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
This action is in response to Applicant’s amendment filed November 17, 2025 in reply to the First Office Action on the Merits mailed July 15, 2025. Claims 2, 4, 15, 17, 24, 26, and 29 have been amended; claims 1, 3, 5, 7, 9, 13, 14, 16, 23, 25, 27, and 30-33 have been canceled; and claims 35-38 have been newly added. Claims 6, 8, 10-12, 18-20, and 34 have been withdrawn. Newly added claims 35, 37, and 38 are directed to non-elected subject matter*** and are thus hereby also withdrawn. Claims 2, 4, 15, 17, 21, 22, 24, 26, 28, 29, and 36 are currently under examination.
***It is noted that “human”, “subject with compromised/reduced immunity”, and “subject with past history of smoking or is a current smoker” were originally presented as alternative species of subject. Applicant elected “human”, not “subject with compromised/reduced immunity” or “subject with past history of smoking or is a current smoker”.
Withdrawal of Prior Objection - Abstract
The abstract of the disclosure has been satisfactorily amended. Therefore, the objection to the abstract presented in the First Office Action on the Merits mailed July 15, 2025 is hereby withdrawn.
Withdrawal of Prior Objection - Drawings
The drawings have been satisfactorily amended on corrected drawing sheets in compliance with 37 CFR 1.121(d). Therefore, the objections to the drawings presented in the First Office Action on the Merits mailed July 15, 2025 are hereby withdrawn.
Withdrawal of Prior Claim Rejections - 35 USC § 112(d)
Claim 26 has been satisfactorily amended. Therefore, the 35 USC 112(d) rejection presented in the First Office Action on the Merits mailed July 15, 2025 is hereby withdrawn.
Claim Objections
Claims 15, 17, 29, and 36 are objected to because of the following:
i). In claim 15, the expression “is selected from a viral infection and/or bacterial infection” is awkward. If Applicant wishes that the infection can be a viral infection, a bacterial infection, or both, Applicant is advised to amend the expression to “is selected from a viral infection and a bacterial infection”, or to simply “is a viral infection and/or a bacterial infection”.
ii). In claim 17, the term “(MERS)-corona virus” should be “(MERS)-coronavirus”.
iii). In claim 29, the element “rhesus monkeys mammals cattle” is not a known entity, and there seems to be a lack of proper punctuation. Applicant is advised to amend the expression to “rhesus monkeys, mammals, cattle”. Indeed, because Applicant includes “mammals” in the Markush group, the entirely of the remainder of the Markush group is effectively non-limiting and redundant. Applicant is thus advised to amend claim 29 to simply state “wherein the subject is a mammal”.
iv). In claim 36, the expression “the subject is human” should be “the subject is a human”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2-4, 15, 17, 21, 22, 24, 26, 28, and 29 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 2, as now amended, provides for “at least one immunomodulator selected from polyinosinic acid:polycytidylic acid (poly (I:C)) and a STING agonist”. One of ordinary skill in the art would thus interpret the claim as requiring either poly(I:C) or a STING agonist. However, it would seem that poly(I:C) itself could be categorized as a STING agonist (see e.g. Dixon et al. iScience: 24, 103055; and Chera et al. Vet Vaccine. 2023; 2: 100016). One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of “STING agonist”. For example, is “STING agonist” necessarily limited to the specific STING agonists expressly enumerated in the original specification, i.e. cGAMP, cAMP, cGMP, c-di-AMP and c-di-GMP.
Claims 4, 15, 17, 21, 22, 24, 26, 28, 29, and 36 are indefinite for depending from an indefinite claim.
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 2, 4, 15, 17, 21, 22, 24, 26, 28, 29, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Bhide et al. (Frontiers in Immunology. 2019; 10: 1-13), in view of Tahara et al. (Int. J Pharm. 2018; 543: 311-317).
Applicant Claims
Applicant’s elected subject matter is directed to a method of treating a viral infection of the respiratory tract (e.g. coronavirus) comprising administering via the nasal route to a subject (e.g. human) in need thereof a liposomal composition comprising dimethyldioctadecyl-ammonium (DDA) bromide, monomycoloyl glycerol (MMG), and a STING agonist; wherein the DDA and MMG are present in the amounts of 2.5 mg/ml and 0.5 mg/ml, respectively; and wherein the liposomal composition is administered 2-3 times per week.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Bhide et al. disclose a method of preventing/treating a viral infection of the respiratory tract comprising administering via the nasal route to a subject in need thereof “CAF09”, i.e. a liposomal composition comprising dimethyldioctadecyl-ammonium (DDA) bromide, monomycoloyl glycerol (MMG), and Poly(I:C) (i.e. a STING agonist); wherein it is well known in the art that for “CAF09”, the DDA and MMG are present in the amounts of 2.5 mg/ml and 0.5 mg/ml, respectively.
Tahara et al. disclose that cationic liposomes can effectively inhibit viral infection without causing cytotoxicity by binding to cell membranes and blocking viral entry without the need for antigens and active agents, and that these anti-viral effects, which are comparable in efficacy to that of the antiviral drug acyclovir, are correlated to physical properties such as the positive zeta potential and particle size of the liposomes.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Bhide et al. do not explicitly disclose that “CAF09” can treat an existing viral infection without the need for an antigen or an antiviral active agent. This deficiency is cured by the teachings of Tahara et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Bhide et al. and Tahara et al., outlined supra, to devise Applicant’s claimed method.
Bhide et al. disclose a method of preventing/treating a viral infection of the respiratory tract comprising administering via the nasal route to a subject in need thereof “CAF09”, i.e. a cationic liposome comprising dimethyldioctadecyl-ammonium (DDA) bromide, monomycoloyl glycerol (MMG), and Poly(I:C). Bhide et al., however, is limited to administering the “CAF09” with WIV as a vaccination before a viral infection is actually present to thus prevent a viral infection. However, since Tahara et al. disclose that cationic liposomes can effectively treat/inhibit viral infection even after the viral infection is present by binding to cell membranes and blocking viral entry without the need for antigens and active agents, and without causing cytotoxicity, and that these anti-viral effects, which are comparable in efficacy to that of the antiviral drug acyclovir, are correlated to physical properties of the liposome itself, such as the positive zeta potential and particle size; one of ordinary skill in the art would thus be motivated to administer the “CAF09” cationic liposome via the nasal route to a subject with a viral infection of the respiratory tract; with the reasonable expectation that the resulting method will successfully treat the viral infection without causing toxicity to the treated cells.
Moreover, since coronavirus is a well-known virus that infects the respiratory tract, but that can be hard to treat by more conventional means, one of ordinary skill in the art would thus be motivated to administer the “CAF09” cationic liposome via the nasal route to a subject with a coronavirus infection of the respiratory tract; with the reasonable expectation that the resulting method will successfully treat the coronavirus infection without causing toxicity to the treated cells.
Finally, Tahara et al. disclose that cationic liposomes can be very effective at treating a viral infection, e.g. inhibiting the viral infection by over 80%, by optimizing the liposomal concentration and exposure time with cells, i.e. in other words, by optimizing the administration dosage regimen. Hence, it would be within the skill of the ordinary mechanic in the art to optimize the dosage of the cationic liposome, such as “CAF09”, for a particular subject, such as a human, to treat a particular viral infection, such as coronavirus, to thus arrive at an administration dosage regimen of 2-3 times per week.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed November 17, 2025 have been fully considered but they are not persuasive.
i) Applicant contends that Bhide “teaches away from treating a viral infection with an adjuvant alone” but rather “only teaches to use the mentioned adjuvants…as classical adjuvants, and not as a medicament by itself…without vaccine antigens”; that Tahara “correlated physicochemical properties of liposomes, such as zeta potentials and particle sizes, with virus infectivity” and “demonstrated that cationic liposomes with incorporated stearylamine inhibit viral infectivity without preloaded active pharmaceutical ingredients” and thus Tahara “exclusively suggests that the cationic liposome containing DSPC and cholesterol should contain stearylamine in order to provide a strong inhibitory effect”.
The Examiner, however, would like to point out the following:
1. In stark contrast to Applicant’s assertion, Bhide does not “teach away” from treating a viral infection with CAF09. Even if Bhide is primarily reporting the success of employing CAF09 as an adjuvant with WIV, one of ordinary skill in the art in no way would understand the results of this study to somehow mean that CAF09 cannot or should not be employed alone to treat a viral infection. The results of the Bhide study simply do not reasonably lead to this conclusion. Indeed, on the contrary, Bhide discloses that CAF09 itself generates strong T cell and antibody responses, and that CAF09 is capable of inducing a potent CD8+ T cell response (see e.g. page 2 left column). It is further noted that only claim 22 appears to provide that the composition being administered necessarily excludes an antigen.
2. Bhide has not been cited for individually anticipating the presently claimed subject matter. The prior art rejection is under 35 USC 103, based on the combination of Bhide and Tahara, and what these references expressly disclose and reasonably suggest to one of ordinary skill in the art, who is one of ordinary creativity and not an automaton. Not only does Bhide disclose that the cationic liposome CAF09 itself generates strong T cell and antibody responses, and in particular is capable of inducing a potent CD8+ T cell response, and is administered via the intranasal route, Tahara discloses that cationic liposomes can effectively inhibit viral infection without causing cytotoxicity by binding to cell membranes and blocking viral entry without the need for antigens and active agents, and that these anti-viral effects, which are comparable in efficacy to that of the antiviral drug acyclovir, are correlated to physical properties such as the positive zeta potential and particle size of the liposomes. In other words, in view of the cited prior art as a whole, one of ordinary skill in the art could thus arrive at the claimed method with a reasonable expectation of success.
3. In stark contrast to Applicant’s argument that Tahara “exclusively suggests that the cationic liposome containing DSPC and cholesterol should contain stearylamine in order to provide a strong inhibitory effect”, Applicant is advised that a liposome containing DSPC and cholesterol itself is not a cationic liposome. Rather, the inclusion of stearylamine is required to make the liposome cationic. Contrary to Applicant’s assertion, the conclusion one of ordinary skill in the art would draw from Tahara is not that the specific compound stearylamine itself is the critical factor, but rather the positive charges that stearylamine thus imparts to the liposome. Hence, the liposome comprising DSPC and cholesterol is not a cationic liposome. Only when stearylamine is included does the liposome become cationic. Again, Tahara discloses that cationic liposomes can effectively inhibit viral infection without causing cytotoxicity by binding to cell membranes and blocking viral entry without the need for antigens and active agents, and that these anti-viral effects, which are comparable in efficacy to that of the antiviral drug acyclovir, are correlated to physical properties such as the positive zeta potential. In other words, the conclusion drawn from Tahara is that the cationic nature of the liposome is what is critical, not merely the specific compound stearylamine itself, as Applicant would want us to believe. Because CAF09 is also a cationic liposome, one of ordinary skill in the art would reasonably expect that CAF09 will also have a similar antiviral effect, even without any antigen or active agent.
For the foregoing reasons, the 35 USC 103 rejection is hereby maintained.
Conclusion
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617