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
Claim Status
Claims 2-9 are pending. Claims 8-9 have been amended. Claims 2-6 and 8 are being examined in this application. In the response to the restriction requirement, Applicants elected cu-538-1 and cu-538-2. Claims 7 and 9 are withdrawn as being drawn to a nonelected species.
Claim Rejections - 35 USC § 112
The rejection of claim 8 under 35 USC 112(d) is withdrawn in view of the amendments to the claims.
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.
This rejection is maintained.
Claims 2-6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (PLoS ONE 8(5): e62946, 2013) in view of Ines et al. (Peptides 71 (2015) 100-112) and Kim et al. (J Control Release. 2007 Jun 2;122(3):375–383), as evidenced by Kanda et al. (The Journal of Antibiotics (2017) 70, 691-694).
Li et al. teach xantholysin A having the following structure (Fig. 2):
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Please note that xantholysin A corresponds to the claimed compounds cu-538-1 and cu-538-2.
Li et al. do not teach promoting cell layer permeation.
Ines et al. teach that lipopeptides such as xantholysin have pore forming capacity (page 101, left column, 2nd para; page 101 right column, 2nd para).
Kim et al. teach that magainin, a peptide known to form pores in bacterial cell membranes, can increase skin permeability by disrupting stratum corneum lipid structure (abstract).
Kim et al. further teach that “[T]his study also introduces the novel concept of using a first chemical enhancer to increase penetration of a second chemical enhancer into the skin to synergistically increase skin permeability to a model drug”.
Kim et al. also teach that the combination of magainin and NLS-ethanol synergistically increases skin permeability, because NLS-ethanol increased magainin penetration into stratum corneum, which further increased stratum corneum lipid disruption and skin permeability. We believe this is the first study to use a pore-forming peptide as a skin penetration enhancer and the first study to use one chemical enhancer to increase penetration of another chemical enhancer into the skin (page 9, 2nd para).
It would have been obvious to one of ordinary skill in the art to administer xantholysin to the skin in order to promote cell layer permeation and thus increase skin permeability of a drug because Kim et al. teach that magainin forms pores in bacterial cell membranes, thus increasing penetration of a drug.
The skilled artisan would have reasonably expected xantholysin to promote cell layer permeation and thus increase skin permeability of a drug, just as magainin did, because Ines et al. teach that lipopeptides such as xantholysin have pore forming capacity.
With respect to the limitation “wherein the promotion of cell layer permeation by the compound of formula (2) is reversible”, it is noted that the promotion of cell layer permeation is an inherent property of the compound of formula (2).
Furthermore, as evidenced by Kanda et al. (The Journal of Antibiotics (2017) 70, 691-694), which teaches that “[U]nlike the mode of action of a reversible TJ opener, capsaicin, the permeability increase induced by MA026 was irreversible for at least 5 h” (page 694, left column, 1st para).
Therefore, the reference implies that the compound MAO26 (depicted below), which corresponds to the instantly claimed compounds cu-538-1 and cu-538-2, would eventually reverse TJ opening.
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With respect to claim 6, Ines et al. teach that “[C]andida acts as a commensal in animal hosts and colonizes in skin, nails, mucous membranes, gastrointestinal and genitourinary tracts.The available synthetic antifungal drugs show high toxicity to host tissues causing adverse effect. Lipopeptide surfactants are among the natural compounds reported to inhibit the growth of this pathogenic yeast” (page 108, left column, 4th para).
Therefore, one of ordinary skill in the art concerned with the treatment of Candidiadis, would have been motivated, with a reasonable expectation of success, to administer xantholysin A to mucous membranes in order to promote cell layer permeation and thus increase skin permeability of a drug such as for e.g. fluconazole, clotrimazole, etc.
Response to Arguments
Applicant’s arguments filed on 8/21/2026 have been fully considered but they are not persuasive.
Applicant argues that “[I]nes provides pore-forming capacity, but not the claimed reversible tight-junction opening. Kim shows a different permeability mechanism involving disruption of stratum comeum lipid structure. Kanda does not supply the missing reversibility limitation because Kanda repeatedly characterizes MA026 as an irreversible TJ opener and distinguishes its mechanism from that of a reversible TJ opener. Accordingly, the cited references do not establish that administration of the compound recited in claim 2 results in reversible opening of tight junctions to allow the substance to permeate via a paracellular route”.
Applicant’s arguments are not persuasive.
The MPEP 2112.01 states that “'Products of identical chemical composition cannot have mutually exclusive properties.’ A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
In the instant case, the compound taught by the references cited corresponds to the instantly claimed compound of general formula (2), thus, it would inherently have the same properties (i.e. promote reversible cell layer permeation).
Furthermore, Kanda et al. teaches that “[U]nlike the mode of action of a reversible TJ opener, capsaicin, the permeability increase induced by MA026 was irreversible for at least 5 h” (page 694, left column, 1st para), thus implying that MAO26 (which corresponds to the instantly claimed compound of general formula (2)), would eventually reverse TJ opening.
Therefore, one of ordinary skills in the art would have been motivated, with a reasonable expectation of success, to administer xantholysin to the skin in order to promote cell layer permeation and thus increase skin permeability of a drug as instantly claimed.
For the reasons stated above the rejection is maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
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