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 .
Response to Amendment
The amendment filed 03/27/2026 is acknowledged. Regarding the Office action mailed 12/30/2025:
The rejection of claim 9 under 35 USC 112(b) is withdrawn in view of the amendment.
The rejection of claims 1-5, 7-12, 15 and 18 under 35 USC 102(a)(1) over GenBank Accession M25464 is withdrawn in view of the amendment.
The rejection of claims 1-5, 7-12, 15, 18 and 19 under 35 USC 102(a)(1) over Dower is withdrawn in view of the amendment.
The rejection of claims 1-5, 7-12, 15 and 18 under 35 USC 101 is withdrawn in view of the amendment.
New rejections are set forth below in response to the amendment.
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) 1-5, 7-12, 15, 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bochkov (BioTechniques 41(3):283-292 (2006)).
Regarding claims 1 and 2, Bochkov taught a construct, pF/R-wt, Fig. 2, comprising a promoter (either CMV or T7) operably linked to a polynucleotide comprising a first nucleic acid unit (encoding Fluc, a first unit payload protein) and a second nucleic acid unit (encoding Rluc, a second unit payload protein). Each of these proteins is encoded by an open reading frame beginning with a start codon, and there is inevitably a three-nucleotide element immediately upstream of each of these start codons. These elements are inherently tunable, as they could be changed, if one desired, to any other three-nucleotide sequence. Each open reading frame also inherently comprises a translation initiation site, since both of these proteins were translated (see Fig. 2B). The term “engineered” does not structurally distinguish over these translation initiation sites.
The promoters (CMV or T7) were capable of producing a bicistronic transcript comprising coding sequences of both nucleic acid units, which were capable of being translated by eukaryotic ribosomes (Bochkov demonstrated this using a rabbit reticulocyte lysate in vitro translation system, in which the T7 promoter was used to produce the bicistronic transcript; see “Cell-Free Translation” on page 286. This cell-free translation system is a “cell-like environment”.
It is noted in figure 2B that the second nucleic acid unit (encoding Rluc) produced significantly more protein than the first nucleic acid unit (encoding Fluc); see lane 4, which indicates an approximately 10-fold higher expression of Rluc compared to Fluc. This indicates the translation initiation site of the second nucleic acid unit (provided by an internal ribosome entry site, or IRES) was stronger than the translation initiation site of the first nucleic acid unit.
Regarding claims 3-5, these limitations are presumed inherent since the level of protein encoded by the second nucleic acid unit is higher than the level of protein encoded by the first nucleic acid unit.
Regarding claims 7 and 8, as all possible triplet sequences of nucleotide are recited in the claims, the construct of Bochkov inherently comprised one of these (in DNA form in the plasmid, as recited in claim 7; in RNA form in the polycistronic transcript, as recited in claim 8).
Regarding claim 9, the second nucleic acid unit (encoding Rluc) produced significantly more protein than the first nucleic acid unit (encoding Fluc); see lane 4, which indicates an approximately 10-fold higher expression of Rluc compared to Fluc.
Regarding claim 10, the term “predetermined stoichiometry” is not limited to a particular stoichiometry, and therefore the 10-fold higher level of Rluc compared to Fluc produced by Bochkov’s construct constitutes a “predetermined stoichiometry” of 1:10.
Regarding claim 11, there is no “upstream ORF” in Bochkov, as that term is defined by Applicant, and the proteins expressed (Fluc, Rluc) are more than 30 amino acids in length.
Regarding claim 12, there is no mention of any non-native amino acids provided in the rabbit reticulocyte lysate system, and therefore the proteins produced in Bochkov’s experiment did not comprise any non-native amino acids.
Regarding claim 15, the term “synthetic protein circuit” does not distinguish over Bochkov’s system.
Regarding claim 19, Bochkov put this construct into cells; see “Cellular Techniques”, page 286, and see Fig. 3.
Conclusion
Claims 13, 14, 16-18 and 20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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, GARY BENZION can be reached at 571-272-0782. 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.
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
Prosecution Insights