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
Claims 7-10 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group III, claims 7-10, drawn to a method of production comprising the steps of adding APTES, adding TEOS, centrifuging, removing the supernatant, washing and storing the product in the reply filed on February 24, 2026 is acknowledged.
Claims 1-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 7-10 as filed on January 30, 2024 are under consideration.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 30, 2024 and January 23, 2026 were considered.
Consideration by the examiner of the information submitted in an IDS means nothing more than considering the documents in the same manner as other documents in Office search files are considered by the examiner while conducting a search of the prior art in a proper field of search. See MPEP 609.
Claim Objections
Claims 7-10 are objected to because of the following informalities:
Claims 7-10 are objected to because they depend from a withdrawn claim .
Claim 7, preamble: “the silicon dioxide vaccine delivery system” properly recites “a silicon dioxide vaccine delivery system”.
Claims 8, 9: “a concentration” is properly “the concentration” because antecedent basis is implicit.
Claim 8, in the step (1), “in the reaction system” should presumably recite “in the dispersion system” consistent with step (1) of claim 7.
Claim 8, in the step (2), “in the reaction systems” should presumably recite “in the reactant” consistent with step (2) of claim 7.
Claim 9: “a vaccine” should presumably recite “the vaccine” or “the vaccine delivery system” or some variation thereof.
Claim 10: “a stirring speed” is properly “the stirring speed”.
Appropriate correction is required.
Priority
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
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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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 7 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. “Construction of core-shell hybrid nanoparticles templated by virus-like particles,” RSC Advances 7:56328, 2017.
Lui teaches core-shell hybrid nanoparticles templated by virus-like particles wherein silication was carried out by treating CCMV (cowpea chlorotic mottle virus (virus-like particle)) with APTES ((3-aminopropyl)triethoxysilane), followed by TEOS (tetraethoxysilane) (title; page 56329, lhc, 1st paragraph under “Results and Discussion”).
Lui exemplifies a process wherein native 4 mg/mL CCMV in buffer (aqueous) was treated with TEOS and APTES solution and was left on a rotator (stirring) for 3 days at room temperature (about 20 – 25 ºC) (title; page 56332, rhc, “Synthetic procedures”). The silicified CCMV nanoparticles were separated by centrifugation at 10k rpm for 10 minutes, and the supernatant was collected (to obtain a product for storage) (page 56332, rhc, “Synthetic procedures”). Prior to centrifugation the CCMV nanoparticle suspension was dialyzed against Milli-Q (ultra-pure) water to completely remove non-reacted silane and salt (page 56332, rhc, “Synthetic procedures”).
Lui further exemplifies a process wherein gold-core/CCMV/silica nanoparticles were washed against Milli-Q water with centrifuge filter for three times to completely remove salt (page 56332, rhc, “Synthetic procedures”).
Lui further teaches the core-shell hybrid nanoparticles have functionalities as vaccine storage (page 56328, lhc, 1st paragraph).
Lui does not specifically teach or exemplify an embodiment of process comprising all of the steps of as required by claim 7, however, Lui expressly teaches washing against Milli-Q water with a centrifuge is an art-recognized obvious variant of dialysis for the purpose of removing salt. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the process of preparing silica / virus hybrid nanoparticles of Lui to further comprise a step of washing against Milli-Q water with a centrifuge in order to remove salt.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. “Construction of core-shell hybrid nanoparticles templated by virus-like particles,” RSC Advances 7:56328, 2017 as applied to claim 7 above, and further in view of Sartbaeva et al. (WO 2018/025044, published February 8, 2018, of record) as evidenced by Wikipedia “Tetraethyl orthosilicate,” last edited January 30, 2026.
The teachings of Liu have been described supra.
Liu teaches 4 mg/mL CCMV in buffer (aqueous), as required by instant claim 8.
Liu teaches room temperature (about 20 – 25 ºC), as required by instant claim 10.
Liu further teaches TEOS (MW = 208.33) and APTES (MW = 221.37) in a ratio of 90 : 10 mol% (page 56332, rhc, “Synthetic procedures”).
Liu does not specifically teach 0.1 to 100 mM APTES and 0.1 to 500 mM TEOS as required by claim 8.
Liu does not teach (1) stirring at 300 to 1500 rpm for 10 s to 30 min and (2) stirring at 300 to 1500 rpm for 30 min to 30 hr as required by claim 10.
These deficiencies are made up for in the teachings of Sartbaeva.
Sartbaeva teaches biomolecule preservation in one or more layers of covalently bonded amorphous silica, forming a cage or shell (title; abstract; claims). Biomolecules include virus-like particles (claim 13). An individual biomolecule can be enveloped with silica to form a nanoparticle (page 8, line 17). Sartbaeva further teaches a method of enveloping the biomolecule comprising the steps of hydrolysing TEOS, and contacting the hydrolysed TEOS with an aqueous solution of the biomolecule, wherein the TEOS precipitates about the biomolecule (claims 24-38; Figure 1B). The aqueous solution of the biomolecule has a concentration of the biomolecule which is less than that which causes aggregation, such as 4 mg/mL (claim 34; page 11, lines 17-23). In example 2, 20 mL TEOS (density = 0.933 g/mL as evidenced by Wikipedia) is combined with 20 mL water to form the pre-hydrolysate under stirring at 350 rpm for at least 30 minutes and checking every 30 minutes thereafter until the mixture has become homogenous, and 2 mL of the pre-hydrolysate is added to 100 mL solution (1 mL TEOS or 0.933 g TEOS per 102 mL total solution ~ = (0.993 g TEOS / 102 mL) x (1000 mL / L) x (1 mole / 208.33 g TEOS) x (1000 millimoles / mole) ~=44 mM TEOS), as required by instant claim 8.
Regarding claim 8, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the process of preparing silica / virus hybrid nanoparticles of Lui to add the TEOS to the virus-like particle solution in amounts as exemplified by Sartbaeva such as 44 mM because this amount is suitable to encapsulate 4 mg/mL biomolecules. Additionally, it would have been obvious to optimize therein because the quantity of silica is result-effective. See MPEP 2144.05. "[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). And because Lui teaches TEOS (MW = 208.33) and APTES (MW = 221.37) in a ratio of 90 : 10 mol% (broadly and reasonably approximate as 90 : 10 wt% in view of the similar MW), it would have been obvious to modify the process of preparing silica / virus hybrid nanoparticles of Lui and Sartbaeva to add the APTES in the virus-like particle solution in amounts of about 44 mM / 9.
Regarding claim 10, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the process of preparing silica / virus hybrid nanoparticles of Lui to comprise stirring at 350 rpm for at least 30 minutes and checking every 30 minutes thereafter as taught by Sartbaeva in lieu of leaving on a rotator for 3 days in order to accelerate the process. Additionally, it would have been obvious to optimize therein, e.g., to stir at a sufficient rate for sufficient time to achieve complete mixing. See MPEP 2144.05.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. “Construction of core-shell hybrid nanoparticles templated by virus-like particles,” RSC Advances 7:56328, 2017 as applied to claim 7 above, and further in view of Weigandt et al. (US 2011/0123620, published May 26, 2011, IDS reference filed January 30, 2024) and Sun et al. (CN 111658767 A, published September 15, 2020, IDS reference filed January 23, 2026, as evidenced by the Google translation).
The teachings of Liu have been described supra.
Liu does not specifically teach a storage concentration of 5 to 100 µg/mL virus-like particles and 0.02 to 20 mg/mL silica required by claim 9.
This deficiency is made up for in the teachings of Weigandt and Sun.
Weigandt teaches silicon dioxide nanoparticles comprising an antigen and the use thereof for vaccination (title; abstract; claims). The concentration of the nanoparticles can vary between 0.1 to 100 wt% (paragraph [0054]).
Sun teaches an antigen vaccine delivery system comprising mesoporous silica nanoparticles (title; abstract; claims). The mass ratio of the antigen to the silica is 1:1 to 1:20 (claims).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the silica / virus hybrid nanoparticles of Lui to have a mass ratio of the virus (antigen) to the silica of 1:1 to 1:20 as taught by Sun because this ratio is suitable for a vaccine delivery system and it would have been obvious to formulate the vaccine delivery system of Lui in view of Sun to have a concentration of nanoparticles of between 0.1 and 100 wt% as taught by Weigandt because this concentration is suitable for vaccination. The combined teachings of Liu, Sun and Weigandt render obvious, for example, a concentration of silica / virus hybrid nanoparticles of at least 0.1 wt% ~= 0.001 g nanoparticles / 1 g water ~= (0.001 g nanoparticles / 1 g water) x (1 g water / mL) x (1000 mg / g) ~ = 1 mg / mL, wherein 1 part of 21 parts is the virus and 20 parts of 21 parts is the silica. Additionally, it would have been obvious to optimize therein in order to produce an efficacious vaccine. See MPEP 2144.05.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sun et al. (CN 114377120 B, as evidenced by the Google translation) corresponds to the priority document of the instant Application.
Cao et al. (CN 101805407, IDS reference filed January 30, 2024, as evidenced by the Google translation) teaches a method for wrapping protein with nano silicon dioxide wherein APTES is covalently linked to the protein, and TEOS is subsequently condensed (title; abstract; claims).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
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/ALISSA PROSSER/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619