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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/01/2026 has been entered.
Claim Interpretation
Claims 20 and 36 describe a solid vaccine composition and the method of manufacturing of said composition. Specifically, the claims refer to the process of “the plurality of aragonite particles are impregnated with CO2”. This is defined in paragraph 097 of the specification as “coupled with”, therefore prior art reading on the definition of “coupled with” (linked or combined with something else) will read on the claimed method of impregnating aragonite with CO2.
Claim Rejections - 35 USC § 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 (i.e., changing from AIA to pre-AIA ) 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.
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, 8, 10, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Sammatur et al. (US 2020/0230057 A1) in view of Cunningham et al. (US 2009/0029902 A1)
Regarding Claim 1: Sammatur teaches methods for preparing a dried preparation comprising lipids and a therapeutic agent. (57) Sammatur further teaches an embodiment of the invention which consists of a “dried preparation” (0149) where the drying is performed by lyophilization. (0151) Lastly, Sammatur teaches that viral vectors to be used in the claimed invention may be adenoviruses (0446) which may include a heterologous protein of interest. (0441) This reads on the claimed method of a composition comprising a lyophilized adenovirus vector comprising a nucleic acid molecule encoding a heterologous protein. Sammatur fails to teach use of a filler comprising a carbonite material.
Cunningham et al. teaches calcium carbonite binding domains which may be incorporated in the delivery of functional compounds. (0007) Cunningham further specifies that calcium carbonate compositions may be used in pharmaceuticals, including vaccines, and provide a pharmaceutical benefit by means of preventing infectious germs when coming into contact with a surface or item. (0199) This reads on the claimed method of use of a filler comprising a carbonite mineral.
Regarding the viral recovery upon exposure to acidic conditions increasing the viral recovery, per the Specification submitted 03/22/2023, there is an increase in viral recovery when using the aragonite composition (Example 1 and Figs. 3A-D). In addition to this, per the Remarks dated 03/01/2026, the acidic conditions of an oral route of delivery had less negative impact on viral recovery when the aragonite composition was used. (Pg 3, last paragraph). As such, as reflected in the Remarks, uncoated aragonite helps neutralize the pH of the composition which is the reason as stated by the Applicant for increased viral recovery, making it an inherent property of using aragonite as part of the composition.
Regarding Claims 8 and 10: Sammatur teaches an embodiment of the invention wherein the “dried preparation” contains less than 0.05% residual moisture. (0149)
Regarding Claim 15: Cunningham teaches use of calcium carbonate in vaccine compositions (0199). Both Sammatur and Cunningham fail to teach use of lactose, sucrose, magnesium stearate, glucose, mannitol, sorbitol, starch, dextrose, maltodextrin, maltitol, or plant cellulose as fillers.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the lyophilized adenovirus preparation method of Sammatur with the incorporation of aragonite as a calcium carbonate filler of Cunningham to create a composition comprising a lyophilized adenovirus vector comprising an aragonite filler with a moisture content of less than 3% residual moisture. One would have had a reasonable expectation of success at doing so and motivation to do so based on the teachings of Cunningham, who details that calcium carbonate fillers can contribute pharmaceutical benefits to a composition by providing antimicrobial effects to the composition.
Claims 2 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Sammatur et al. (US 2020/0230057 A1) in view of Cunningham et al. (US 2009/0029902 A1) and Jones et al. (US 2020/0155662 A1)
The teachings of Sammatur and Cunningham are disclosed above. Both Sammatur and Cunningham fail to teach use of a type 5 adenovirus with deletions in the E1, E2b, and E3 regions in addition to use of a heterologous protein coming from a virus or coating.
Regarding Claim 2: Jones teaches methods of generating enhanced immune responses using adenovirus vectors which allow for multiple vaccinations. (57) Jones further teaches an embodiment of the invention which makes use of a type 5 adenovirus vector comprising deletions in the E1, E2b, and E3 regions. (0011) Jones specifies that adenoviruses with deletions in both the E1 and E2b regions are safer and superior to just E1 region deletions due to being more antigen-specific (0077) and that E3 region deletions can prevent expression and/or function of the gene product encoded by that region. (0138)
Regarding Claim 17: Jones teaches use of pharmaceutical compositions comprising the claimed vector compositions which can be combined with pharmaceutically acceptable inert carriers such as tablets, capsules, or elixirs used to treat human diseases. (0315)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the dried therapeutic preparation as taught by Sammatur and the use of calcium carbonate as taught by Cunningham with the use of a type 5 adenovirus comprising deletions in the E1, E2b, and E3 regions and use of a capsule as taught by Jones to create a pharmaceutical composition comprising an encapsulated type 5 adenoviral composition with E1, E2b, and E3 deletions. One would have been motivated to do so and had a reasonable expectation of success due to the teachings of Jones, who details that deletions in the E1, E2b, and E3 regions are more antigen specific and can prevent expression and/or function of the gene product encoded by the region.
Claims 3-7, 14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Sammatur et al. (US 2020/0230057 A1) in view of Cunningham et al. (US 2009/0029902 A1) and Csiszovszki et al. (US 10,973,909 B1)
The teachings of Sammatur and Cunningham are disclosed above. Neither Sammatur nor Cunningham teach a heterologous protein (spike, nucleoplasmid, or membrane) coming from SARS-CoV-2 which matches at least 80% of SEQ ID 1, use of lactose, sucrose, magnesium stearate, glucose, mannitol, sorbitol, starch, dextrose, maltodextrin, maltitol, or plant cellulose, or use of sodium chloride, potassium chloride, sodium citrate, sodium phosphate, sucrose, dimethylglycine, glycine, methylsulfonylmethane, or yeast lysate.
Regarding Claim 3: Csiszovszki et al. teaches polypeptides, vaccines, and pharmaceutical compositions which aid in the prevention or treatment of SARS-CoV-2. (57) Specifically, Csiszovszki teaches that it is advantageous to administer vaccines comprising multiple polypeptide components in order to combat viral infections which may be heterologous. (Col 9, ln 18-37) This reads on the claimed method of use of a heterologous protein that comes from a virus.
Regarding Claims 4 and 5: Csiszovszki teaches in Example 1 a method of construction for a polyPEP1-SCoV-2 vaccine comprising one or more peptides capable of inducing positive T and B cell responses in SARS-CoV-2 infections. (Col 18, Example 1) This reads both on the method of claim 4 of use of a virus selected from the group consisting of SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-NL63, HCoV-229E, HCoV-OC43, HKU1, and influenza virus and also the method of claim 5, in which the heterologous protein comes from SARS-CoV-2.
Regarding Claim 6: Csiszovszki teaches that embodiments of the invention comprise at least one polypeptide comprising fragments of the surface, nucleoplasmid, membrane, or envelope proteins. (Col 4, ln 17-36)
Regarding Claim 7: Csiszovszki teaches use of SEQ ID NO. 122, which has a 99.9% match to the claimed SEQ ID NO. 4. Specifically, SEQ ID NO. 122 is a spike glycoprotein used in an embodiment of the claimed vaccine construct. (Col 28, ln 45) This is taught in Example 4, which is an example of a way of modelling transmission of SARS-CoV-2 in order to better understand the disease. (Col 27-28, ln 65-40) The alignment of SEQ ID NO. 122 as compared to the claimed SEQ ID NO. 4 is provided for reference below:
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Regarding Claim 14: Csiszovszki teaches an embodiment of the invention in which pharmaceutical compositions comprise one or more pharmaceutically acceptable carriers, which typically are slowly metabolized. Examples given are trehalose, lipid aggregates, and lactose. (Col 12, ln 5-20) This reads on the claimed method of use of one or more of the following: lactose, sucrose, magnesium stearate, glucose, mannitol, sorbitol, starch, dextrose, maltodextrin, maltitol, and plant cellulose.
Regarding Claim 16: Csiszovszki teaches an embodiment of the invention which comprises sodium salts, with sodium chloride named as a specific example. (Col 12, ln 55-58) This reads on the claimed method of use of one or more compounds selected from the group consisting of sodium chloride, potassium chloride, sodium citrate, sodium phosphate, sucrose, dimethylglycine, glycine, methylsulfonylmethane, and yeast lysate.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the dried therapeutic preparation as taught by Sammatur and the use of calcium carbonate as taught by Cunningham with the teachings of Csiszovszki of use of a heterologous protein consisting of SARS-CoV-2, specifically the spike protein of SEQ ID NO 122, and use of lactose as a filler and sodium chloride as a salt. One would have been motivated to do so and had a reasonable expectation of success due to the teachings of Csiszovszki, who detail that use of a SARS-CoV-2 heterologous composition comprising a spike protein (SEQ ID NO. 122) matching the claimed SEQ ID NO. 4 is a useful model for studying disease transmission, that lactose is an acceptable carrier as it is metabolized slowly, and that sodium chloride is an acceptable sodium salt for use in a vaccine composition.
Claims 17-18, 20, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Sammatur et al. (US 2020/0230057 A1) in view of Cunningham et al. (US 2009/0029902 A1) and Wagner-Hattler et al. (US 2020/0155458 A1)
The teachings of Sammatur and Cunningham are disclosed above. Neither Sammatur nor Cunningham teach a solid dosage form for delivery of an aragonite composition impregnated with CO2, a biocompatible polymer, disintegrating agent, or enteric coating.
Regarding claims 17 and 18: Wagner-Hattler teaches an embodiment of the invention which has a capsule comprising polymeric walls through which active or inactive agents can pass through diffusion. (0003) As the definition of “enteric coating” is that of a polymer barrier which is applied to an oral medication, this reads on both the claimed method of the composition being contained within a capsule and the capsule being enteric coated.
Regarding Claims 20 and 36: Sammatur teaches methods for preparing a dried preparation comprising lipids and a therapeutic agent. (57) Sammatur fails to teach an aragonite composition comprising a plurality of aragonite particles which have been impregnated with CO2, a biocompatible polymer, and a disintegrating agent.
Wagner-Hattler teaches an embodiment of the invention comprising calcium carbonate in the dosage form of a tablet, mini-tablet, pellet, capsule, or granule (0044) and states that oral dosage forms such as powder or tablets are well known in the art. (0255-0256) This reads on the solid dosage form comprising a powder, tablet, or capsule. Wagner-Hattler further teaches a method of making the claimed invention involving providing a suspension of natural or precipitated calcium carbonate (i.e. aragonite), providing gaseous CO2 and contacting the calcium carbonate with CO2 as described in the following (0085):
providing a suspension of natural or precipitated calcium carbonate
adding at least one acid
treating the suspension with CO2
contacting said natural or precipitated calcium carbonate with the acid and CO2 to form a water-soluble calcium salt
This reads on the claimed method of an aragonite composition comprising a plurality of aragonite particles which are impregnated with CO2.
Wagner-Hattler further teaches that finalized dosage forms typically comprise compatible disintegrants in order to produce a dosage form (0002) and provides an embodiment of the invention which comprises a disintegrant such as cellulose gum. (0033) In addition to this, Wanger-Hattler teaches use of biodegradable polymer resins which are capable of being broken down with the help of bodily fluids, thereby delivering the composition contained within the solid form dosage. (0136-0138) Specifically, a hot-melt extruded polymer resin is used (0139), thereby reading on the claimed method of mixing a biodegradable polymer and disintegrating agent with the aragonite composition.
Regarding the viral recovery upon exposure to acidic conditions increasing the viral recovery, per the Specification submitted 03/22/2023, there is an increase in viral recovery when using the aragonite composition (Example 1 and Figs. 3A-D). In addition to this, per the Remarks dated 03/01/2026, the acidic conditions of an oral route of delivery had less negative impact on viral recovery when the aragonite composition was used. (Pg 3, last paragraph). As such, as reflected in the Remarks, uncoated aragonite helps neutralize the pH of the composition which is the reason as stated by the Applicant for increased viral recovery, making it an inherent property of using aragonite as part of the composition.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the dried therapeutic preparation as taught by Sammatur and the use of calcium carbonate as taught by Cunningham with the teachings of Wagner-Hattler of the method of synthesizing PCC (i.e. aragonite) by impregnation with CO2, use of a biocompatible polymer, and a disintegrating agent to create a solid-dose vaccine composition in the form of a powder, tablet, or capsule. One would have been motivated to do so and had a reasonable expectation of success based on the teachings of Wagner-Hattler, who details a method of synthesis of aragonite by way of treatment with CO2, that disintegrants are necessary to produce a dosage form, and that use of biodegradable polymer resins which can be broken down by bodily fluids are necessary in the delivery of the composition contained within the solid form dosage.
Response to Arguments
Applicant's arguments filed 03/01/2026 have been fully considered but they are not persuasive. Applicant first argues that there is no motivation to combine the teachings of Sammatur and Cunningham, and that one skilled in the art would have no motivation to select an adenovirus, “much less a dried preparation of adenoviral vectors”. This is unpersuasive. Sammatur exclusively teaches dried preparations comprising lipids and therapeutic agents, as stated in the abstract of the invention. (57) Furthermore, Sammatur references an example of the preparation method of an adenovirus vector as well as the method for constructing it (0447), as referenced in US 4920209. Having the construction method clearly laid out would indeed give a person skilled in the art motivation to use specifically a dried preparation of adenoviral vectors, as the construction method is already established in the art.
Regarding there being no motivation to combine the teachings of Cunningham, Examiner references the motivation laid out in the non-final rejection dated 09/04/2025 which states that Cunningham teaches that aragonite is orthorhombic in its structure (0153) and that use of calcium carbonite fillers provide antimicrobial effects to the composition. (0199)
Applicant further argues that there is an unexpected result when using aragonite in the composition as it aids in viral recovery in acidic conditions (which mimics oral route of administration). However, use of aragonite in a viral composition as taught by the combinations of references of Sammatur and Cunningham would also result in an increase of viral vector recovery as it is an inherent property of aragonite that it helps to maintain a neutral pH when used in an uncoated state. Therefore, any methodology teaching use of uncoated aragonite in a viral composition would also inherently aid in vector recovery as the pH would be held closer to neutral by virtue of using uncoated aragonite.
Based on the above discussion, the 35 U.S.C. 103 rejections of independent claims 1, 20, and 36 are maintained. As claims 2-8, 10, and 14-18 depend from claim 1 and inherit all the limitations of said claim, the 35 U.S.C. 103 rejections are maintained on the same basis.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. 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, Tracy Vivlemore, can be reached on (571) 272-2914. 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.
/HANNA MARIE THUESON/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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