!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 .
Application Status
This action is written in response to applicant’s correspondence received on 07/21/2026. Claims 1-16 are currently pending. Claims 1-8 are withdrawn from prosecution as being drawn to nonelected
subject matter. The restriction requirement mailed on 12/02/2025 is still deemed proper. Applicant's elected Group II (claims 9-16) with traverse in the reply filed on 02/08/2026. Accordingly, claims 9-16 are examined herein.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant’s amendments and arguments have been thoroughly reviewed, but are not
persuasive to place the claims in condition for allowance for the reasons that follow.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 of PCT/US2020/064497 filed on 12/11/2020, and it claims priority to PRO 62/946,561 filed on 12/11/2019.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 non-obviousness.
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 9-11, 16 are rejected under 35 U.S.C. 103 as being unpatentable over Lawman (US20170232090A1, published in 2017) in view of Milligan (Nucleic Acids Res. 1987;15(21):8783-98).
Lawman (2017) teaches a method to develop and use mRNA vaccines, i.e. an exogenous immunogenic bacterial protein (Specification, page 1, ¶[0005]; Page 3, ¶[0023], last 5 lines), using double-stranded DNA templates (Page 3, ¶[0034]) that incorporate synthetic DNA molecule (Page 8, ¶[0095]-[0098]; Page 15, ¶[0178]; SEQ ID NO: 12), the method comprising:
1) Obtaining Template DNA: Plasmid DNA, double stranded (Page 8, ¶[0096]), and "gene of interest" (Page 10, ¶[0129]);
2) "message [RNA] is created through an in vitro transcription reaction…” (Page 10, ¶[0131]);
3) "an emmL mRNA is successfully transfected into a cancer cells..." (Page 3, ¶[0023]);
4) "Once inside the cells the mRNA will produce and display the M-like protein on the cell surface..." (Page 10, ¶[0133]).
Lawman does not teach that “…and wherein the synthetic DNA is not plasmid-based”.
However, Milligan (1987) teaches a method of synthesizing small RNAs of defined length and sequence via in vitro transcription using synthetic DNA template: “The use of synthetic DNA templates for the synthesis of relatively short RNA fragments by T7 polymerase would be expected to have several advantages. First, the unwanted 5' flanking sequences that are often introduced as part of the cloning procedure can be eliminated. Second, the sequence of the 3' end of the transcript is not limited by the need for a restriction site to linearize the template. Finally, the time consuming cloning, sequencing, and plasmid DNA preparation can be avoided entirely.” (Page 8783, the last ¶).
Regarding claim 9, It would have been obvious to persons having ordinary skills in the art (PHOSITAs) before the effective filing date of the claimed invention to have modified the DNA template used by Lawman for in vitro transcription of RNA products by replacing plasmid-based DNA templates with PCR-amplified synthetic DNA templates taught by Milligan (1987). It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to do so because preparing synthetic DNA templates is rapid and efficient, as taught by Milligan. One would have reasonable expectations of success because DNA templates of different sources, regardless of whether it is in circular or linear forms, have identical functions for in vitro transcription and because Milligan further teaches “that synthetic DNA provides as good a template for in vitro transcription as does bacterial plasmid DNA” (Page 8788, first 2 lines).
Regarding claims 10 and 11, Lawman further teaches that “After the template has been prepared, the message is created through an in vitro transcription reaction. … including the capping of the 5' end and addition of a poly(A) tail for increased stabilization" (Page 10, ¶[0131]).
Regarding claim 16, Lawman further teaches that the claimed invention comprises a ribonucleic acid message (mRNA) (SEQ ID NO: 1; Claims 12, 14, 16; see attached NPL_Lawman_2017_SEQ ID NO 1.pdf listed in the PTO-892 form) that encodes an immunogenic bacterial protein used as vaccine. SEQ ID NO: 1 shows a nucleic acid sequence of 1854bp, which is between 100 and 10,000 base pairs in length.
Lawman further teaches an embodiment of the structure of a double stranded DNA molecule used in the production of synthetic mRNA shown as a schematic map in FIG. 11. The DNA molecule in FIG. 11 contains a T7 bacteriophage RNA polymerase promoter, a 5' untranslated region, “a polylinker … used to insert the coding region of emmL”, i.e. a region for inserting the nucleic acid of interest, “a portion of the … 3' untranslated region” (FIG. 11; Page 3, ¶[0034]), and FIG. 11 confirms the 5’ to 3’ order of each recited element in the claimed invention.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lawman (2017) in view of Milligan (1987), further in view of Zarghampoor (Gene. 2019;707:231-238), as evidenced by Nakagawa (Nucleic Acids Res. 2008;36(3):861-71) and Cheetham (Curr Opin Struct Biol. 2000;10:117-23).
The teachings of Lawman (2017) and Milligan (1987) have been discussed above as applied to claims 9-11, 16. Neither Lawman nor Milligan teaches a Kozak sequence.
However, Zarghampoor (2019) teaches "...modifications with native Kozak (K1) sequence of human beta-globin enhanced the stability of destabilized GFP mRNA up to 48 h..." (Page 231, Abstract, lines 10-11) while also stating that “Translation efficiency could potentially be influenced by the presence
of the cap structure, 5’ UTR sequence, and the Kozak sequence” (Page 231, last ¶).
Regarding claim 13, Zarghampoor further teaches "the most efficient Kozak sequence is gccRccAUGG (R=purine)" (Page 232, first ¶, line 9), which is the RNA format of the same sequence as the claimed SEQ ID NO: 6, gccrccatgg, or GCCRCCAUGG in RNA format.
Regarding claims 14-15, Lawman further teaches an RNA promoter sequence that is an RNA polymerase promoter from a bacteriophage based on the recitation “One distal design element is the DNA sequence for a bacteriophage RNA polymerase promoter region. Examples of bacteriophage RNA polymerases are T7, T3 and SP6" (Page 8, ¶[0087]). As evidenced by Cheetham (2000), T7 is a DNA dependent RNA polymerase (Page 117, Abstract, line3).
It would have been obvious to PHOSITAs before the effective filing date of the claimed invention to have modified the in vitro transcription double-stranded DNA template taught by Lawman, as evidenced by Cheetham, by adding a Kozak sequence between the 5’UTR and the coding sequence of the gene of interest, demonstrated by Zarghampoor, because it is highly desirable to enhance the ultimate translation of the gene of interest in a target biological system. It would merely amount to a simple combination of known elements in the art according to known methods to achieve predictable results. One would have the motivation to do so because Zarghampoor teaches the benefits of including a Kozak sequence. One would have reasonable expectations for success because Zarghampoor demonstrates high level of gene of interest translation at protein levels with proven success in using double-stranded DNA template for in vitro transcription-based mRNA synthesis (Page 236, Figure 4).
Response to Arguments
Applicant's arguments filed on 07/21/2026 have been fully considered but they are not persuasive. Applicant argues on page 3 of the Remarks:
“As amended claim 9 recites: A method of making an exogenous protein from a synthetic deoxyribonucleic acid (DNA) comprising … wherein the synthetic DNA is not plasmid-based.
As currently amended, claim 9, from which claims 12-15 depend, recites that the synthetic DNA is not plasmid-based. … For this reason alone, the claims are not obvious. ....”
Applicant’s arguments with respect to claims 9-16 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground 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 Delphinus D. Yu whose telephone number (571) 272-1576. The examiner can normally be reached Mon-Thr 7:30am to 4:30pm Fri 10am to 2pm 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, Neil P Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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