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 .
DETAILED ACTION
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 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.
Response to Amendments
Applicant’s amendments, corrected drawings and specification, and response filed Apr. 3, 2026 have been received and entered into the case.
Status of the Claims
Claims 1-6, 8, and 10-22 are currently pending.
Claims 1, 6, and 8 are amended.
Claims 13-17 and 19-22 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 7 and 19 are cancelled.
Claims 1-6, 8, and 10-12 have been considered on the merits.
Drawing Objections
The drawing objections are withdrawn due to amendment.
Specification Objections
The specification objections are withdrawn due to amendment.
Claim Objections
The claim objections are withdrawn due to amendment.
Claim Rejections - 35 USC § 103
The claim rejections under 35 USC § 103 are withdrawn due to amendment. New claim rejections under 35 USC § 103 have been added to address the claim amendments.
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 1-3, 5, 6, 8, 10-12, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Ahern et al. (WO 2019/090154 A1, published May 9, 2019) (ref. of record) as evidenced by Arnold et al. (Gene, 1987) and STIC search results (see Supplemental Content of Application) in view of Shanker et al. (Immuno-oncology Insights, 2017).
With respect to claim 1, Ahern teaches a DNA oligonucleotide sequence encoding an anti-codon edited-tRNA (ACE-tRNA) and a promoter (pg. 3 lines 9-11, pg. 4 lines 1-11 and 29-31 and Fig. 4).
With respect to claim 3, Ahern teaches the molecule further including a 5’ leader sequence which is the 5’ leader sequence of human tRNA gene (pg. 54 lines 32-34), a transcription enhancing 5’ leader sequence as evidence by Arnold (abstract).
With respect to claims 10 and 11, Ahern teaches the ACE-tRNA comprises the sequence of SEQ ID NO. 1, 4, 5, 8, 79 and 94. SEQ ID NO. 48 of Ahern shares 100% homology with instant SEQ ID NO. 1 (Result 1 of N_Geneseq in Supplemental Contents, Search Results). SEQ ID NO 548 of Ahern shares 100% homology with instant SEQ ID NO. 4 (Result 1 of N_Geneseq). SEQ ID NO 607 of Ahern shares 100% homology with instant SEQ ID NO. 5 (Result 1 of N_Geneseq). SEQ ID NO 109 of Ahern shares 100% homology with instant SEQ ID NO. 8 (Result 2 of N_Geneseq). SEQ ID NO 170 of Ahern shares 100% homology with instant SEQ ID NO. 79 (Result 1 of N_Geneseq). SEQ ID NO 199 of Ahern shares 100% homology with instant SEQ ID NO. 94 (Result 1 of N_Geneseq).
With respect to claim 12, Ahern teaches the molecule and a pharmaceutically acceptable carrier (pg. 4 lines 15-17). With respect to claim 18, Ahern teaches a host cell with the molecule (pg. 4 lines 26-28).
Ahern does not teach the DNA molecule where it is a closed end, circular, non-viral, non-plasmid DNA molecule as recited in claim 1. Similarly, Ahern does not teach that the molecule is a closed end DNA thread (CEDT) molecule or a minicircle (MC) molecule as recited in claim 2. Ahern does not explicitly teach the DNA molecule being free of any bacterial nucleic acid sequence as recited in claim 5. Ahern does not teach the molecule comprises 4 or less CpG dinucleotides or is free of CpG dinucleotide as recited in claim 6. Additionally Ahern does not teach the DNA molecule is about 200-600 bp in size as recited in claim 1 or about 500 bp in size as recited in claim 8.
However, Shanker teaches DNA molecules that are minicircles (MCs) for gene therapy (abstract). Shanker teach MC vectors are safe and ideal non-viral vectors for both quiescent and dividing cells with better performance than standard non-viral vectors such as plasmids (pg. 292 Col. 2 para. 1). Shanker reports MCs are maintained in a higher copy number and were expressed for a longer time, MC offer freedom with the size for the therapeutic transgene construct, and have an excellent safety profile (pg. 292 Col. 2 para. 1). Shanker teaches a goal in vector development is to produce supercoiled DNA lacking bacterial backbone sequences, which are used for amplification in bacterial cultures and uncontrolled expression of these sequence can have detrimental effects such as the dissemination of antibiotic resistance genes (abstract). Shanker teaches minicircle (MC) DNA consists almost of only the active gene cassette (abstract). Shanker teaches minicircles of significantly different sizes can be produced, for example MC.shGFP of 501 bp to a MC.DP2rs of 21870 bp and that extremely small MCs can be generated (pg. 286-287 bridging para. and Fig. 4).
Shanker teaches the bacterial backbone and unmethylated CpG dinucleotides are removed in the MCs (pg. 286 Col. 1 last para. and pg. 290 last para.). In addition, Shanker teaches that CpG-free plasmids have been developed to prevent in promoter silencing in mammalian cells and are capable of sustained transgene expression and a reduction in the inflammatory response through Toll-like receptor 9 (pg. 291 Col. 1 para. 2).
Additionally, Ahern teaches the DNA molecule for treating cystic fibrosis and genetic disease associated with a premature stop codon (pg. 2 lines 31-34, pg. 4 lines 24-28). Ahern teaches a viral or plasmid vector containing the transgene or nucleic acid encoding the modified tRNA (pg. 4 lines 9-14). Ahern further teaches that the gene delivery vehicle can be any delivery vehicle known in the art including eukaryotic, prokaryotic, and viral vectors and naked DNA that is facilitated by a receptor and/or lipid mediated transfection (pg. 15 line 19 to pg. 16 line 3).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern so that the transgene is within a minicircle molecule for the benefit of providing enhanced transgene expression such as higher copy numbers and longer expression, a safe vector for gene therapy, and no risk of dissemination of antibiotic resistant genes as taught by Shanker. In addition, one would have been motivated to use a minicircle with no CpG dinucleotides and no bacterial nucleic acid sequences as the delivery vehicle for the benefit of reducing inflammation and removing unnecessary components when used as a gene therapy as taught by Shanker. It would have been obvious to one of ordinary skill in the art to modify the DNA molecule of Ahern to substitute the viral or plasmid vector for another vector that is known to be successful in gene therapy, such as the minicircle molecule with no CpG dinucleotides and bacterial nucleic acid sequences that is taught by Shanker. Furthermore, Ahern teaches that any known gene delivery vehicle can be used to deliver the ACE-tRNA. Additionally, one of ordinary skill would have had a reasonable expectation of success in such a modification to the DNA molecule of Ahern, since Shanker teaches the successful delivery of such minicircle molecules and the expression of transgenes within minicircle molecules.
Additionally, one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern to be a minicircle of about 200 to 600 bp for the benefit of having a MC DNA that consists almost of only the active gene cassette as taught by Shanker. Furthermore, it would have been obvious to one of ordinary skill in the art to make such a modification to the DNA molecule of Ahern, since Shanker teaches MC DNA molecules consists almost of only the active gene cassette (abstract). It would have been obvious to one of ordinary skill in the art to modify the DNA molecule of Ahern to substitute the viral or plasmid vector for another vector that is known to be successful in gene therapy, such as a MC that is 200-600 bp in size, contains no CpG dinucleotides and no bacterial nucleic acid sequences that is taught by Shanker, since MCs within this size were known as taught by Shanker. Additionally, one of ordinary skill would have had a reasonable expectation of success in such a modification to the DNA molecule of Ahern, since Shanker teaches the successful delivery of such minicircle molecules and the expression of transgenes within minicircle molecules. Furthermore, one of ordinary skill in the art would recognize that the size of the MC is a result effective variable and that the size of the MC would be matter of routine optimization as evidenced by Shanker. Shanker teaches minicircles of significantly different sizes can be produced, for example MC.shGFP of 501 bp to a MC.DP2rs of 21870 bp and that extremely small MCs can be generated (pg. 286-287 bridging para. and Fig. 4).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 3 and 4 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ahern in view of Shanker (as applied to claims 1-3, 5, 6, 8, 10-12, and 18 above), and further in view of Vaysse et al. (The Journal of Gene Medicine, 2006).
The teachings of Ahern and Shanker can be found in the previous rejection above.
Ahern does not teach the molecule containing a DNA nuclear targeting sequence (DTS) which is SV40-DTS as recited in claims 3 and 4, respectively.
However, Vaysse teaches that by including the SV40 nuclear localization signal (NLS) or DNA nuclear targeting sequence in a minicircle enhances the nuclear import of the DNA minicircle and potentiate gene expression (abstract).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the DNA molecule taught by the combined teachings of Ahern and Shanker to include a SV40-DTS for the benefit for enhancing nuclear import of the DNA minicircle and potentiate gene expression as taught by Vaysse. It would have been obvious to one of ordinary skill in the art to modify the DNA molecule taught by the combined teachings of Ahern and Shanker to include a SV40-DTS, since Vaysse teaches inclusion of such a sequence improves expression of transgenes. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success in making such a modification to the DNA molecule taught by the combined teachings of Ahern and Shanker, since such a modification to a minicircle DNA containing a transgene was known to successfully express the transgene as taught by Vaysse.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 1-3, 5, 6, 10-12 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Ahern et al. (WO 2019/090154 A1, published May 9, 2019) (ref. of record) as evidenced by Arnold et al. (Gene, 1987) and STIC search results (see Supplemental Content of Application) in view of Li et al. (PLoS One, 2013) and Hardee et al. (Genes, 2017) as evidenced by Shanker et al. (Immuno-oncology Insights, 2017).
With respect to claim 1, Ahern teaches a DNA oligonucleotide sequence encoding an anti-codon edited-tRNA (ACE-tRNA) and a promoter (pg. 3 lines 9-11, pg. 4 lines 1-11 and 29-31 and Fig. 4).
With respect to claim 3, Ahern teaches the molecule further including a 5’ leader sequence which is the 5’ leader sequence of human tRNA gene (pg. 54 lines 32-34), a transcription enhancing 5’ leader sequence as evidence by Arnold (abstract).
With respect to claims 10 and 11, Ahern teaches the ACE-tRNA comprises the sequence of SEQ ID NO. 1, 4, 5, 8, 79 and 94. SEQ ID NO. 48 of Ahern shares 100% homology with instant SEQ ID NO. 1 (Result 1 of N_Geneseq in Supplemental Contents, Search Results). SEQ ID NO 548 of Ahern shares 100% homology with instant SEQ ID NO. 4 (Result 1 of N_Geneseq). SEQ ID NO 607 of Ahern shares 100% homology with instant SEQ ID NO. 5 (Result 1 of N_Geneseq). SEQ ID NO 109 of Ahern shares 100% homology with instant SEQ ID NO. 8 (Result 2 of N_Geneseq). SEQ ID NO 170 of Ahern shares 100% homology with instant SEQ ID NO. 79 (Result 1 of N_Geneseq). SEQ ID NO 199 of Ahern shares 100% homology with instant SEQ ID NO. 94 (Result 1 of N_Geneseq).
With respect to claim 12, Ahern teaches the molecule and a pharmaceutically acceptable carrier (pg. 4 lines 15-17). With respect to claim 18, Ahern teaches a host cell with the molecule (pg. 4 lines 26-28).
Ahern does not teach the DNA molecule where it is a closed end, circular, non-viral, non-plasmid DNA molecule as recited in claim 1. Similarly, Ahern does not teach that the molecule is a closed end DNA thread (CEDT) molecule or a minicircle (MC) molecule as recited in claim 2. Ahern does not explicitly teach the DNA molecule being free of any bacterial nucleic acid sequence as recited in claim 5. Ahern does not teach the molecule comprises 4 or less CpG dinucleotides or is free of CpG dinucleotide as recited in claim 6.
However, Li teaches closed-ended DNA linear molecules (CELiD) or closed end DNA thread (CEDT) molecule for the delivery of transgenes (abstract and pg. 1 para. 1). Li teaches CELiD DNA result in long-term, stable transgene expression in mice liver and are an alternative to bacterial plasmid DNA (abstract). Li teaches that “ideally, DNA for non-viral gene transfer would contain only the gene of interest be devoid of prokaryotic modifications that can trigger an innate immune response, be in an exonuclease-resistant form, and lack detectable endotoxin contamination” (pg. 1 para. 1). Li further teaches the CELiD DNA does not contain prokaryotic DNA (pg. 1 para. 1). Li teaches that CpG dinucleotides occur more frequently in prokaryote-derived plasmid DNA and are reported to elicit a T cell-mediated immune response (pg. 12 Col. 1 para. 2).
Additionally, Ahern teaches the DNA molecule for treating cystic fibrosis and genetic disease associated with a premature stop codon (pg. 2 lines 31-34, pg. 4 lines 24-28). Ahern teaches a viral or plasmid vector containing the transgene or nucleic acid encoding the modified tRNA (pg. 4 lines 9-14). Ahern further teaches that the gene delivery vehicle can be any delivery vehicle known in the art including eukaryotic, prokaryotic, and viral vectors and naked DNA that is facilitated by a receptor and/or lipid mediated transfection (pg. 15 line 19 to pg. 16 line 3).
Accordingly, at the effective time of filing of the claimed invention one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern so that the transgene is within a closed-ended DNA linear molecules (CELiD) or closed end DNA thread (CEDT) molecule for the benefit of providing enhanced transgene expression as taught by Li. In addition, one would have been motivated to use a CELiD (CEDT) with no CpG dinucleotides and no bacterial nucleic acid sequences as the delivery vehicle for the benefit of eliciting an immune response when used as a gene therapy as taught by Li. It would have been obvious to one of ordinary skill in the art to modify the DNA molecule of Ahern to substitute the viral or plasmid vector for another vector that is known to be successful in in gene therapy, such as a CELiD (CEDT) with no bacterial nucleic acid sequences that is taught by Li. Furthermore, Ahern teaches that any known gene delivery vehicle can be used to deliver the ACE-tRNA. Additionally, one of ordinary skill would have had a reasonable expectation of success in such a modification to the DNA molecule of Ahern, since Li teaches the successful delivery of such a CELiD (CEDT) and the expression of transgenes within CELiD (CEDT) molecules.
Additionally, neither Ahern or Li teach the DNA molecule is about 200-600 bp in size as recited in claim 1 or about 500 bp in size as recited in claim 8.
However, Hardee teaches that the benefits of reducing vector length for gene delivery and transgene expression has been well-established (pg. 8 para. 2). Hardee teaches naked DNA vectors less than ~1200 bp completely survive aerosolization (pg. 8 para. 2). Hardee teaches there is a length dependence for naked DNA vectors surviving human serum and the smaller the vector the longer the survival (pg. 8 para. 2).
Additionally, one of ordinary skill in the art would have been motivated to modify the DNA molecule taught by the combined teachings of Ahern and Li to be smaller, such as that is 200-600 bp in size, for the benefit of having vector that has a longer survival and the ability to be aerosolized if delivered nasally as taught by Hardee. Furthermore, it would have been obvious to one of ordinary skill in the art to make such a modification to the DNA molecule of Ahern and Li, since Hardee teaches the desire to decrease the size of DNA vector as much as possible. Additionally, one of ordinary skill would have had a reasonable expectation of success in such a modification to the DNA molecule of Ahern, since Hardee teaches the advantages of small vectors. Furthermore, one of ordinary skill in the art would recognize that the size of the vector is a result effective variable and that the size of the vector would be matter of routine optimization as evidenced by Shanker. Shanker teaches minicircles of significantly different sizes can be produced, for example MC.shGFP of 501 bp to a MC.DP2rs of 21870 bp and that extremely small MCs can be generated (pg. 286-287 bridging para. and Fig. 4).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed Apr. 3, 2026 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 103, Applicant argues that Ahern does not teach a circular, non-viral, and non-plasmid DNA molecule that is about 200-1000 bp or 500 bp in size as claimed and instead teaches viral vectors and non-plasmid DNA molecules that are completely different structures (Remarks pg. 9-10 bridging para.). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Ahern is being relied upon for the teaching of a DNA oligonucleotide sequence encoding an anti-codon edited-tRNA (ACE-tRNA) and a promoter. The claim amendments required a new rejection and now Shanker is being relied upon for the teaching of a circular, non-viral, and non-plasmid DNA molecule that is about 200-1000 bp or 500 bp in size. Applicant addressed each prior art reference separately and only with regard to the specific limitations of that reference. However, when the prior art references are taken as a whole, they teach that the skilled artisan knows each step of the method as currently claimed.
Applicant argues that Arnold does not remedy the deficiencies of Ahern and there is motivation to combine Ahern and Arnold to arrive at the claim invention with a reasonable expectation of success, since Arnold does not teach a circular, non-viral, and non-plasmid DNA molecule that is about 200-600 bp in size as recited in claim 1 (Remarks pg. 10 para. 2). Applicant is reminded that Arnold is an evidentiary reference supporting the 5’ leader sequence which is the 5’ leader sequence of human tRNA gene taught by Ahern is a transcription enhancing 5’ leader sequence. Arnold is not a reference supporting a rejection under U.S.C. §103, and thus is not being used to establish obviousness of a particular limitation.
Applicant argues that the STIC results do not remedy the deficiencies of Ahern and Arnold (Remarks pg. 10 para. 3). Applicant is reminded that the STIC results is an evidentiary reference supporting sequences taught by Ahern have are the same as those claims in claims 10 and 11. The STIC results not a reference supporting a rejection under U.S.C. §103, and thus is not being used to establish obviousness of a particular limitation.
Applicant argues that Munye does not remedy the deficiencies of Ahern, Arnold and the STIC results, since Munye describes a minicircle that is 2.9 kb which is much larger than the claimed minicircle that is 200-600 bp. Applicant further argues that even if the firefly luciferase gene is replaced with the 80 bp ACE-tRNA, the minicircle would be around 1000 bp (Remarks pg. 10 para. 4). Applicant argues that this difference is critical, since Munye’s gene therapy requires minicircles that are large enough to carry entire gene expression cassettes and Munye’s system would not work with the claimed smaller size minicircles since the no therapeutic gene could be accommodated within that size (Remarks pg. 11 para. 1). The Applicant’s amendments limiting claim 1 to a DNA molecule that is 200-600 bp necessitated the withdrawal of previous rejections. Applicant’s arguments are drawn to Munye failing to teach this new limitation. However, this new limitation is addressed in the new rejection. Additionally, Applicant’s arguments with respect to Munye have been considered but are moot because Munye is no longer being used in the current rejection.
Applicant argues that the claimed invention works because ACE-tRNAs are small enough to fit within this size range while retaining functional activity (Remarks pg. 11 para. 1). However, this argument was not found to be persuasive, since this new limitation is addressed in the new rejection.
Applicant argues that one of ordinary skill in the art would not have been motivated to reduce the minicircle size of Munye or combine Munye with the teachings of Ahern, Arnold and the STIC results, since that would defeat the purpose of the conventional gene therapy taught by Munye (Remarks pg. 11 para. 1-2). Applicant’s arguments with respect to Munye have been considered but are moot because Munye is no longer being used in the current rejection.
Applicant argues that the claimed DNA molecule exhibits unexpected results. Specifically, the DNA molecule has a reduced size that retains functional activity, and as stated in the specification has several features including ability to overcome obstacles during intracellular trafficking which improves bioavailability, a higher cell-entry efficiency, possession of transcriptionally active structure, and a sustained transgene expression without genomic integration (Remarks pg. 11 para. 3). Applicant argues that they have generated the smallest ever therapeutic expression vector to their knowledge (Remarks pg. 12 para. 2). Applicant argues that another advantage of the present invention is that it provides facile expression and cell specific delivery, since the entire system is compact (Remarks pg. 12 para. 2). However, these arguments were not found to be persuasive, since the prior art teaches the claimed invention as explained in the new set of rejections. Briefly, Shanker reports minicircles (MCs) are maintained in a higher copy number and were expressed for a longer time, MC offer freedom with the size of the therapeutic transgene construct, and have an excellent safety profile (pg. 292 Col. 2 para. 1). In addition, Shanker teaches a minicircle MC.shGFP that is 501 bp. It is maintained that one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern so that the ACE-tRNA expression cassette is in a minicircle for the benefits of longer gene expression and safety characteristics.
Similarly, Applicant argues that Examples 3 and 4 demonstrate the efficacy of PTC suppression by minicircles and closed end DNA threads encoding ACE-tRNA and Example 4 further demonstrates ACE-tRNAs inhibit NMD of endogenous CFTR (cystic fibrosis transmembrane conductance regulator) mRNA with CF causing PTCs (premature stop codons) (Remarks pg. 12 para. 3). Applicant argues that these unexpected results demonstrated in Examples 3 and 4 support the nonobviousness of the claimed DNA molecule (Remarks pg. 13 para. 1). However, these arguments were not found to be persuasive, since the prior art teaches the claimed invention as explained in the new set of rejections as explained above. Briefly, Shanker reports minicircles (MCs) are maintained in a higher copy number and were expressed for a longer time, MC offer freedom with the size of the therapeutic transgene construct, and have an excellent safety profile (pg. 292 Col. 2 para. 1). In addition, Shanker teaches a minicircle MC.shGFP that is 501 bp. It is maintained that one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern so that the ACE-tRNA expression cassette is in a minicircle for the benefits of longer gene expression and safety characteristics.
Applicant argues that Vaysse does not remedy the deficiencies of Ahern and Munye, since Vaysse does not teach a DNA molecule encoding a tRNA and teaches minicircles that are much larger than the claimed minicircle (Remarks pg. 13 para. 3).
Applicant’s arguments are drawn to Vaysse failing to teach this new limitation. However, this new limitation is addressed in the new rejection.
Additionally, Applicant argues in light of the unexpected results, the claimed DNA molecule is non-obvious (Remarks pg. 13 para. 3). However, this argument was not found to be persuasive, since the prior art teaches the claimed invention as explained in the new set of rejections as explained above.
Applicant argues that Bates does not remedy the deficiencies of Ahern and Munye, since Bates is directed to using small DNA circles as tools for studying the physical and topological properties of closed-circular DNA and does not teach the circles for encoding a gene product (Remarks pg. 14 para. 3). Applicant further argues that Bates teaches that small DNA circles of 500-1000 bp cannot replicate independently (Remarks pg. 14 para. 3). Applicant argues that Bates does not teach the following features of the claimed DNA molecule: a promoter, a sequencing encoding an ACE-tRNA and a closed end, circular non-viral and non-plasmid DNA that where the DNA molecule is about 200-600 bp in size (Remarks pg. 14-15 bridging para.). Applicant argues given the different purpose and features of the DNA molecules of Bates, one of ordinary skill in the art would have had no motivation to combine these teachings with Ahern and Munye or reasonable expectation of success in doing so to arrive at the claimed invention (Remarks pg. 14 para. 1). The majority of Applicant’s arguments are drawn to Bates failing to teach the new limitations. However, the new limitations are addressed in the new rejections. Additionally, Applicant’s arguments with respect to the difference in purpose and features of the DNA molecules taught in Bates compared to the other cited art and claimed invention have been considered but are moot because Bates is no longer being used in the current rejection.
Additionally, Applicant argues in light of the unexpected results, the claimed DNA molecule is non-obvious (Remarks pg. 14 para. 1). However, this argument was not found to be persuasive, since the prior art teaches the claimed invention as explained in the new set of rejections as explained above.
Applicant argues that Li does not remedy the deficiencies of Ahern and Munye, since Li is directed to closed-ended linear duplex molecules (CELiDs) which are structurally different from closed end, circular, non-viral, and non-plasmid DNA molecule, Li does not teaches a sequence encoding ACE-tRNA and instead teaches reporter genes; and the DNA molecules in Li are over 4 times the maximum size claimed (Remarks pg. 15 last para.). Applicant’s arguments are drawn to Li failing to teach this new limitation. However, this new limitation is addressed in the new rejection.
Additionally, Applicant argues in light of the unexpected results, the claimed DNA molecule is non-obvious (Remarks pg. 15-16 bridging para.). However, this argument was not found to be persuasive, since the prior art teaches the claimed invention as explained in the new set of rejections as explained above.
Applicant argues given the different purpose and features of the DNA molecules of Li, one of ordinary skill in the art would have had no motivation to combine these teachings with Ahern and Munye or a reasonable expectation of success in doing so to arrive at the claimed invention (Remarks pg. 16 para. 1). However, these arguments were not found to be persuasive, since Li is direct to non-viral gene transfer without prokaryotic modifications in eukaryotic cells and to gene therapy like the reference, Ahern (abstract, pg. 1 para. 1). Furthermore, it is noted that Li reports that mini-linear, covalent closed (mini-lcc) DNA such as closed-ended linear duplex molecules (CELiDs) possess all the benefits of “mini-circle” DNA vectors and eliminates the potential for undesirable vector integration events (pg. 12 Col. 1 last para.). It is maintained that one of ordinary skill in the art would have been motivated to modify the DNA molecule of Ahern so that the transgene is within a closed-ended DNA linear molecules (CELiD) or closed end DNA thread (CEDT) molecule for the benefit of providing enhanced transgene expression as taught by Li.
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.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Thibault, Thomas, et al. "Production of DNA minicircles less than 250 base pairs through a novel concentrated DNA circularization assay enabling minicircle design with NF-κB inhibition activity." Nucleic acids research 45.5 (2017): e26-e26.
Thibault reports that they developed DNA minicircles that are less than 250 bp (abstract).
Thibault teaches that “reducing the size of conventional plasmids to small dsMCs offers several advantages such as increased resistance to the shearing forces associated with nucleic acid delivery system, significantly better biostability in human serum and in the living cells and an improvement in DNA intracellular delivery and trafficking” (pg. 1 Col. 2).
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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