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 .
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 11/7/2025 is acknowledged.
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/7/2025.
Claims 1-21 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/11/22, 1/26/24, 6/20/24, 8/13/24, 7/25/25, 12/24/25 and 2/13/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: claim 7 recites, “a-CoV”. However, the specification does not mention this term.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites in line 1, “CoV” without also providing what this acronym stands for. While the acronym DNA can be recited without spelling out its mean, DNA is also a well recognized acronym, whereas CoV is not. It is therefore suggested that claim 1 be amended to recite, “A vaccine for preventing coronavirus (CoV) infection…”. Appropriate correction is required
Claim 2 is objected to because of the following informalities: the claim recites in line 1, “an SI region”, however, based on a review of the presented claims, it appears that this should read “an S1 region”. Appropriate correction is required.
Claim 7 recites in line 1, “wherein the CoVis”, however, it would appear that this should state “wherein the CoV is”. Appropriate correction is required.
Claim 19 recites in line 1, “wherein the CoVis”, however, it would appear that this should state “wherein the CoV is”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a vaccine capable of inducing an immune response, does not reasonably provide enablement for a vaccine for preventing Coronavirus infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the invention/Breadth of the claims. The claims are drawn to a vaccine for preventing CoV infection, comprising: at least one sequence selected from the group consisting of a CoV DNA sequence which codes at least a portion of a modified S protein for the CoV, a CoV RNA sequence which codes at least a portion of a modified S protein for the CoV, and a protein sequence for at least a portion of a modified S protein of the CoV, wherein the modified S protein contains at least one modification. The specification does not provide a definition for preventing or prevention of an infection. The limitation “for preventing CoV infection” is interpreted to require that the composition can stop a coronavirus infection from occurring once administered to a host.
State of the prior art/Predictability of the art. The state of the art related to coronavirus vaccines, such as vaccines for vaccinating against COVID-19, teaches that some vaccines are effective at reducing severe illness, but that preventing infection is not realistic. For example, Table 19 presented herein is from the package insert of a SPIKEVAX injectable vaccine by ModernaTX, Inc. This vaccine has proven to be reliable at reducing the severity of COVID-19 infections. This version of the COVID-19 vaccine is a 2025-2026 formula. Table 19 summarized the vaccine efficacy of SPIKEVAX at 93% in all 14, 287 participates tested. However, approximately 9.6 per 1,000 Persons of those receiving the vaccine still contracted COVID-19. Therefore, the SPIKEVAX vaccine has been proven to be effective, but it did not prevent infection in all recipients that received it.
PNG
media_image1.png
755
1124
media_image1.png
Greyscale
Working examples. Applicants have provided a working example in which mice received two intramuscular injections on day 1 and day 17. The injections delivered a viral vector that encodes a full-length S protein from a MERS-CoV. On day 19, the mice were challenged with a MERS virus and neutralizing antibodies were identified in mice that received the viral vector, whereas the placebo group did not produce neutralizing antibodies. [see figure 3] This working example did not determine if mice lost weight, indicative of an infection, or what the survival rate was, or if virus particles were present in the lungs or liver.
Guidance in the specification. The specification provides guidance towards using the claimed modified spike protein of a coronavirus, DNA sequence coding for the modified spike protein or a RNA sequence encoding the modified spike protein to prevent a coronavirus infection.
Amount of experimentation necessary. Additional research is required in order to determine how effective a vaccine comprising a CoV DNA sequence which codes at least a portion of a modified S protein for the CoV, a CoV RNA sequence which codes at least a portion of a modified S protein for the CoV, and a protein sequence for at least a portion of a modified S protein of the CoV, wherein the modified S protein contains at least one modification would be at preventing a Coronavirus infection.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
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 1-4, 7-9, 10, 17, 18 and 19 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.
Claims 1, 9 and 10 recite, “a CoV DNA sequence” or “a beta-CoV DNA sequence”. However, coronaviruses do not possess a DNA genome or have an intermediate DNA sequence during viral replication because they replicate in the cytoplasm and their genome is a positive sense RNA sequence. Therefore it is unclear what the claims encompass by calling the sequence a CoV DNA sequence. It is suggested that applicants amend the claims to recite, “a DNA sequence encoding a CoV S protein” or “a DNA sequence encoding a beta CoV S protein”
Claim 2 recites, “wherein the S protein has an S1 region, and the least one modification is selected from the group consisting of a full deletion of the S1 region…” and claim 17 recites: “A modified CoV S protein comprising an S1 region and at least one modification in the S1 region selected from the group consisting of…a full deletion of the S1 region…”.
It is unclear how the claims can require that the S protein has or comprises an S1 region, but at the same time the same S protein has a modification which fully deletes the S1 region.
Claim 3 recites, “wherein the S1 region has at least one variable region and the at least one modification is selected from the group consisting of a full deletion of the at least one variable region… and claim 18 recites, “wherein the S1 region has at least one variable region, and the at least one modification is selected from the group consisting of a full deletion of the at least one variable region…”
It is unclear how the claims can require that the S1 protein has or comprises an S1 region, but at the same time the same S protein has a modification which fully deletes the S1 region.
Claims 4 and 19 recite, “wherein the CoV is a SARS-2 Beta-CoV and the at least one variable region is between amino acid residues 342 and 533. However, the variable region is part of the S1 region of a CoV spike protein. Since the variable region, the S1 region and the spike protein of CoV have different lengths and it is unclear if the residues of 342 and 533 are located relative to the N-terminus, C-terminus, found in a variable region, a full-length S1 or full-length spike protein or a fragment thereof.
Claims 7 and 8 recite, “wherein the CoV is a a-CoV” and “wherein the CoV is a Beta-CoV”. These claims depend from claim 1, which recites at least two CoV (one causing the infection and one providing the RNA, protein or the DNA sequence). Therefore, it is unclear if claims 7 and 8 are further limiting the CoV causing the infection, the CoV providing the RNA, Protein or DNA sequence, or both.
Claim 7 recites in line 1, “an a-CoV”, however, it is unclear what “a-CoV” is directed to.
Claim Rejections - 35 USC § 101
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 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is
directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the
Supreme Court decision in Association for Molecular Pathology V. Myriad Genetics, Inc., --
U.S. -- (June 13, 2013) (hereafter "Myriad").
Claims 1, 7, 8 and 11-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally-occurring element of nature that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology V. Myriad Genetics, Inc., -- U.S. -- (June 13, 2013) (hereafter "Myriad").
Based upon an analysis with respect to the claims as a whole, claim(s) 1, 7, 8 and 11-16 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more (these claims are interpreted in light of the most recent Guidelines (See https://www.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter-eligibility)
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes the claims are directed to an ineligible product/process as further detailed below. In this case, claim(s) 1, 7, 8 and 11-16 recite a vaccine comprising a CoV RNA sequence which codes for at least a portion of a modified S protein for the CoV or a protein sequence for at least a portion of a modified S protein of the CoV. The limitations of “at least a portion” is interpreted to include full-length RNA or protein sequences. In addition, the RNA sequence or protein sequence are from a Beta coronavirus, such as SARS-CoV-2. Therefore, these claims are drawn to a composition of matter (Step 1) and recite natural phenomenon(s) (in this case, a naturally occurring protein or RNA sequence) that are directed to a judicial exception (in this case, a natural phenomenon)(Step 2A).
Pandey et al. (OFID, 2020, pages 1-9) teach that at least one isolate of a SARS-CoV-2 virus possess amino acid modifications (substitutions) in the Spike protein at position 614 (mutant D614G). [see page 3, last paragraph] Therefore, this isolate possesses a modified RNA and protein sequence of the spike protein of a SARS-CoV-2.
Therefore, the claimed vaccine is interpreted as naturally occurring.
Thus the claimed product is not markedly different from its naturally occurring counterpart. To summarize, the claims read upon a composition of matter as recited in Step 1 and a natural phenomenon as recited in Step 2A and the claims do not recite the integration of the judicial exception into a practical application.
Further, in view of Step 2B and the "No" pathway, the claims do not recite additional elements that amount to significantly more than the judicial exception. The claimed invention does not require a limitation that does not amount to significantly more than the judicial exception. For example, the rejection could be overcome by requiring that an adjuvant be present with the vaccine comprising the claimed RNA or protein sequences.
As pursuant to the Office's interpretation of the Myriad decision, a recitation of a
naturally-occurring nucleic acid, protein and virus, or any natural product of nature that does not have a substantial or marked difference from the natural product is not patent eligible subject matter.
Therefore, claims 1, 7, 8 and 11-16 as written, read upon a polypeptide that was found to have occurred naturally in nature without being subject to the "hand-of-person" and resulting in a substantial or markedly different product from that found in nature.
Therefore, claim(s) 1, 7, 8 and 11-16 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter. This rejection is necessitated by expanded 35 USC § 101 USPTO training in view of the
USPTO's interpretation of Myriad. Applicant is directed towards the USPTO memos, which support the analysis of the claims; please review the latest materials regarding 35 USC § 101 rejections. Applicant is cautioned to amend the claims according to these suggestions utilizing limitations for which the application would have support.
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.
Claim(s) 1-3, 6, 8-15, 17, 18 and 21 are rejected under 35 U.S.C. 102a1 as being anticipated by Baric et al. (US PGPub 2017/0096455).
The claimed invention is drawn to a vaccine for preventing CoV infection, comprising: at least one sequence selected from the group consisting of:
a CoV DNA sequence which codes at least a portion of a modified S protein for the CoV,
a CoV RNA sequence which codes at least a portion of a modified S protein for the CoV, and
a protein sequence for at least a portion of a modified S protein of the CoV,
wherein the modified S protein contains at least one modification.
The S protein has an SI region, and the at least one modification is selected from the group consisting of a full deletion of the S1 region, a partial deletion of the S1 region, a full replacement of the S1 region, and a partial replacement of the S1 region.
The S1 region has at least one variable region, and the at least one modification is selected from the group consisting a full or partial deletion of at least one variable region or a full or partial replacement of at least one variable region.
The at least one modification can be replacing in part or in full the variable region with a peptide linker. *The claims nor the specification define what the peptide linker is so for purposes of examining this claim any peptide sequence that is present in the variable region of the S protein meets the requirements of a peptide linker.
The coronavirus is a Beta-Coronavirus. *For the purpose of examining this limitation, the coronaviruses of SARS, MERS and SARS2 (COVID-19) met the requirements of a beta coronavirus.
The sequence of the vaccine is an CoV (beta-CoV) DNA sequence or CoV (beta-CoV) RNA sequence or a CoV (beta-CoV) protein sequence.
The claimed limitation of “for preventing CoV infection” is interpreted as an intended use limitation, which MPEP § 2111.02 (II) recites, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the pre-amble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limita-tions, then the preamble is not considered a limitation and is of no significance to claim construction.” Therefore, the claimed vaccine is examined based on the structural requriments and not how it may be used.
The Prior Art
Baric et al. teach the generation of an immunogenic composition comprising a chimeric coronavirus spike protein. The spike protein HKU3-Smix is chimeric due to the RBD (a variable region located in the S1 portion of the Spike protein) of a HKU3 spike protein being replaced with that of a SARS-CoV RBD. The amino acids involved are the N-terminal residues 322 to 500. [see figure 2] In addition, the insertion of the SARS-CoV RBD into the S1 protein serves as a linker between the Ectodomain and the S1/S2 region. [see figure 2 below]
PNG
media_image2.png
386
731
media_image2.png
Greyscale
The coronavirus, SARS, is a beta-coronavirus and the chimeric spike protein is taught to be used in a method of eliciting an immune response against coronavirus. [see paragraph 10] Baric et al. also teach that pharmaceutical compositions comprising nucleic acid sequence which encodes the chimeric coronavirus spike protein are also of interest. [see paragraphs 8 and 58] The nucleic acid sequence can be cDNA. [see paragraphs 58] Additionally, the nucleic acid sequence can be one that…is separated from other nucleic acid molecules that are present in the natural source of the nucleic acid molecule, which is mRNA since the genome of SARS is positive sense RNA. [see paragraph 96]
Therefore, Baric et al. anticipate the instant invention.
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.
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(s) 4, 5, 16, 19 are rejected under 35 U.S.C. 103 as being unpatentable over Baric et al. as applied to claims 1-3, 6-15, 17, 18, 20 and 21 above, and further in view of GenBank Accessions QHR63250 (published March 18th, 2020) and MN996527 (published March 18th, 2020).
The claimed invention also requires that the CoV is a SARS-2 Beta-CoV and the at least one variable region is between amino acid residues 342 and 533 and the variable region includes a receptor binding domain (RBD). The claimed invention also requires that the sequence is a SARS-2 Beta-CoV sequence.
The teachings of Baric et al. are summarized above, however, they do not teach that the CoV is a SARS-2 Beta-CoV and the variable region is between amino acids 342 and 533 and it includes the receptor binding domain (RBD); or that the sequence of the vaccine is a SARS-2 Beta-CoV sequence.
QHR63250 provides the amino acid sequence of a SARS-CoV-2 spike protein of isolate WIV02 and identifies the receptor binding domain at amino acids 319 to 541. MN996527 provides the RNA genome of isolate WIV02, with the spike protein ORF located at nucleotides 21530 to 25351.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Baric et al. in order to formulate one of their compositions with a sequence from other SARS viruses, such as SARS-CoV-2, which is a beta coronavirus or to modify at least one variable region of the SARS-CoV-2 S1 region between amino acids 342 and 533, which also comprises the RBD. One would have been motivated to do so, given the suggestion by Baric et al. that compositions comprising chimeric coronavirus spike proteins possessing SARS spike protein RBD can be readily generated and that compositions can also comprise nucleic acid sequence from these viruses. There would have been a reasonable expectation of success, given the knowledge that the spike protein and the resident RBD of another coronavirus, SARS-CoV-2 were previously known, as taught by GenBank QHR63250, and also given the knowledge that the RNA sequence encoding this spike protein was also previously known, as taught by MN996527. 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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6, 8-12, 14-18 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-8, 13, 14, 15, 19, 20, 21, 24, 27, 28 and 29 of copending Application No. 17996727 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions require a DNA or RNA or protein sequence of a SARS-CoV-2 (beta coronavirus) with either a particle S protein or an S protein that has a missing RBD and also the S protein possesses a peptide linker in place of the RBD.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 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, Michael Allen can be reached at (571) 270-3497. 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.
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671