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 .
Priority
This application claims priority to application 63/214,073 filed 06/23/2021.
Response to Arguments
The Amendments and Remarks filed 01 December 2025 in response to the Office Action 04 September 2025 are acknowledged and have been entered. Claims 1, 11, 23, 28, 30, and 34 are amended, and claims 9-10 have been cancelled. Claims 1-8 and 11-36 are pending and being examined on the merits.
Any rejection or objection not reiterated herein has been overcome by applicants claim amendments.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
The petition to accept color drawings filed on 12/02/2025 is acknowledge and the office is processing this request.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in 0096. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The disclosure is objected to because of the following informalities: The ‘Brief Description of the Figures’ section describes figures having color and a petition for color photographs or color drawings have not been accepted. In the event that the petition is not filed, the references to the colored figures will need to be removed.
Appropriate correction is required.
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 1-5, 7, 11-15, 17-19, 21-30 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Sloan (WO 2018/118567 A1, published 6/28/2018) in view of Eoh (Eoh et al. Biomater. Sci., 2019, 7, 1240‐1261), Patrick (Patrick. 2014. Plasmids 101: Mammalian Vectors; https://blog.addgene.org/plasmids-101-mammalian-vectors#:~:text=For many experiments%2C it is,vs 20 min%2C respectively) and Thomas (US 2020/0385718 A1). This is a new rejection in view of applicants claim amendments.
Regarding claims 1-3, Sloan teaches a composition for treating a viral infection where the composition includes a nucleic acid encoding a gene editing material that is encapsulated in a lipid nanoparticle (LNP) that comprises the human papillomavirus (HPV) capsid protein on the outer surface (i.e. a virus like particle (VLP)) [pg. 3, last paragraph – pg. 4, para 2; pg. 10, para 2; pg. 18, para 2].
Regarding claims 5 and 7, Sloan teaches that the capsid protein can be L1 or L2 capsid proteins [pg. 18, para 2].
Regarding claims 11-14, Sloan teaches that the gene editing material comprises of a programmable nuclease that may be complexed with a guide RNA (gRNA), such as Cas9, ZFNs, TALENs, Cpf1, NgAgo, and any other programmable nuclease [pg. 3, last paragraph – pg. 4, pg. 7, para 7].
Regarding claim 17, Sloan teaches that the gRNA refers to either format where the gRNA comprises a crRNA or a crRNA and a tracrRNA combined into a single guide RNA [pg. 8, last paragraph].
Regarding claims 22, Sloan teaches that the programmable nucleases, or gene editing material, may be prepared and delivered as plasmid DNA (double stranded) [pg. 10, para 2].
Regrading claims 23-26, Sloan teaches that the composition of the invention can be delivered to human skin and cells, thereby teaching a human cell comprising the HPV delivery vehicle [pg. 21, last paragraph-pg. 22, para 2].
Regarding claim 1, Sloan does not teach where the DNA encoding the gene editing material is a minicircle encapsulated by the capsid, without a sequence of a bacterial origin.
Eoh teaches the use of minicircles for Cas9 and sgRNA delivery [see 4.5 Supramolecular assembly for creating delivery nanoparticles, 2nd paragraph]. Eoh teaches that minicircles enhance transgene expression in comparison with regular plasmids. Patrick teaches that a bacteria origin of replication (ORI) will not allow for replication in mammalian cells [para 1].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the delivery vehicle of Sloan where the DNA encoding the gene editing material comprises a minicircle without a sequence of a bacterial origin as taught by Eoh and Patrick. One of ordinary skill would be motivated to make the modification for the enhanced gene expression in mammalian cells given Eoh’s teaching that gene editing materials delivered using minicircles can enhance gene expression, and Patrick’s teaching that any vector with an ORI will not replicate in mammalian cells.
Regarding claims 4, 18, 19, and 27, Sloan does not teach where the mammalian papillomavirus is an HPV-16; where the HPV delivery vehicle comprises the GFP reporter protein; and a hematopoietic stem cell, a progenitor cell, a satellite cell, a mesenchymal progenitor cell, an astrocyte cell, a T-cell, a B cell, a hepatocyte cell, a heart cell, a muscle cell, a retinal cell, a renal cell, or a colon cell comprising the HPV delivery vehicle.
Thomas teaches a method for producing a non-human papilloma pseudovirus or virus like particle comprising capsid proteins and packaging it with a therapeutic agent for expression in eukaryotic cells (regarding claim 24), synthesizing of the sequences and cloning of the synthesized sequences into expression vectors, and producing non-human papilloma pseudovirus or virus like particles [abstract, 0079]. Thomas teaches where the therapeutic agent is a CRISPR/Cas [0081].
Regarding claim 4, Thomas teaches that HPV, especially HPV-16, works quite well as gene delivery vehicles.
Regarding claims 18 and 19, Thomas teaches that the virus-like particles can comprise a reporter gene, where the reporter gene can be GFP [0078-0079].
Regarding claim 27, Thomas teaches directing virus-like particle to liver cells, lung cells, heart cells, kidney cells, blood cells, brain cells, gut cells, stem cells, cells of the mucosa of the throat or the nose, or cancer cells [claim 7].
Regarding claims 4, 18, 19, and 27, it would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the delivery vehicle as taught and suggested by Sloan, Eoh, and Patrick where the mammalian papillomavirus is an HPV-16, where the HPV delivery vehicle comprises GFP, and directing the HPV delivery vehicle to stem, hepatocyte, heart, and renal cells. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Sloan and Thomas teach the methods and compositions of producing and using viral particles for gene delivery and therapeutics. Additionally, Thomas specifically teaches that HPV viral particles, such as HPV-16, can be used as a gene delivery vehicles.
Regarding claim 21, Sloan does not teach where the gene editing material is single-stranded DNA editing material. Thomas teaches that the non-human papilloma pseudovirus or virus-like particle of the invention can contain an antisense oligonucleotide, as a therapeutic agent [0087]. Thomas teaches that an "antisense oligonucleotide" as used herein refers to a single strand DNA and/or RNA molecule that is capable of interfering with DNA and/or RNA processing [0087]. It would have obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the vehicle of Sloan where the gene editing material is an single stranded DNA. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Sloan and Thomas teach the methods and compositions of producing and using HPV viral particles for gene delivery and therapeutics.
Regarding claims 28-29, Sloan does not teach a method of synthesizing a papillomaviral delivery. Thomas teaches a method of producing a non-human papilloma pseudovirus or virus-like particle (VLP) comprising the steps of transfecting an expression vector comprising a codon-optimizing of a DNA-sequence coding for a non-human papillomavirus capsid protein L1 and/or L2, for expression in eukaryotic cells or cell lines, preferably human cells or cell lines, in a cell, thereby producing non-human papilloma pseudovirus or virus-like particles [0112]. Thomas teaches harvesting of the VLPs after transfection [0138]. Thomas teaches that the non-human papilloma pseudovirus or virus like particle of the invention can contain the (CRISPR/Cas) system [0089]. Thomas teaches that other plasmids needed to be included in the VLP, like a reporter plasmid, can also be added to the cell [0136].
Regarding claims 30 and 34, Sloan teaches using a programmable nuclease in a composition for modifying genetic material within a target cell [pg. 17, para 4]. Thomas teaches that the HPV particles allows for genome editing [0089].
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention that the HPV delivery vehicle as taught and suggested by Sloan, Eoh, and Patrick can be produced by transfecting an expression vector comprising a codon-optimizing of a DNA-sequence coding for a non-human papillomavirus capsid protein L1 and/or L2, and an expression vector comprising a DNA encoding a gene editing material into a cell, thereby producing non-human papilloma pseudovirus or virus-like particles which can be harvested after transfection; and can be used in a method of editing a genome in a cell. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill in the art would have a reasonable expectation of success since both Sloan and Thomas teach the methods and compositions of producing and using HPV viral particles for gene delivery and therapeutics.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Sloan (WO 2018/118567 A1, published 6/28/2018) in view of Eoh (Eoh et al. Biomater. Sci., 2019, 7, 1240‐1261) and Patrick (Patrick. 2014. Plasmids 101: Mammalian Vectors; https://blog.addgene.org/plasmids-101-mammalian-vectors#:~:text=For many experiments%2C it is,vs 20 min%2C respectively) as applied to claim 1 and 5, and further in view of Jackson (US 20050100554 A1). This is a new rejection in view of applicants claim amendments.
The teachings of Sloan, Eoh, and Patrick are discussed above as applied to claims 1 and 5, and similarly apply to claim 6. Sloan, Eoh, and Patrick does not teach where the L1 capsid protein comprises an amino acid sequence of SEQ ID NO: 26.
Jackson teaches that HPV genomes are highly conserved and express the capsid proteins of L1 and L2 [0004]. Jackson teaches HPV-16 L1 and teach SEQ ID NO: 115 which translates to a sequence that comprises a sequence that is 100% identical to SEQ ID NO: 26.
It would have obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the vehicle of Sloan where the L1 capsid protein comprises an amino acid sequence translated from SEQ ID NO: 115 of Jackson. This modification would amount to a simple substitution of one known L1 protein for another.
The BRI given to claim is that the L1 capsid is required to comprise an (i.e., any two or more) amino acid sequences in the SEQ ID NOs listed. If the entire SEQ ID NOs listed is intended, it would be remedial to modify the claims to say “the amino acid sequence”.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Sloan (WO 2018/118567 A1, published 6/28/2018) in view of Eoh (Eoh et al. Biomater. Sci., 2019, 7, 1240‐1261) and Patrick (Patrick. 2014. Plasmids 101: Mammalian Vectors; https://blog.addgene.org/plasmids-101-mammalian-vectors#:~:text=For many experiments%2C it is,vs 20 min%2C respectively) as applied to claim 1 and 7, and further in view of Murata (US 20100260792 A1). This is a new rejection in view of applicants claim amendments.
The teachings of Sloan, Eoh, and Patrick are discussed above as applied to claims 1 and 7, and similarly apply to claim 8. Sloan, Eoh, and Patrick does not teach where the L2 capsid protein comprises an amino acid sequence of SEQ ID NO: 27.
Murata teaches . Murata teaches SEQ ID NO:112 as the full-length sequence of HPV-16 L2 protein [0079]. SEQ ID NO:112 comprises a sequence that is 100% identical to SEQ ID NO: 27.
It would have obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the vehicle of Sloan where the L2 capsid protein comprises an amino acid sequence translated from SEQ ID NO: 112 of Murata. This modification would amount to a simple substitution of one known L2 protein for another.
The BRI given to claim is that the L2 capsid is required to comprise an (i.e., any two or more) amino acid sequences in the SEQ ID NOs listed. If the entire SEQ ID NOs listed is intended, it would be remedial to modify the claims to say “the amino acid sequence”.
Claims 11, 15-16, 20, 31-33 and 35-36 is rejected under 35 U.S.C. 103 as being unpatentable over Sloan (WO 2018/118567 A1, published 6/28/2018) in view of Eoh (Eoh et al. Biomater. Sci., 2019, 7, 1240‐1261), Patrick (Patrick. 2014. Plasmids 101: Mammalian Vectors; https://blog.addgene.org/plasmids-101-mammalian-vectors#:~:text=For many experiments%2C it is,vs 20 min%2C respectively), and Thomas (US 2020/0385718 A1) as applied to claims 1, 30 and 34, and further in view of Fauser (US20200063114 A1). This is a new rejection in view of applicants claim amendments.
The teachings of Sloan, Eoh, Patrick, and Thomas are discussed above as applied to claims 1, 30, and 34, and similarly apply to claims 11, 15-16, 20, 31-33 and 35-36. Sloan, Eoh, and Patrick do not teach where the nuclease is a Cas13a nuclease or where the delivery vehicle consist of a nuclease coupled to a ABE7.10 deaminase. While Sloan and Thomas teaches editing a polynucleotide, Sloan, Eoh, Patrick, and Thomas do not teach knocking down a DNA or RNA polynucleotide target.
Fauser teaches methods and compositions to selectively edit DNA in a cell (for example, a base editor) using CRISPR/Cas systems [0008, 0024]. Fauser teaches that the base editing compositions (systems) described herein can directly change the identity of individual DNA base pairs without inducing double-stranded breaks.
Regarding claims 11 and 20, Fauser teaches linking the ABE7.10 deaminase to Cas proteins for gene editing [0242; 0249; Fig. 3].
Regarding claim 15-16, Fauser teaches that the base editor, Cas13a (i.e., RNA-targeting, RNA binding, RNA cleaving nuclease) and an adenosine or cytosine deaminase, may also be used in gene editing systems [0121, 0196].
Regarding claims 11, 15-16, and 20, it would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the delivery vehicle as taught and suggested by Sloan, Eoh, and Patrick where the nuclease is Cas13a or the Cas13a nuclease is coupled to a ABE7.10 deaminase. One of ordinary skill would be motivated to make the modification for the advantage of editing DNA in a cell without inducing double-stranded breaks. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill would have a reasonable expectation of success since both Sloan and Fauser teach using CRISPR Cas systems to modify polynucleotides.
Regarding claims 31-32 and 35-36, Fauser teaches that the base-editor complex induced DNA or RNA modifications [0038].
Regarding claim 33, Fauser teach methods and compositions to selectively edit DNA in a cell with a base editor that can be used for gene knockout of gene expression of a targeted gene [0008, 0036, 101].
Regarding claims 31-33 and 35-36, it would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention that the delivery vehicle as taught and suggested by Sloan, Eoh, Patrick, Thomas, and Fauser where the nuclease is Cas13a coupled to a ABE7.10 deaminase can be used to further knock down the DNA or RNA polynucleotide target. One of ordinary skill would be motivated to make the modification for the advantage of editing DNA in a cell. The combination of prior art elements according to known methods to yield predictable results supports can support a conclusion of obviousness. See MPEP 2143(I). One of ordinary skill would have a reasonable expectation of success since Sloan, Thomas and Fauser teach using CRISPR Cas systems to modify/edit polynucleotides.
Response to Arguments
Applicant's arguments filed 01 December 2025 have been fully considered but they are not persuasive. Applicant’s arguments with respect to claim(s) 1-3, 5, 7, 11-15, 17, 21-22, and 24 were rejected under 35 USC 102(a)(1) and the claims rejected under 35 USC 103 as being anticipated or obvious over Sloan and have been considered but are moot as the arguments are directed to the newly amended claims.
Applicant’s arguments, with respect to the rejection(s) of claim(s) 9 and 10 were rejected under 35 USC 103 have been fully considered and are not persuasive. Applicants argue that Eoh’s teachings are not applicable to the claims since the claims is not directed to Cas9 in its protein form but instead directed to a minicircle DNA and fails to suggest a minicircle DNA for Cas9. Claim 1 requires that the minicircle encoding a gene editing material, not specifically Cas9. Claim 11 requires that the gene editing material can be a nuclease or a gRNA. Eoh specifically teaches the use of nanoparticles to successfully deliver Cas9 and sgRNA minicircles to U87 and GS5 cells as discussed in the rejections (see section 4.5); therefore, Eoh’s teachings are applicable to the claims.
Conclusion
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637