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 .
Amendments Received
Amendments to the claims were received and entered on 05/26/2026.
Status of Claims
Claims 3, 5-9, and 13-33 have been cancelled.
Claims 1-2, 4, and 10-12 are currently pending and under consideration.
Priority
The present application claims status as a 371 (National Stage) of PCT/US2022/028801 filed on 05/11/2022. Acknowledgment is made of applicant’s claim for benefit under 35 U.S.C. 119(e) of Provisional application No. 63/187,924, filed on 05/12/2021. The present application and all claims are being examined with an effective filing date of 05/12/2021. In future actions, the effective filing date may change due to amendments or further review of priority documents.
Withdrawn Objections
In view of Applicant’s amendments, the objection to claim 12 is hereby withdrawn.
Withdrawn Rejections
In view of Applicant’s cancellation of claims 3, 5-9, and 13-33, all rejections of claims 3, 5-9, and 13-33 are now moot, and are hereby withdrawn.
In view of Applicant’s amendments, rejection of claims 1-2, 4, and 10-12 under 35 USC § 112(a) is hereby withdrawn.
In view of Applicant’s amendments, rejection of claim 4 under 35 USC § 112(b) is hereby withdrawn.
In view of Applicant’s amendments, rejections of claims 1-2, and 10 under 35 USC § 103 over Glasgow, Shephard and Quindos are hereby withdrawn.
In view of Applicant’s amendments, rejection of claim 4 under 35 USC § 103 over Glasgow, Shephard and Quindos, further in view of Sancho are hereby withdrawn.
In view of Applicant’s amendments, rejections of claims 11 and 12 under 35 USC § 103 over Glasgow, Shephard and Quindos, further in view of Liu are hereby withdrawn.
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.
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.
Claims 1-2, 4, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Glasgow et al. (“Engineered ACE2 receptor traps potently neutralize SARS-CoV-2,” PNAS, Vol 117, no. 45, 2020, pg. 28046-28055, cited in the IDS), Shephard et al. (Virucidal action of sore throat lozenges against respiratory viruses parainfluenza type 3 and cytomegalovirus, Antiviral Research 123 (2015), pg. 158–162, cited in a previous office action), Quindos et al. (Therapeutic tools for oral candidiasis: Current and new antifungal drugs, Med Oral Patol Oral Cir Bucal. 2019 Mar 1;24 (2):e172-80, cited in the IDS), and Liu et al. (Carbohydrate-Binding Protein from the Edible Lablab Beans Effectively Blocks the Infections of Influenza Viruses and SARS-CoV-2. Sci Rep 10, 17356, Cell Reports 32, 108016, cited in the IDS).
Glasgow et al. discloses engineered angiotensin-converting enzyme 2 (ACE2) receptor “traps” that bind to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and neutralize viral infection, because SARS-CoV-2 infection begins with viral spike protein binding to the human ACE2 receptor (Abstract). It is noted that SARS-CoV-2 is from the coronavirus and the RBD of the spike protein is on the surface of the virus (pg. 28046, left column). Specifically, Glasgow et al. describe engineering soluble variants of the extracellular domain of ACE2 to generate “receptor traps” that bind the spike RBD and “potently block SARS CoV-2 infection of cells”, teaching that these engineered ACE2 receptor traps are affinity-optimized soluble extracellular ACE2 proteins that block viral spike protein binding to cellular ACE2, thereby inhibiting infection (Abstract; pg. 28046, right column and pg. 28053, left column). Furthermore, Glasgow et al. teaches that these ACE2 receptor traps exhibit measurable binding affinity (KD values in the nanomolar range) for the SARS-CoV-2 spike RBD, including KD values of approximately 10.8 nM and 2.8 nM for the variants ACE2(614) and ACE2(740), respectively, thereby demonstrating specific and strong binding affinity for a viral surface protein. Additionally, Glasgow et al. teaches that ACE2 neutralizes SARS-CoV-2 infection, significantly reducing viral RNA levels, with reported IC50 values in the nanogram per milliliter range, thereby demonstrating reduction of viral load at low concentrations (pg. 28050, right column and Fig. 4D–F). However, Glasgow et al. does not teach orally administering the ACE2 (i.e., trapping molecule) to a subject via a carrier, nor wherein the virus comprises at least one of Influenza A virus, Influenza B virus, and Influenza C virus; wherein said trapping molecule is an influenza virus A (IVA) blocking peptide comprising virus binding portions of HA and, or neuraminidase proteins and, or a FRIL molecule from lablab bean powder that binds a glucan on a virus surface, and traps influenza viral particles.
Liu et al. discloses that the lectin FRIL, isolated from Lablab purpureus (lablab bean), exhibits potent anti-influenza activity and neutralizes multiple representative human and avian influenza strains, including influenza A (H1N1, H3N2, H5N1, H7N9) and influenza B strains, at low nanomolar concentrations (pg. 1-3 and Fig. 2). Liu et al. further teaches that influenza hemagglutinin (HA) is heavily glycosylated and contains complex-type N-glycans on the viral surface (pg. 1-2) and that FRIL binds preferentially to complex-type N-glycans present on influenza viral envelope glycoproteins via FRIL’s carbohydrate-binding domain (pg. 4-5; pg. 7; and Fig. 3). Liu et al. teaches that FRIL aggregates influenza virions through multivalent binding, forming large three-dimensional aggregates of viral particles and that FRIL first binds and extracellularly cross-links virus particles, creating aggregates that prevent viral entry and nuclear import. This aggregation effectively “traps” influenza viral particles and halts infection at the late endosomal stage (pg. 7-8 and Fig. 4-5). Furthermore, Liu et al. discloses in vivo administration of FRIL in a mouse influenza infection model wherein FRIL was administered intranasally to BALB/c mice prior to viral challenge and repeatedly following infection. The treated mice exhibited increased survival and delayed mortality compared to controls, demonstrating in vivo antiviral efficacy against influenza virus (pg. 3-4 and Fig. 2D-F). Liu et al. explicitly suggests the potential therapeutic applications of FRIL for prevention and/or treatment of influenza and COVID-19 and proposes oral delivery formats such as aerosol mists or inhalers (pg. 12).
Shepherd et al. discloses locally/orally delivered lozenge formulations for treatment of viral respiratory tract infections. Shepherd teaches that “locally delivered formats such as lozenges and sprays are useful as they enable active ingredients to reach the site of infection directly,” and that such localized delivery allows treatment at the throat/oral cavity while minimizing systemic side effects (Abstract and pg. 159, left column). Shepherd et al. evaluated virucidal activity in vitro by dissolving the lozenge formulations in artificial saliva, incubating the resulting solution with parainfluenza virus type 3 (PIV3) or cytomegalovirus (CMV) for contact times of 1-10 minutes, neutralizing the mixture, and quantifying remaining infectious virus using a TCID50 assay in host cells (pg. 159–160). Shepherd et al. discloses multi-log reductions in infectious viral titer under these artificial saliva conditions (pg. 160-161; Figs. 1–3), supporting oral administration of a lozenge formulation to a subject infected with a viral respiratory tract infection. Shepherd et al. concludes that such lozenges have the potential to provide local antiviral effects in patients with sore throat due to viral respiratory tract infections and support their use as a first-line treatment for sore throat caused by viral RTIs (pg. 161, Conclusions). Although Shepherd et al. does not expressly teach administering the lozenge to a subject confirmed to be suffering from a viral respiratory tract infection and measuring viral titer in vivo, the artificial saliva contact model simulates the dissolution of a lozenge within the oral cavity and short-term exposure of virus to the active agents in saliva. Thus, the reported reductions in infectious viral titer in artificial saliva represent the antiviral activity expected when the lozenge is orally administered and dissolved in the oral cavity.
With respect to the limitation reciting “wherein the administering takes place before or after the subject is exposed to the virus and reduces recovery time for or minimizes at least one complication from viral infection” in claim 2, Shephard et al. teaches administering lozenges for treatment of viral respiratory tract infections, which necessarily occurs after exposure to the virus. Additionally, the method of Shephard et al. explicitly teaches a reduction in viral titer which corresponds to reduction in infectious viral burden. A person or ordinary skill in the art would understand that reducing viral burden at the site of infection would reasonably be expected to lessen severity and duration of viral illness, thereby reducing recovery time and minimizing complications associated with viral infection.
Quindos et al. teaches that the antifungal nystatin binds to ergosterol in the fungal plasma membrane and forms pores, resulting in fungicidal activity, corresponding to a trapping molecule having affinity for a microorganism (fungus). It is noted that the binding and resulting fungicidal effect reduces Candida burden in the oral cavity, thereby reducing microorganism load in the oral cavity of the subject. Quindos et al. further teaches antifungal formulations are “marketed as oral suspensions, tablets, pastilles, gels, mucoadhesive tablets, toothpastes, etc. for facilitating their therapeutic action…” (pg. e176). Therefore, Quindos et al. discloses a successful method for reducing Candida in the oral cavity, comprising administering a composition, comprising a carrier (e.g., tablet) including a trapping molecule.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, Glasgow et al. taught engineered soluble ACE2 receptor traps that bind SARS-CoV-2 surface spike protein and neutralize viral infection, thereby reducing viral load. Shepherd et al. taught locally administered oral antiviral formulations, including lozenges, for delivering antiviral agents directly to the oral cavity and reducing infectious viral titer under saliva-like conditions. Liu et al. further taught that FRIL isolated from lablab bean functions as a viral trapping molecule by binding complex-type N-glycans on influenza viral surface glycoproteins, aggregating and trapping influenza virions, neutralizing influenza A and B viruses, and providing antiviral efficacy in vivo. Thus, the teachings of Glasgow et al. and Liu et al. establish known viral-binding agents capable of binding and trapping coronavirus or influenza virus, respectively, while Shepherd et al. establishes a known locally administered oral carrier for delivery of antiviral agents to reduce viral burden at the site of infection. A person of ordinary skill in the art would therefore have been motivated to incorporate such known viral-binding agents, including FRIL, into the locally administered oral formulation taught by Shepherd et al. for the purpose of binding and reducing the corresponding viral burden in the oral cavity. Such a substitution of one known viral-binding protein for another in a known delivery format constitutes the use of a known element according to its established function. Therefore, it would be obvious for a person of ordinary skill in the art, to make these substitutions and expect predictable results (see MPEP 2144.06, “Substituting equivalents known for the same purpose”).Furthermore, given the demonstrated viral-binding and neutralizing activity of the trapping molecules and Shepherd et al.’s demonstration that oral lozenge formulations provide local antiviral activity under saliva-like conditions, a person of ordinary skill in the art would have reasonably expected the combination to successfully result in a method for debulking viral load from the oral cavity in a subject, as recited in the instant claims. Moreover, Quindos et al.’s teaching that locally administered oral formulations, including pastilles and suspensions, successfully reduce infectious burden in the oral cavity further supports a reasonable expectation of success for local oral delivery of a pathogen-directed agent. Accordingly, use of the known viral-binding agents in the known local oral delivery format constitutes the use of known elements according to their established functions to obtain predictable results. Therefore, the claimed invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments for Prior Art Rejections
In the Response filed May 26, 2026, Applicant argues that the cited references fail to teach or suggest the presently claimed FRIL-containing lablab bean powder and IVA blocking peptide embodiments; that Liu et al. is directed to purified FRIL and therefore teaches away from the use of FRIL present in lablab bean powder in an oral carrier; that the cited references fail to provide a motivation to combine or a reasonable expectation of success in reducing viral load in the oral cavity; and that the proposed combination relies upon impermissible hindsight reconstruction. Applicant’s arguments have been considered in full and have not been found persuasive for the reasons set forth below.
Applicant’s arguments regarding the failure of Glasgow, Shepherd, and Quindos individually to disclose FRIL or the presently claimed influenza embodiments are not persuasive because the rejection does not rely upon those references alone for these limitations. As set forth above, Liu et al. teaches FRIL isolated from Lablab purpureus, its binding to complex-type N-glycans on influenza viral surface glycoproteins, aggregation and trapping of influenza virions, neutralization of influenza A and B viruses, and antiviral efficacy in vivo. Shepherd et al. further teaches locally administered oral lozenge formulations that reduce infectious viral titer under saliva-like conditions. Thus, Applicant’s arguments address the references individually rather than the collective teachings of the references as relied upon in the rejection.
Applicant’s argument that Liu teaches away from the claimed invention because Liu utilizes purified FRIL is not persuasive. As amended, claim 1 recites “FRIL isolated from lablab bean powder,” and does not require unpurified FRIL, crude lablab bean powder, or the presence of lablab bean powder in the administered composition. Liu teaches FRIL isolated from Lablab purpureus and utilizes purified FRIL preparations in demonstrating its antiviral activity. Thus, Liu’s purified FRIL falls within the scope of the recited “FRIL isolated from lablab bean powder.” Moreover, even if the claims were construed as requiring a less-purified FRIL preparation, Liu reports antiviral activity in crude aqueous extracts of Lablab purpureus prior to purification, with subsequent fractionation and purification identifying FRIL as the component responsible for the observed antiviral activity. Thus, Liu does not teach that purification is necessary for FRIL antiviral activity and does not teach away from the use of FRIL in a less-purified preparation. Applicant’s assertions that impurities, competing proteins, saliva, excipients, or carrier formulations would interfere with FRIL activity are therefore not persuasive. Finally, Applicant’s argument that Liu utilizes intranasal administration rather than localized oral administration using chewing gum, lozenges, or tablets is not persuasive because the rejection does not rely upon Liu to teach the recited oral delivery system. Rather, as set forth above, Liu is relied upon for its teachings regarding FRIL and its influenza-binding, aggregation, and antiviral activity, while Shepherd teaches locally administered oral formulations, including lozenges, for delivering antiviral agents and reducing infectious viral titer under saliva-like conditions. One cannot show nonobviousness by attacking references individually where the rejection is based upon a combination of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Accordingly, Liu need not independently disclose the oral carrier limitations taught by Shepherd.
Applicant’s arguments regarding lack of motivation to combine and reasonable expectation of success are likewise not persuasive. As set forth in the rejection, the cited art teaches known viral-binding agents capable of binding and trapping the recited viruses and a known locally administered oral delivery format for reducing viral burden at the site of infection. The proposed combination therefore uses the known viral-binding agents according to their established antiviral function in a known oral delivery format for the same purpose of reducing viral burden. Accordingly, the rejection is based upon the teachings of the prior art and the predictable use of known elements according to their established functions, rather than Applicant’s disclosure as a roadmap. Lastly, in response to applicant’s argument that the examiner’s conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, as evidenced by the prior art of record discussed above, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
No claim is in condition for allowance.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAGHMEH NINA MOAZZAMI whose telephone number is (703)756-4770. The examiner can normally be reached Monday-Friday, 9:00-5:00.
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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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