 2D, 3M, 3N); and 29,footnotes 24-25