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
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional applications 63/136,296 (filed on 01/12/2021).
Election/Restrictions
Applicant’s election without traverse of Group I, corresponding to claims 1-3, 8, 10-12, 15-18, 20, 21, and 23, in the reply filed on 16 February 2026 is acknowledged. Claims 25-26, 28-29, and 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 16 February 2026.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
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.
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, 16-17, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Fuller (US 2010 0221349 A1, US-IDS, filed 04/02/2024) and further in view of Bachmann, et al. (WO 2020 205604 A1, FOR-IDS, filed, 04/02/2024, hereinafter “Bachmann”).
Regarding claim 1, Fuller teaches a nucleic acid construct that encodes the influenza (Orthomyxoviridae) hemagglutinin and has an intron inserted into the construct (¶0008), which may be artificial (¶0264), and can form a 3’ and 5’ splice site with the viral segment (¶0263) and has branch site (¶0263) that is 20-50 bases downstream of the 5’ end (¶0262). Fuller does not teach that the 3’ end of the intron comprises the sequence AC and the 5’ end of the intron comprises the sequence CU. However, Bachmann teaches that the optimal arrangement of RNA elements that efficiently drive RNA splicing (pg. 24 lines 5-6) include the sequence AC at the 3’ end of the artificial intron for U12-dependent introns (pg. 46, lines 8-9) and the sequence CU at the 5’ end also for U12 dependent introns (pg. 36, lines 3-4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fuller for a nucleic acid construct with the artificial intron with the teachings of Bachmann for the splice sites of AC and CU. Bachmann provides motivation by teaching that these splice sites are the optimal arrangement of RNA elements to efficiently drive RNA splicing (pg. 24 lines 5-6). One of skill in the art would have had a reasonable expectation of success in combining the teachings of Fuller and Bachmann because they both teach artificial introns.
Regarding claim 16, Fuller teaches that the intron is spliced into the influenza viral antigen, hemagglutinin, which is a protein from a viral segment that is not natively spliced or contains multiple reading frames (¶0281).
Regarding claim 17, Fuller teaches that the influenza virus can be influenza virus A (¶0298).
Regarding claim 21, Fuller teaches that the recombinant viral segment is a DNA construct (¶0423)
Accordingly, the claimed invention was 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.
Claims 2-3 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Fuller and Bachmann as applied to claims 1, 16-17, and 21 above, and further in view of Bonano, et al. (Nat Protoc 2, 2166–2181 (2007), NPL-IDS, filed, 04/02/2024, hereinafter “Bonano”).
As discussed above claims 1, 16-17, and 21 were rendered prima facie obvious over Fuller and Bachmann.
Regarding claims 2-3, Fuller and Bachmann do not teach that the 3’ end of the artificial intron comprises the sequence ACUCAC. However, Bonano teaches an artificial intron that is used as a reporter and is amplified by a primer with the sequence ACTCAC (see below) at the 3’ end of the intron (Table 1, MO 899).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fuller and Bachmann for a nucleic acid construct with the artificial intron with the teachings of Bonano for a reporter artificial intron with a 3’ sequence of ACUCAC. Bonano provides motivation by teaching this reporter artificial intron can be used to investigate splicing regulation (Abstract). One of skill in the art would have had a reasonable expectation of success in combining the teachings of Fuller, Bachmann, and Bonano because they all teach artificial introns.
Regarding claims 11-12, Fuller teaches inserting an artificial intron into a viral gene within a viral segment (see claim 1) and, Bonano further teaches the reporter Rint which is an artificial intron which is inserted into the same reading frame as the ORF of other proteins.
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Accordingly, the claimed invention was 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.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Fuller and Bachmann as applied to claims 1, 16-17, and 21 above, and further in view of IMGT (IMGT Aide-mémoire – splicing sites, available at https://www.imgt.org/IMGTeducation/Aide-memoire/_UK/splicing/#refs and https://web.archive.org/web/20120912064028/http://www.imgt.org/IMGTeducation/Aide-memoire/_UK/splicing/#refs, published Sep 12 2012).
As discussed above claims 1, 16-17, and 21 were rendered prima facie obvious over Fuller and Bachmann.
Regarding claims 8 and 10, Fuller and Bachmann do not teach that the intron is flanked by CUU at the 3’ end and CAC at the 5’ end. However, IMGT teaches consensus splicing sites for introns that include AAG (5’) and GTG (3’) (see figure below) which are the reverse complement of the viral sequence.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have inserted the artificial intron into the viral segment where it is flanked by CUU on the 3’ end and CAC on the 5’ end as there are a defined and limited number of sequences that can be the donor and acceptor sequences for alternative splicing of the intron (see IMGT and figure below). One of ordinary skill in the art would have had a reasonable expectation of success in inserting the artificial intron between the sequences CUU and CAC because they are known splice sites.
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Accordingly, the claimed invention was 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.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Fuller, Bachmann, and Bonano as applied to claims 2-3 and 11-12 above, and further in view of Chen, et al. Adv Drug Deliv Rev. 2013 Oct;65(10):1357-69., hereinafter “Chen”).
As discussed above claims 2-3 and 11-12 were rendered prima facie obvious over Fuller, Bachmann, and Bonano.
Regarding claim 15, Fuller, Bachmann, and Bonano do not teach a linker. However, Chen teaches that linkers are necessary to construct stable, bioactive fusion proteins (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fuller, Bachmann, and Bonano for a recombinant viral segment with a reporter artificial intron with the teachings of Chen for a linker. Chen provides motivation by teaching that linkers are necessary to construct stable, bioactive fusion proteins (Abstract). One of ordinary would have had a reasonable expectation of success of combining Fuller, Bachmann, Bonano, and Chen because they all teach encoding proteins.
Accordingly, the claimed invention was 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.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Fuller and Bachmann as applied to claims 1, 16-17, and 21 above, and further in view of Racaniello (Influenza virus RNA genome published 1 May 2009, available at https://virology.ws/2009/05/01/influenza-virus-rna-genome/).
As discussed above claims 1, 16-17, and 21 were rendered prima facie obvious over Fuller and Bachmann.
Regarding claim 18, Fuller teaches inserting the intron into segment 4 (HA) of the influenza genome (see claim 16). Fuller and Bachmann do not teach inserting the artificial intron into segments 5 or 6. However, Racaniello teaches that segments 4-6 are all not alternatively spliced (see figure below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted inserting the artificial intron into influenza segment 4 as taught by Fuller for inserting the artificial intron into influenza segments 5 or 6 taught by Racaniello. See KSR rationale (B): Simple substitution of one known element for another to obtain predictable results (MPEP 2141(III). One of ordinary skill would have had reasonably expectation of success of substituting inserting the artificial intron into influenza segment 4 for inserting the artificial intron into influenza segments 5 or 6 reporter because both were known influenza segments that are not naturally alternatively spliced.
Accordingly, the claimed invention was 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.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Fuller and Bachmann as applied to claims 1, 16-17, and 21 above, and further in view of Bonano and England, et al. (Bioconjug Chem. 2016 May 18;27(5):1175-1187., hereinafter “England”).
As discussed above claims 1, 16-17, and 21 were rendered prima facie obvious over Fuller and Bachmann
Regarding claim 20, as further discussed above, Fuller and Bachmann teach the 3’ and 5’ ends of the artificial intron, while Bonano teaches a reporter artificial intron. Fuller, Bachmann, and Bonano do not teach instant SEQ ID NO: 31, an artificial intron that expresses the reporter NanoLuc. However, England teaches the reporter NanoLuc which has increased sensitivity high stability, and is small (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the Rint reporter taught by Bonano for the NanoLuc reporter taught by England. See KSR rationale (B): Simple substitution of one known element for another to obtain predictable results (MPEP 2141(III). One of ordinary skill would have had reasonably expectation of success of substituting the Rint reporter for the NanoLuc reporter because both were known reporters.
Instant SEQ ID NO: 31, is an artificial intron that encodes the reporter NanoLuc. The sequence is a result of combining the 3’ and 5’ ends of the intron which allow the artificial intron to be inserted into a gene segment and allow for the intron to be alternatively spliced (Fuller, Bachmann, and Bonano) and the NanoLuc reporter which is a highly sensitive and stable reporter (England). Therefore, as an artificial intron encoding the NanoLuc reporter is obvious (see above), instant SEQ ID NO: 31, which is an artificial intron encoding the NanoLuc reporter was also prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention over the intron ends taught by Fuller and Bachmann and the reporter taught by England.
Accordingly, the claimed invention was 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.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Fuller and Bachmann as applied to claims 1 and 16-17 above, and further in view of Fodor, et al. (J Virol. 1999 Nov;73(11):9679-82., hereinafter “Fodor”).
As discussed above claims 1 and 16-17 were rendered prima facie obvious over Fuller and Bachmann
Regarding claim 23, Fuller and Bachmann teach the recombinant viral segment of claim 1. Fuller and Bachmann do not teach a virus comprising the recombinant viral segment. However, Fodor teaches rescuing influenza by transfection of plasmid, which include recombinant viral segments (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Fuller and Bachmann for a recombinant viral segment with the teachings of Fodor for rescuing influenza viruses. Fodor provides motivation by teaching that these reverse genetics technique facilitates the generation of recombinant influenza viruses containing specific mutations (Abstract). One of ordinary would have had a reasonable expectation of success of combining Fuller, Bachmann, and Fodor because they all teach manipulating nucleic acid constructs.
Accordingly, the claimed invention was 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.
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/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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