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 .
Claim Status
Applicant’s submission filed 03/30/2026 has been received and entered. Claims 10, 12, 18, 19, 21 and 24-27 have been cancelled. Claims 1-9, 11, 13-17, 20 and 22-23 have been amended. Accordingly, claims 1-9, 11, 13-17, 20 and 22-23 are pending and under current examination.
Status of Prior Rejections/Response to Arguments
The objection to Abstract is withdrawn:
The objection to the abstract of the disclosure have been withdrawn due to applicant’s amendment to the abstract and submitted as a single paragraph on a separate sheet as required.
The objection to claims 22-23 and 25-27 is withdrawn:
The cancellation of claims 25-27 renders the objection thereto moot.
Applicant’s amendment to the instant claims 22-23 replaces “a method of claim 14” with “the method of claim 14” obviates the current objection on record. The objection is withdrawn.
The rejection to claims 12 and 14-27 under 35 U.S.C. § 112(b) is withdrawn:
The cancellation of claims 12, 18-19, 21 and 24-27 renders the rejection thereto moot.
Applicant’s amendment to claim 14 replaces “enhancing the function of DNA constructs once that have been introduced into eukaryotic cells” with “protecting an introduced DNA construct from enzymatic digestion in a eukaryotic packaging cell independently of a helper adenovirus” is effective to obviate the rejection on record. The rejection is withdrawn.
The rejection to claims 1, 3-14, 16, 18-19 and 21 under 35 U.S.C. § 102 over Chamberlain et al., as evidenced by Pronk et al. and Dunsworth-Browne et al. is withdrawn:
The cancellation of claims 10, 12, 18, 19 and 21 renders the rejection thereto moot.
Applicant’s amendment to claims 1 in step (c)(ii) and claim 14 in step (c)(ii) is effective to obviate the current rejection on record since Chamberlain et al. do not teach such limitations. The rejection is withdrawn.
The rejection to claims 1, 2, 4, 7, 11, 12, 14, 15 and 21 under 35 U.S.C. § 102 over Lieber et al., as evidenced by Pronk et al. and Dunsworth-Browne et al. is withdrawn:
The cancellation of claims 12 and 21 renders the rejection thereto moot.
Applicant’s amendment to claims 1 in step (c)(ii) and claim 14 in step (c)(ii) is effective to obviate the current rejection on record since Lieber et al. do not teach such limitations. The rejection is withdrawn.
The rejection to claims 24-25 and 27 under 35 U.S.C. § 102(a)(1) over Dunsworth-Browne et al. is withdrawn:
The rejection to claims 24 and 26 under 35 U.S.C. § 102(a)(1) over Ni et al. is withdrawn:
The cancellation of claims 24-27 renders the rejection thereto moot. The rejection is withdrawn.
The rejection to claims 1, 3-14, 16-19 and 21-22 under 35 U.S.C. § 103 over Chamberlain et al., as evidenced by Pronk et al. and Dunsworth-Browne et al., in view of Redrejo-Rodríguez et al. is withdrawn:
The rejection to claims 1, 3-14, 16-21 and 23 under 35 U.S.C. § 103 over Chamberlain et al., as evidenced by Pronk et al. and Dunsworth-Browne et al., in view of Redrejo-Rodríguez et al., and further in view of Rijnders et al. is withdrawn:
The cancellation of claims 10, 12, 18, 19, 21 and 24-27 renders the rejection thereto moot.
Applicant’s amends claims 1 and 14, adds the limitation that introducing into the packaging cell a packaging expression plasmid that provides adenoviral genes required for replication and packaging, wherein the packaging expression plasmid lacks a packaging signal and at least one inverted terminal repeat (ITR) sequence for encapsidating the adenovirus-derived genome independently of a helper adenovirus. None of Chamberlain et al., Pronk et al., Dunsworth-Browne et al., Redrejo-Rodríguez et al. or Rijnders et al. teach such limitation. Therefore Applicant’s amendment overcomes the rejection on record. The rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has traversed the rejection, asserting that Chamberlain and Lieber, alone or in combination with the additional reference, fail to teach or suggest the amended limitations (Remarks, p9). In response, the Examiner submits that the amended limitation is taught by the new provided prior art Brennan et al.. In particular, Brennan et al. teach fully-deleted adenovirus-based gene delivery vectors packaged without helper adenovirus, which comprise a replication defective circular packaging construct having a subset of adenoviral late genes including L1, L2, L3, L4, L5, E2A, and E4, while being absent of at least one inverted terminal repeat and a packaging signal (Col 55, L20-30, claim 1), reads on the step (c)(ii) of amended claim 1. Brennan et al. also teach the fully-deleted adenoviral vector construct is a linear, double-stranded DNA molecule with inverted terminal repeats (ITRs) separated by approximately 28 to 37 kb, the viral packaging signal (Ψ), and at least one DNA insert (all or a fragment of at least one gene of interest (GOI)) which comprises a gene sequence encoding a protein of interest (Col 11, L24-31), which reads on the step (c)(i) of amended claim 1. Brennan et al. do not teach providing a eukaryotic expression vector that codes for the expression of a terminal protein (Tp) and a DNA polymerase (Pol) to the packaging cell. However, Chamberlain et al. teach packaging cell lines expressing Tp and Pol allow the production of infectious recombinant virus containing deletions in the E1 and E2b regions without the use of helper virus (Col 12, L60-63), and allow the high-level growth of E1, preterminal, and polymerase deleted Ad vectors (Col 26, L43-45), therefore PHOSITA would be taught or suggested to modify Brennan et al.’s fully-deleted adenovirus-based gene delivery vectors, and use packaging cells which expressing Tp and Pol (i.e., expressing a eukaryotic expression vector that codes for the expression of Tp and Pol) as taught by Chamberlain et al. in order to obtain high-level growth of the fully-deleted adenoviral vectors.
New grounds of rejection are set forth as necessitated by Applicant’s amendment.
New Grounds of Rejections
New Claim Objections
Claims 1 and 13-14 are newly objected to because of the following informalities:
Claim 1 recites “a linear adenovirus-derived genome that carries terminal sequences on both 5'- and 3'-ends of the linear fragments adenovirus derived genome” in step (c)(i), herein the phrase “the linear fragments adenovirus derived genome” needs to be amended to “the linear adenovirus-derived genome fragments”;
Claim 13 recites “packaging expression plasmid”, needs to be amended to “the packaging expression plasmid”;
In claim 14 step c(ii), the half quote symbol after the word “wherein” needs to be deleted.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites the preamble “increasing propagation of adenoviruses and adenovirus-based gene transfer vectors by a packaging cell independently of a helper adenovirus”, claim 14 recites the preamble “protecting an introduced DNA construct from enzymatic digestion in a eukaryotic packaging cell independently of a helper adenovirus”, as well as the phrase “(the terminal protein binds to the terminal sequences of the DNA construct in the eukaryotic cell) to reduce enzymatic degradation of the DNA construct” in step (c)(ii), each of them merely state the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02.
New 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.
Claims 1, 3-9, 11, 13-14 and 16 are newly rejected under 35 U.S.C. 103 as being unpatentable over Brennan et al. (US 8,871,515 B2, patented in 2014) in view of Chamberlain et al. (US006083750A, patented in 2000), as evidenced by Pronk et al. (Chromosoma, 1992, 102:S39-S45) and Dunsworth-Browne et al. (Nucleic Acids Res. 1980 Feb 11;8(3):543-54). The rejection is necessitated by Applicant’s amendment.
Brennan et al. teach the construction of fully-deleted Adenovirus-based gene delivery vectors packaged without helper Adenovirus, and more particularly to their use in gene therapy for gene and protein expression, vaccine development, and immunosuppressive therapy for allogeneic transplantation (Abstract).
Regarding claim 1, Brennan et al. teach a method for propagating a fully-deleted adenoviral
based gene transfer vector comprising: (a) providing an Adenovirus packaging cell line; (b) transfecting into the cell line a fully-deleted Adenoviral vector construct; and (c) transfecting into the cell line a replication defective circular packaging construct having a subset of Adenoviral late genes including L1, L2, L3, L4, L5, E2A, and E4, while being absent of at least one inverted terminal repeat and a packaging signal (Col 55, L20-30, claim 1). Herein the replication defective circular packaging construct reads on the packaging expression plasmid in (c)(ii). Brennan et al. teach the fully-deleted Adenoviral vector construct is a linear, double-stranded DNA molecule with inverted terminal repeats (ITRs) separated by approximately 28 to 37 kb, the viral packaging signal (Ψ), and at least one DNA insert (all or a fragment of at least one gene of interest (GOI)) which comprises a gene sequence encoding a protein of interest (Col 11, L24-31). Herein the fully-deleted Adenoviral vector construct reads on the linear adenovirus-derived genome in (c)(i). Brennan et al. do not specifically point out the adenovirus derived genome that carries terminal sequences on both 5'- and 3'-ends of the linear fragments adenovirus derived genome can be bound by the terminal protein as recited in (c)(i), however, such is an inherent feature and known in the prior art as evidenced by Dunsworth-Browne et al.. Dunsworth-Browne et al. teach the adenovirus genome exists within the virion and in infected cell nuclei as a DNA-protein complex: a 35 kb duplex DNA molecule covalently attached via the 5' termini of each strand to terminal proteins (p543, Introduction). This teaching reads on the adenovirus derived genome can be bound by the terminal protein, as recited in instant claim.
Brennan et al. do not teach the method comprising steps (a) providing a eukaryotic expression vector that codes for the expression of a terminal protein (Tp) and a DNA polymerase (Pol); and (b) transfecting the eukaryotic expression vector into the packaging cell. However, this was disclosed by Chamberlain et al. at the time of instant invention.
Chamberlain et al. provide improved adenovirus vectors and packaging cell lines (Abstract).
Regarding claim 1, Chamberlain et al. teach one type of improved adenoviral vector comprises deletions within the E2b region of the adenoviral genome. These E2b-deleted virus are used in conjunction with novel cell lines that constitutively express E2b gene products (Abstract). E2b encodes the viral DNA polymerase and preterminal protein (pTP) (Col 1, L24-25). Preterminal protein is the precursor form of terminal protein and will form mature terminal protein after cleavage by a viral protease. pTP functions as a primer in initiation and becomes covalently bound to the newly synthesized DNA as a result of the protein priming mechanism that is used by adenovirus, as evidenced by Pronk et al. (see pS39, Introduction). Chamberlain et al. teach cell lines capable of supporting the propagation of Ad virus containing deletions within the E2b region (Col4, L31-33), the packaging cell lines coexpressing pTP and Ad DNA polymerase, contain within their genome (Col 4, L64-65).
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 modify Brennan et al.’s method for propagating a fully-deleted adenoviral based gene transfer vector, and use a packaging cell line coexpressing pTP and Ad DNA polymerase as taught by Chamberlain et al., which can be achieved by constructing a vector that codes for the expression of a terminal protein (Tp) and a DNA polymerase (Pol). The skilled artisan would have been motivated to use such packaging cell line coexpressing pTP and Ad DNA polymerase since Chamberlain et al. teach such packaging cell lines allow the production of infectious recombinant virus containing deletions in the E1 and E2b regions without the use of helper virus (Col 12, L60-63), and allow the high level growth of E1, preterminal, and polymerase deleted Ad vectors (Col 26, L43-45). There would be a reasonable expectation of success of using the cell line packaging cell lines coexpressing pTP and Ad DNA polymerase which can be achieved by constructing a vector that codes for the expression of pTp and a Pol since it is a regular operation in the art to construct a vector codes for the expression of two proteins (i.e., Tp and Pol), and Chamberlain et al. teach the sequence of Tp and Pol (see Col 17).
Regarding claims 3 and 4, following the discussion above, Chamberlain et al. teach cell lines which constitutively express the adenovirus preterminal protein (pTP) gene product (in addition to E1 proteins and DNA polymerase) (Col 4, L51-54).
Regarding claim 5, following the discussion above, Chamberlain et al. teach E2b encodes the
viral DNA polymerase and preterminal protein (pTP) (Col 1, L24-25). Chamberlain et al. provide packaging cell lines and demonstrates that the E2b gene products, DNA polymerase and preterminal protein, can be constitutively expressed in 293 cells along with the E1 gene products (Col 13, L43-47). This teaching reads on the eukaryotic expression vector that codes for the expression of an adenoviral terminal protein, also encodes for the expression of an adenoviral DNA polymerase.
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 modify Brennan et al.’s method for propagating a fully-deleted adenoviral based gene transfer vector, and use a packaging cell line coexpressing pTP and Ad DNA polymerase as taught by Chamberlain et al., which can be achieved by constructing a vector that codes for the expression of a terminal protein (Tp) and a DNA polymerase (Pol), therefore the vector can stably express adenoviral terminal protein as well as adenoviral DNA polymerase. The skilled artisan would have been motivated to use such packaging cell line coexpressing pTP and Ad DNA polymerase since Chamberlain et al. teach such packaging cell lines allow the production of infectious recombinant virus containing deletions in the E1 and E2b regions without the use of helper virus (Col 12, L60-63), and allow the high level growth of E1, preterminal, and polymerase deleted Ad vectors (Col 26, L43-45). There would be a reasonable expectation of success of using the cell line packaging cell lines coexpressing pTP and Ad DNA polymerase which can be achieved by constructing a vector that codes for the expression of Tp and Pol since it is a regular operation in the art to construct a vector codes for the expression of two proteins (i.e., Tp and Pol), and Chamberlain et al. teach the sequence of Tp and Pol (see Col 17).
Regarding claim 6, as discussed above, Brennan et al. teach the fully-deleted Adenoviral vector construct is a linear, double-stranded DNA molecule with inverted terminal repeats (ITRs) separated by approximately 28 to 37 kb, the viral packaging signal (Ψ), and at least one DNA insert (all or a fragment of at least one gene of interest (GOI)) which comprises a gene sequence encoding a protein of interest (Col 11, L24-31).
Regarding claim 7, Brennan et al. teach in figure 2, the FDV2 and FDV4 still have subset of Ad late genes, reads on the adenovirus-derived genome is partially deleted of endogenous adenoviral genes.
Regarding claims 8 and 9, Brennan et al. teach in figure 2, the FDV1 and FDV3 are fully deleted of all endogenous adenoviral genes, as well as fully deleted of endogenous adenoviral genetic structures except the adenoviral left and right inverted terminal repeats (ITRs) and the adenoviral packaging signal (Ψ).
Regarding claim 11, as discussed above, Brennan et al. teach the fully-deleted Adenoviral vector construct is a linear, double-stranded DNA molecule with inverted terminal repeats (ITRs) separated by approximately 28 to 37 kb, the viral packaging signal (Ψ), and at least one DNA insert (all or a fragment of at least one gene of interest (GOI)) which comprises a gene sequence encoding a protein of interest (Col 11, L24-31). Herein the DNA insert reads on the adenovirus-derived genome carries modified and/or non-adenoviral genes.
Regarding claim 13, Brennan et al. teach a system that includes (a) an Adenovirus packaging cell line; (b) a fully-deleted Adenoviral vector construct; and optionally (c) a packaging construct, wherein the fully-deleted adenoviral vector construct and optionally the packaging construct can transfect the Adenovirus packaging cell line resulting in the encapsidation of a fully-deleted Adenoviral vector independent of helper Adenovirus (Col 6, L10-16).
Regarding claim 14, following the discussion above, Brennan et al. teach a method for propagating a fully-deleted adenoviral based gene transfer vector comprising: (a) providing an Adenovirus packaging cell line; (b) transfecting into the cell line a fully-deleted Adenoviral vector construct; and (c) transfecting into the cell line a replication defective circular packaging construct having a subset of Adenoviral late genes including L1, L2, L3, L4, L5, E2A, and E4, while being absent of at least one inverted terminal repeat and a packaging signal (Col 55, L20-30, claim 1). Herein the replication defective circular packaging construct reads on the “packaging expression plasmid” as recited in (c)(ii).
Brennan et al. teach the fully-deleted Adenoviral vector construct is a linear, double-stranded DNA molecule with inverted terminal repeats (ITRs) separated by approximately 28 to 37 kb, the viral packaging signal (Ψ), and at least one DNA insert (all or a fragment of at least one gene of interest (GOI)) which comprises a gene sequence encoding a protein of interest (Col 11, L24-31). Herein the fully-deleted Adenoviral vector construct reads on “a linear DNA construct” as recited in (c)(i). Brennan et al. also teach packaging cell line such as A549 cells (i.e, Example 4) and 293 cells (Col2, L29) which are eukaryotic cells. Brennan et al. do not specifically point out that “the terminal sequences at the 5'- and 3'-ends (of the fully-deleted Adenoviral vector construct) are capable of binding the terminal protein” as well as “the terminal protein binds to the terminal sequences of the DNA construct in the eukaryotic cell to reduce enzymatic degradation of the DNA construct”. However, Dunsworth-Browne et al. provide evidence that the adenovirus genome exists within the virion and in infected cell nuclei as a DNA-protein complex: a 35 kb duplex DNA molecule covalently attached via the 5' termini of each strand to terminal proteins (p543, Introduction), and the terminal protein protects 5' terminated single stranded regions from digestion by a cellular exonuclease (Abstract). Therefore Brennan et al.’s teaching reads on a method comprising (c) as recited in instant claim.
Brennan et al. do not teach steps (a) providing a eukaryotic expression vector that codes for the expression of a terminal protein capable of binding to terminal sequences of a DNA construct; and (b) transfecting the eukaryotic cell with the eukaryotic expression vector. However, Chamberlain et al. teach one type of improved adenoviral vector comprises deletions within the E2b region of the adenoviral genome. These E2b-deleted virus are used in conjunction with novel cell lines that constitutively express E2b gene products (Abstract). E2b encodes the viral DNA polymerase and preterminal protein (pTP) (Col 1, L24-25). Chamberlain et al. teach cell lines which constitutively express the adenovirus preterminal protein (pTP) gene product (Col 4, L51-54). The example of pTP gene product is illustrated in Example 1, the expression plasmid pRSV-pTP, which can be expressed in LP-293 cell line (see Col 17). LP-293 cell is a eukaryotic cell.
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 modify Brennan et al.’s method for propagating a fully-deleted adenoviral based gene transfer vector, and use a packaging cell line expressing pTP as taught by Chamberlain et al.. The skilled artisan would have been motivated to use such packaging cell line expressing pTP since Chamberlain et al. teach the pTp-expressing cell line (i.e., C-7 cell line) can be used as a packaging cell line to allow the high level growth of E1, preterminal, and polymerase deleted Ad vectors (Col 26, L43-45). There would be a reasonable expectation of success of using the cell line packaging cell lines expressing pTP since Chamberlain et al. teach the method and sequence of pTp (see Example 1).
Regarding claim 16, following the discussion above, Chamberlain et al. teach cell lines which constitutively express the adenovirus preterminal protein (pTP) gene product (Col 4, L51-54).
Claims 1, 3-9, 11, 13-14 and 16 are newly rejected under 35 U.S.C. 103 as being unpatentable over Brennan et al. (US 8,871,515 B2, patented in 2014) in view of Chamberlain et al. (US006083750A, patented in 2000), as evidenced by Pronk et al. (Chromosoma, 1992, 102:S39-S45) and Dunsworth-Browne et al. (Nucleic Acids Res. 1980 Feb 11;8(3):543-54), as applied to claims 1, 3-9, 11, 13-14 and 16 above, and further in view of Lieber et al. (Nat Biotechnol. 1997 Dec;15(13):1383-7). The rejection is necessitated by Applicant’s amendment.
The teaching of Brennan et al. and Chamberlain et al. is set forth above.
Regarding claims 2 and 15, Brennan et al. and Chamberlain et al. do not teach eukaryotic expression vector is transiently maintained within the packaging cell. However, this was disclosed by Lieber et al. at the time of instant invention.
Lieber et al. teach a mini-adenoviral genome (9 kb) deleted for viral E1, E2, E3, and late genes, but containing the viral inverted terminal repeats (ITRs), transgene expression cassette (human α1-antitrypsin), and the viral E4 genes was equally efficient at transducing cells in vitro or in vivo as first generation, E1-deleted vectors. Coexpression of the adenoviral E2-preterminal protein from the vector or in trans stabilizes the mini-genome in vitro and in vivo without evidence of cellular toxicity (Abstract).
Regarding claims 2 and 15, Lieber et al. teach expression plasmids with the individual E2 genes, pTP, DBP, or pol individually or in combination were co-transfected onto 5 X 105 HeLa cells, wherein these genes are transiently expressed (see p1384, left column).
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 modify Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein and/or DNA polymerase, and transiently express the vector in cells as taught by Lieber et al.. The only difference between instant claim and Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein is instant claim transiently express the vector expressing terminal protein. Given that Lieber et al. teach the pTP and pol can be transiently expressed in cells (see p1384, left column), one of ordinary skill in the art would have substituted the method of constitutively express the adenovirus preterminal protein (pTP) gene and/or Pol, and transiently express the vector comprising the genes as needed depends on their research interest. This simple substitution of one known element (transiently express the vector comprising terminal protein and/or DNA polymerase) for another known element (constitutively express the vector comprising terminal protein and/or DNA polymerase) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3-9, 11, 13-14, 16-17 and 22 are newly rejected under 35 U.S.C. 103 as being unpatentable over Brennan et al. (US 8,871,515 B2, patented in 2014) in view of Chamberlain et al. (US006083750A, patented in 2000), as evidenced by Pronk et al. (Chromosoma, 1992, 102:S39-S45) and Dunsworth-Browne et al. (Nucleic Acids Res. 1980 Feb 11;8(3):543-54), as applied to Claims 1, 3-9, 11, 13-14 and 16 above, and further in view of Redrejo-Rodríguez et al. (Virology468-470(2014)322–329). The rejection is necessitated by Applicant’s amendment.
The teaching of Brennan et al. and Chamberlain et al. is set forth above.
Regarding claim 17, Brennan et al. and Chamberlain et al. do not teach the eukaryotic expression vector for the terminal protein codes for the expression of a bacteriophage or bacterial terminal protein. However, this was disclosed by Redrejo-Rodríguez et al. at the time of instant invention.
Redrejo-Rodríguez et al. teach various bacteriophage TPs have been shown to have DNA-binding capacity that targets TPs and their attached genomes to the host nucleoid. Furthermore, a number of bacteriophage TPs from different viral families and with diverse hosts also contain putative nuclear localization signals and localize in the eukaryotic nucleus, which could lead to the transport of the attached DNA (Abstract).
Regarding claim 17, Redrejo-Rodríguez et al. teach protein primed based replication of adenoviruses and several bacteriophages from different families like Φ29 or PRD1 can duplicate the full-length genome continuously from both origins, without requiring Okazaki fragments or other accessory proteins (p323, left column). Redrejo-Rodríguez et al. teach many proteins from eukaryotic viruses contain NLSs, including adenovirus and plant positive-strand RNA viruses, which direct or contribute to localization of viral replication and transcription in the host nucleus. Analogously, Φ29 TP targets the
host nucleoid by means of a sequence-independent DNA-binding ability, which provides the correct localization for virus early replication and transcription, and facilitates recruitment of the DNAP (p325, right column). This teaching indicates bacteriophages Φ29 is analogous to adenoviral TP, and have the same mechanism to start replication.
Regarding claim 22, Redrejo-Rodríguez et al. teach many proteins from eukaryotic viruses contain NLSs, including adenovirus and plant positive-strand RNA viruses, which direct or contribute to localization of viral replication and transcription in the host nucleus (p325, right column). Adenovirus is a eukaryotic virus and the terminal protein of Adenovirus is also eukaryotic.
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 modify Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein, and use bacteriophages terminal protein Φ29 as taught by Redrejo-Rodríguez et al.. The only difference between instant claim and Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein is instant claim uses terminal proteins codes for the expression of bacteriophage or bacterial terminal protein. Given that Redrejo-Rodríguez et al. teach bacteriophage terminal protein such as Φ29 has an similar mechanism of targeting to DNA with adenovirus terminal protein (see p324-325), and bacteriophages are the most abundant biological entity on Earth and they coevolved along with their bacterial hosts but also with eukaryotic organisms, therefore bacteriophage Φ29 TP has a high capacity of enhancing gene delivery or mediating horizontal gene transfer (see p327, left column), one of ordinary skill in the art would have substituted adenovirus terminal protein for bacteriophage terminal protein Φ29, depends on their research preference or the purpose of mediating horizontal gene transfer. This simple substitution of one known element (using bacteriophages terminal protein such as Φ29) for another known element (using adenovirus terminal protein) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3-9, 11, 13-14, 16-17, 20 and 22-23 are newly rejected under 35 U.S.C. 103 as being unpatentable over Brennan et al. (US 8,871,515 B2, patented in 2014) in view of Chamberlain et al. (US006083750A, patented in 2000), as evidenced by Pronk et al. (Chromosoma, 1992, 102:S39-S45) and Dunsworth-Browne et al. (Nucleic Acids Res. 1980 Feb 11;8(3):543-54), and further in view of Redrejo-Rodríguez et al. (Virology468-470(2014)322–329), as applied to Claims 1, 3-9, 11, 13-14, 16-17 and 22 above, and further in view of Rijnders et al. (Nucleic Acids Res. 1983 Dec 20). The rejection is necessitated by Applicant’s amendment.
The teaching of Brennan et al., Chamberlain et al. and Redrejo-Rodríguez et al. is set forth above.
Regarding claims 20 and 23, Brennan et al. and Chamberlain et al. do not teach the DNA construct has been modified to enhance the binding of a bacteriophage or bacterial terminal protein or an adenovirus terminal protein. However, such was disclosed by Rijnders et al..
Rijnders et al. purified the pTP-pol complex of adenovirus type 5 and studied its binding to double-stranded DNA (Abstract).
Regarding claims 20 and 23, Rijnders et al. teach binding of pTP-pol to plasmids with deletions in the adenovirus origin (p8786m, table 3), which indicates modifying the DNA construct to change the binding efficiency of terminal proteins.
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 modify Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein, and use adenovirus terminal protein or bacteriophages terminal protein Φ29 as taught by Redrejo-Rodríguez et al., and modify the DNA sequence to change (e.g., enhance) the binding of DNA to terminal protein as taught by Rijnders et al.. The only difference between instant claim and Brennan et al. in view of Chamberlain et al.’s vector expressing terminal protein is instant claim has the DNA construct modified to enhance the binding of said protective proteins. Given that Rijnders et al. teach deletions in the adenovirus origin can change the binding to the terminal protein, one of ordinary skill in the art would have substituted Brennan et al. and Chamberlain et al.’s DNA construct comprising adenovirus origin (5’ termini), and have a modified (e.g., having deletion of nucleic acids) adenovirus origin (5’ termini) in order to obtain a change of binding efficiency (e.g., enhance the binding to terminal protein). This simple substitution of one known element (having modified adenovirus origin in the DNA construct) for another known element (Brennan et al. in view of Chamberlain et al.’s DNA construct comprising adenovirus origin) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Conclusion
No claims are allowed.
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.
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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.
/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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