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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/17/2025 has been entered.
Claim Status
Claims 2-5 are pending. Claim 2 has been amended. Claims 2-5 are being examined in this application. In the response to the restriction requirement, Applicants elected cu-538-1 and cu-538-2.
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 2-5 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).
Li et al. teach xantholysin A having the following structure (Fig. 2):
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Please note that xantholysin A corresponds to the instantly claimed compound of general formula (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)
Response to Arguments
Applicant’s arguments filed on 6/5/2025 have been fully considered but they are not persuasive.
Applicant argues that “[L]i discloses xantholysin A but only in the context of antimicrobial and hemolytic activity, with no mention of permeation or reversibility. Since Li never suggests permeation enhancement for drug delivery, a skilled artisan would have no reason to investigate such use, let alone discover reversibility. The recognition of this previously unknown, advantageous, and unpredicted effect constitutes direct evidence of non-obviousness”.
Applicant also argues that “[I]nes describes pore-forming lipopeptides in antimicrobial contexts, implying irreversible membrane disruption rather than controlled, reversible permeation. Kim reports magainin's disruption of stratum corneum lipids, again irreversible and damaging, especially when combined with ethanol. Taken together, these references teach irreversible mechanisms and do not provide motivation toward the claimed reversible permeation”.
Applicant’s arguments are not persuasive
Xantholysin A taught by Li et al., which corresponds to the instantly claimed compound of general formula (2), would inherently promote reversible cell layer permeation.
Furthermore, Ines et al. teach that lipopeptides such as xantholysin have pore forming capacity, and 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).
Therefore, in contrary to Applicant’s arguments, one of ordinary skill in the art would have been motivated 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.
One of ordinary skill in the art would have reasonably expected Xantholysin A to promote cell layer permeation because Ines et al. teach that lipopeptides such as xantholysin have pore forming capacity.
For the reasons stated above the rejection is maintained.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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, MELISSA FISHER can be reached at 571-270-7430. 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.
/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658