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 .
Priority
This Application is a 371 of PCT/US2021/047935, filed Aug. 27, 2021 and claims priority benefit of U.S. Provisional Application No. 63/071,564, filed Aug. 28, 2020.
Claim Status
Claims 1, 5-10 and 13-14 are currently pending.
Pursuant to Applicant’s election without traverse of Group I, in the reply filed on Sept. 24, 2025, claims 1, 8-10 and 13-14 are currently active and subject to examination. Claims 5-7 are withdrawn.
Claim Rejections – Withdrawn – Overcome by Amendment
The rejection of claims 11-12 and 15 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn.
The rejection of claims 1 and 8-15 under 35 U.S.C. 102(a)(1) as being anticipated by “The Use of Brazilian Green Propolis Extract (EPP-AF) in Patients Affected by COVID-19. (Bee-Covid)” (NCT04480593, ClinicalTrials.gov, p. 1-11, published July 20, 2020) (herein “Bee-Covid”) evidenced by Berretta et al. (Molecules, Vol. 28, 7128, p. 1-25, published Oct. 17, 2023) and Barretta et al. (Superfood and Functional Food: An Overview of Their Processing and Utilization, Chapter 4, Published: 01 March 2017, p. 55-98) is withdrawn.
The above rejections were overcome by Applicant’s amendments to the claims.
Claim Rejections – 35 USC § 102 – New Grounds of Rejection Necessitated by Amendment
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.”
Claim(s) 1, 8-10 and 13-14 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ludwig et al. (US 2022/0152080 A1; Published May 19, 2022; PCT filed Mar. 19, 2020) as evidenced by Smith et al. (Bioorganic & Medicinal Chemistry, Volume 15, Issue 14, 15 July 2007, Pages 5018-5034).
Smith is cited to show the structure of the compound SL0101 taught by Ludwig (extra references or other references can be used to show the meaning of a term used in the primary reference) (MPEP § 2131.01.II).
Claim 1 is directed towards a method for inhibiting a virus infection comprising administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound, in which the compound is selected from a compound having the structure of formula VII:
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a compound having the structure of formula VIII:
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and a combination thereof.
Ludwig teaches a method for inhibiting viral infections comprising administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of the RSK inhibitor SL0101 (SL0101-1):
The present invention relates to an RSK inhibitor for use in a method for the prophylaxis and/or treatment of a viral disease. Specifically, the RSK inhibitor can be selected from the group consisting of BI-D1870, SL0101-1, LJH685, LJ1308, BIX 02565, FMK and a selective RSK1 inhibitor or a derivative, metabolite or pharmaceutically acceptable salt thereof.
Ludwig, Specification, ¶ [0011];
[I]nhibitors of Rsk have antiviral activity against viruses by preventing export of viral genomes from the nucleus. Surprisingly, it has been found that this object can be achieved by an RSK inhibitor according to the invention, in particular by pharmaceutical compositions comprising a RSK1 inhibitor compound.
Ludwig, Specification, ¶ [0045];
FIG. 4(A-H) show decreased M1-NP binding upon RSK-inhibition and nuclear retention of progeny vRNPs upon RSK-inhibition or RSK1 knockdown, as demonstrated in Example 2. (I-P) show that the specific RSK-inhibitors BI-D1870 and SL0101-1 inhibit viral propagation as described in Example 2
Ludwig, Specification, ¶ [0075];
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Ludwig, Fig. 4N-P;
To analyze the antiviral effect of RSK inhibitors we used BI-D1870 as well as SL0101-1 and determined the progeny virus titers after 24 h treatment with increasing concentrations from 1.56 μM to 100 μM (FIGS. 4K, N). Both inhibitors reduced the viral titers but BI-D1870 (EC50=2.808 μM) showed a higher effectiveness against the influenza infection than SL0101-1 (EC50=10.54 μM) (FIGS. 4L, O). Specifically, A549 cells were infected with WSN/H1N1 (MOI 0.01). After infection cells were treated with the depicted concentrations of BI-D1870 (I), SL0101-1 (L) or DMSO (0.1%). 24 h p.i. progeny virus titers were analyzed by standard plaque assay. Titers of DMSO-treated cells were set to 100%. Data represents mean of three independent experiments. Each experiment was performed in triplicates. Statistical significance was evaluated by one-way ANOVA followed by Dunnett's multiple comparison test (***p≤0.001). The results are shown in FIGS. 4K and 4N). Furthermore, in FIGS. 4L and 4O, progeny virus titers from (I,L) were used to calculate EC50 values. Finally, in FIGS. 4M and 4P, A549 cells were treated with depicted concentrations (L) of BI-D1870. 24 h p.i. cell viability and cell membrane integrity was measured with the LDH cytotoxicity assay. Data in combination with (E) were used to calculated CC50 values.
Ludwig, Specification, ¶ [0091].
Ludwig does not show the structure of SL0101, however, the structure of SL0101 is commonly known in the art. Smith et al. is cited to show that SL0101 (SL0101-1) is the compound having formula VII (extra references or other references can be used to show the meaning of a term used in the primary reference) (MPEP § 2131.01.II):
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Smith, Fig. 2, p. 5022.
Therefore, claim 1 is anticipated.
Claim 8 is directed towards the method of claim 1, wherein the virus is a coronavirus. Claim 9 is directed towards the method of claim 8, wherein the coronavirus is selected from SARS, MERS, and SARS-COV-2. Claim 10 is directed towards the method of claim 8, wherein the coronavirus is SARS-COV-2.
Ludwig teaches that the compound SL0101-1 can treat infections caused by coronaviruses such as SARS-COV-2:
In another aspect, the method of the invention is for the prophylaxis and/or treatment of a viral disease which is an infection caused by positive strand RNA virus such as, for example, Coronaviruses such as SARS-CoV, MERS-CoV or SARS-CoV-2 that cause respiratory tract infections such as SARS, MERS or Covid19.
Ludwig, Specification, ¶ [0058].
Therefore, claims 8-10 are anticipated.
Claim 13 is directed towards the method of claim 1, further comprising administering at least one additional anti-virus therapeutic agent.
Ludwig teaches that the method can comprise further administering one or more additional antiviral agent(s):
In addition, the RSK inhibitor may be administered together with a second antiviral agent. The second antiviral agent may be administered prior to, concomitantly with or after the administration of the RSK inhibitor. In addition, the RSK inhibitor and the second antiviral agent may be administered in one dosage form or in two separate dosage forms. It is also contemplated that the RSK inhibitor may be administered together with two or more antiviral agents.
Ludwig, Specification, ¶ [0067].
Therefore, claim 13 is anticipated.
Claim 14 is directed towards a method for treating or preventing a virus infection through inhibiting a cysteine protease in a virus comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound as set forth in claim 1.
Ludwig teaches a method for treating or preventing a virus infection comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound as set forth in claim 1 (SL0101):
[T]he present invention provides a method for the prophylaxis and/or treatment of a viral disease comprising administering an RSK inhibitor to a patient in need thereof.
Ludwig, Specification, ¶ [0056];
The RSK inhibitors of the invention are selected preferably from BI-D1870, SL0101, LJH685, LJI308, BIX 02565, FMK and a selective RSK1 inhibitor or a derivative, metabolite or pharmaceutically acceptable salt thereof.
Ludwig, Specification, ¶ [0059];
In the medical uses of the invention, the RSK inhibitor may be administered orally, intravenously, intrapleurally, intramuscularly, topically or via inhalation. Preferably, the RSK inhibitor is administered via nasal inhalation or orally to a subject or patient.
Ludwig, Specification, ¶ [0063];
The pharmaceutical composition comprising the RSK inhibitor may be in the form of orally administrable suspensions or tablets; nasal sprays, sterile injectable preparations (intravenously, intrapleurally, intramuscularly), for example, as sterile injectable aqueous or oleaginous suspensions or suppositories.
Ludwig, Specification, ¶ [0065].
While Ludwig does not teach that the compound inhibits a cysteine protease in a virus, this is an inherent property of the compound. By administering a composition comprising SL0101 to the subject, the cysteine protease would inherently be inhibited because the protease would be exposed to the compound which has this inhibitory activity. “‘[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).” (MPEP § 2112.I).
Therefore, claim 14 is anticipated.
Claim Rejections – 35 USC § 103 – New Grounds of Rejection Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
“A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.”
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 8-10 and 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ludwig et al. (US 2022/0152080 A1; Published May 19, 2022; PCT filed Mar. 19, 2020), as applied to claims 1, 8-10 and 13-14 above, and further in view of Smith et al. (Bioorganic & Medicinal Chemistry, Volume 15, Issue 14, 15 July 2007, Pages 5018-5034).
The rejection of claims 1, 8-10 and 13-14 above under 35 U.S.C. 102(a)(2) as being anticipated by Ludwig is incorporated herein by reference. These claims are anticipated because Ludwig teaches the compound of formula VII for the treatment of viral infections: “‘When a claim covers several structures or compositions, either generically or as alternatives, the claim is deemed anticipated if any of the structures or compositions within the scope of the claim is known in the prior art.’ Brown v. 3M, 265 F.3d 1349, 1351, 60 USPQ2d 1375, 1376 (Fed. Cir. 2001)” (MPEP § 2131). The obviousness rejection below addresses the compound of formula VIII, which is not explicitly taught by Ludwig.
As previously shown, Claim 1 is directed towards a method for inhibiting a virus infection comprising administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound, in which the compound is selected from a compound having the structure of formula VII:
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a compound having the structure of formula VIII:
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and a combination thereof.
As shown in the rejection of claim 1, Ludwig teaches a method for inhibiting viral infections comprising administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of the RSK inhibitor SL0101 (SL0101-1) (the compound of formula VII).
While Ludwig does not teach a method of treating a viral infection comprising administering to the subject in need thereof a compound of formula VIII, one of ordinary skill in the art would have a reasonable exepctation of success to inhibit a viral infection with a comopund of formula VIII because the compound of formula VIII is structurally analagous to the compound of formula VII/ SL0101 and is known to have similar properties.
For example, Smith teaches that SL0101 (compound (1)) and the compound of formula VIII (compound (32)) are both RSK inhibitors with similar properties:
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Smith, Fig. 2, p. 5022.
We have shown that the ability of RSK to interact with SL0101 depends on the sugar moiety because RSK has a 40-fold greater affinity for SL0101 (1) compared to kaempferol (31) (Fig. 2).2 During the isolation of SL0101 we also identified compounds that differ from SL0101 (1) only in the number and position of the acetyl groups on the rhamnose moiety ((32) and (33)) and we found that RSK was able to bind these compounds with similar in vitro affinities as SL0101 (1) (Fig. 2).18 Furthermore, acylation of all the hydroxy groups on the rhamnose to generate tri-O-Ac-SL0101 (29) did not substantially alter the inhibitory potency or specificity for inhibiting RSK activity in vitro (Fig. 2).18
Smith, col. 2, p. 5024.
Therefore, claim 1 was prima facie obvious at the time of filing.
One of ordinary skill in the art would also have a reasonable expectation of success to inhibit a coronavirus infection, in particular SARS-CoV-2 (claims 8-10), administer an additional antiviral agent (claim 13), and treat or prevent a viral infection (claim 14), with the compound of formula VIII because Smith teaches these methods with the compound of formula VII/ SL0101, which is commonly known in the art to be structurally and functionally analogous to the compound of formula VIII. For example, see Smith above.
Therefore, claims 8-10 and 13-14 were prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629