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.
Election/Restrictions
Applicant’s election without traverse of Invention I, claims 1-6, 8, 10-12 and 18, in the reply filed on Oct. 10, 2025 is acknowledged.
Claims 1-6, 8, and 10-22 remain pending in the current application, claims 13-17 and 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The requirement for the restriction of Inventions 1-III is still deemed proper and is therefore made FINAL.
Claims 1-6, 8, 10-12 and 18 have been considered on the merits.
Status of the Claims
Claims 1-6, 8, and 10-22 are currently pending.
Claims 13-17 and 19-22 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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, 10-12 and 1 have been considered on the merits.
Drawings
The disclosure is objected to because of the following informalities:
The drawings are objected to because of the following informalities: illegible text in Fig. 3; there is description of color in the Specification of Fig. 5 on pg. 4 line 32 to pg. 5 line 5, and on pg. 72 line 3 and the various colors cannot be distinguished from each other since the figures are in black and white.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the terms: NanoLuc® on pg. 5 line 12, pg. 74 lines 11 and 12; CELLECTRA® on pg. 41 line 11, pg. 62 line 1; Zetasizer® Nano ZS on pg. 53 line 22, which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
The disclosure is objected to because of the following informalities:
Claim 1 is objected to in the recitation of “(1)” in line 1 and “(ii)” in line 2, and in the interest of improving claim form, it is suggested that either “(1)” be changed to “(i)” or “(ii)” be changed to “(2)”.
Appropriate correction is appreciated.
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.
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, 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 Munye et al. (Scientific Reports, 2016) (ref. of record).
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, Munye teaches DNA molecules that are minicircles for gene therapy (abstract). Munye teaches that minicircle DNA provide enhanced transgene expression in a variety of organs and teaches the successful enhanced transgene gene expression when the transgene is contain within a minicircle compared to a plasmid DNA (abstract, pg. 2 para. 4, and pg. 9-10 bridging para). Munye teaches that plasmid DNA payloads that have been optimized to enhance or prolong transgene expression by the removal of all CpG motifs to reduce inflammation (pg. 2 para. 3). Munye further teaches that plasmids contain bacterial backbones containing replication origin sequences and antibiotic resistances genes to allow for easy propagation and purification of plasmid DNA and these components are not needed for gene therapy (pg. 2 para. 3). Munye teaches that the unnecessary bacterial backbone has been removed from plasmid DNA to produce minicircle DNA (pg. 2 para. 4).
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 as taught by Munye. 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. 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 Munye. 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 Munye teaches the successful delivery of such minicircle molecules and the expression of transgenes within minicircle molecules.
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 Munye (as applied to claims 1-3, 5, 6, 10-12, and 18 above), and further in view of Vaysse et al. (The Journal of Gene Medicine, 2006).
The teachings of Ahern and Munye 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). In further support, Munye teaches that plasmid DNA payloads that have been optimized to enhance or prolong transgene expression by include promoters, enhancer elements and polyadenylation signals and the removal of all CpG motifs to reduce inflammation (pg. 2 para. 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 taught by the combined teachings of Ahern and Munye 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 Munye to include a SV40-DTS, since Li teaches inclusion of such a sequence improves expression of transgenes and Munye teaches optimizing the DNA molecules to improve expression. 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 Munye, since such a modification to a minicircle DNA containing a transgene was known to successfully express the transgene as taught by Li.
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.
Claim 8 is rejected under 35 U.S.C. 103(a) as being unpatentable over Ahern in view of Munye (as applied to claims 1-3, 5, 6, 10-12, and 18 above), and further in view of Bates et al. (Biochemical Society Transactions, 2013).
The teachings of Ahern and Munye can be found in the previous rejection above.
Ahern does not teach the molecule is about 200 to about 1,000 bp in size or is about 500 bp in size as recited in claim 8.
However, Bates teaches a rigorous definition of DNA minicircles would be molecules that are less than 500-1000 bp in size (pg. 566 Col. 1 para. 3). Bates teaches the large size of plasmid DNAs present difficulties for at least analyzing the DNA (pg. 565 Col. 2 para. 2). In further support, Munye teaches that there is an inverse correlation between plasmid DNA size and transfection efficiency and that extragenic sequences lower levels of transgene expression and persistence (pg. 7-8 bridging para.).
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 Munye to be about 200-1000 bp or 500 bp or relatively small for the benefit for avoiding the complications of larger plasmid DNA as taught by Bates and for improving transgene expression and persistence as taught by Munye. 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 Munye to be about 200-1000 bp or 500 bp, since Bates teaches minicircle molecules of this size. 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 Munye, since minicircle molecules were known of to be about 200-1000 bp or 500 bp as taught by Bates.
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).
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.
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.
Conclusion
No claims are allowed.
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