DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 12/01/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments with respect to the instant claim(s) 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.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-5, 7-9, 11, 16-18, 21, 24, 28 are rejected under 35 U.S.C. 103 as being unpatentable over Kazi et al (J Res Pharm, 2020, 24(2), 251-263), in view of Nudelman et al (US 2020/0164086A1).
Kazi taught natamycin (e.g., antifungal agent) cubosome nanoparticles (e.g., non-lamellar lyotropic liquid crystalline phase particle) with enhanced corneal permeation, so as to effectively treat (e.g., reads on therapeutically effective amount) ocular fungal keratitis. X-ray diffraction (XRD) studies affirmed the complete encapsulation of natamycin into cubosome vesicles. Ex vivo corneal permeation (e.g., reads on administration) studies revealed enhanced corneal permeation, in comparison to a pure drug suspension.
Additionally, ocular irritation studies performed on rabbits (e.g., reads on administration) indicated the cubosome to be non-irritant. Finally, the natamycin-cubosome nanoparticles demonstrated sustained drug release and increased corneal penetration. The cubosomes were formulated with monoolein (e.g., fusogenic amphiphilic lipid).
Kazi differs from the instant claim 1 in that Kazi did not teach oleoyl, a cationic lipid, or phosphatidylethanolamine, as recited.
Nudelman taught cubosome [0006] lipid nanoparticles [0048] formed of oleoyl, linoleoyl, linolenoyl, DOPE (e.g., a phosphatidylethanolamine) [0068 and claim 18] and DOTAP (e.g.,. cationic lipid) [0067, claims 9-10].
Since Kazi taught cubosome nanoparticles, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kazi, oleoyl, linoleoyl, linolenoyl, phosphatidylethanolamine and DOTAP, as taught by Nudelman. The ordinarily skilled artisan would have been motivated to form the cubosome, as taught by Nudelman. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, it is prima facie obvious to select oleoyl, linoleoyl, linolenoyl, phosphatidylethanolamine and DOTAP for incorporation into a composition, based on their recognized suitability for the intended use as cubosome-forming lipids, as taught by Nudelman [0006, 0048, 0067-0068 and at claims 9-10].
Kazi, in view of Nudelman, reads on claims 1-5, 7-8, 16-18, 21 and 28.
Claim 9 is rendered prima facie obvious because Kazi taught the lipid monoolein.
The instant claim 9 recites an internal curvature induced splay of less than -0.05 nm-1. The instant Specification [0105-0114] disclosed that the MO lipid is a fusogenic lipid with this characteristic (e.g., internal curvature induced splay of less than -0.05 nm-1). It appears that the compositions of the instant claims (cubosomes comprising MO) and those of the prior art (cubosomes comprising monoolein) would reasonably be expected to have substantially the same physical and chemical properties (an internal curvature induced splay of less than -0.05 nm-1).
Inherent features need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. MPEP 2112 II. It should be noted that a chemical composition and its properties are inseparable. If the prior art teaches the identical chemical compounds, then the properties that the Applicant discloses and/or claims are necessarily present.
Claim 11 is rendered prima facie obvious because Kazi taught the particle diameter of 150-200 nm [page 257, section 2.6].
The instant claim 11 recites a diameter of greater than about 50 nm.
Kazi taught a diameter of 150-200 nm. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claim 24 is rendered prima facie obvious because Kazi taught natamycin present at 50 mg/mL in 5 mL solution [page 259, section 4.1].
The instant claim 24 recites the antifungal agent present between 0.1 to 30 mol %. Kazi taught natamycin present at 50 mg/mL in 5 mL solution. A prima facie case of obviousness exists because of overlap, as discussed above.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kazi et al (J Res Pharm, 2020, 24(2), 251-263), in view of Nudelman et al (US 2020/0164086A1) and further in view of Lai et al (International Journal of Nanomedicine, 2010, 5, 13-23).
The 35 U.S.C. 103 rejection over Kazi and Nudelman was previously discussed.
Additionally, Kazi taught poloxamer 407 as a stabilizer [page 252, section 2.1], but was silent an amount of 6-18 wt. %, as recited in claim 12.
Lai taught cubic nanoparticles prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization [abstract]. Clear and viscous gels were formed using the GMO/poloxamer 407 binary systems with a GMO/poloxamer 407 ratio of 500 mg/40 mg (7.4%, w/w, poloxamer 407 weight percentage) to 500 mg/100 mg (16.7%, w/w) [page 16, Results and discussion, 1st paragraph].
Since Kazi taught cubic nanoparticles generally comprising fusogenic amphiphilic lipids (e.g., monoolein) and poloxamer 407, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kazi, poloxamer 407 at 7.4-16.7 %, as taught by Lai et al. The ordinarily skilled artisan would have been motivated to form the cubic particle, as taught by Lai et al at the Results/Discussion section.
The instant claim 12 recites a stabilizer present at 6-18 %.
Kazi taught poloxamer 407 as a stabilizer, and Lai taught poloxamer 407 at 7.4-16.7 %. A prima facie case of obviousness exists because of overlap, as discussed above.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kazi et al (J Res Pharm, 2020, 24(2), 251-263), in view of Nudelman et al (US 2020/0164086A1) and further in view of Gentile et al (US 2020/0197306 A1).
The 35 U.S.C. 103 rejection over Kazi was previously described.
Kazi and Nudelman did not teach amounts, as recited in claim 13; non-amphiphilic charged compounds, as recited in claim 14.
Gentile taught liquid crystalline nanoparticles comprising cationic phospholipids, glycerol monooleate and PLURONIC® F-127 (e.g., poloxamer-407). The cationic phospholipids were comprised at 1-10 mole %. Cationic phospholipids included DOTAP and CTAP, where CTAP also reads on a non-amphiphilic charged compound [claims 1, 7, 11; ¶ 0073].
Since Kazi taught liquid crystalline particles generally comprising fusogenic lipids and stabilizers, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kazi, amounts of positively charged lipids, as taught by Gentile. The ordinarily skilled artisan would have been motivated to form the particle, as taught by Gentile. The skilled artisan would have included the lipids within Kazi at 1-10 mole % because at the said amount, the lipids contributes to the formation of the particle, as taught by Gentile, at claims 1, 7 and 11 and at [0073].
The instant claim 13 recites a positively charged lipid at 0.1 to less than 20 mol %.
Gentile taught positively charged lipids at 1-10 mole %. A prima facie case of obviousness exits because of overlap, as discussed above.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kazi et al (J Res Pharm, 2020, 24(2), 251-263), in view of Nudelman et al (US 2020/0164086A1) and further in view of Boge et al (ACS Appl Mater Interfaces, 2019, 11, 21314-21322).
The 35 U.S.C. 103 rejection over Kazi and Nudelman was previously described.
As discussed, Kazi generally taught cubosome delivery of antifungal agents; however, was silent gram-negative bacteria antibacterial agents, as recited in claim 19.
Nevertheless, Boge taught cubosomes with antibacterial efficacy against Escherichia coli (e.g., gram-negative bacteria), when loaded with the antimicrobial peptide LL-37 (e.g., the antibacterial agent) [abstract]. The cubosomes were prepared with the lipid GMO, and the stabilizer poloxamer 407 [page 21315, Materials]. Doge concluded that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, thereby functioning as an antimicrobial unit [abstract].
Since Kazi generally taught cubosomes prepared with fusogenic amphiphilic lipids (e.g., monoolein) and stabilizers (e.g., poloxamer 407) for the delivery of therapeutic (e.g., antifungal) agents, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kazi, gram-negative bacteria antibacterial agents, as taught by Boge. The ordinarily skilled artisan would have been motivated to include, within Kazi, functioning antimicrobial units, as taught by Boge at the abstract.
Nonstatutory Double Patenting
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7-9, 11-19, 21, 24 and 28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 11-20 and 23 of copending Application No. 18/869,179, in view of Kazi et al (J Res Pharm, 2020, 24(2), 251-263) and further in view of Nudelman et al (US 2020/0164086A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims require an antifungal agent and one or more fusogenic amphiphilic lipids , which are not required of the copending claims.
Kazi taught natamycin (e.g., antifungal agent) cubosome nanoparticles (e.g., non-lamellar lyotropic liquid crystalline phase particle) with enhanced corneal permeation, so as to effectively treat ocular fungal keratitis.
Nudelman taught cubosome lipid nanoparticles formed of oleoyl, linoleoyl, linolenoyl, phosphatidylethanolamine and DOTAP.
It would have been prima facie obvious to one of ordinary skill in the art to include an antifungal agent within the copending claims, as taught by Kazi. The ordinarily skilled artisan would have been motivated to treat a disease or condition, as taught by Kazi et al.
It would have been prima facie obvious to one of ordinary skill in the art to include, within the copending claims, oleoyl, linoleoyl, linolenoyl, phosphatidylethanolamine and DOTAP, as taught by Nudelman. The ordinarily skilled artisan would have been motivated to form the non-lamellar lyotropic liquid crystalline phase particle, as taught by Nudelman.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments with respect to the instant claim(s) 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.
Conclusion
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.
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/CELESTE A RONEY/ Primary Examiner, Art Unit 1612