DETAILED ACTION
Disposition of Claims
Claims 1-16 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US2024/0009297A1, Published 01/11/2024.
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/09/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See ¶[0068] “https://www.cdc.gov/vaccinesafety/concerns/adjuvants.html Oct. 24, 2018” ; ¶[0091] items [3] and [4].
Claim Objections
Applicant is advised that should claim 9 be found allowable, claim 16 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). It is suggested that claim 16 be amended to depend upon claim 10.
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 and 10 and dependent claims 2-9 and 11-16 thereof are 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.
The terms “stable”, “robust”, and “durable” in claims 1 and 10 are relative terms which renders the claim indefinite. The terms “stable”, “robust”, and “durable” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For instance, it is unclear if the “stable” composition refers to a specific length of time in which the antigen is present within the composition at a temperature (e.g. ambient temperature, below 0 deg C, etc.) or is able to elicit a specific type of response after storage at a certain time and/or temperature. With respect to “robust” and “durable” as they relate to an immune response, it is unclear if specific types of immune responses (e.g. “Th1-skewed”, “Th2-skewed”, humoral, cellular, etc.) are indicative of said response, the length of time in relation to the response being “durable” (e.g. the inoculated host generates a protective response against viral challenge 1 year, 5 years, 10+ years after initial inoculation, etc.) and how one of skill in the art would measure if said composition was “robust” and/or “durable”. As the metes and bounds of these terms in relation to the claimed methods have not been defined, and there is no art-accepted metric for determining these limitations, the claims are rejected on the grounds of being indefinite.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 1 and 10 are rejected on the grounds of being indefinite. Claims 2-9 and 11-16 are also rejected since they depend from claim 1 or 10, but do not remedy these deficiencies of claim 1 or 10.
Claims 8-9 and 15-16 are 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.
The term “thermostabilized” in claims 8-9 and 15-16 is a relative term which renders the claim indefinite. The term “thermostabilized” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if the “thermostabilized” components mean said components have specific elements in their compositions (e.g. reagents, sugars, amino acids, etc.) or are lacking specific elements, or if the components are in a specific state (e.g. freeze dried, lyophilized, etc.) or what temperature said elements must be stable at and for what length of time (e.g. stable at 40 deg C for longer than 2 weeks, etc.) One suggestion is to claim these elements in a specific state or to claim said elements as having specific components (e.g. “…wherein the protein subunit and the adjuvant have each been lyophilized separately prior to combining.” or “…wherein the protein and the adjuvant are lyophilized together in the same process.”)
For at least these reasons, claims 8-9 are rejected on the grounds of being indefinite.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a method of inducing protective immunity against a coronavirus (CoV) within an individual, comprising providing a stable immunogenic composition capable of eliciting a robust and durable immune response to the coronavirus, wherein the composition comprises a protein subunit comprising a recombinant protein specific to the coronavirus and at least one adjuvant; and administering an effective amount of the composition to the individual.
Further limitations on the method of claim 1 are wherein the recombinant protein specific to the coronavirus is expressed using insect cells (claim 2); wherein the protein subunit is a spike (S) protein from the coronavirus (claim 3), wherein the spike protein is further purified using immunoaffinity purification (claim 4); wherein the protein subunit is present in the composition from about 1 ug to about 25 ug (claim 5); wherein the at least one adjuvant is a sucrose fatty acid sulphate ester (claim 6); wherein the at least one adjuvant is present in the composition from about 0.3 mg to about 10 mg (claim 7); wherein the protein subunit and the at least one adjuvant are each thermostabilized separately before being combined in the composition (claim 8); wherein the protein subunit and the at least one adjuvant are thermostabilized together before being combined in the composition (claim 9).
Claim 10 is drawn to a method of adjuvanting subunit vaccines, comprising:
providing an effective amount of an adjuvant,
providing a protein subunit, and
combining the adjuvant and the protein subunit to create a stable immunogenic composition capable of eliciting a robust and durable immune response to a coronavirus, wherein the adjuvant is a sucrose fatty acid sulphate ester at a concentration selected from the group consisting of between 0.3 and 1 mg, 1 mg and 5 mg, and 5 mg and 10 mg.
Further limitations on the method of claim 10 are wherein the protein subunit is specific to the coronavirus and is expressed using insect cells (claim 11); wherein the protein subunit is a spike (S) protein from the coronavirus (claim 12), wherein the spike (S) protein is further purified using immunoaffinity purification (claim 13); wherein the protein subunit is present in the composition from about 1 ug to about 25 ug (claim 14); wherein the protein subunit and the adjuvant are each thermostabilized separately before being combined in the composition (claim 15); and wherein the protein subunit and the at least one adjuvant are thermostabilized together before being combined in the composition (claim 16).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burt et. al. (US20060286124A1; Pub. 12/21/2006; hereafter “Burt”.)
The Prior Art
Burt teaches methods for compositions for treating and inhibiting coronavirus (CoV) infection, and the development of vaccines against CoVs such as severe acute respiratory syndrome CoV (entire document; see abstract.) Burt teaches that vaccine compositions can be generated using spike (S) or nucleocapsid (N) polypeptides, domains, or fragments thereof (abstract; ¶[0042]). Said compositions may also comprise effective amounts of adjuvants (¶[0088]; instant claims 1, 3). Burt teaches the CoV polypeptides may be generated using insect cells (¶[0159]; instant claim 2) and could be immunoaffinity purified (¶[0160]; instant claim 4.) Burt teaches the S protein and adjuvant can be present in the composition at about 10 ug/mL (¶[0031][0161][0167][0170][0173]; instant claim 5) and bulk adjuvant could be generated at 5mg/mL (¶[0155].) Burt teaches the components may be lyophilized, mixed, or co-precipitated to effectuate a stable formulation (¶[0100][0122]).
For at least these reasons, Burt teaches the limitations of instant claims 1-5, and anticipates the invention encompassed by said claims.
Claims 1, 3, and 5-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gupta et. al. (Gupta T, et. al. Int Immunopharmacol. 2020 Sep;86:106717. Epub 2020 Jun 18.; hereafter “Gupta”) as evidenced by Haun et. al. (Haun BK, et. al. bioRxiv [Preprint]. 2020 Jul 26:2020.07.24.220715. Update in: Front Immunol. 2020 Oct 30;11:599587.; hereafter “Haun”) and ContractPharma (ContractPharma. “Soligenix Licenses BTG’s CoVaccine HT for SARS-CoV-2”. 2020/04/16. https://www.contractpharma.com/content-microsite/covid-19/2020-04-16/soligenix-licenses-btgs-covaccine-ht-for-sars-cov-2.; hereafter “ContractPharma”.)
The Prior Art
Gupta teaches extensive efforts were underway to develop vaccines against the novel coronavirus causing the coronavirus 2019 disease (COVID-19), severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2)(entire document; see abstract.) Gupta teaches that the adjuvant COVACCINE HT™, which is a sucrose fatty acid sulfate ester immobilized on the oil droplets of a submicron emulsion of squalene-in-water, is currently within phase I clinical trials as an adjuvant within other vaccine formulations (Table 1). As evidenced by ContractPharma and Haun, the composition taught by Gupta as the COVID-19 vaccine candidate of Soligenix is a spike (S) protein subunit vaccine (S1 domain) of SARS CoV-2 adjuvanted with COVACCINE HT™ (p. 9, left col., ¶1; Table 7; See abstract of Haun and entirety of ContractPharma; instant claims 1, 3, 6). Sino Biological 40592-V05H). As evidenced by Haun, the S1 is present within the composition at a concentration of 5ug (Figure 1; claim 5).
Gupta, as evidenced by Haun and ContractPharma, teaches the limitations of instant claims 1, 3, and 5-6, and anticipates the invention encompassed by said claims.
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.
Claims 6-16 are rejected under 35 U.S.C. 103 as being unpatentable over Burt as applied to claims 1-5 above, and further in view of Hanon (US20230256090A1, Priority 06/29/2020; hereafter “Hanon”); Blom et. al. (Blom AG, et. al. Vaccine. 2004 Dec 21;23(6):743-54.; hereafter “Blom”); and Clements et. al. (WO2019051098A1; 03/14/2019; CITED ART OF RECORD; hereafter “Clements”.)
The Prior Art
The teachings of Burt have been set forth supra. While Burt teaches SARS CoV vaccines which comprise S protein antigens and adjuvants, Burt is silent as to said adjuvants being sucrose fatty acid sulphate esters (SFASE). However, the use of SFASE as adjuvants was known in the art, as evidenced by the teachings of Hanon, Blom, and Clements.
Hanon teaches immunization using carrier-formulated mRNAs in conjunction with squalene emulsion adjuvants (entire document; see abstract), wherein the mRNAs encode coronavirus (CoV) antigens, namely prefusion-stabilized forms of the spike (S) protein from SARS CoV-2 (¶[0004][0157]]). The adjuvant includes CoVaccine (¶[0090]), which is noted by the specification and Hanon to include a sucrose fatty acid sulfate ester (SFASE) immobilized on the oil droplets of a submicrometer emulsion of squalene-in-water (oil-in-water emulsion, instant ¶[0088]). Hanon teaches the dose of mRNA may be anywhere from 0.001 to 1000 ug (¶[0202]), and the emulsion adjuvants may be present anywhere from 0.8 to 100 mg/mL (¶[0261-0262]). The vaccine and adjuvant formulations may be liquid or dry in the same or separate containers (e.g. lyophilized)(¶[0241][0250-0253]).
Blom teaches their formulation for adjuvanting human vaccines, namely COVACCINE™ HT, consists of a sucrose fatty acid sulfate ester immobilized on the oil droplets of a submicron emulsion of squalene-in-water, and that both humoral and cell-mediated responses were enhanced in a dose-dependent fashion against a wide range of antigens, such as inactivated viruses, bacterial subunits, recombinant proteins, virus-like particles and peptide–protein conjugates (entire document; see abstract.)
Clements teaches viral vaccine formulations comprising insect cell expressed surface viral glycoprotein (GP) and a highly effective adjuvant (entire document; see abstract.) Clements teaches the adjuvant is a SFASE (reference claim 1) and teaches a dose of 1 mg of said COVACCINE HT™ adjuvant (¶[0073]). Clements teaches the viral surface glycoprotein antigens may be immunoaffinity purified (¶[0089]) and that the antigens may be lyophilized with or without adjuvant (¶[0023][0146-0147]).
Given the teachings of Burt, one of skill in the art would be apprised as to the need to generate viral surface glycoprotein subunit antigen vaccines to treat CoV infections, wherein the viral CoV S protein antigen would be useful in compositions comprised with an adjuvant. Given the teachings of Hanon, Blom, and Clements, one of skill in the art would be motivated to try a SFASE adjuvant such as COVACCINE HT™. Given the teachings of Hanon, one of skill in the art would be motivated to try the COVACCINE HT™ antigen in SARS CoV-based vaccine formulations, and given the motivation from Blom and Clements, one of skill in the art would find it obvious to try and use said adjuvant for adjuvanting viral glycoprotein subunit vaccine formulations. Given the guidance from Clements, one of skill in the art would be apprised as to the potential concentrations of the adjuvant, and the combined teachings of Burt, Hanon, and Clements would motivate a skilled artisan with a reasonable degree of success to try and lyophilize formulations, either separately or together, to determine if the vaccines could be made to be stable at a broader range of temperatures over longer periods of time. Therefore, given the combined teachings of Burt, Hanon, Blom, and Clements, one of skill in the art would find the limitations of instant claims 6-16 obvious.
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Burt in order to utilize a specific adjuvant, thereby generating a CoV subunit vaccine with an effective immune response against said CoV. One would have been motivated to do so, given the suggestion by Hanon that COVACCINE HT™ could be used against CoV antigens, and that COVACCINE HT™ would be useful in subunit vaccines, as taught by Blom. There would have been a reasonable expectation of success, given the knowledge that Clements generated more effective antiviral vaccines when combining COVACCINE HT™ adjuvant with viral surface proteins in vaccine formulations over traditional subunit vaccine antigens. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671