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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/29/2026, has been entered.
Claims 19-28 and 32-33 are pending.
Withdrawal of Claim Rejections
Any previous rejection not reiterated herein has been withdrawn.
Declaration Insufficient In-Part
The Declaration of Roghieh Suzanne Saffie-Siebert, Ph.D., under 37 CFR 1.132 filed 4/29/2026 is insufficient to overcome the rejection of claims 19 based upon 35 U.S.C. 103 as being unpatentable over Saffie-Siebert in view of She et al.; claims 20 and 26-28 based upon 35 U.S.C. 103 as being unpatentable over Saffie-Siebert and She et al. in further view of Willey et al.; and claim 32 based upon 35 U.S.C. 103 as being unpatentable over Saffie-Siebert, She et al. and Willey et al. in further view of Meng et al. as set forth in the last Office action because
Regarding paragraph 12 of the declaration (“Decl.”), the declarant asserts that “5-FU is chemically different from the compounds of Saffie-Siebert does disclose.” Page 4 of Decl. To further the argument, the declarant asserts that 5-FU is a stabilizing agent and has delocalized lone pairs within its pyrimidine ring. However, the line of argument is misguided. First, 5-FU is not claimed to be a stabilizing agent. Second, the delocalization would appear to improve drug loading. See Abstract of She et al. (“Higher drug loading was observed at pH of 7.4 and 8.5 as 5-fluorouracil becomes more deprotonated in alkaline conditions.”)
Regarding paragraph 13 of the declaration, the declarant asserts that “She et al. fail to teach or suggest the use of phospholipids for [optimizing 5-FU loading].” Page 5 of the Decl. However, this is immaterial because Saffie-Siebert teaches phospholipids. The declarant also attempts to capitalize on apparent differences between silicon and silica, but reliance of the difference seems misplaced. Given the “surface reactivity [of silicon] that is entirely absent in silica,” as the declarant states, see page 6, it would suggest that silicon would have more reason for being electrostatically associated with silicon than silica. Nonetheless, perhaps this line of argument could carry more weight if the scope of the claims were narrowed to requiring electrostatic association with the phospholipid layer. In fact, the declaration lends no support for claiming electrostatic association with silicon when the declarant is uncertain as to how 5-FU is associating with silicon. See id. Still, any amendment in this regard would require further search and consideration and would have to account for any prior art regarding ionic attraction between opposite charges generally and a phospholipid layer and fluorouracil, specifically.
Incidentally, for the sake of being thorough, it is noted in paragraph 13 that the declarant alleges properties such as degradability and prolonged drug release. See id. However, none of these properties are claimed.
Regarding paragraph 14 of the declaration, it is merely an opinion on the ultimate legal issue of obviousness.
Regarding paragraphs 18-24 of the declaration, these statements are not persuasive because they are premised on the same assertions made in preceding paragraphs discussed above.
Declaration Sufficient In-Part
The Declaration of Roghieh Suzanne Saffie-Siebert, Ph.D., under 37 CFR 1.132 filed 4/29/2026, is sufficient to overcome the rejection of claim 33 based upon 35 U.S.C. 103 as being unpatentable over Saffie-Siebert in view of She et al.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 19 and 21-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saffie-Siebert (WO2011012867A1) in view of She et al., J. Nanomaterials, Vol. 2015, Article ID 872035, 1-9, http://dx.doi.org/10.1155/2015/872035.
Regarding claim 19, Saffie-Siebert teaches “[w]hile silica and silicon-based formulation have been used as a carrier system for several applications, polymerization is a major safety issue if silicon is used as a drug carrier.” According to Saffie-Siebert, “[t]here remains a need for a silicon-based delivery system in which the silicon containing carrier material reliably degrades to OSA and in which polymerisation of the OSA can be prevented.” Page 8, lines 27-29. To this end, Saffie-Siebert teaches a “delivery system comprising a carrier system made from a solid, hydrolysable, silicon-containing material, said delivery system being able to deliver an active ingredient whilst also providing the benefit of releasing orthosilicic acid as the carrier system degrades at a controlled rate.” Page 8, lines 32-35. Saffie-Sieber also teaches that “the composition comprises at least 5 % by weight stabilizing agent, for example at least 20 wt%, typically at least 30 wt% and especially at least 50 wt% stabilising agent based on the total weight of the composition. In one embodiment the molar ratio of the stabilising agent to silicon is at least 0.8 to 1, for example at least 1 to 1, typically at least 1.5 to 1.” Page 14, lines 32-36. This teaches and/or suggests “at least 50% by weight hydrolysable silicon.” Stabilizing agents include phosphatidylcholine (current claim 21), see page 17, line 25, as well as amino acids including glycine. See page 19, lines 25-32.
Saffie-Sieber further teaches that “the stabilizing agent is an electrostatically absorbed species that binds to the surface of the silicon by van der Waal’s forces.” Page 17, lines 34-35. Saffie-Sieber also teaches that “[i]n some embodiment the particles may be modified to promote interactions with the stabilizing agent and/or the bioactive compounds . . . The adsorption of the active compounds on the modified silicon particles prevents the formation of agglomerates.” Para 21, lines 14-18. Further, Saffie-Siebert teaches “[b]y modifying the surface chemistry of nanoparticles silicon-containing material the compounds can be coupled by iconic, covalent or H bonds to an agent to be delivered.” Page 27, lines 32-33 (emphasis added). “[T]he surface of silicon-containing material can be modified to include, -NH2, (amine), -SH (thiol), -POO and -COOH (carboxylic acid) functional groups.” Page 25, lines 11-13. “[T]he choice of reagent will depend on what functional groups are available for linkage in the substance chosen to be attached, whether these groups can react without adversely affecting the functional properties of the substance and the sensitivity of the beneficial substance to the conditions required for the cross-linking reaction.” Page 25, lines 23-27
Saffie-Siebert does not teach fluorouracil.
She et al. relates to the functionalization of hollow mesoporous silica nanoparticles for improved 5-FU loading. See Title. In this regard, She et al. explains effect of electrostatic forces on drug loading.
The loading capacity of the hollow mesoporous silica nanoaprticles [sic] to the anticancer drug, 5-fluorouracil, can be controlled via precise functionalization. The presence of amine groups on the surface of nanoparticles resulted in the highest loading capacity of 28.89%, due to the amine functionalized nanoparticles having a similar hydrophilicity but reverse charge to the drug. In addition, the change in pH leads to the variation of the intensity of electrostatic force between nanoparticles and the drug, which finally affects the loading capacity of amine functionalized hollow mesoporous silica nanoparticles to some extent. Higher drug loading was observed at pH of 7.4 and 8.5 as 5-fluorouracil becomes more deprotonated in alkaline conditions. The improved drug loading capacity by amine functionalized hollow mesoporous silica nanoparticles has demonstrated that they can become potential intracellular 5-fluorouracil delivery vehicles for cancers.
Abstract.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention in view of the combined teaches of Saffie-Siebert and She et al. to arrive at the claimed invention. In this instance, it would have been prima facie obvious for one of ordinary skill in the art to incorporate fluorouracil as taught by She et al. Indeed, established precedent holds that it is generally obvious to add known ingredients to known compositions with the expectation of obtaining their known function. See, e.g., In re Linder, 457 F.2d 506, 507 (CCPA 1972); see also In re Dial, 326 F.2d 430,432 (CCPA 1964). Here, it would have been obvious to incorporate fluorouracil as a therapeutic in the particle of Saffie-Siebert. Further, one of ordinary skill in the art would have been motivated to adsorb fluorouracil with the stabilizing agent or the modified silicon particles to prevent agglomerations. Furthermore, it would have been prima facie obvious to do so electrostatically, such as by ionic attraction, to improve loading and had a reasonable expectation of success in view of the ability of functionalizing both silicon and silica with similar functional groups.
Claim(s) 20 and 26-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saffie-Siebert (WO2011012867A1) in view of She et al., J. Nanomaterials, Vol. 2015, Article ID 872035, 1-9, http://dx.doi.org/10.1155/2015/872035, as applied to claims 19, 21-25 and 33 above, and further in view of Willey et al. (CA3070107).
Teachings of Saffie-Siebert and She et al. are discussed above.
Regarding claim 20, the references do no teach willow bark extract.
Willey et al. teaches methods of treating diseases and disorders of the skin including non-melanoma skin cancer and actinic keratosis (current claim 26). See page 1, Field of Invention. To this end, Willey et al. teaches the use of one or more anti-acne agents including willow bark extract. See pages 37-38.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention to further modify the combined teachings of Saffie-Siebert and She et al. with Willey et al. and arrive at the claimed invention. In this regard, it is prima facie obviousness to select a known material based on its suitability for its intended use. See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Regarding claims 27 and 28, Willey et al. teaches that the method includes treating hypertrophic scarring. See page 12.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saffie-Siebert (WO2011012867A1) in view of She et al., J. Nanomaterials, Vol. 2015, Article ID 872035, 1-9, http://dx.doi.org/10.1155/2015/872035 and view of Willey et al. (CA3070107), as applied to claims 19-28 and 33 and further in view of Meng et al.
Teachings of Saffie-Siebert, She et al. and Willey et al. are discussed above.
None of the references are presumed to teach a topical cream or gel containing up to 5% w/w fluorouracil.
Meng et al. teaches a “silicasome carrier that is comprised of mesoporous silica nanoparticles (MSNPs) coated with a lipid bilayer.” Para. [0445]. Meng et al. further teaches that “drug-loaded silicasome can be incorporated into a broad range of topical dosage forms . . . for the treatment of a topical cancer.” Para. [0345]. Meng et al. further teaches the delivery of 5-fluorouracil. See e.g., paras. [0010] and [0315]. The drug carrier has a drug loading capacity of at least about 8% w/w. See para. [0076].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention in view of the combined teaches of Saffie-Siebert and Meng et al. to arrive at the claimed invention. In this instance, it would have been prima facie obvious for one of ordinary skill in the art to incorporate fluorouracil as taught by Meng et al. with the carrier of Saffie-Siebert. In this instance, one of ordinary skill in the art would find motivation to combine Saffie-Siebert and Meng et al. with a reasonable expectation of success because both references teach stable silicon-based nanoparticles associated with a drug cargo for purposes of topical administration. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.”) Furthermore, established precedent holds that it is generally obvious to add known ingredients to known compositions with the expectation of obtaining their known function. See, e.g., In re Linder, 457 F.2d 506, 507 (CCPA 1972); see also In re Dial, 326 F.2d 430,432 (CCPA 1964). Here, it would have been obvious to incorporate fluorouracil as a therapeutic in the particle of Saffie-Siebert for skin cancer therapy in the amounts as taught by Meng et al. See page 28, lines 30-31.
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 ROBERT S CABRAL whose telephone number is (571)270-3769. The examiner can normally be reached M-F 8 am - 5 pm.
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/ROBERT S CABRAL/Primary Examiner, Art Unit 1614
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