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
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.
Response to Amendment
The amendment filed August 12, 2026 has been entered. Claims 1-18 and 20-21 have been amended, claim 19 has been cancelled. Applicant’s amendments to the claims have overcome the objections to the specification, claims as well as the 112b, 102, and 103 rejections previously set forth in the Non-Final Office Action mailed May 12, 2026. Applicants cancellation of claim 19 have rendered the corresponding rejections moot. As such, these rejections and objections are hereby withdrawn.
This application is a 371 of PCT/EP2022/069172 filed 07/08/2022 and claims benefit of US provisional application 63/220,598 filed 07/12/2021.
Claims 1-18 and 20-21 are pending in this application.
Response to Arguments
The previous office action noted that claim 19 contained allowable subject matter, for the limitation of “solid formulation with lactose monohydrate with a DL90 < 5 um prepared by spray drying”, however, upon the discovery of additional prior art, new rejections are made herein. As a result this action is Non-Final. The Examiner apologizes for this inconvenience.
Applicant’s arguments with respect to the claims have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. The new 103 rejections utilize Basa (Drug development and Industrial pharmacy, 2008, cited on PTO-892) which accounts for the argued limitation.
New rejections addressing Applicant’s amendment are addressed below.
This action is Non-Final.
Claim Objections
Claim 15 is objected to because of the following informalities: The phrase “intermediated” should read “intermediate”. Appropriate correction is required.
New 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 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Bruzzese (WO 98/02168, cited in previous action) in view of Ferrari (WO 99/66902, IDS filed January 9, 2024) and Brasa (Drug development and Industrial pharmacy, 2008, cited on PTO-892) as evidenced by Yu (Biomolecules, 2025, cited in previous action).
Regarding claims 17-18: Bruzzese teaches complexes between N'-dimethylaminoacetylpartricin A dimethylaminoethylamide or the pharmaceutically acceptable salts thereof, and cholesterol 3-sulphate, and pharmaceutical compositions containing them, useful in the treatment of systemic mycoses (abstract). Bruzzese teaches a composition comprising SPA-S-843 and cholesterol-3-sulfate sodium salt in complex (pg. 13, example 5, lines 9-14). According to the instant specification amcipatricin diascorbate is also known as SPA-S-843 (pg.4, lines 17-22). According to Yu, cholesterol sulfate is a steroid (pg. 1, para. 2). Bruzzese teaches the administration could be by oral, respiratory, or parenteral routes, such as intravenous administration (pg. 10, lines 11-14). Bruzzese compares activity of the complexes to Amphotericin B (pg. 5, lines 5-7). Bruzzese teaches SPA-S-7 53 intramuscular administration leads to its partial precipitation which has a negative influence on tolerance of the product (pg. 3, lines 14-19).
Bruzzese does not teach wherein the formulation is a solid formulation with lactose monohydrate with a DL90 < 5 um prepared by spray drying.
However, Ferrari teaches new injedtable pharmaceutical formulations containing patricin derivatives (abstract). The partricin derivative enclosed in the formulations of the invention is, preferably, in the form of solution, of micellar pseudosolution, of encapsulated inclusion compound, or of suspension of sub-micronized particles, their size being smaller than 5 μm, preferably smaller or equal to 3 μm, to avert the risk of pulmonary embolism (pg. 4, lines 7-12). Ferarri teaches formulations comprise lactose (pg. 9, lines 5-22).
Additionally, Brasa teaches solid dosage forms for antifungal agents to enhance dissolution and bioavailability (abstract, pg. 1209, col. 1, para. 1). Brasa teaches solid formulations prepared by spray drying comprising lactose monohydrate (pg. 1212, table 3, pg. 1216, col. 1, para. 1, pg. 1213, col. 2, para. 1). The prepared formulations have a DL90< 5 um (pg. 1213, col. 2, para. 2, pg. 1214, figure 1, pg. 1215, figure 2).
Taken together it would have been prima facie obvious to modify the composition of Bruzzese such that it is a solid formulation with lactose monohydrate with a DL90 < 5 um prepared by spray drying as taught by Brasa and Ferrari. A person of ordinary skill in the art would have had the motivation to so with a reasonable expectation of success in order to enhance bioavailability for the treatment of fungal infections. Applying a known technique to a known product ready for improvement to yield predictable result is prima facie obvious (see MPEP 2143 (I)).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Bruzzese (WO 98/02168, cited in previous action), Ferrari (WO 99/66902, IDS filed January 9, 2024), Brasa (Drug development and Industrial pharmacy, 2008, cited on PTO-892), and Yu (Biomolecules, 2025, cited in previous action) as applied to claims 17-18 in view of Shah (Pharmazie, 2004, cited on PTO-892)
Regarding claim 20: As discussed above Bruzzese renders obvious the composition of claim 17.
Bruzzese does not teach wherein the formulation is the form of a dry powder inhaler (DPI) as recited by instant claim 20.
However, Shah teaches antinfectious drugs can be administered via dry powder inhalers (DPI) with lactose carriers (abstract). Shah teaches that amphotericin B is one such drug that can be administered as an aerosol (pg. 198, table 4).
Taken together, it would have been prima facie obvious to a person of ordinary in the art to modify the composition of Bruzzese such that it is administered via a dry powder inhaler as suggested by Shah. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as metered dose inhalers are known methods of administration of antifungal agents.
Claims 21 is rejected under 35 U.S.C. 103 as being unpatentable over Bruzzese (WO 98/02168, cited in previous action), Ferrari (WO 99/66902, IDS filed January 9, 2024), Brasa (Drug development and Industrial pharmacy, 2008, cited on PTO-892), and Yu (Biomolecules, 2025, cited in previous action) as applied to claims 17-18 in view of Ehrmann (Intensive Care Med., 2016, cited in previous action).
Regarding claim 21: As discussed above Bruzzese renders obvious the composition of claim 17.
Bruzzese does not teach wherein the formulation is the form of a liquid metered inhaler (MDI) as recited by instant claim 21.
However, Ehrmann teaches antinfectious drugs can be administered via metered dose inhalers (abstract). Ehrmann teaches that amphotericin B is one such drug that can be administered as an aerosol (pg. 198, table 4).
Taken together, it would have been prima facie obvious to a person of ordinary in the art to modify the composition of Bruzzese such that it is administered via a metered dose inhaler as suggested by Ehrmann. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as metered dose inhalers are known methods of administration.
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Bruzzese (Eur. J. Med. Chem., 1996, cited in previous action) in view of Ferrari (WO 99/66902, IDS filed January 9, 2024) and Brasa (Drug development and Industrial pharmacy, 2008, cited on PTO-892).
Regarding claims 16-17: Bruzzese teaches a series of patricin A amides using the active ester method by reaction with several amines on the carboxy group and then with some acids on the mycosamine group of patricin A (abstract). Bruzzese teaches most of the derivatives are potent antifungals compared to amphotericin B (abstract). Bruzzese teaches amides substituted with basic groups may be given hydrosoluble salts, useful for injectable formulations, and two derivatives were selected for further development, one of which being compound 22 or N-dimethylaminoacetyl-patricin A 2-dimethylaminooethylamide (abstract). Bruzzese teaches that compound 22 has the following structure
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168
490
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wherein R is
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41
143
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and R1 is
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33
125
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(pg.965, figure 1, pg. 968, table 1, compound 22). Bruzzese teaches that compound 22 exhibits antifungal activity against C. albicans and mucor sp. (pg. 969, table II). Compound 22 can be made hydrosoluble in the form of diascorbate salt, also known as SPA-S-843 (pg. 970, col. 2, para. 1). According to the instant specification amcipatricin diascorbate is also known as SPA-S-843 (pg.4, lines 17-22). Thus, compound 22 in diascorbate form is identical to amcipatricin diascorbate as instantly claimed. Bruzzese teaches compound 22 is less toxic than amphotericin B (pg. 970, col. 1, para. 3). Bruzzese teaches amphotericin B is an effective polyene antibiotic available for the treatment of mycotic infections in humans (pg. 966, col. 1, para. 4). Bruzzese teaches the intravenous administration of compound 22 as the diaspartate salt (pg. 972, col. 2, para. 3). Wherein Bruzzese does teaches the formulation of the diascorbate for intravenous administration, and either diascorbate or diaspartate as hydrosoluble forms, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06).
Bruzzese does not explicitly teach a method of treating a fungal infection caused by mucor species comprising administering compound 22 as the diaspartate salt.
However, it would have been prima facie obvious to a person of ordinary skill in the art to do so with a reasonable expectation of success as Bruzzese establishes compound 22 exhibits antifungal activity against mucor species, and compound 22 can be made hydrosoluble via formulation of a diascorbate salt for intravenous administration.
Bruzzese does not teach wherein the formulation is a solid formulation with lactose monohydrate with a DL90 < 5 um prepared by spray drying.
However, Ferrari teaches new injedtable pharmaceutical formulations containing patricin derivatives (abstract). The partricin derivative enclosed in the formulations of the invention is, preferably, in the form of solution, of micellar pseudosolution, of encapsulated inclusion compound, or of suspension of sub-micronized particles, their size being smaller than 5 μm, preferably smaller or equal to 3 μm, to avert the risk of pulmonary embolism (pg. 4, lines 7-12). Ferarri teaches formulations comprise lactose (pg. 9, lines 5-22).
Additionally, Brasa teaches solid dosage forms for antifungal agents to enhance dissolution and bioavailability (abstract, pg. 1209, col. 1, para. 1). Brasa teaches solid formulations prepared by spray drying comprising lactose monohydrate (pg. 1212, table 3, pg. 1216, col. 1, para. 1, pg. 1213, col. 2, para. 1). The prepared formulations have a DL90< 5 um (pg. 1213, col. 2, para. 2, pg. 1214, figure 1, pg. 1215, figure 2).
Taken together it would have been prima facie obvious to modify the composition of Bruzzese such that it is a solid formulation with lactose monohydrate with a DL90 < 5 um prepared by spray drying as taught by Brasa and Ferrari. A person of ordinary skill in the art would have had the motivation to so with a reasonable expectation of success in order to enhance bioavailability for the treatment of fungal infections. Applying a known technique to a known product ready for improvement to yield predictable result is prima facie obvious (see MPEP 2143 (I)).
Allowable Subject Matter
Claims 1-14 are allowed.
The following is a statement of reasons for the indication of allowable subject matter: Regarding claims 1-14: Bruzzese (Eur. J. Med. Chem., 1996, cited in previous action.). AS discussed above Bruzzese teaches compound 22. Bruzzese teaches the synthesis of compound 22 comprises: synthesizing Patricin A 2-dimethylaminoethyl amide using particin A and 2-dimethylaminoethylamine and diphenylphosphorazidate (pg. 971, col. 1, example 2), followed by conversion to compound 22 by reacting further with dimethylaminoacetic acid, triethylamine, and diphenyl phosphorazidate (pg. 971, col. 1, example 3). Bruzzese does not teach utilizing pentafluorophenol to form a pentafluorophenylester as recited by instant claim 1. It would be improper hindsight to suggest a person of ordinary skill in the art would have had the motivation to utilize these reagents as there is no teaching/suggestion in the prior art there is benefit from doing so or that it would be successful. Thus the method of claim 1 is allowable over the prior art. Similiarly one would not arrive at intermediates 1 and 2, rendering claims 14-15 also allowable. Wherein claim 1 cannot be anticipated/rendered obvious over the prior art, dependent claims 2-13 would similarly be allowable. Claim 15 would be allowable if rewritten or amended to overcome the claim objection set forth in this Office action.
Conclusion
Claims 1-14 are allowed in this action.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
