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 Nov. 25, 2025. Claims 1-20 are pending and currently examined.
Claim Objections
Claims 1 and 14 are objected to because of the following informalities: claims 1 and 14 recite “acceptable pharmaceutically acceptable vehicle.” Here, the first “acceptable” appears to be redundant. Appropriate correction is required.
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.
(Previous Rejection – Partially Maintained and Extended Necessitated by Amendment) Claims 14-20 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.
Claim 14, which claims 15-20 depend from, as amended, is directed to the pharmaceutical composition of claim 1, further comprising inducing an immune response in a subject which comprises utilizing the pharmaceutically acceptable carrier and/or vehicle.
Claims 14-20 recite product and process in the same claim. A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05 (p).
To facilitate examination, the process step is not considered as there is no evidence that the recited process steps further limit the structure and/or properties of the claimed composition.
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.
(Previous Rejection – Maintained) Claims 1-2 and 10-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because it is directed to a judiciary exception.
A claim directed to a judicial exception must be analyzed to determine whether the elements of the claim, considered both individually and as an ordered combination, are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself. To be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way, such that it is more than a drafting effort designed to monopolize the exception.
These claims are directed to a pharmaceutical composition comprising a sequence encoding a SARS-CoV-2 spike antigen and a sequence encoding a SARS-CoV-2 nucleocapsid antigen comprised in an effective amount of one or more self-replicating RNA molecule, and a pharmaceutically acceptable carrier or vehicle. The self-replicating RNA molecule reads on the genome of SARS-CoV-2. The claims do not specify the terms “pharmaceutically acceptable carrier” and “pharmaceutically acceptable vehicle”. Therefore, they are considered to read on naturally occurring products, such as a body fluid of a subject of infection containing SARS-CoV-2.
Regarding claim 10, an adjuvant may read on a naturally occurring product, e.g., a cytokine existing in host body fluid. A simple combination of two or more naturally occurring products do not change the fact that they are all judicial exceptions.
Regarding claims 11-13, a SARS-CoV-2 virus is considered as a nanoparticle encapsulated by a lipid bilayer.
Claims 14-20 further specify an intention and/or a step for use of the claimed composition. There is no evidence that the additional limitations change the structure and/or properties of the claimed composition.
Therefore, claims 1-2 and 10-20 read on a naturally occurring product which is a judicial exception.
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)(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.
(Previous Rejection – Maintained) Claims 1-2 and 10-20 are rejected under 35 U.S.C. 102(a) as being anticipated by Gao et al. (Science 369, 77–81 (2020)).
Gao teaches a study on development of an inactivated vaccine candidate for SARS-CoV-2. Gao teaches that the authors developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2–specific neutralizing antibodies in mice, rats, and nonhuman primates. See Abstract.
Since the vaccine is developed by inactivating the SARS-CoV-2 virus, it is expected to comprise the whole genome of the virus, which is in turn expected to comprise self-replicating RNA molecules encoding the viral Spike protein and the nucleocapsid protein.
Regarding claim 10, Gao teaches that the vaccine contains alum adjuvant. See page 1, right column, para 3.
Regarding claims 11-13, the SARS-CoV-2 virus is considered as a nanoparticle containing a genome nucleic acid.
Claims 14-20 further specify an intention or a step for use of the claimed composition. There is no evidence that the additional limitations change the structure and/or properties of the claimed composition.
Accordingly, Gao anticipates claims 1-2 and 10-20.
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.
(Previous Rejection – Maintained) Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Erasmus et al. (bioRxiv [Preprint]. 2020 May 28:2020.05.28.121640) in view of Ahmed et al. (Viruses 2020, 12, 254; published: 25 February 2020) and/or Dutta et al. (J Virol 94:e00647-20; published on Jun. 16, 2020).
The base claim 1, as amended, is directed to a pharmaceutical composition comprising: (1) a sequence encoding a SARS-CoV-2 Spike protein antigen and a sequence encoding a SARS-CoV-2 Nucleocapsid antigen, wherein the sequence encoding the SARS-CoV-2 Spike protein antigen and the sequence encoding the SARS-CoV-2 Nucleocapsid protein antigen are comprised in an effective amount of one or more self-replicating RNA molecules; and (2) a pharmaceutically acceptable carrier and/or vehicle.
Claims 3-9 further specify that the self-replicating RNA molecules are derived from an alphavirus and comprise a sequence encoding for nonstructural alphavirus proteins.
Claims 10-20 are directed to the pharmaceutical composition of claim 1, further specify process steps of using the pharmaceutical composition. As indicated in the 112(b) rejection above, the process steps are not considered since there is no evidence that the steps further limit the structure and/or property of the claimed composition.
Erasmus teaches a single-dose replicating RNA vaccine against SARS-CoV-2. The authors developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. Intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. A single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection. See Abstract.
Figure 1 of Erasmus shows the structure and characterization of the repRNA-CoV2S construct. See below.
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Accordingly, Erasmus teaches a vaccine composition comprising a self-replicating RNA construct, repRNA-CoV2S, comprising a sequence encoding a SARS-CoV-2 Spike antigen and a sequence from an alphavirus, VEEV strain TC-83 (see page 5, para 1), encoding the alphavirus nonstructural proteins nsP1, nsP2, nsP3, nsP4, that confer the construct the ability to self-replicate. Erasmus further teaches that the repRNA-CoV2S construct is incorporated in Lipid InOrganic Nanoparticle (LION), which also functions as an adjuvant (see page 5, para 2). However, Erasmus is silent on a SARS-CoV-2 vaccine construct comprising a sequence encoding SARS-CoV-2 nucleocapsid (N) protein antigen built on the same alphavirus platform.
Ahmed teaches that the authors sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, they identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. Their findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2. See Abstract.
Dutta discusses about the potential of the nucleocapsid protein of SARS-CoV-2 as a target for vaccine development. It teaches that, in construct to the S protein which has a high mutation rate, the N gene is more conserved and stable, with 90% amino acid homology and fewer mutations over time. N proteins of many coronaviruses are highly immunogenic and are expressed abundantly during infection. High levels of IgG antibodies against N have been detected in sera from SARS patients, and the N protein is a representative antigen for the T-cell response in a vaccine setting, inducing SARS-specific T-cell proliferation and cytotoxic activity. The middle or C-terminal region of the SARS-CoV N protein have been shown to be important for eliciting antibodies against SARS-CoV during the immune response. Several reports offer important and timely insights relevant to the SARS-CoV-2 N protein, a vaccine target that has some distinct advantages over other potential SARS-CoV-2 antigens. Because of the conservation of the N protein sequence, the expanding knowledge of its genetics and biochemistry, and its strong immunogenicity, the N protein of SARS-CoV-2 should be strongly considered as a vaccine candidate for SARS-CoV-2. See pages 1 and 2.
Accordingly, teachings of both Ahmed and Dutta suggest that the nucleocapsid protein of SARS-CoV-2 is a potential vaccine target.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Erasmus, Ahmed and Dutta to arrive at the invention as claimed. One would have been motivated to do so to evaluate the vaccine potential of a self-replicating alphavirus-based nucleic acid construct, similar to that of Erasmus, that comprises a sequence encoding a SARS-CoV-2 nucleocapsid antigen.
Regarding claims 6-7, Erasmus teaches using the full-length S protein in the repRNA-CoV2S vaccine construct while Ahmed discloses potential immunogenic epitopes in the S and N proteins of SARS-CoV-2 that can be targeted (see Tables 3-4). One of skill in the art would have found it obvious to select regions of the S protein to be included for expression in a nucleic acid vaccine construct for best protection effect through routine experimental optimization, including a truncated form of the S protein as claimed, unless there is evidence that the claimed truncated form is critical.
Interview Summary
An Applicant-initiated interview was held on Dec. 8, 2025 with Applicant’s representatives, IONA KAISER and MERON GHIDEY, who presented additional arguments. See attached interview agenda. These arguments are addressed below together with the arguments filed on Nov. 25, 2025.
Response to Applicant’s Arguments
Applicant’s arguments in the response filed on Nov. 25, 2025 and presented in the interview held on Dec. 8, 2025 are fully considered and are addressed as follows.
To the 112(b) rejection, Applicant argues that claims 17-19 have been amended to remove “for use according to” and amended to recite “the pharmaceutical composition of claim 14”. Applicant argues that, as claim 14 is a methods claim dependent on the pharmaceutical composition of claim 1, claims 17-19 are reciting a further limitation of the apparatus of claim 1 and are thus defined.
Applicant’s arguments are not persuasive. Applicant has not addressed the finding in Office action that the claims recite product and process in the same claim, and that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See MPEP 2173.05 (p). It is noted that claim 14 as well as claims 15-20 depending from claim 14 are not method claims, as currently worded. Applicant may consider using a proper method claim language, e.g., “A method of inducing an immune response in a subject, comprising administering to the subject the pharmaceutical composition of claim 1……” to turn them into method claims.
To the 101 rejection, Applicant argues that claim 1 has been amended to recite that the pharmaceutical composition comprises an effective amount of “one or more self-replicating RNA molecules”, that the effective amount is described as amount sufficient to elicit expression of a detectable amount of SARS-CoV-2 antigen to induce a SARS-CoV-2 antigen specific suitable to result in a therapeutic effect, and that the pharmaceutically acceptable carrier/vehicle may include a liposome and are well known terms of art sufficiently described in the disclosure. Applicant argues that claims 11-13 require that the self-replicating molecules may be encapsulated in a lipid nanoparticle for stabilization, and that claims 14 and 15 have been amended to recite a method step.
Applicant’s arguments are not persuasive. The arguments have not explained why the amended pharmaceutical composition is different from a naturally occurring product (e.g., a sample from a SARS-CoV-2 patient that contains the virus). The genome of SARS-CoV-2 is a self-replicating RNA and contains the sequence encoding the Spike and Nucleocapsid proteins, and can induce immune response when introduced into a host; the immune response induced can, in turn, protect the host from further infection of a similar virus. Additionally, a naturally occurring SARS-CoV-2 virus particle is a nanoparticle encapsulated by a lipid bilayer.
To the 102 rejection over Gao et al., Applicant argues that the genomic sequences in Gao correspond to the viral genome of an inactivated SARS-CoV-2 virus strains, and do not correspond to a multivalent vaccine comprising self-replicating RNA molecules encoding for both the SARS-CoV-2 S and N antigens.
Applicant’s argument is not persuasive. The genome of the SARS-CoV-2 virus is a self-replicating RNA molecule comprising and expressing sequences encoding the S and N antigens. Gao teaches live and inactivated SARS-CoV-2 virus preparations (see Figure 1), both contain the full-length genome RNA molecules that can self-replicate, and both read on the claimed “pharmaceutical composition”.
To the 103 rejection over Erasmus, Ahmed and Dutta, Applicant argues that there is no motivation to combine the virus-derived replicon RNA (repRNA), delivered in Venezuelan equine encephalitis virus-like RNA particles (VRP) of Erasmus with the epitopes of Ahmed and/or Dutta. Applicant refers to a prior art publication, Deming et. al.; PLoS Medicine; December 2006 Vol. 3: issue 12; e525, arguing that those of ordinary skill in the art may be aware of the difficulties of eliciting an immunizing (i.e., protective) response with a self-replicating VRP expressing the SARS-CoV strain nucleocapsid protein, and in fact may incur sever pathological changes. Applicant argues that, in accordance with MPEP 2141 and 2143.02(II), it may not have been obvious to those of ordinary skill in the art to combine the self-replicating RNA antigen-encoding sequences of the SARS-CoV- 2 spike protein and nucleocapsid simultaneously as a multivalent vaccine to successfully overcome the innate and adaptive immune response or interference (see as-filed paragraphs [0007] and [0012]).
In the Applicant-initiated interview held on Dec. 8, 2025, Applicant presented that Deming teaches explicitly against the combination of spike and nucleocapsid antigens because of a lack of measurable benefit in terms of immunological titers, and, an increased pathology risk. Deming at page 2371, right column: “… As noted for the homologous challenge studies, the combination of VRP-S+N did not enhance protection from heterologous challenge, but may actually have weakened it, with senescent animals showing even lower anti-S antibody responses and an even higher rate of viral replication, albeit with reduced titers, and increased lung pathology”.
Applicant’s arguments are not persuasive. First, Deming explicitly teaches the construction of potential SARS-CoV vaccines based on an alphavirus self-replicating vector, Venezuelan equine encephalitis virus replicon particle (VRP), expressing the SARS-CoV S, N, or S+N proteins, indicating that inclusion of the N protein in a self-replicating alphavirus replicon-based vaccine format was contemplated and investigated before the time of invention for a different coronavirus. One of skill in the art would have reasonably been motivated to pursue the same study with a different coronavirus, e.g., SARS-CoV-2, to find out if the observation reported in Deming could be repeated for SARS-CoV-2. Secondly, even though Deming teaches experimental observations on the drawbacks of combining the N protein with the S protein in the study of self-replicating VEEV vector-based coronavirus vaccines, it does not teach that inclusion of the N protein antigen should be prohibited. Rather, Deming teaches that their research provides a model for future experiments designed to characterize the components and inducers of the VRP-N-enhanced pulmonary inflammation, and suggests that vaccine regimens that contains N protein should be used with caution in human populations until further testing. See page 2373, left column, para 1.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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