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 .
Priority
Acknowledgment is made of Applicants’ claim for benefit to prior filed US Provisional application 63/138,121 (filed on 01/15/2021).
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/138,121 filed on 01/15/2021, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application: Claims 1, 4-11, 14, 17-24, and 27. Therefore, claims 1, 4-11, 14, 17-24, and 27 do not receive domestic benefit to the provisional application No. 63/138,121 filed on 01/15/2021 because it does not disclose the SARS-CoV-2 omicron variant as recited by the claims. Additionally, the SARS-CoV-2 omicron variant which was not isolated and reported to the WHO until 26 November 2021 (Update on Omicron Statement from WHO published 28 November 2021, available at https://www.who.int/news/item/28-11-2021-update-on-omicron). For purposes of applying prior art, the filing date for claims 1, 4-11, 14, 17-24, and 27 is 01/14/2022.
Election/Restrictions
Applicant’s election without traverse of Group I, SEQ ID NO: 12, and SEQ ID NO: 18, corresponding to claims 1, 4-11, 14, 17-24, and 27 in the reply filed 12 February 2026 is acknowledged.
Claims 2-3, 13, 16, 28-32 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 February 2026.
Claim Interpretation
Claim 11 is drawn to SEQ ID NO: 1 which is an amino acid sequence of Ad4-SARS-CoV-2 spike vector. The Specification (pg. 36) defines SEQ ID NO: 1 as “amino acid sequence of Ad4-SARS-CoV-2 spike vector.” The Specification further defines the Ad4-SARS-CoV-2 spike vector as an Ad4 vaccine vector backbone with a partial deletion of the E3 region and the SARS-CoV-2 S protein inserted in place of the deleted portion of the E3 region.
For the purposes of compact prosecution and applying prior art, claim 11 was interpreted as an Ad4 vaccine vector backbone with a partial deletion of the E3 region and the SARS-CoV-2 S protein inserted in place of the deleted portion of the E3 region.
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.
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.
Claim 6 is 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.
Claim 6 is drawn to, inter alia, SEQ ID NO: 12, which is an amino acid sequence of the SARS-CoV-2 S protein. The Specification (pg. 12) defines SEQ ID NO: 12 as “the amino acid sequence of a stabilized SARS-CoV-2 omicron variant spike protein with a double proline substitution.” The Specification further defines the omicron variant being used as B.1.1.529 (pg. 1). The SARS-CoV-2 spike protein for the omicron variant B.1.1.529 (now BA.1) can be found at GenBank: UFO69279.1, this sequence does not have the stabilizing double proline mutation (see alignment below, box 2). The instant SEQ ID NO: 12 has a mutation at amino acids 208-211 that is not present in the SARS-CoV-2 amino acid sequence (see alignment below, box 1). The Specification does not mention or define this mutation in SEQ ID NO: 12. As the mutation is not present in the omicron (B.1.1.529) SARS-CoV-2 spike glycoprotein sequence it is unclear if instant SEQ ID NO: 12 is the claimed omicron sequence of SARS-CoV-2.
For the purposes of compact prosecution and applying prior art, claim 6 was interpreted consistent with the Specification to include the amino acid sequence of a stabilized SARS-CoV-2 omicron variant B.1.1.529 or BA.1 spike protein with a double proline substitution.
PNG
media_image1.png
820
537
media_image1.png
Greyscale
PNG
media_image2.png
537
512
media_image2.png
Greyscale
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection and art may be readily applied in a subsequent final Office action.
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 1, 7-8, 14, 20-21, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Mayall, et al. (US 2011/0123564 A1, hereinafter “Mayall”) and further in view of the SARS-CoV-2 omicron variant (GenBank: UFO69279.1, published 30 November 2021, hereinafter “GenBank”) and evidenced by Purkayastha, et al. (J Virol. 2005 Feb;79(4):2559-72., hereinafter “Purkayastha”).
Regarding claims 1, 7-8, 14, and 20-21, Mayall teaches a recombinant adenovirus type 4 (Ad4) vaccine (Abstract) expressing the protective antigen from anthrax (¶0196) that is replication competent and comprises a deletion in the E3 region of the Ad4 (Abstract) and an insertion of a coding sequence for the protective antigen (PA) protein (¶0196) in the place of the E3 region (¶0151 and 0196). Mayall does not teach that the viral protein expressed by the Ad4 is a SARS-CoV-2 spike protein. However, GenBank teaches the SARS-CoV-2 omicron variant (B.1.1.529) spike protein. The GenBank spike protein has 96.87% identity with instant SEQ ID NO: 2 (see alignment below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the protein of interest (PA) taught by Mayall for the omicron spike protein taught by GenBank to create an Ad4 vaccine expressing the SARS-CoV-2 spike protein of the omicron variant. Mayall teaches that bacterial recombination with two plasmids was used to create the Ad4 vaccine expressing the protein of interest. The first plasmid contains the Ad4 vaccine strain which includes the deletion of the E3 region and the second plasmid contains the protein of interest and sufficient flanking Ad4 regions to allow for homologous recombination (Example 1) and that the Ad4 vector can be used for multiple infectious proteins of interest (Abstract). One of ordinary skill in the art would have substituted the protein of interest, PA, taught by Mayall with the omicron spike protein taught by GenBank to create a vaccine against the SARS-CoV-2 omicron variant. One of skill in the art would have has a reasonable expectation of success of substituting the proteins because they are both antigens from infectious pathogens.
Regarding claims 7 and 20, Mayall teaches an Ad4 vaccine that deletes all of the open reading frames of E3 except for the 12.1K ORF (Table 18). Purkayastha evidences that the E3 protein has 9 ORFs, 12.1K, 23.3K, 19K, 24.8K, 6.3K, 29.7K, 10.4K, 14.5K, and 14.7K (Table 2), so deletion of all ORFs except 12.1K includes deletion of 23.3K, 19K, 24.8K, 6.3K, 29.7K, 10.4K, 14.5K, and 14.7K E3 ORFs.
Regarding claim 27, Mayall teaches an Ad4 vaccine that is formulated to be administered intranasally (¶0037). Intranasal administration reasonably requires and encompasses the formulation of the recombinant Ad4 with a pharmaceutical excipient or carrier.
PNG
media_image3.png
375
1220
media_image3.png
Greyscale
PNG
media_image3.png
375
1220
media_image3.png
Greyscale
Accordingly, the claimed inventions were prima facie obvious to one or ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 4-6, 11, 17-19, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Mayall and GenBank as applied to claims 1, 7-8, 14, 20-21, and 27 above and in further view of Mercado, et al. (Nature 586, 583–588 (2020), hereinafter “Mercado”) and evidenced by Pallesen, et al. (Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357., hereinafter “Pallesen”).
As discussed above, claims 1, 7-8, 14, 20-21, and 27 were rendered prima facie obvious over Mayall and GenBank.
Regarding claims 4-6 and 17-19, Mayall and GenBank teach a recombinant Ad4 expressing a SARS-CoV-2 omicron variant spike protein (see claims 1 and 14). Mayall and GenBank do not teach the spike protein has a double proline stabilizing mutation.
However, Mercado teaches a SARS-CoV-2 Ad26 vaccine, wherein the vaccine is replication incompetent and protects against the original SARS-CoV-2 strain. Mercado further teaches a double proline mutation in the spike protein to stabilize the spike protein in the prefusion confirmation (pg.583, column 2). The double proline mutation for stabilization used in Mercado was first used in Pallesen, which evidences that the stabilizing proline mutation is K986P and V987P (Figure 1A).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Mayall and GenBank for a recombinant Ad4 expressing a SARS-CoV-2 omicron variant spike protein with the teachings of Mercado for a stabilizing double proline mutation in the spike protein. Mercado provides motivation by teaching that the stabilized pre-fusion spike protein is antigenically optimal and has an increased immune response compared to non-mutated vaccines (pg. 587). One of ordinary skill would have had a reasonable expectation of success combining Mayall, GenBank, and Mercado because they all teach antigens from infectious pathogens.
Regarding claims 11 and 24, Mayall and GenBank teach a recombinant Ad4 expressing a SARS-CoV-2 spike protein with deletion of the 23.3K, 19K, 24.8K, 6.3K, 29.7K, 10.4K, 14.5K, and 14.7K E3 ORFs (see claims 1, 7, 14, and 20). Mayall and GenBank do not teach the double proline mutation. However, Mercado teaches the K986P and V987P mutations (see claims 5 and 18). As discussed above, SEQ ID NO: 1 is being interpreted as a recombinant Ad4 (Mayall Abstract) expressing a SARS-CoV-2 spike protein (GenBank) with the claimed double proline mutation (Mercado, pg. 583 column 2) that is at least 95% identical to instant SEQ ID NO: 2 (GenBank) and has a deletion of the 23.3K, 19K, 24.8K, 6.3K, 29.7K, 10.4K, 14.5K, and 14.7K E3 ORFs (Mayall Table 18). Instant SEQ ID NO: 1 is a result of combining the recombinant Ad4 that has deletions of the 23.3K, 19K, 24.8K, 6.3K, 29.7K, 10.4K, 14.5K, and 14.7K E3 ORFs and a protein of interest inserted in the E3 region that is taught by Mayall, the SARS-CoV-2 omicron variant spike protein taught by GenBank, and the stabilizing double proline mutation taught by Mercado. Therefore, instant SEQ ID NO: 1 was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention over the recombinant Ad4 taught by Mayall expressing the SARS-CoV-2 spike protein taught by GenBank and the double proline mutation taught by Mercado.
Accordingly, the claimed inventions were prima facie obvious to one or ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claims 9-10 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Mayall and GenBank as applied to claims 1, 7-8, 14, 20-21, and 27 above and further in view of Fuglsang (Protein Expression and Purification Volume 31, Issue 2, October 2003, Pages 247-249).
As discussed above, claims 1, 7-8, 14, 20-21, and 27 were rendered prima facie obvious over Mayall and GenBank.
Regarding claims 9-10 and 22-23, Mayall and GenBank teach a recombinant Ad4 expressing a SARS-CoV-2 omicron variant spike protein (see claims 1 and 14). Mayall and GenBank do not teach the omicron spike protein codon optimized nucleotide sequence.
However, Fuglsang teaches codon optimization involves producing the same protein (in this case instant SEQ ID NO: 12 and GenBank sequence) but increasing yield by substituting rare codons (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to have modified the teachings of Mayall and GenBank for a recombinant Ad4 expressing a SARS-CoV-2 omicron variant spike protein with the teachings of Fuglsang for codon optimization to improve protein yield to obtain a sequence with 100% sequence identity to instant SEQ ID NO: 18. Fuglsang provides motivation by teaching that optimizing codons improves protein yield by using rare codons (Abstract). The software Fuglsang suggests that optimized polynucleotide sequences can be found by inputting the desired polynucleotide sequence into the computer and the software analyzes all the codons for optimization. As such, in the absence of evidence to the contrary, the claimed sequence was readily derivable using the software taught by Fuglsang. One of skill in the art would have had a reasonable expectation of success at combining Mayall, GenBank, and Fuglsang because they all teach antigenic proteins.
Accordingly, the claimed inventions were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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, Thomas J. Visone can be reached at 571-270-0684. 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.
/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
Prosecution Insights