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
Acknowledgement is hereby made of receipt and entry of the communication filed on Aug. 4, 2026. Claims 1-30 are pending. Claims 3, 11, 12, 20, 24, and 25 are withdrawn. Claims 1-2, 4-10, 13-9, 21-23 and 26-30 are currently examined.
Election/Restrictions
Applicant's election with traverse of the species of SEPIVAC SWE as adjuvant, in the reply filed on Aug. 4, 2026, is acknowledged.
Applicant argues that Kurup et al. relied upon in the restriction/election requirement neither discloses nor suggests the presently claimed vaccine formulations or the technical advantages achieved thereby. Applicant’s argument is not persuasive. The restriction relates to two distinct species: 1) an adjuvanted vaccine formulation comprising an vaccine antigen that is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 spike protein, and adjuvant SEPIVAC SWE, and 2) an adjuvanted vaccine formulation comprising an vaccine antigen that is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 spike protein, and adjuvant MemVax. The technical feature shared between the two species is the vaccine antigen, i.e., inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 spike protein. This shared technical feature is not a special technical feature because it is taught in Kurup et al.
For the reasons above, the Restriction is deemed to be proper, and is made Final. Accordingly, claims 3, 11, 12, 20, 24 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species.
Specification
The specification uses tradenames, such as “SEPIVAC SWE” and “MemVax”. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered. Applicant' s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 29-30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because claims 29-30 are directed to “use” of adjuvants or vaccine formulation.
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.
Claims 1-2, 4-10, 13-9, 21-23 and 26-30 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. This rejection has the following grounds.
A. These claims recite the trademark/trade names “SEPIVAC SWE” and “MemVax”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. See MPEP 2173.05(u).
B. Claim 1 recites “wherein the antigen is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 spike protein”. This limitation renders the claim indefinite since it is not clear how to clearly and exclusively interpret “expressing S1 domain of the SARS-CoV-2 spike protein”. It is known in the art that the spike protein of SARS-CoV-2 contains S1 subunit and S2 subunit which respectively have the receptor binding and membrane fusion function. The receptor binding S1 subunit contains the NTD domain and RBD domain. See Fig. 1 in Yang et al. (Sig Transduct Target Ther 6, 95 (2021)). It is not clear how to determine if a vector expresses “S1 domain” of the SARS-CoV-2 spike protein. E.g., it is not clear if the term “S1 domain” requires the entire S1 subunit, or a fragment of the S1 subunit would suffice; additionally, it is not clear if a vector that expresses a larger polypeptide that contains the S1 subunit, such as the entire spike protein, also reads on the claimed limitation.
C. Claims 4-6, 26-28 recite “the one or more stabilizers” or “the one or more preservatives”, which renders the claim indefinite because claim 1 which they depend from do not require “one or more stabilizers” or “one or more preservatives”, instead, these limitations are specified as optional.
D. Claim 7 recites “The vaccine formulation as claimed in claim 1, wherein the antigen and SEPIVAC SWE and/or MemVax are present in 1:1 ratio (v/v).” This claim specifies that a 1:1 volume ratio (v/v) for antigen to adjuvant. However, the claim does not provide a clear definition for the “antigen” except that it is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 Spike Protein, which does not provide information about volume and if the “antigen” may comprise additional ingredients.
To facilitate prosecution, the term “antigen” as used in claim 7 is considered as reading on the vaccine composition comprising the antigen in solution with a volume, without the specified adjuvant, and the claimed 1:1 ratio (v/v) is considered as reading on the mixing ratio between an antigen-containing vaccine composition and an adjuvant-containing composition.
Claim Rejections - 35 USC § 102
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)(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 1-2, 6-8, 13-19, 21 and 29-30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Schnell et al. (US 11,478,543 B1, patented on Oct. 25, 2022; filed on Mar. 5, 2021).
Independent claim 1 is directed to an adjuvanted vaccine formulation against COVID-19 infection, comprising: a. vaccine antigen that is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 Spike Protein; and b. one or more adjuvants selected from SEPIVAC SWE and MemVax.
Independent claim 18 is directed to a method of preparing an adjuvanted vaccine formulation against COVID-19 infection, comprising: a. providing an antigen that is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 Spike Protein; and b. providing one or more adjuvants selected from SEPIVAC SWE and MemVax; and c. mixing the antigen and adjuvant in 1:1 ratio (v/v).
Independent claims 29 and 30 are directed to use of the adjuvants or vaccine formulation in development of COVID-19 vaccines.
Schnell teaches an invention relating to a vaccine comprising a SARS-CoV-2 spike protein (S) or portion thereof and methods of use thereof. See Abstract. Fig. 2 of Schnell presents a rabies virus vector (RABV) expressing codon-optimized Covid-S1. The map shows the viral sequence, including the plasmids utilized to create the recombinant virus. The sequence is shown in SEQ ID NO: 2 and features are shown in FIG. 8. The sequence and features are also shown in FIG. 18 ("BNSP333-COVID19-S1-RVG"). See column 2, lines 56-61. Schnell teaches that, in some embodiments, the recombinant fusion protein comprises the sequence of the S1 domain of the SARS-CoV-2 spike protein (S) fused to a rabies glycoprotein (G) or portion thereof, shown as element "WuS1-RABVG" in "BNSP333-COVID19-Sl-RVG" in FIG. 18. See column 370, lines 53-57.
Schnell teaches that described therein is a vaccine against the SARS-CoV-2 virus that uses a rabies virus-based vector that has proven to be an efficient vector against emerging and re-emerging infectious diseases, and that it was previously demonstrated that inactivated rabies virus particles containing MERS-CoV spike S1 protein induce potent immune responses against MERS-CoV and RABV and provide protection in animal systems. See column 11, lines 1-8.
Schnell teaches that the method includes the step of administering to the subject a vaccine comprising a rabies virus-based SARS-CoV-2 vaccine. In another aspect, a vaccine for cats, dogs, or ferrets is provided, the vaccine comprising a rabies virus-based SARS-CoV-2 vaccine. In some embodiments, the vaccine comprises a recombinant rabies virus comprising a SARS-CoV-2 spike protein (S) or a portion thereof. In some embodiments, the vaccine comprises a recombinant rabies virus comprising a fusion of (a) a glycoprotein (G) of a virus or a portion thereof, and (b) a SARS-Co V-2 spike protein (S) or a portion thereof. In some embodiments, the vaccine comprises an inactivated virus. In particular embodiments, the vaccine comprises an adjuvant. See column 382, lines 40-54.
Schnell teaches that the term "pharmaceutical composition" refers to a mixture of at least one compound useful within the invention with other chemical components, such as carriers, stabilizers, diluents, adjuvants, dispersing agents, suspending agents, thickening agents, and/or excipients. The pharmaceutical composition facilitates administration of the compound to an organism. Multiple techniques of administering a compound exist in the art including, but not limited to: intravenous, oral, aerosol, parenteral, ophthalmic, pulmonary and topical administration. See column 9, lines 18-27. Schnell teaches that in one embodiment, the pharmaceutical compositions useful for practicing the method of the invention may comprise an adjuvant, and that the adjuvant may comprise Sepivac SWE™ adjuvant. See column 375, lines 27-34.
Schnell teaches that to evaluate the reactogenicity and safety of BBV151 (inactivated rabies vector platform Corona Virus) vaccine administered via the intramuscular route, a dose escalation study of an intramuscular inactivated rabies vector platform Corona Virus Vaccine (rDNA-BBV151) in healthy volunteers will be performed, that CORAVAX (rDNA-BBV151) is an adjuvanted rabies vectored Corona virus vaccine, that express the S1 domain of the SARS-CoV-2 spike (S) protein fused to part of the N terminal domain of the RABV glycoprotein (G) and is incorporated in RABV particles. CORAVAX (rDNABBV151) vaccine has two presentations. See Example 6 and Table 1.
Table 1 (in column 392) of Schnell shows the composition of the CORAVAX (rDNA-BBV151) vaccine. See below:
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Table 1 indicates that the SEPIVAC SWE adjuvant is an oil-in-water emulsion.
Accordingly, Schnell teaches an adjuvanted vaccine formulation comprising an antigen that is an inactivated rabies virus vector expressing S1 domain of SARS-CoV-2 Spike Protein and adjuvant SEPIVAC SWE that is an oil-in-water emulsion, a method of preparing the vaccine formulation by mixing the ingredients, as well as use of the vaccine formulation in development of SARS-CoV-2 vaccines.
Regarding claims 6 and 8, Table 1 (above) shows that 2-phenoxyethanol (2-PE) is present as an inactive ingredient at 2.5 mg in 0.25 ml of the vaccine-only composition I and the 0.5 ml complete vaccine composition (I + II), corresponding to 1% and 0.5% (w/v), respectively.
Regarding claim 7, Table 1 (above) shows that the complete vaccine composition is a mixture of composition I (vaccine composition) and composition II (SEPIVAC SWE oil-in-water emulsion at 0.25 ml: 0.25 ml giving a 1:1 ratio (v/v).
Regarding claims 8 and 21, Table 1 (above) shows that the antigen (Cornavirus Vaccine (rDNA) BBVI51) is present in 15 or 30 mcg.
Regarding claims 13-17, since the vaccine composition of Schnell disclosed in Table 1 above is indistinguishable from that as claimed, one of skill in the art would readily envisage that it would have the same functional effects as claimed.
Therefore, Schnell anticipates claims 1-2, 6-8, 13-19, 21 and 28-30.
Claims 9, 10, 22 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Schnell et al. (US 11,478,543 B1, patented on Oct. 25, 2022; filed on Mar. 5, 2021), as evidenced by Xu et al. (Vaccine 41 (2023) 2793–2803), de Jonge et al. (npj Vaccines (2020) 5:38 ; https://doi.org/10.1038/s41541-020-0187-4), and/or Ventura et al. (Vaccine, Volume 31, Issue 12, 15 March 2013, Pages 1641-1645).
Claims 9-10 and 22-23 specify concentration of squalene in the adjuvant SEPIVAC SWE.
Relevance of Schnell is set forth supra. However, even though Schnell teaches use of squalene in the formulation of adjuvants (see e.g. columns 375-376), it is silent on the content of squalene in the adjuvant SEPIVAC SWE.
The instant specification teaches that SEPIVAC SWE is an oil in water emulsion, which is free of Intellectual Property Rights. This adjuvant has been developed by the Vaccine Formulation Laboratory for technology transfer in order to empower developing countries vaccine manufacturers. Over the years, SWE has demonstrated safe and effective, both in terms of enabling adjuvanticity and dose-sparing, when included in numerous preclinical vaccine candidates, including against Inactivated Polio Virus, Influenza, Respiratory Syncytial Virus, Rabies, and Group A streptococcus. See PGPub [0008]. This teaching indicates that SEPIVAC SWE is an existing specific product, provided by a manufacture, the Vaccine Formulation Laboratory.
Xu teaches that the adjuvant Sepivac SWETM is a squalene-based oil-in-water adjuvant, comprising squalene (3.9 %, w/v), sorbitan trioleate (0.47 %, w/v), and polyoxyethylene (80) sorbitan monooleate (0.47 %, w/v) dispersed in 10 mM citrate buffer at pH 6.5 [18], and that Sepivac SWETM was developed by the Vaccine Formulation Institute (Switzerland) and Seppic (France) and is available at GMP grade under an open access model [17]. See page 2799, right column, para 5.
de Jonge, cited in Xu (ref. 18) for the composition of Sepivac SWETM , teaches that SWE is a squalene-in-water emulsion adjuvant comprising a metabolizable oil (squalene 3.9%, w/v), sorbitan trioleate (0.47%, w/v), and polyoxyethylene (80) sorbitan monooleate (0.47%, w/v) dispersed in 10mM citrate buffer at pH 6.5, and that manufacturing of SWE was performed by adding an aqueous phase containing polyoxyethylene sorbitan monooleate in citrate buffer at pH 6.5 to the oil phase, containing squalene and sorbitan trioleate. See page 11, left column, para 2.
Ventura, cited in Xu (ref. 17), teaches that the Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia’s state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. See Abstract. Ventura teaches that the adjuvant involved in the transfer and study comprises a metabolizable oil (squalene 3.9%, w/v), sorbitan trioleate (0.47%, w/v), and polyoxyethylene (80) sorbitan monooleate (0.47%, w/v) dispersed in 10 mM citrate buffer at pH 6.5. See page 1642, left column, para 4.
Accordingly, teachings of Xu, de Jonge and Ventura, together with the teachings of instant specification, indicate that the commercially available adjuvant, Sepivac SWETM , has a formulation of a metabolizable oil (squalene 3.9%, w/v), sorbitan trioleate (0.47%, w/v), and polyoxyethylene (80) sorbitan monooleate (0.47%, w/v) dispersed in 10 mM citrate buffer at pH 6.5.
Therefore, evidenced by the teachings Xu, de Jonge and Ventura, the Sepivac SWETM of Schnell is expected to comprise the same concentration of squalene as specified in claims 9-10 and 22-23.
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 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.
Claims 4, 5, 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Schnell et al. (US 11,478,543 B1, patented on Oct. 25, 2022; filed on Mar. 5, 2021) in view of Cardoso et al. *Acta virologica 61: 231 – 239, 2017) and Olayan et al. (Biomed Res Int. 2019 Mar 17;2019:4518163).
Claims 4-5 and 26-27 specify stabilizers, selected from Trehalose, Sucrose, Maltose and Human Serum Albumin (HSA) or combination thereof.
Relevance of Schnell is set forth supra. However, even though it teaches that pharmaceutical compositions of the invention may comprise stabilizers, Schnell is silent on stabilizers being Trehalose, Sucrose, Maltose, Human Serum Albumin (HSA) or combination thereof.
Cardoso reviews studies on viral vaccine stabilizers. Table S3 of Cardoso discloses stabilizers used in various licensed vaccines, including human serum albumin (HSA), sucrose, maltose, and trehalose, as claimed.
Olayan teaches a study on evaluation of different stabilizers and inactivating compounds for the enhancement of Vero Cell Rabies vaccine stability and immunogenicity. It teaches that inactivation of rabies virus is essential for rabies vaccine preparation where the inactivating compound that is currently recommended for rabies vaccine preparation is 𝛽-propiolactone (𝛽-PL). It teaches that the use of HemaGel (plasma substitute) for testing vaccine stabilization was compared with the currently used vaccine stabilizers (human albumin and lactose). HemaGel yielded better stability than the other tested stabilizers. Monitoring of cellular and humoral immune responses indicated that both the total IgG level against rabies vaccine and the IFN and IL5 levels obtained with the HemaGel-stabilized vaccines were higher than those obtained with human albumin- and lactose-stabilized vaccine candidates. See Abstract. Olayan teaches that Lactose (5%), HemaGel (5%), and human albumin (2%) were used as vaccine stabilizers. Human serum albumin and lactose were sterilized through membrane 0.45 𝜇m filters (Millipore-USA), whereas HemaGel was prepared by steam degradation sterilization of 0.4% gelatin. See page 3, left column, para 2.
Accordingly, Cardoso and Olayan together teach trehalose, sucrose, maltose and Human Serum Albumin (HSA), as claimed, can be used as stabilizers in viral vaccine formulation.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Schnell, Cardoso and Olayan to arrive at the invention as claimed. One would have been motivated to do so to evaluate the effect of different stabilizers, including those as claimed, taught in Cardoso and Olayan in the vaccine formulation study of Schnell. As to the claimed concentration, Olayan teaches that human albumin at 2% can be used, which is reminiscent of the claimed region of 0.5%-5%.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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