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. 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. This office action is a response to applicant’s response to election submitted February 23, 2026. Claims filed May 23, 2023, wherein claims 3, 6, 10-11, 20-21, 26, 33, 39, 41, 45, 54, 57, 65, 69-70, and 72 were preliminarily amended and claims 4-5, 12-19, 22-25, 27-32, 34-38, 40, 42-44, 46-53, 58-64, and 75-94 were cancelled, are examined herein. Claims 1-3, 6-11, 20-21, 26, 33, 39, 41, 45, 54-57 and 65-74 are pending in this application. Election Applicant’s election of Group I (claims 1-3, 6-11, 20-21, 26, 33, 39 41, 45, and 54-57) without traverse in the reply filed February 23, 2026 is acknowledged. Claim s 65-74 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-3, 6-11, 20-21, 26, 33, 39 41, 45, and 54-57 are encompassed by the election and examined herein. Priority This application is a 371 of PCT/EP2021/054914 filed February 26, 2021 and claims the benefit of provisional application 62/981,762 filed February 26, 2020. Drawings The drawings are objected to because: Figures 1-4 use the term AmBisome ® which is a trade name or a mark used in commerce (See USPTO trademark registry). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Specification The disclosure is objected to because of the following informalities: The following structure: which appears on pages 1-5 , 9, 13, and 23 of the instant specification, has a black box in the structure, rendering the atom at this position unclear. Additionally the subscript “3” on the CH3 groups is illegible. The following structure: which appears on pages 2-4, 9, 13, and 23 of the instant specification has a subscript “3” on the CH3 groups that is illegible. On page 27, at the bottom of the page, table 1 is overlapped by the page number. The use of the terms Kolliphor ® ( pg. 16, lines 16-27, pgs. 50-53, table 29 ) , Brij® ( pg. 16, lines 16-27, pgs. 50-53, table 29 ) , AmBisome ® ( throughout the specification and description of the drawings ), Miglylol ® ( pg. 6, line 16, pg. 17, line 19, pg. 24, line 16 ), Captex ® ( pg. 6, line 16, pg. 17, line 19, pg. 24, line 16 ), and Kollisolv ® ( pg. 6, line 16, pg. 17, line 19, pg. 24, line 16 ) which are a trade name or a mark used in commerce, has been noted in this application (See USPTO trademark registry) . The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. 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 appl icant regards as his invention. Claim 39 is 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. Regarding claim 39: Claim 39 recites inter alia, “ wherein the pharmaceutical composition further comprises a pharmaceutically acceptable stabilizer.”. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. V. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). It is unclear whether the phrase “stabilizer” is meant to include species which stabilize the overall composition, or stabilization of the active pharmaceutical ingredient within the composition . According to the instant specification, “surfactants may be used to stabilize pharmaceutical compositions” (pg. 16, line 16). The instant specification also states “Stabilizers may be used to stabilize pharmaceutical compositions…..non-limiting examples of stabilizers include vanillin, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, and 6-O-palmitoyl-L-ascorbic acid.” (pg. 17, lines 1-3). The instant specification describes “Vanillin was tested for its effect on the stability of Compound 1A,” (pg. 55, lines 14-15) . Thus it is unclear as to what is encompassed by the phrase “stabilizer” and it is unclear whether the stabilizer is meant to stabilize the overall composition, or stabilize the compound within the composition. This lack of clarity renders claim indefinite, as a person of ordinary skill in the art would be unable to ascertain the metes and bounds of the claim. Claim Rejections - 35 USC § 103 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. Claims 1-3, 6-8, 20, 33, 39, 45, and 54-56 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (US 9,878,041, IDS filed February 23, 2026) in view of Zotchev (US 8,415,312, cited in previous action ). Regarding claims 1-3, 6-8, 20, 33, 39, 45, and 54-56 : Lee teaches a tissue adhesive including cyanoacrylate bulk monomer and cyanoacrylate nanoparticles containing a therapeutic (abstract). Lee teaches methods of preventing infection of a wound (abstract). Lee teaches the prep a ration of drug-loaded poly( butyl cyanoacrylate ) (PBCA) particles (col. 15, lines 19-20). Lee teaches the preparation of nanoparticles comprises neutralization after polymerization (i.e. pH 7.0) , freeze-dried in a lyophilizer (i.e. lyophilized) and resuspended in distilled water (col. 15, lines 54-59). Lee teaches the composition can comprise amphotericin B as the therapeutic (col. 6, lines 5-15, table 1). Lee teaches the compositions can be formulated for injection with sterile aqueous solutions or dispersions (col. 7, lines 59-64). The carrier can be a solvent such as water, ethanol or mixtures thereof (cols. 6-7, bridging para.). Lee teaches the compositions can include surfactants or nonaqueous vehicles such as cotton seed oil (col. 8, lines 3-6). Lee teaches various additives, such as those that enhance stability (i.e. a stabilizer) can be added (col. 8, lines 10-11). Lee does not teach wherein the active ingredient is that which is recited by instant claims 1-2 , , . However, Zotchev teaches nystatin derivatives which are anti-fungal agents of the following formula (abstract). Zotchev teaches the following specific compound 1 (drawings sheet 21, figure 16, compound 1, cols. 23-24, table 1, compound 1). Zotchev teaches compound 1, a nystatin derivative has comparable anti-fungal activity to amphotericin B (col. 48, lines 25-58). Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Lee, such that amphotericin B is replaced with compound 1 as taught by Zotchev . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that both compounds are established equivalent anti-fungal agents, and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lee (US 9,878,041, IDS filed February 23, 2026) and Zotchev (US 8,415,312, cited in previous action ) as applied to claims 1-3, 6-8, 20, 33, 39, 45, and 54-56 above, in view of Park (J. Applied Polymer Science, 2003, cited on PTO-892) . Regarding claim 9: As discussed above, the prior art render obvious the composition of claim 8 comprising drug-loaded poly( butyl cyanoacrylate ) (PBCA) particles. Lee teaches alkyl cyanoacrylate monomers have been used as tissue adhesives for several decades (col. 1, lines 34-35). Lee teaches the choice of cyanoacrylate alkyl chain length and its effect on degradation rate can also be used to control dosing (col. 5, lines 56-48). Lee teaches methyl and ethyl alkyl chain cyanoacrylates were used as tissue adhesives but had rapid in vivo degradation, resulting in significant tissue toxicity compared to longer-chain cyanoacrylates such as butyl and octyl cyanoacrylate (col. 1, lines 39-45). Lee teaches both octyl cyanoacrylate and methoxy isopropyl cyanoacrylate formulations (col. 4, lines 47-57). They do not teach wherein the polymeric excipient is poly( ethylhexyl cyanoacrylate as recited by instant claim 9. However, Park examined the toxicity an degradation of some alkyl polycyanoacrylates including ethyl, 2-octyl, n-octyl, ethylhexyl , and ethyl cyanoacrylollactate (abstract, pg. 3273, col. 1, para. 2, col. 2, figure 1). Park prepared polymers of poly( ethylhexyl cyanoacrylate) (P(EHCA) , pg. 3273, col. 1, para. 3). Park teaches that ethylhexyl cyanoacrylate polymers are useful for application to tissue adhesives and have improved biocompatibility over lower alkyl side groups, such as ethyl (pg. 3278, col. 2, para. 1). Taken together it would have been prima facie obvious to modify the composition rendered obvious over Lee and Zotchev by utilizing poly( ethylhexyl cyanoacrylate) (P(EHCA) as the poly(alkyl cyanoacrylate) instead of octyl cyanoacrylate as suggested by Park. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that both cyanoacrylates are established equivalent polymers useful as tissue adhesives and have improved biocompatibility, and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Claim s 21 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (US 9,878,041, IDS filed February 23, 2026) and Zotchev (US 8,415,312, cited in previous action ) as applied to claims 1-3, 6-8, 20, 33, 39, 45, and 54-56 above, in view of Yamamoto (J. Oral and Maxillofacial Surgery, Medicine, and Pathology , 2017 , cited on PTO-892) and Morch (WO 2018/060437, IDS filed February 23, 2026) . Regarding claims 21 and 26: As discussed above, Lee and Zotchev render obvious a composition of claim 7 comprising the active ingredient recited by instant claims 1-2 in poly(alkyl cyanoacrylate) nanoparticles, wherein the active ingredient is an alternative to amphotericin B. Lee teaches They do not teach wherein the composition further comprises microbubbles that comprise a perfluorocarbon. However, Yamamoto teaches microbubble formulations comprising amphotericin B and perfluoropropane gas for the inhibition of candida albicans (abstract). Morch teaches a multifunctional drug delivery system that comprises gas-filled microbubbles associated with nanoparticles in therapy (pg. 3, lines 31-33). Morch teaches the nanoparticles may be surface-associated to the micro bubble and covering at least a part of the micro bubble surface, optionally the at least one of the nanoparticles are polymeric, such as poly(alkyl cyanoacrylate) (PACA) nanoparticle (pg. 8, lines 4-7) . Morch teaches the therapeutic agent is loaded within the nanoparticles and may contain co-stabilizers (pg. 8, para. 7-11). The surface-associated polymeric nanoparticles stabilizes the microbubble and will influence the possible circulation time of the microbubbles in the blood (pg. 8, lines 18-20). Morch teaches such nanoparticle-stabilized microbubbles are shown to have long shelf life (pg. 16, lines 15-16). Morch teaches the microbubble may be filled with a gas selected from perfluorocarbon, air, N2, O2, or CO2 (pg. 8, lines 33-34). Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to further modify the composition by incorporating microbubbles comprising perfluoropropane as suggested by Yamamoto and Morch . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as nanoparticle-microbubble combinations are a known technique in the art of drug delivery and are both techniques are individually known to be beneficial to the delivery of amphotericin B, of which the claimed active ingredient is an equivalent of. A person of ordinary skill in the art would recognize the benefit of combining the techniques for improved stabilization of the drug delivery system. Claims 1-3, 10, 20, 39, and 54-56 are rejected under 35 U.S.C. 103 as being unpatentable over Wu (CN 106821962, IDS filed February 23, 2026 , the English language translation relied upon by the Examiner has been provided on the PTO-892 for citation purposes ) in view of Zotchev (US 8,415,312, cited in previous action ). Regarding claims 1-3, 10, 20, 39, and 54-56 : Wu teaches amphotericin B liquid crystal nanoparticles for the improvement of oral bioavailability and stability of amphotericin B during oral administration (English translation, abstract). Wu teaches amphotericin B Is a known broad spectrum antifungal antibiotic (English translation, pg. 3, para. 5). Wu teaches the composition comprises micellar material that can be polylactic acid-glycolic acid copolymer (PLGA) , and a stabilizer poloxamer 407 (English translation, pg. 4, para. 4). According to the instant specification poloxamer is a surfactant (pg. 16, lines 15-27). Wu teaches the preparation comprises diluting a phosphate buffer solution of pH 6-6.4, freeze drying (i.e. lyophilize), resuspending in water (i.e. pH ~ 7, English translation, pg. 4, para. 17). Wu teaches PLGA has better effects and achieves higher encapsulation efficiency (English translation, pg. 8, last para.). Wu does not teach wherein the active ingredient is that which is recited by instant claims 1-2 , . However, Zotchev teaches nystatin derivatives which are anti-fungal agents of the following formula (abstract). Zotchev teaches the following specific compound 1 (drawings sheet 21, figure 16, compound 1, cols. 23-24, table 1, compound 1). Zotchev teaches compound 1, a nystatin derivative has comparable anti-fungal activity to amphotericin B (col. 48, lines 25-58). Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Wu , such that amphotericin B is replaced with compound 1 as taught by Zotchev . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that both compounds are established equivalent anti-fungal agents, and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Regarding claim 41: As discussed above, Wu and Zotchev render obvious the composition of claim 39. Wu is directed towards an oral formulation. Wu does not teach wherein the formulation comprises a pharmaceutically acceptable stabilizer that is vanillin. However, Zotchev further teaches vanillin can be included in the pharmaceutical composition as a flavoring agent (col. 22, lines 51-56). Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to incorporate vanillin into the oral composition of Wu as suggested by Zotchev . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to improve the flavor of the composition, thereby increasing patient satisfaction. Although Zotchev does not teach vanillin as a stabilizer, wherein it would have been obvious to incorporate vanillin, this property necessarily flows as result of making the composition, as products of identical chemical composition cannot have mutually exclusive properties (See MPEP 2112.02 (II). Claims 1-3, 11, 20, 33, 54-55, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Casa (J. Nanosci . Nanotechnol ., 2015, cited on PTO-892) in view of Zotchev (US 8,415,312, cited in previous action ). Regarding claims 1-3, 11, 20, 33, 54-55, and 57 : Casa teaches nanoparticles based on bovine serum albumin (BSA, i.e. a protein) containing amphotericin B ( Amb , abstract). Casa teaches AmB is effective against Candida albicans species (abstract). Casa teaches BSA nanoparticles are potential carriers for AmB , reducing its molecular aggregation, and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity (abstract). Casa teaches lyophilized BSA nanoparticles containing AmB were suspended in DMSO ( dimethylsulfoxide ) /sodium phosphate buffer at pH 7.4 ( pg. 10184, col. 1, para. 3, col. 2, para. 4). According to the instant specification dimethylsulfoxide is a polar organic solvent (pg. 6, lines 31-34). Casa teaches lyophilized BSA nanoparticles containing AmB were suspended in sodium phosphate buffer at pH 7.4 containing 2% polysorbate (i.e. aqueous solution, pg. 10184, col. 2, para. 5). According to the instant specification, polysorbate is a surfactant (pg. 5, lines 25-26). Casa do es not teach wherein the active ingredient is that which is recited by instant claims 1-2 , . However, Zotchev teaches nystatin derivatives which are anti-fungal agents of the following formula (abstract). Zotchev teaches the following specific compound 1 (drawings sheet 21, figure 16, compound 1, cols. 23-24, table 1, compound 1). Zotchev teaches compound 1, a nystatin derivative has comparable anti-fungal activity in Candida albicans to amphotericin B (col. 48, lines 25-58, table 5). Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Casa, such that AmB is replaced with compound 1 as taught by Zotchev . A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as protein nanoparticles for drug delivery are a known technique in the art for purpose of prolonging the release of the active agent. G iven that both compounds are established equivalent anti-fungal agents, and it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)). Conclusion No claims are allowed in this action. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : Tevyashova ( Antimicrobial Agents and Chemotherapy, 2013, cited on PTO-892) teaches the following nystatin analogs (pg. 3816, figure 1, compounds 4-5). Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT SAMUEL L GALSTER whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0933 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 8:00 AM - 5:00 PM . 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, FILLIN "SPE Name?" \* MERGEFORMAT Scarlett Y Goon can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-5241 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SAMUEL L GALSTER/ Examiner, Art Unit 1693