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 and Formal Matters
This action is in response to papers filed 11/5/2025.
Claims 1-9, 14-18, 21-24 are pending.
Claims 1-2, 5, have been amended.
Claims 21-24 have been added by amendment.
Applicant’s election without traverse of the DNA double strand repair event to include homologous recombination, HEK293FY cells and BFP in the reply filed on 7/3/2025 is acknowledged.
The previous objection to the claims has been withdrawn in view of the amendment.
Priority
The instant application filed 06/21/2022 Claims Priority from Provisional Application 63212937 , filed 06/21/2021.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Response to Arguments
This is a new ground of objection.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: Claims have been amended to recite” first reporter gene,” “second reporter gene,” “third reporter gene,” “destroy activity,” “epigenic” Review and searching of the specification did not reveal antecedent basis for these limitations in the originally filed specification.
Response to Arguments
This is a new ground of objection necessitated by amendment.
Drawings
The specification teaches, “Sequence alignment of EGFP and BFP show that two base substitutions (orange) correspond to the two changes in amino acid sequence responsible for the shift in fluorescence from EGFP to BFP. “ Thus the specification appears to teach the figures are in color. 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).
Response to Arguments
This is a new ground of objection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 14-18, 21-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
A method for simultaneously detecting homologous recombination (HR) DNA double strand repair and/or non-homologous end-joining (NHEJ) DNA double strand repair on a DNA strand in a cell, the method comprising:(a) delivering a dual reporter system comprising a first reporter gene and a second reporter gene, a gene-editing agent, and a gene-repair template into a cell, wherein the gene-editing agent generates a DNA double strand break on the DNA strand of the second reporter gene, and wherein repair of the double strand break through non-homologous end joining (NHEJ) causes mutation of the second reporter gene to destroy its reporter activity, while repair of the double strand break by homologous recombination (HR) using the gene-repair template causes a switch of the second reporter gene to a third reporter gene with different fluorescence; and(b) detecting a presence or absence of fluorescence from the first reporter gene, the second reporter gene, and the switched, third reporter gene, wherein a presence of fluorescence from the first reporter gene indicates transfection of the dual reporter system into the cell, and wherein(i) a presence of fluorescence from the switched third reporter gene indicates HR DNA double strand repair of the DNA double strand break and (ii) an absence of fluorescence from the mutated second reporter and an absence of fluorescence from the switched third reporter gene expression indicates NHEJ DNA double strand repair of the DNA double strand break of the DNA double strand break.” The response does not indicate where support for the amendment. Review and searching of the specification did not reveal antecedent basis for the claims.
More specifically the specification does not teach, “” first reporter gene,” “second reporter gene,” “third reporter gene,” and “destroy activity.”
Further the claim lack adequate written description as the claims as written encompass any dual reporter system comprising a first reporter gene and a second reporter gene, a gene-editing agent, and a gene-repair template into a cell, wherein the gene-editing agent generates a DNA double strand break on the DNA strand of the second reporter gene, and wherein repair of the double strand break through non-homologous end joining (NHEJ) causes mutation of the second reporter gene to destroy its reporter activity, while repair of the double strand break by homologous recombination (HR) using the gene-repair template causes a switch of the second reporter gene to a third reporter gene with different fluorescence, any first reporter gene, any second reporter gene, and any third reporter gene. This encompasses an enormous genus. The specification provides no limiting definition of reporter gene. However the teachings of the specification appear to be limited to “ reporter gene can include a DsRed, an EGFP, a BFP reporter gene, or any combinations thereof.”
Further the claim requires, “wherein repair of the double strand break through non-homologous end joining (NHEJ) causes mutation of the second reporter gene to destroy its reporter activity, while repair of the double strand break by homologous recombination (HR) using the gene-repair template causes a switch of the second reporter gene to a third reporter gene with different fluorescence; and(b) detecting a change in a presence or absence of fluorescence from the first reporter gene, the second reporter gene, and the switched, third reporter gene expression, wherein a presence of fluorescence from the first reporter gene indicates transfection of the dual reporter system into the cell, and wherein(i) a presence of fluorescence from the switched third reporter gene indicates HR DNA double strand repair of the DNA double strand break and (ii) an absence of fluorescence from the mutated second reporter and an absence of fluorescence from the switched third reporter gene expression indicates NHEJ DNA double strand repair of the DNA double strand break of the DNA double strand break.”
Thus the claims require specific first reporter gene, second reporter gene, and third reporter gene with specific sequences and constructs. However the specification is limited to a single species. Thus the claims lack adequate written description.
Further claim 24 has been added by amendment and recites, “epigenic.” This appears to be new matter as the specification does not recite the limitation. Thus the amendment appears to be new matter.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9, 14-18, 21-24 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 has been amended to recite, “delivering a dual reporter system comprising a first reporter gene and a second reporter gene, a gene-editing agent, and a gene-repair template into a cell, wherein the gene-editing agent generates a DNA double strand break on the DNA strand of the second reporter gene, and wherein repair of the double strand break through non-homologous end joining (NHEJ) causes mutation of the second reporter gene to destroy its reporter activity, while repair of the double strand break by homologous recombination (HR) using the gene-repair template causes a switch of the second reporter gene to a third reporter gene with different fluorescence;.” The metes and bounds are unclear as the specification and claims do not require the reporter gene has activity or fluorescence. Thus it is unclear what activity is destroyed and what different fluorescence requires. “Different fluorescence” and “destroy activity” are relative terms, the specification and claims provide no standard to differentiate the different fluorescence from not different fluorescence and destroyed activity from intact activity.
Claim 24 recites, ”epigenic.” The metes and bounds are unclear what is required of epigenic as it is not an art accepted term and it is not defined by the specification.
Response to Arguments
.These are new grounds of rejection necessitated by amendment.
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.
Claim(s) 1-14, 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wilson (ACS Chem Biol. 2018 July 20; 13(7): 1721–1733.), Gomez-Cabello (PLoS ONE (2013) 8(10): e77206. doi:10.1371/journal.pone.0077206), Certo (Nature Methods (2011) volume 8, pages 671-676), Koch ( Nature Protocols (2018) volume 13, pages 1465-1487), Devlertere (Development of a screening assay for homologous recombination and optimization of the CRISPR/Cas9 system through promoter analysis, 2019) and Glaser (: Molecular Therapy—Nucleic Acids (2016) 5, e334)
Wilson provides a review of fluorescent probes for studying DNA probes. Wilson teaches, “Host cell reactivation probes are distinct from the above probes because they are used to assay the activity of an entire repair pathway in a living cell rather than a single enzyme. As the name suggests, these probes function by measuring the ability of a cell to repair, or reactivate, a damaged plasmid which expresses a fluorescent protein. Only upon repair of the damage will the fluorescent protein be properly expressed (Figure 3d). Cells that are mutated or lack the proper repair pathways will not fluoresce. The idea of using host cell reactivation to couple DNA repair to expression of a fluorescent protein was first put forward by Roguev and Russev in 2000.103 To assess the overall repair capacity of a cell, the authors took enhanced GFP constructs and irradiated them with UV light, causing photodamage of the plasmid DNA. Following transfection of the damaged plasmid, they were able to monitor the rate at which fluorescence was restored relative to the unirradiated construct. This was a broad probe of DNA photodamage repair since the damage was not site specific or homogeneous. The probe was used to identify repair deficient cell lines. The concept was taken further by the groups of Sun and Dong through the introduction of specific mismatches into the GFP construct to measure mismatch repair activity in different cell lines.104–106 In 2014, the group of Samson developed a flow-cytometric host cell reactivation assay to measure multiple DNA repair pathways at once.107 They have since used this assay to measure several different repair deficiencies in a wide array of cell types.108,109 Host cell reactivation probes have been used to study outcomes in double strand breaks well.110,111 These probes are biochemically complex, and interpreting a negative result (no expression) can be a challenge.” (page 11)
Gomez-Cabello teaches, “In summary, we have designed specific reporters to study the balance between homology-directed and homology-independent repair of DSBs. These systems can be used to analyze in an unbiased way the effect of any factor on this repair pathway choice. This will allow us to isolate and characterize new factors involved in this regulation. For our reporters, it is irrelevant if a factor has an increased or reduced ability to perform either HR or NHEJ or both, since we instead study its role in maintaining the balance. Our systems could be applied to understand one specific factor or an entire pathway, or to genome-wide screenings and drug discovery. Moreover, our findings can be applied to increase gene-targeting efficiency, a beneficial tool for a broad audience in the biological sciences.” (page 8)
Gomez-Cabello teaches
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Certo teaches,” we introduced at an embedded nuclease cleavage site (in this case, an I-SceI site), and repair of the break generates distinct fluorescent signals upon resolution either through HDR with an exogenous donor template or through mutNHEJ (Fig. 1a,b): in the former case, a functional enhanced GFP (eGFP) open reading frame is restored by the exogenously provided donor template to signal gene targeting9; in the latter case a frameshift places a monomeric (m)Cherry coding sequence in-frame to signal gene disruption. By design, the eGFP coding sequence contains an alternative +3 reading frame (Supplementary Fig. 1), and the T2A ‘dis-linker’ enables the downstream-encoded mCherry to escape degradation of the misfolded protein encoded in this +3 reading frame of eGFP (Supplementary Fig. 2 and Supplementary Note 1). We designated our construct the traffic light reporter (TLR).” (671, 2nd column, bottom)
Certo teaches:
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While Wilson, Gomez-Cabello and Certo teach the use of fluorescent reporter proteins to examine or measure DNA repair of double strand DNA strand breaks, They do not specifically teach gene editing agent or a gene repair template.
However, Koch teaches, “Our genome-editing approach is based on methods described by Ran et al.5 and Trevino et al.6 that use Cas9 nickase to perform genome editing in eukaryotic systems. All nucleases used for genome editing in mammalian cells (e.g., zinc-finger nucleases (ZFNs), transcription-activator-like effector nuclease and CRISPR–Cas9) trigger a double-strand DNA (dsDNA) break at a specific genomic locus that can be repaired by two major DNA repair pathways: nonhomologous end joining (NHEJ) and HDR7.” (page 1465, 1st column, bottom)
Develtere teaches, “Although HR has many applications in genome editing (such as specific nucleotide substitutions or complete gene insertions), in plants it only occurs 0.01 to 1% of the time (compared to 5 - 20% in animal cells), making it a very inefficient process. Assays to measure the HR frequency have predominantly been reported for animal systems. Here, we developed a screening method in tobacco Bright Yellow-2 and Arabidopsis PSB-D cell cultures. The assay employs a reporter line stably expressing a blue fluorescent protein (BFP). The reporter line is transformed with Cas9
targeting the BFP gene, and a template containing the necessary substitution to convert BFP to GFP. An estimate on the HR frequency can be made based on the number of GFP-expressing cells. Using the assay, we compared three different guides and four templates with different homology arm lengths in their efficiency to repair a DSB using the HR pathway. The data showed that the guide choice can have a large impact on the HR efficiency. Based on this, it is recommended to include multiple guides in CRISPR/Cas studies to increase the chance for high HR efficiency. Additionally, we observed that increasing the length of the homology arms from 50 to 200 bp
resulted in a 5.5-fold HR increase. This suggests that increasing the homology arms could be used as a way to boost HR.”(abstract).
Develtere teaches, “Another assay based on fluorescent proteins accounts for these under- and overestimations: the GFP-to-BFP conversion assay (Glaser et al, 2016). The reporter system exploits the ability of GFP to be converted to BFP by a single mutation (T196C). In a GFP-containing reporter line, a gRNA guides Cas9 to a specific site in the GFP gene. The base substitution can be achieved by HR repair using a template containing the required mutation to transform GFP to BFP. Cells in which no DSB was induced remain blue, cells repaired through HR or NHEJ are green and non-fluorescent respectively. This reporter system can also be used to determine the efficiency of base editors (Coelho et al, 2018).” (page 11)
Glaser teaches, “Our data shows that a single 196T > C substitution using ssODN1 is sufficient to convert GFP to BFP. However, low fluorescence intensity and a low HDR frequency were observed in comparison with the other templates in K562-50 cells (Figure 1d,e). An additional 194C > G substitution in ssODN2, corresponding to a reversion of the EGFP amino acid sequence back to that of wild-type GFP, was sufficient to restore BFP fluorescence intensity to that observed with the PCR template (Figure 1e). The low HDR frequency observed with ssODN1 was theorized to result from recutting of the repaired sequence by Cas9, as the sequence resulting from HDR retains the complete target sequence for gRNA1 and contains only one mismatch in the gRNA2 target site. The 194C > G substitution introduces an additional mismatch in the gRNA2 target site and eliminates the gRNA1 protospacer adjacent motif sequence. To further reduce the target sequence similarity with gRNA1 after HDR, ssODN2 was designed with an additional silent mutation (201C > G). In accordance with our expectations, the highest HDR frequency was achieved with ssODN2 in both K562-50 and HEK293T-EGFP cells (5.8% and 23.3%, respectively, Figure 2a). No significant difference was observed between sense and antisense configuration of ssODN2 (Figure 1d). The assay was validated through sequencing of clones grown from the GFP+, BFP+, and nonfluorescent populations after editing with gRNA1 and ssODN2 in K562-50 cells (Figure 2b)”(page 1-page 2).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to deliver fluorescent reporter gene (eGFP), CRISP/cas9 and gRNA to HEK293 cells to examine double stranded DNA repair by detecting a change in fluorescence. The artisan would be motivated to use the reporter gene (eGFP), CRISP/cas9 and gDNA for conversion of eGFP to BFP to provide a specific reagent for single and double stranded DNA cleavage to examine DNA repair and/or repair rates at specific controlled sites. The artisan would have a reasonable expectation of success as the artisan is merely using known method to examine known DNA repair mechanisms.
With regards to claim 2, 5, Glaser and Develtere teaches eGFP and BFP.
With regards to claim 3, Glaser and Develtere teach CRISPR/Cas9.
With regards to claim 4, Glaser and Develtere teach the use of gRNA.
With regards to claim 6-7, Glaser teaches ssODN1 and ssODN2 which are about 100nt (figure 1)
With regards to claim 8-9 Gomez-Cabello teach the use of lentrivirus.
With regards to claim 14., Gomez-Cabello teaches the use of flow cytometry (page 3, 1st column)
With regards to claim 16, Glaser teaches mutations relative to BFP.
With regards to claims 17-19, 21-24, Certo teaches, “identifying new proteins involved in DNA repair or pathway choice, evaluating new approaches to induc-ing targeted breaks, screening for small-molecule modulators of specific repair pathways, and rapidly and comprehen-sively vetting ‘third party’ manipulations aimed at increasing endonuclease-induced engineering efficiency.” (page 675, 2nd column, bottom)
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use any molecules that are known to play a role in cancer including methylation or DNA repair. The artisan would be motivated to examine methylation as it is known to regulate gene expression, cancer, development, etc. The artisan would have a reasonable expectation of merely using known reagents.
Response to Arguments
The response traverses the rejection by asserting that each reference individually does not teach all the limitations of the claims. This argument has been thoroughly reviewed but is not considered persuasive as the instant rejection is an obviousness rejection. Thus the rejection concedes each reference does not anticipate the claims.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wilson (ACS Chem Biol. 2018 July 20; 13(7): 1721–1733.), Gomez-Cabello (PLoS ONE (2013) 8(10): e77206. doi:10.1371/journal.pone.0077206), Certo (Nature Methods (2011) volume 8, pages 671-676), Koch ( Nature Protocols (2018) volume 13, pages 1465-1487), Devlertere (Development of a screening assay for homologous recombination and optimization of the CRISPR/Cas9 system through promoter analysis, 2019) and Glaser (: Molecular Therapy—Nucleic Acids (2016) 5, e334) as applied to claims 1-14, 16-20 above, and further in view of Yuan (The Scattered Twelve Tribes of HEK293. Biomed Pharmacol J 2018;11(2).)
The teachings of Wilson, Gomez-Cabello, Certo, Koch , Devlertere and Glaser are set forth above.
While Wilson, Gomez-Cabello, Certo, Koch , Devlertere and Glaser teach the use of HEK293T cells they do not specifically teach the use of HEK293FT,
However, Yuan teaches, “HEK293FT – HEK293 FT is a fast growing variant of HEK293T. HEK293FT cells were cloned from the HEK293T cell line and adapted to commercial media.13 HEK293FT is designed for lentiviral production. Similar to HEK293T, the 293FT cells stably express the SV40 large T antigen from the pCMVSPORT6TAg. neo plasmid. Expression of the SV40 large T antigen is controlled by the human cytomegalovirus (CMV) promoter and is high-level and constitutive.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use HEK293FT in the methods of Wilson, Gomez-Cabello, Certo, Koch , Devlertere and Glaser. The artisan would be motivated as HEK293FT cells as it allows for commercial media and designed for lentiviral production. The artisan would have a reasonable expectation of success as the artisan is substituting one HEK 293 cell for another variant of HEK 293.
Response to Arguments
The response traverses the rejection for the reasons set forth with respect to the independent claims. These arguments are not persuasive for the reasons of record.
Summary
No claims are allowed.
Conclusion
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 STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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