FINAL REJECTION
Receipt is acknowledged of Applicants' Amendments and Remarks, filed Jan. 30, 2026.
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The rejections and/or objections set forth below are either maintained or newly applied, and constitute the complete set presently applied to the instant claims.
STATUS OF THE CLAIMS
Claims 16, 17, 20, 21, and 23 have been canceled.
No claims have been amended, and no new claims have been added.
Claims 5, 6, 18, 19, and 22 stand withdrawn as drawn to nonelected inventions and/or species.
Thus, claims 1-4 and 7-15 now represent all claims currently pending and under consideration.
INFORMATION DISCLOSURE STATEMENT
No new Information Disclosure Statements (IDS) have been submitted.
MAINTAINED REJECTIONS
The following rejections are maintained from the previous Office Action dated Nov. 6, 2025, on the ground that the references cited therein continue to read on the limitations of the instant claims.
Claim Rejections - 35 USC § 103
Claims 1-4 and 7-15 stand rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Perco (WO 2022/023533) in view of McIntosh et al. (WO 2013/016754).
Perco discloses and claims methods of treating a subject infected with or at risk of being infected with a virus such as a coronavirus, comprising administering an effective amount of liraglutide or gefitinib (p. 8, line 13-17), wherein the administration is in combination with an additional active agent, e.g., the elected compound, miglustat (claims 13-15).
In a specific embodiment, liraglutide can be administered by inhalation, in combination with one or more active substances, e.g., miglustat, to a subject who has been infected or is at risk of being infected with coronavirus (p. 7, lines 13-24).
In particular, Perco claims pharmaceutical compositions for use in prophylactic or therapeutic treatment of a disease condition which is caused by or associated with an infection by a coronavirus, including SARS-CoV-1, SARS-CoV-2, MERS-CoV, HCoV-OC43, and HCoV-HKUI , or mutants thereof (claims 1-2).
The compositions of Perco are preferably formulated for application to the upper and lower respiratory tract via the pulmonary route of administration, e.g., as an aerosolized powder (claims 10-11). An aerosolized powder is implicitly a dry powder formulation, administered via a dry powder inhaler, i.e., via oral inhalation, as recited by claims 9, 10, and 13.
Thus, Perco discloses and claims methods for treating or preventing a viral respiratory infection in a subject, caused by a coronavirus, e.g., SARS-CoV-2, comprising pulmonary administration of a therapeutically effective amount of an α-glucosidase inhibitor to the subject, wherein the α-glucosidase inhibitor is miglustat, as recited by claims 1-4, 7, and 8.
Perco discloses and claims administration of miglustat in combination with one or more additional therapeutic agents, e.g., liraglutide, which counterbalances inflammatory processes and oxidative stress. Levels of TNF, IL 1b, IL6, IL 17 and IL21, key players in inflammatory response after COVID-19 infection, are reduced by liraglutide (p. 5, lines 21-25).
Thus, Perco discloses and claims the administration of miglustat in combination with an additional therapeutic agent (liraglutide) which is an immunomodulator and an anti-inflammatory agent, as recited by claims 14-15.
Perco differs from the instant claims in that Perco does not disclose that the dry powder formulation is a spray-dried formulation, as recited by claim 11; or that particles of the dry powder formulation have a mass median aerodynamic diameter (MMAD) of less than 10 μm, as recited by claim 12.
However, preparing dry powder formulations by spray-drying, comprising inhalable particles having a mass median aerodynamic diameter under 10 μm, was known in the art.
For example, McIntosh et al. disclose methods of drug delivery in the form of dry powders for inhalation, methods for preparing dry powder formulations, and methods for their use (abstract), such as for the treatment or prevention of a disease or condition comprising administering by inhalation a dry powder formulation (claim 9).
In particular, McIntosh et al. claim methods of spray drying an aqueous solution or suspension to produce the dry powder for inhalation, wherein said dry powder is inhaled into the pulmonary system via the mouth (claims 1 and 13). McIntosh disclose that, in order for the dry powder to be highly aerosolizable, the particles will generally have a mass median aerodynamic diameter (MMAD) of less than 10 μm (p. 9, lines 5-14), as recited by claims 11-12.
It would have been predictable to one of ordinary skill in the art as of the effective filing date to make the aerosolized dry powder formulations of Perco by spray drying, comprising particles with a mass median aerodynamic diameter less than 10 μm in diameter, as taught by McIntosh et al., with a reasonable expectation of success, because spray drying was a known method for making dry powders for inhalation with a particle size less than 10 μm to optimize the therapeutic dose delivered to the lungs.
As recognized by MPEP §2143, combining prior art elements according to known methods to yield predictable results would motivate the skilled artisan to modify the references with a reasonable expectation of success. The rationale to support a conclusion of prima facie obviousness is that all the claimed elements were known in the prior art, and a skilled artisan could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See KSR Int'l Co. v. Teleflex Inc. (550 U.S. 398, 409).
Claims 1-4 and 7-15 stand rejected under 35 U.S.C. § 103 as being unpatentable over Kester et al. (WO 2020/185675) in view of McIntosh et al. (WO 2013/016754).
Kester et al. disclose and claim compositions and methods for treating and/or inhibiting a viral infection in a subject, comprising administering to a subject infected with and/or at risk for infection with a virus, e.g., a coronavirus or COVID-19, a composition comprising a glucosylceramide synthase inhibitor, e.g., miglustat, via a route and in an amount effective for treating and/or inhibiting the viral infection in the subject (claims 1, 2, 6, and 9).
Suitable methods for administration include, e.g., nebulization, dry powder inhalation, aerosol inhalation, and combinations thereof (p. 51, lines 1-15), i.e., oral inhalation, as recited by claims 9, 10, and 13.
Thus, Kester et al. disclose and claim methods for treating or preventing a viral respiratory infection in a subject, caused by a coronavirus, e.g., SARS-CoV-2, comprising pulmonary administration of a therapeutically effective amount of an α-glucosidase inhibitor to the subject, wherein the α-glucosidase inhibitor is miglustat, as recited by claims 1-4, 7, and 8.
The compositions and methods of Kester et al. may comprise an additional therapeutic agent, e.g., to treat associated pain and inflammation (p. 20, lines 3-12), such as a non-steroidal anti-inflammatory drug (NSAID), e.g., naproxen, acetaminophen, or ibuprofen (p. 50, lines 17-30), as recited by claims 14-15.
Kester et al. do not disclose that the dry powder formulation is a spray-dried formulation, as recited by claim 11; or that particles of the dry powder formulation have a mass median aerodynamic diameter of less than 10 μm, as recited by claim 12.
However, preparing dry powder formulations by spray-drying, comprising inhalable particles having a mass median aerodynamic diameter under 10 μm, was known in the art.
For example, McIntosh et al. disclose methods of drug delivery the form of dry powders for inhalation, methods for preparing dry powder formulations, and methods for their use (abstract), such as for the treatment or prevention of a disease or condition comprising administering by inhalation a dry powder formulation (claim 9).
In particular, McIntosh et al. claim methods of spray drying an aqueous solution or suspension to produce the dry powder for inhalation, wherein said dry powder is inhaled into the pulmonary system via the mouth (claims 1 and 13). McIntosh disclose that, in order for the dry powder to be highly aerosolizable, the particles will generally have a mass median aerodynamic diameter (MMAD) of less than 10 μm (p. 9, lines 5-14), as recited by claims 11-12.
It would have been predictable to one of ordinary skill in the art as of the effective filing date to make the aerosolized dry powder formulations of Kester et al. by spray drying, comprising particles with a mass median aerodynamic diameter less than 10 μm in diameter, as taught by McIntosh et al., with a reasonable expectation of success, because spray drying was a known method for making dry powders for inhalation with a particle size less than 10 μm to optimize the therapeutic dose delivered to the lungs.
As recognized by MPEP §2143, combining prior art elements according to known methods to yield predictable results would motivate the skilled artisan to modify the references with a reasonable expectation of success. The rationale to support a conclusion of prima facie obviousness is that all the claimed elements were known in the prior art, and a skilled artisan could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. See KSR Int'l Co. v. Teleflex Inc. (550 U.S. 398, 409).
RESPONSE TO ARGUMENTS
Applicant’s arguments (see Remarks, p. 9, filed Jan. 30, 2026), with respect to the rejection of claims 1-4, 7-10, and 13-15 under 35 U.S.C. § 102(a)(2) as being anticipated by Perco (WO 2022/023533) have been fully considered and are persuasive. Therefore, the rejection under 35 U.S.C. § 102(a)(2) over Perco has been withdrawn.
With respect to the rejections of claims 1-4 and 7-15 under 35 U.S.C. § 103 over (1) Perco in view of McIntosh and (2) Kester et al. in view of McIntosh, Applicant's arguments filed Jan. 30, 2026 have been fully considered but they are not persuasive.
Applicant argues that Kester et al. is silent on how to formulate glucosylceramide synthase inhibitors for pulmonary delivery. Miglustat is mentioned only as one of many possible inhibitors, while pulmonary administration is listed among numerous potential delivery routes. However, there is no teaching or suggestion that would lead one of ordinary skill in the art to formulate miglustat in pulmonary formulation with a reasonable expectation of success. Absent the teaching of the present disclosure, one of ordinary skill in the art would not have had a reasonable expectation of success of formulating miglustat in a pulmonary formulation (Remarks, p. 10).
Applicant argues that, at best, the cited references provide a general reference to pulmonary administration among numerous potential delivery routes and a laundry list of possible inhibitors, which do not provide a motivation to select miglustat and apply it for pulmonary administration, let alone with an expectation of success (Remarks, pp. 10-11).
With respect to McIntosh, Applicant argues that McIntosh teaches general spray-drying methods for producing inhalable dry powders comprising biologically active peptides and proteins (such as oxytocin), which are fundamentally different from miglustat, a highly hydroscopic small molecule drug. In addition, McIntosh discloses pulmonary delivery of very small doses of oxytocin dry powder (e.g., 10 mg of dry powder in Example 5) but is silent on how to achieve the high-dose delivery required for the compositions of the present disclosure.
Applicant contends that one of ordinary skill in the art would understand that miglustat is chemically distinct from the active compounds disclosed in McIntosh (e.g., oxytocin and its derivatives) and therefore would not be motivated to apply McIntosh's general peptide formulation techniques to miglustat, a different class of drug, let alone with an expectation of success (Remarks, p. 11).
Applicant further argues that the combination of the cited prior art documents ignores the unforeseen AGI-specific technical problems and relies on hindsight knowledge of the solution to these problems provided by the present application. In relation to dry powder formulations of miglustat, it should be noted that miglustat is highly hygroscopic, which can lead to the formation of physically unstable highly amorphous particles (see, e.g., [00117] of the present application). Thus, even if a skilled person were motivated to try pulmonary administration of miglustat for treating viral respiratory tract infections, it would not be obvious how to formulate it in order to avoid the formation of unstable amorphous particles, as both Perco and Kester et al. are silent on how to formulate miglustat for pulmonary administration. Neither would the skilled person have had any reasonable expectation that peptide formulation techniques (McIntosh) would be useful in the dry powder formulation of miglustat (i.e., a small molecule). Accordingly, the cited references do not provide a motivation to combine the references with a reasonable expectation of success to arrive at the claimed methods (Remarks, p. 11).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., high-dose delivery) are not recited in the rejected claims, which do not recite any doses at all, beyond "a therapeutically effective amount" as recited in claim 1. Additionally, the claims are drawn to methods of treatment, not to methods of preparing miglustat for pulmonary administration. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
With regard to Kester et al., claims 1, 2, and 6 are drawn to a method for treating and/or inhibiting a viral infection in a subject comprising administering a composition comprising a glucosyl-ceramide synthase inhibitor (claim 1), wherein the virus is a coronavirus, e.g., COVID-19 (claim 2), and the first-listed glucosylceramide synthase inhibitor is N-butyl-deoxynojiri-mycin (miglustat) (claim 6) (p. 84).
This is not a laundry list, but rather a clear and direct teaching of miglustat to treat a coronaviral infection. While Kester et al. disclose the suitability of any route of administration reasonably expected to deliver the composition to a desired target site, e.g., a site of infection or possible infection with a virus (p. 50, lines 32-33), Kester et al. specify nebulization, dry powder inhalation, or aerosol inhalation (p. 51, lines 13-14). This would have motivated one of ordinary skill in the art to select pulmonary administration to treat a coronavirus, i.e., a respiratory virus, not only to deliver the drug directly to the site of infection, but also to avoid the main side effects of orally administered miglustat, diarrhea and flatulence (as evidenced by, e.g., Williams et al., of record, p. 1291, first ¶), to improve patient compliance.
With regard to McIntosh, the instant specification discloses that "suitable methods for preparing formulations of biologically active agents for delivery by inhalation are disclosed in WO 2013/016754 [McIntosh], the entire contents of which are incorporated herein by cross-reference" (para. [00108]).
This amounts to an admission that McIntosh teaches useful methods for preparing dry powder inhalation formulations. One of ordinary skill in the art, reading the Applicant's own disclosure, would have been motivated to look to the incorporated reference for guidance on formulating the claimed compounds for pulmonary administration, particularly when seeking to adapt a known anti-viral agent for pulmonary delivery, as disclosed, taught, and suggested by Perco and Kester et al. The Applicant's own incorporation of the McIntosh reference is evidence that such techniques were considered useful and relevant to the claimed genus of small molecule imino sugars, including the elected compound, miglustat.
As recognized by MPEP § 2163.07(b), the information incorporated is as much a part of the application as filed as if the text was repeated in the application, and is treated as part of the text of the application as filed.
For the foregoing reasons, the rejections of claims 1-4 and 7-15 under 35 U.S.C. § 103 are maintained.
Citation of Additional Prior Art
Additional references made of record are considered pertinent to applicant's disclosure:
US Pub. 2011/0269795 (claims 1 and 4); WO 2011/095772 (claims 35-39); and US Pub. 2008/0220078 (all cited on PTO-892).
CONCLUSION
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 SARA E. TOWNSLEY whose telephone number is 571-270-7672. The examiner can normally be reached on Mon-Fri from 10:00 am to 6:00 pm (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jeff S. Lundgren, can be reached at 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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/SARA E. TOWNSLEY/Examiner, Art Unit 1629
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