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 .
Claim Status
Applicant’s election without traverse of claims 1 – 2, 4, 9, 16, 20, 28, 40 – 43, 154, 162 and 195 in the reply filed on July 8, 2026, is acknowledged.
Claims 95, 139, 151 – 153, 155, 161, 163, 182, 188 and 193 – 194 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 8, 2026.
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.
Claims 1, 4, 16, 20 and 154 are rejected under 35 U.S.C. 103 as being unpatentable over Berger et al. (W.O. Patent application Publication No. 2005/085456; cited on IDS, hereinafter Berger) in view of Dong (Construction and characterization of a synthetic Baculovirus-inducible 39K promoter, Journal of Biol Eng, 2018; hereinafter Dong).
Regarding claims 1, 4, 16, Berger discloses a bacmid (pFBDM and pUCDM combined) for multigene applications comprising a functional arrangement according to Fig. 1 (pp. 24 – 25, Figure 1 Description); wherein the integration site is selected from the group consisting of the transposon elements Tn7, site specific recombinases (Cre-lox), a F-replicon (p. 30, 2nd para.), and a chloramphenicol selection sequence (or kanamycin, p. 9, 3rd para.). Berger further discloses that the vector has an arabinose-inducible (p. 31, 3rd para.) promoter. Berger does disclose reporter genes (p. 11, 6th para.) but does not disclose a second reporter gene operably linked to a baculovirus-inducible promoter.
Dong discloses a synthetic baculovirus-inducible promoter (39 K) operably linked to Firefly luciferase and/or Renilla luciferase (Fig. 1a). Dong provides the motivation for generating a baculovirus-inducible system was to construct a pathogen-inducible promoter in disease resistance breeding and gene therapy for insect genetic engineering research.
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 incorporate the baculovirus-inducible promoter of Dong in the MultiBac bacmid of Berger. Doing so would allow for the MultiBac to have a reporter gene linked to a promoter that was engineered to be highly active in baculovirus-infected insect cells.
Regarding claim 20, Berger discloses that the vectors created in the application are useful for the incorporation of heterologous DNA elements, preferably genes (p. 10, 3rd para.) and that Tn7 transposition disrupts a lacZα gene (pp. 24 – 25, Figure 1 Description).
Regarding claim 154, Berger discloses the preferred insect host cells for the bacmid are Sf9 and Sf21 (p. 9, 2nd para.).
Claims 2, 9, 40 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Berger and Dong as applied to claims 1, 4, 16, 20 and 154 above, and further in view of Lee et al. (U.S. Patent No. 5,348,886; hereinafter Lee).
Regarding claim 2, Berger and Dong teach all of the elements of the current invention as stated above except a mini-F bacterial replicon. However, Lee discloses a mini-F replicon, which allows for autonomous replication and stable segregation of plasmids at a low copy number (Col. 7, line 50 – 55).
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 exchange the F-replicon of Berger with the mini-F replicon of Lee. Doing so would allow for autonomous replication and stable segregation of plasmids at a low copy number, according to Lee.
Regarding claim 9, Berger and Dong teach all of the elements of the current invention as stated above except the insertion of a transposon that does not disrupt the reading frame of the first reporter gene (lacZα). Lee discloses a plasmid, pMON14192, in which the EcoRI/SalI mini-attTN7 does not disrupt the reading frame of the lacZα region (Col. 15, line 30 – 35). Lee further discloses that the mini-Tn7 is modified to contain a selectable drug resistance marker, a baculovirus promoter, and a transcription termination poly(A) signal (Col. 8, line 35 – 45). Lee provides the motivation for using the mini-Tn7 by stating that the mini-Tn7 plasmids are small compared to traditional baculovirus vectors and are easily manipulated in regard to adding or removing restriction sites or different genetic elements (Col. 8, line 65 – 69).
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 exchange the TN7 of Berger with the mini-attTN7 transposon of Lee. Doing so would provide a smaller vector that is easily manipulated, according to Lee.
Regarding claims 40 and 41, Berger and Dong teach all of the elements of the current invention as stated above except a mini-attTn7 site. However, Lee discloses a mini-attTN7 (Col. 15, line 30 – 35) site. If a mini-attTn7 is engineered to be inserted into the same chromosomal context as the full attTN7 of Berger, it would behave similarly. Therefore, the reading frame disruption of Berger would remain the same. Also, it would be obvious to engineer the baculovirus-inducible (39 K) promoter of Dong to be operably linked to a gene encoding a fluorescent protein.
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 utilize the mini-attTN7 of Lee and link a gene encoding a fluorescent protein to the baculovirus-inducible promoter of Dong in the MultiBac bacmid of Berger. Doing so would provide a smaller vector that is easily manipulated as stated above for the rejection of claim 9 in regard to the mini-attTN7. Also, it would provide another embodiment for the bacmid to express fluorescence for fluorescence-based applications such as gene expression.
Claim 162 is rejected under 35 U.S.C. 103 as being unpatentable over Berger and Dong as applied to claims 1, 4, 16, 20 and 154 and in further view of Kotin et al. (U.S. Patent Application Publication No. 2019/0032083; hereinafter Kotin).
Regarding claim 162, Berger and Dong teach all of the elements of the current invention as stated above except for a method of generating a closed ended DNA (ceDNA) molecule. However, Kotin discloses an example (Example 7: Sf9 Infection to Produce ceDNA, starting at para. [0221 – 0230]) that showcases the method for generating a ceDNA. Kotin further discloses the motivation for the generation of ceDNA was for the ability to have nucleic acids having asymmetric interrupted self-complementary sequences to be readily produced in large quantities while avoiding scale up issues associated with other gene therapy vectors (viral).
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 utilize Kotin’s method for the ceDNA production of the bacmid of Dong and Berger. Doing so would allow for an alternative embodiment for gene therapy and/or the ability to produce high-quality vectors or recombinant proteins in large quantities.
Claims 28 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Berger, Dong, and Lee as applied to claims 2, 9, 40 and 41 above, and further in view of view of Samulski et al. (W.O. Patent Application Publication No. 03/104392; hereinafter Samulski).
Regarding claims 28 and 42, Berger, Dong, and Lee teach all of the elements of the current invention as stated above except a Rep protein isolated from a genome of a member of the viral family Parvovirdae. However, Samulski discloses, in an invention related to methods for producing parvoviruses, a Chimeric AAV-B19 Rep protein (p. 64, Example 19). The mini-F replicon can cause instability in bacmid transgenes.
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 substitute the mini-F Rep of Lee with the AAV-B19 rep of Samulski. Doing so would allow for the rep coding sequences to be stably integrated into the genome of the cell.
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Berger, Dong, Lee, and Samulski as applied to claims 28 and 42 above, and further in view of view of Smith et al. (Comparative Characterization of Rep Proteins from the Helper-Dependent Adeno-Associated Virus Type 2 and the Autonomous Goose Parvovirus. J Virol 73: 1999; hereinafter Smith).
Regarding claim 43, Berger, Dong, Lee, and Samulski teach all of the elements of the current invention as stated above except a GPV Rep protein. However, Smith discloses a GPV Rep 1 (Abstract) that is comparable to AAV Rep78 (Fig. 1A). The AAV-B19 Rep of Samulski contains elements from AAV2 Rep 78 (p. 64, Example 19). Smith further discloses (p. 2936, last para.) that the GPV Rep 1 recognizes a different DNA motif than Rep78. Smith further suggests that these domain exchanges may result in a functional protein.
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 exchange the AAV-B19 Rep of Samulski with the GPV Rep 1 of Smith. Doing so would allow for the possibility of a functional protein to be made, according to Smith.
Claim 195 is rejected under 35 U.S.C. 103 as being unpatentable over Berger, Dong, Lee, Samulski, and Smith as applied to claim 43 above, and further in view of view of Yan (U.S. Patent Application Publication No. 20160068821; hereinafter Yan).
Regarding claim 195, Berger, Dong, Lee, Samulski, and Smith teach all of the elements of the current invention as stated above except a HBoV1 Rep. However, Yan discloses, in an invention related to generating vectors capable of regulating bocaparvovirus replication, HBoV1 NS1 (para. [0004]), which is the active Rep protein for HBoV1. Yan further discloses that the NS1 has a putative DNA origin binding/endonuclease domain, a helicase activity domain, and a transactivation domain within its N-terminal, middle, and C-terminal regions. A Rep protein that contains a transactivation domain can significantly enhance functional activity. Yan further discloses that a rHBoV1 vector with HBoV1 rep genes can deliver a high level of therapeutic gene expression (para. [0128]).
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 exchange the GPV Rep 1 of Smith with the HBoV1 of Yan. Doing so would allow for a Rep protein with a transactivation domain to be integrated in the Bacmid of Berger and Dong in order to enhance functional activity.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 9:00A - 5:00P.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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