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
Applicant’s arguments, filed 3/9/2026, have been fully considered but they are not deemed to be fully persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objects are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objects are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 6-10, 12, 14-15, 17-18 and 24 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Silica in the form of silicon dioxide (SiO2) is not cationic. Silicon dioxide consists of silicon and oxygen atoms, and while silica can exist in various crystalline forms, it does not exhibit cationic properties. Silica is a covalent compound that forms a strong network structure, and its chemical behavior is consistent with the characteristics of covalent compounds, which do not typically form cations. Similarly, the oxygen in silicon dioxide is not anionic, it is covalently bonded to silicon atoms in a tetrahedral arrangement. It is therefore unclear hos silicon oxide may comprise Si being a cationic element and O being an anionic element.
Rejection under 35 U.S.C. 103
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 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.
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.
Claims 1-2, 6-10, 12, 14-15, 17-18, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Tagaya 1 (Inorganic Chemistry, 2014; IDS filed 9/28/2018) in view of Heinz (Nanoparticle decoration with surfactants: Molecular interactions, assembly, and applications, Surface Science Reports 72 (2017) 1–58). Tagaya 1 teaches a light-emitting nanoparticle comprising silica (silicon dioxide; SiO2; a matrix material; the matrix material comprising at least one cationic element from the group consisting of Si, and at least one anionic element selected from the group consisting of O), and Eu(III) (a metal; a light-emitting substance; a fluorescein-based dye molecule; a rare earth ion; trivalent Eu) for use in bioimaging and observation of cancer cells (Abstract; Experimental Section). The method “possesses attractive features such as… controllable pore size” (Introduction). A pore diameter given is 2.7 nm (Results and Discussion). The compound 3-aminopropyltriethoxysilane (a cell bonding molecule) is bonded to the surface (wherein an amino group bonded to the cationic element is formed at a surface) (Experimental Section). The concentration of Europium is 2.5, 5.0 or 10 mol% (Experimental Section). The particle size is 30-1000 nm (Results and Discussion). The photoluminescence of the nanospheres functionalized with folic acid exhibit a characteristic peak due to energy transfer between FA and Eu3+, and further the orange luminescence could be clearly detected by fluorescence microscopy in air and water. Furthermore, the nanospheres highly dispersed in cell culture medium exhibited nontoxicity in the cellular proliferation stages of the Hela cancer cells and NIH3T3 fibroblasts and specifically bind to the Hela cells (Results and Discussion). The nanospheres after the binding and uptake also showed intense luminescence from the outer/inner cell surfaces for the culture time of 4 days. Therefore, the luminescent FA-functionalized Eu:NPS nanospheres can be used for specific targeting and imaging abilities for cancer cells (Results and Discussion). The amount of 0.226 g of EuCl3·6H2O were used (Experimental Section). The molecular weight of EuCl3·6H2O is 366.41 g/mol, making the above amount is the equivalent of 82.8 mmol, and as the molecular weight of Europium is 152 g/mol, the molar amount of Europium present IS 82.8 mmol x (152 g/mol)(366.41 g/mol) = 32 mmol. The light-emitting nanoparticles were prepared by combining and stirring water, cetyltrimethylammonium bromide, and NaOH, to which was added tetraethoxysilane and an aqueous solution of Eu3+ comprising EuCl3-6H2O, and after stirring at elevated temperature for 2 hours, the resulting solution was filtered, the solid were washed, vacuum dried, and calcined) (Results and Discussion).
Tagaya 1 fails to teach “and a surfactant dispersed in the matrix material together with the light-emitting substance.” Tagaya 1 further fails to teach applicant’s claimed pore diameter of 3.7 to 10 nm (claims 1 and 24), and further fails to teach an average particle diameter of 10 nm to 500 nm (claim 12).
Heinz teaches dispersing surfactants in a host matrix imparts many advantages to nanoparticles for use in diagnostics and therapeutics (abstract; Section 5.4.3). Advantages include (i) a high surface area that provides sites for drug loading and enhances solubility and stability of loaded drugs, (ii) the ability to functionalize the nanoparticles with targeting ligands to enhance therapeutic potency and decrease side effects, (iii) the advantage of multivalent interactions with cell surface receptors and other biomolecules, (iv) enhanced pharmacokinetics and tumor tissue accumulations compared to free drugs, as well as(v) the biological selectivity which allows nanoscale drugs to preferentially accumulate at tumor sites due to their leaky blood vessels (Section 3.5.)
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to provide a surfactant dispersed in the matrix material together with the light-emitting substance. The motivation for this would be to impart the advantages described by Heinz afforded by a surfactant being dispersed in the matrix material. It would have been further obvious to optimize the pore diameter to improve the efficacy of the light-emitting nanoparticles for bioimaging, and in this way, the artisan would find the range of 3.7 to 10 nm through routine experimentation. The prior art provides sufficient guidance to this end, as it teaches that the pore size is a result effective parameter, and further teaches the diameter of 2.7 nm, which nearly touches applicant’s range. It would have been further obvious to optimize the average particle diameter of the light-emitting nanoparticles of Tagaya 1 to improve their efficacy for bioimaging. In this way, one would the applicant’s range of 10 nm to 500 nm. Tagaya 1 provides sufficient guidance to this end as it teaches the range of 30-1000 nm which overlaps with the instant range of 10 nm to 500 nm. “‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” MPEP § 2144.05, II.
Claims 1-2, 6-10, 12, 14-15, 17-18, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Tagaya 2 (Journal of Colloid and Interface Science, 2011; IDS filed 9/28/2018) in view of Heinz (Nanoparticle decoration with surfactants: Molecular interactions, assembly, and applications, Surface Science Reports 72 (2017) 1–58). Tagaya 2 teaches a light-emitting nanoparticle comprising silica (SiO2; a matrix material; the matrix material comprising at least one cationic element from the group consisting of Si, and at least one anionic element selected from the group consisting of O), and Eu(III) (a light-emitting substance; a fluorescein-based dye molecule; a rare earth ion; trivalent Eu), which provides enhanced luminescence for biological applications (Abstract; Introduction Experimental Section). NPSs prepared by its method “possess attractive features such as… controllable pore size” (Introduction). A pore diameter given is 2.7 nm (Fig. 5). The surface is provided with a micropore in which the pore diameter is 2.3-2.7 nm (Section 3.2.). The average particle diameter is between about 200 to about 1350 (Figure 6). The concentration of Eu3+ is 2.5, 5.0, or 10.0 mol% (Table 1). The light-emitting nanoparticles were prepared by combining and stirring water, cetyltrimethylammonium bromide, and NaOH, to which was added tetraethoxysilane and an aqueous solution of Eu3+ comprising EuCl3-6H2O, and after stirring at elevated temperature for 2 hours, the resulting solution was filtered, the solid were washed, vacuum dried, and calcined (wherein the matrix material comprises cetyltrimethylammonium bromide / wherein the matrix material comprises a surfactant molecule) (Section 2.2). The amount of 0.226 g of EuCl3·6H2O were used (Experimental Section). The molecular weight of EuCl3·6H2O is 366.41 g/mol, making the above amount is the equivalent of 82.8 mmol, and as the molecular weight of Europium is 152 g/mol, the molar amount of Europium present IS 82.8 mmol x (152 g/mol)(366.41 g/mol) = 32 mmol. Comparing this to 2.75 mol (0.00275 mol) of cetyltrimethylammonium bromide (the surfactant) (Experimental Section), the mol ratio of the surfactant molecular weigh respect to Eu3+ (a metal element of the matrix material) is 0.03, which reads on applicant’s range of a mol ratio of the surfactant molecular with respect to a metal element of the matrix material is 0.01 or more and 1.5 or less.
Tagaya 2 fails to teach “and a surfactant dispersed in the matrix material together with the light-emitting substance.” Tagay 2 further fails to teach applicant’s claimed pore diameter of 3.7 to 10 nm (claims 1 and 24), and further fails to teach an average particle diameter of 10 nm to 500 nm (claim 12).
Heinz teaches dispersing surfactants in a host matrix imparts many advantages to nanoparticles for use in diagnostics and therapeutics (abstract; Section 5.4.3). Advantages include (i) a high surface area that provides sites for drug loading and enhances solubility and stability of loaded drugs, (ii) the ability to functionalize the nanoparticles with targeting ligands to enhance therapeutic potency and decrease side effects, (iii) the advantage of multivalent interactions with cell surface receptors and other biomolecules, (iv) enhanced pharmacokinetics and tumor tissue accumulations compared to free drugs, as well as(v) the biological selectivity which allows nanoscale drugs to preferentially accumulate at tumor sites due to their leaky blood vessels (Section 3.5.)
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to provide a surfactant dispersed in the matrix material together with the light-emitting substance. The motivation for this would be to impart the advantages described by Heinz afforded by a surfactant being dispersed in the matrix material.
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to decorate the nanoparticles of Tagaya 2 to impart the advantages described by Heinz. It would have been further obvious to optimize the pore diameter to improve the light-emitting particles efficacy for bioimaging, and in this way, the artisan would find the range of 3.7 to 10 nm through routine experimentation. The prior art provides sufficient guidance to this end, as it teaches the pore size is a result effective parameter, and further teaches the diameter of 2.7 nm, which nearly touches applicant’s range. It would have been further obvious to optimize the average particle diameter of the light-emitting nanoparticles of Tagaya 2 to improve their efficacy for biological applications. In this way, one would the applicant’s range of 10 nm to 500 nm. Tagaya 2 provides sufficient guidance to this end as it teaches the range of about 200 to about 1350 (Figure 6) which overlaps with the instant range of 10 nm to 500 nm. “‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’ In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” MPEP § 2144.05, II.
Response to Arguments
Applicant’s arguments have been fully considered but are not found persuasive. The examiner acknowledges that Tagaya 1 and Tagaya 2 fail to teach “and a surfactant dispersed in the matrix material together with the light-emitting substance.” A surface active agent, commonly known as a surfactant, is a compound that reduces the surface tension (or interfacial tension) between two liquids, a gas and a liquid, or a liquid and a solid. They are amphiphilic, meaning they contain both a water-loving (hydrophilic) head and an oil-loving (hydrophobic) tail. Therefore, applicant’s argument has no force. Heinz teaches dispersing surfactants in a host matrix imparts many advantages to nanoparticles for use in diagnostics and therapeutics (abstract; Section 5.4.3). Advantages include (i) a high surface area that provides sites for drug loading and enhances solubility and stability of loaded drugs, (ii) the ability to functionalize the nanoparticles with targeting ligands to enhance therapeutic potency and decrease side effects, (iii) the advantage of multivalent interactions with cell surface receptors and other biomolecules, (iv) enhanced pharmacokinetics and tumor tissue accumulations compared to free drugs, as well as(v) the biological selectivity which allows nanoscale drugs to preferentially accumulate at tumor sites due to their leaky blood vessels (Section 3.5.) It would have been obvious to provide a surfactant dispersed in the matrix material together with the light-emitting substance. The motivation for this would be to impart the advantages described by Heinz afforded by a surfactant being dispersed in the matrix material.
Conclusion
Applicant’s amendment necessitated the new grounds of rejection. THIS ACTION IS THEREFOR MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618
March 21, 2026