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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9 December 2025 has been entered.
Application Status
This action is written in response to applicant’s correspondence received 9 December 2025. Claims 9, 13-14, 17-21, and 25-36 are currently pending. Accordingly, claims 9, 13-14, 17-21, and 25-36 are examined herein. The restriction requirement mailed 24 November 2023 is still deemed proper. Applicant's elected Group II without traverse in the reply filed 29 March 2024.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
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 9, 13-14, 17-20, and 25, and 27-36 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.
Regarding claim 9, the newly amended claim recites the new limitation of “a gene expression product” as opposed to the previously pending “reporter protein” (see newly amended claim 9). However, the specification does not describe any gene expression product, as encompassed by the new claim language of claim 9. Rather, the specification teaches the use of genes encoding SEAP reporter proteins ([00406]-[00411]; see Examples 8-9), peptide-barcode-luciferase constructs ([00444]-[00445]; see Example 19), and various therapeutically effective agents ([00122]). However, the claimed genus of any “gene expression product” encompasses an extraordinarily large genus of expression products including, but not limited to, non-coding gene expression products, RNA molecules of any structure, and proteins of any structure.
Further, the claim recites the newly amended “two or more promoter elements” (see Claim 9). The specification does not provide support for the term “promoter elements” and the currently pending Remarks, filed 9 December 2025, do not identify a specific paragraph from which the newly amended term has support in the specification.
Thus, the claim is rejected under 35 USC 112(a) for introducing new matter because the claim language was not original and the scope of the claim goes beyond what the specification describes.
Regarding claims 13-14, 17-20, and 25, and 27-36, as the claims do not rectify the currently pending 35 USC 112(a) rejection of record, the claims are also rejected under 35 USC 112(a).
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.
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 9, 25-28, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206).
Regarding claim 9, the claimed “two or more promoter elements” is interpreted as encompassing both two or more promoters and combination promoters that comprise a both a promoter and an enhancer or elongation factor (i.e., a promoter that comprises two or more promoter elements).
Williams is drawn to an invention concerned with methods that utilize covalently closed circular recombinant DNA molecules (Abstract). Williams teaches the use of a plasmid termed NTC9385C that comprises an RNA selectable marker and an R6K origin of replication (i.e., a minimized R6K origin of replication) ([0081]). Williams teaches that a transgene could be cloned into the NTC9385C plasmid in order to create a vector (i.e., a DNA molecule) termed NTC9385C2a ([0182]). Williams teaches that the NTC9385C2a vector comprises (i) an EGFP reporter protein (i.e., a gene encoding a gene expression product) that is operably linked to (ii) a CMV promoter, (iv) an origin of replication, and (v) an RNA-OUT selectable marker ([0027], [0211]; see Fig. 7). Williams teaches that the vectors may use combination promoters such as a human or murine CMV-derived enhancer elements combined with the elongation factor 1α (EF1α) promoters (i.e., promoters comprising two or more promoter elements), or the diversity of tissue specific or inducible promoters known in the art such as the muscle specific promoters muscle creatine kinase (MCK), and C5-12 or the liver-specific promoter apolipoprotein A-I (ApoAI) (i.e., Williams teaches that two separate promoters may be utilized to express the vector in a specific tissue) ([0185]). Williams teaches that the origin of replication may be replaced with an alternative R6K origin of replication ([0256]). Williams teaches that the RNA-OUT selectable marker is bacterial ([0250]). Williams teaches that multiple plasmids (i.e., a plurality of DNA molecules) may be transfected into different cell lines using Lipofectamine 2000 ([0291]). Williams teaches that (iii) EGFP expression was determined and visualized via the use of a FLX800 microplate fluorescence reader (i.e., the gene comprises a transcription start site such that the EGFP was able to be expressed and detected) ([0261]). Williams teaches that the plasmids of the invention can be utilized in gene therapy or gene replacement applications, wherein the desired gene product is expressed from the plasmid after administration to the patient ([0005]). Williams teaches that many alternative vector configurations may also be made, including but not limited to vectors with alternative selection markers, alternative promoters, alternative terminators, and different orientations of the various vector-encoded elements or alternative R6K or ColE2 origins ([0256]).
Williams does not teach or suggest that the promoter induces increased expression of said gene expression product in a cancer cell as compared to a non-cancer cell (Claim 9). Williams does not teach or suggest that at least one of the two promoter elements is obtained from KIF20A (Claim 36).
However, one of ordinary skill in the art would have considered the teachings of Zhang and Shi as both references are common fields of endeavor pertaining to the study and use of promoters.
Zhang is drawn to a study concerned with the expression of KIF20A and its association with tumor progression in squamous cell carcinoma (Abstract). Zhang teaches that the mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (i.e., the expression of a KIF20A promoter driving expression of KIF20A mRNA and protein is increased in a cancer cell of a subject as compared to a non-cancer cell of said subject) (pg. 1). Zhang teaches that KIF20A protein expression can be utilized as a biomarker that is associated with poorer survival outcomes in cervical cancer patients (pg. 14). Zhang teaches that the staining of KIF20A protein in most cancerous lesions in the primary cervical tumors was statistically higher than that in the surrounding adjacent normal cervical regions (pg. 7). Zhang teaches that the KIF20A protein expression was generally negative in normal cervical tissues (pg. 7).
Shi is drawn towards a study concerned with how Glioma-associated oncogene 2 (i.e., Gli2) interacts with KIF20A (Abstract). Shi teaches that use of a luciferase reporter vector driven by a FoxM1-binding site that contains a KIF20A promoter (pg. 26209). Shi teaches that overexpression of FixM1 significantly increased luciferase activity driven by the FoxM1-binding site that contains a KIF20A promoter (i.e., a KIF20A promoter can be linked to a reporter gene encoding a gene expression product such that the gene expression product is expressed) (pg. 26209).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute at least one of the two promoters present in the combination promoter of Williams with a KIF20A promoter that is able to be linked to a reporter protein and has increased expression in cancer cells when compared to non-cancer cells, as described by Zhang and Shi. A person of ordinary skill in the art would have been motived to do so in order to express a desired gene product, GFP, in squamous cell carcinoma tumor tissue after administration to a patient and allow for its detection. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams teaches that different combination promoters may be utilized by the invention to detect a GFP protein linked to the promoter while Zhang and Shi teach that KIF20A was a known promoter in the art that is able to be operably linked to a reporter protein such that the reporter protein may be detected in cancerous cells.
Regarding claim 25, Williams teaches that the plasmids can be administered intramuscularly ([0262]).
Regarding claim 26, Williams teaches that the transgene can encode therapeutic genes (i.e., Williams is interpreted as teaching that the reporter protein may encode a therapeutically effective agent) ([0342]).
Regarding claim 27, Williams teaches that the tumor cells were HEK293 and A549 (i.e., not virally-infected) cells ([0260]).
Regarding claim 28, Williams teaches that the nanoplasmids comprising EGFP can be transfected with lipofectamine (i.e., a transfection agent) (pg. 29; see Table 1).
Claim(s) 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Pérez-Torres (NeuroImage 50.2 (2010): 375-382).
Regarding claims 13-14, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that the method further comprise imaging of said cancer, wherein said imaging comprises magnetic resonance imagining (Claim 12), such that said imaging detects a presence of said cancer cell or an absence of said cancer cell (Claim 13).
However, one of ordinary skill in the art would have considered the teachings of Pérez-Torres as the references are common fields of endeavor pertaining to the detection of GFP.
Pérez-Torres is drawn to an invention concerned with the detection of GFP though MRI methodologies (Abstract). Pérez-Torres teaches that magnetization transfer contrast (MTC) imaging is an MRI methodology that can detect GFP both in vitro and in in vivo mouse models (i.e., Pérez-Torres is interpreted as teaching that the expression of GFP can be localized via the use of MTC) (Abstract; pg. 378-379, 380, see Fig. 2 and Fig. 5). Pérez-Torres teaches that utilizing MTC in order to detect GFP is advantageous because it poses no toxicity to the imaged cells (pg. 381).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the detection method rendered obvious by Williams in view of Zhang and Shi for an MRI imaging method, as described by Pérez-Torres. A person of ordinary skill in the art would have been motivated to do so in order to utilize a known GFP detection method that is non-toxic to cells. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi renders obvious the use of a detection method that can localize GFP expression in a subject with Pérez-Torres teaches that localizing GFP through MRI imaging was a known method in the art to localize GFP expression in a subject.
Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Cohen (The Lancet 393.10167 (January 2019): 169-182).
Regarding claims 17-20, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Williams in view of Zhang and Shi does not teach or suggest that the subject had at least one symptom of cancer selected from weight loss and acute pain (Claims 17-18). Williams in view of Zhang and Shi does not teach or suggest that the subject had at least one risk factor selected from being a current smoker (Claim 19). Williams in view of Zhang and Shi does not teach or suggest that the subject had previously received radiological treatment for cancer (Claim 20).
However, one of ordinary skill in the art would have considered the teachings of Cohen as both references are common fields of endeavor pertaining to the study of cervical cancer.
Cohen is drawn towards a review concerned with cervical cancer risk factors, symptoms, and treatments (Abstract). Cohen teaches that patients with cervical cancer are often symptomatic with symptoms that include low back pain radiating to a leg and unexplained weight loss (pg. 177). Cohen teaches that tobacco smoking was found to be a major risk factor for cervical cancer (pg. 170). Cohen teaches that radiotherapy is a known treatment for cervical cancer (pg. 174).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method rendered obvious by Williams in view of Zhang and Shi such that the subject had at least one symptom of, one risk factor for, and was previously treated for cervical cancer, as described by Cohen. A person of ordinary skill in the art would have been motived to do so in order to ensure that the patient being administered cervical cancer-specific DNA molecules had, and was previously treated for, cervical cancer in order to ensure the functionality of the cancer-specific plasmids. A person of ordinary skill in the art would have had a reasonable expectation of success because the nanoplasmids rendered obvious by Williams in view of Zhang and Shi are able to successfully, and selectively express GFP in the presence of cervical cancer while Cohen teaches that patients with cervical cancer were well known in the art to exhibit weight loss, have a risk factor selected from smoking, and can be treated by radiotherapies.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Muñoz-Álvarez (Molecular Therapy 23.4 (2015): 728-736).
Regarding claim 21, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest the use of a gene expression product comprising an epitope tag (Claim 21).
However, one of ordinary skill in the art would have considered the teachings of Muñoz-Álvarez as both references are drawn to the detection of reporter proteins.
Muñoz-Álvarez is drawn to a study concerned with the indirect visualization of a herpes simplex virus thymidine kinase 1 reporter via PET in hepatocellular carcinoma cells (Abstract). Muñoz-Álvarez teaches that VSV (i.e., a peptide epitope tag) can be indirectly visualized via the use of an enhanced simplex virus thymidine kinase 1 reporter (i.e., a positron-labeled binding element that recognizes the peptide epitope tag) (Abstract). Muñoz-Álvarez teaches that the disclosed system allows for highly sensitive in vivo imaging via PET (Abstract; pg. 731, see Figure 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the reporter protein and detection method of Williams in view of Zhang and Shi with the peptide epitope tag/labeled peptide binding element and imaging method disclosed in Muñoz-Álvarez. A person of ordinary skill in the art would have been motivated to do so in order to be able utilize highly sensitive in vivo imaging methods. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi renders obvious the use of a reporter protein that can be detected in cancerous cells via an imaging method while Muñoz-Álvarez teaches that utilizing a peptide epitope tag/labeled peptide binding element as a reporter protein in order to detect cancerous cells via an imaging method was well known in the art.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Elouahabi (Molecular therapy 11.3 (2005): 336-347).
Regarding claim 29, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that the transfection agent comprises lipophilic nanoparticles (Claim 29).
However, one of ordinary skill in the art would have considered the teachings of Elouahabi as all references are common fields of endeavor pertaining to the use of transfection agents to deliver DNA molecules to a target cell of interest.
Elouahabi is drawn to a study concerned with the use of cationic lipid/DNA lipoplexes (i.e., lipophilic nanoparticles) that represent an attractive alternative to viral vectors for cell transfection in vitro and in vivo (Abstract). Elouahabi teaches that the lipoplex-mediated transfection of DNA into a target cell resulted in successful transfection of plasmid DNA (pg. 339; see FIG. 1). Elouahabi teaches that lipoplex-mediated transfection can result in a high transfection efficiency in a given cell type under specific conditions under which other lipoplex or polyplex complexes may be less efficient (pg. 345).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the transfection agent of Williams in view of Zhang and Shi for the lipophilic nanoparticle transfection agent described by Elouahabi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a transfection method that can efficiently transfect DNA molecules to a specific cell type under specific conditions. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that the DNA molecule may be transfected with the use of a transfection agent and Elouahabi teaches that lipophilic nanoparticles can be used to transfect cells with DNA molecules.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Manuel (Journal of drug targeting 9.1 (2001): 15-22).
Regarding claim 30, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that the transfection agent is polyethylenimine (Claim 30).
However, one of ordinary skill in the art would have considered the teachings of Manuel as all references are common fields of endeavor pertaining to the use of transfection agents.
Manuel is drawn to a study concerned with transfection by polyethyleneimine coated microspheres (Abstract). Manuel teaches that polyethylenimine is a known transfection agent that can be used as a DNA delivery mechanism in cells cultures and in vivo (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the transfection agent of Williams in view of Zhang and Shi with the transfection agent comprising polyethylenimine agent described by Manuel. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that the DNA molecule may be transfected with the use of a transfection agent and Manual teaches that polyethylenimine can be used to transfect cells with DNA molecules.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Sunshine (PloS one 7.5 (2012): e37543).
Regarding claim 31, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that the transfection agent comprises a poly(β-amino ester) (Claim 31).
However, one of ordinary skill in the art would have considered the teachings of Sunshine as all references are common fields of endeavor pertaining to the use of transfection agents.
Sunshine is drawn to a study concerned with the use of poly(β-amino ester)-nanoparticle mediated transfection in target cells (Abstract). Sunshine teaches that poly(β-amino ester)s have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with DNA with high efficacy in vitro (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the transfection agent of Williams in view of Zhang and Shi with the poly(β-amino ester) nanoparticle described in Sunshine. A person of ordinary skill in the art would have been motivated to do so in order to use a transfection agent that can transfect a variety of different cell types. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that the DNA molecule may be transfected with the use of a transfection agent and Manual teaches that poly(β-amino ester) can be used to transfect cells with DNA molecules.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Kikuchi (Clinical cancer research 13.15 (2007): 4511-4518).
Regarding claim 32, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that said plurality of nanoplasmids is administered intravesicularly to said subject (Claim 32).
However, one of ordinary skill in the art would have considered the teachings of Kikuchi as all references are common fields of endeavor pertaining to the administration of plasmids to subjects with cancer.
Kikuchi is drawn to a study concerned with vectors that can deliver gene products to bladder cancers after being intravesicularly administered (Abstract). Kikuchi teaches that cancerous malignancies can be treated with the vectors that were intravesicularly administered (pg. 4517). Kikuchi teaches that intravesical administration of vectors allows for direct local tumor contact, circumventing the difficulties associated with tumor targeting via systematic administration (pg. 4511).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the intramuscular administration method rendered obvious by Williams in view of Zhang and Shi with a method of intravesicular administration, as described in Kikuchi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a delivery method that allowed for direct local tumor contact. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that the DNA molecule may be administered to a subject intramuscularly and Kikuchi teaches that intravascular administration of DNA molecules can be used to transfect cells with DNA molecules.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Tada (The Journal of Gene Medicine: A cross‐disciplinary journal for research on the science of gene transfer and its clinical applications 8.8 (2006): 1018-1026).
Regarding claim 33, Williams in view of Zhang and Shi render obvious claims 9, 25-28, and 36 as described above.
Williams in view of Zhang and Shi does not teach or suggest that said plurality of nanoplasmids is administered by injection into or more of the hepatic artery or hepatic portal vein of said subject (Claim 33).
However, one of ordinary skill in the art would have considered the teachings of Tada as both references are common fields of endeavor pertaining to the administration of plasmid DNA in the treatment of cancer.
Tada is drawn to a study concerned with hydrodynamic injection of plasmid DNA via the hepatic artery (Abstract). Tada teaches that hydrodynamic injection of plasmid DNA via the hepatic artery resulted in dramatically increased transgene expression in target cancer cells (Abstract).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the intramuscular administration method rendered obvious by Williams in view of Zhang and Shi with a method of injecting the plasmids into the hepatic artery, as described in Tada. A person of ordinary skill in the art would have been motivated to do so in order to utilize a delivery method that resulted in an increased transgene expression in the subject. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that the DNA molecule may be administered to a subject intramuscularly and Tada teaches that hydrodynamic injection of plasmid DNA via the hepatic artery may be utilized to transfect cancer cells with DNA molecules
Claim(s) 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Zhou (Journal of Histochemistry & Cytochemistry 63.12 (2015): 922-930) and Baczynska (Cellular & molecular biology letters 8.2 (2003): 471-486).
Regarding claim 34, Williams in view of Zhang and Shi render obvious claims 9 and 25-28 as described above.
Williams in view of Zhang and Shi does not teach or suggest that at least one of the two promoter elements is obtained from CEACAM5 (Claim 34).
However, one of ordinary skill in the art would have considered the teachings of Zhou and Baczynska as both references are common fields of endeavor pertaining to the use of cancer-specific promoters that can drive visualization of GFP.
Zhou is drawn to a study concerned with the identification of CEACAM5 as a biomarker for prewarning and prognosis in gastric cancer (Abstract). Zhou teaches that CEACM5 is highly expressed in cancer cells and not expressed in non-cancer cells (pg. 925; see Figure 1). Zhou teaches that utilizing CEACAM5 as a biomarker for gastric cancer prognostic evaluation is promising (Abstract).
Baczynska is drawn to a study concerned with CEACAM5 and its role in the formation of tumors (Abstract). Baczynska teaches the use of a CEACAM5 promoter that was operably linked to luciferase (i.e., a reporter gene expression product) in a plasmid (pg. 478). Baczynska teaches that the luciferase activity was able to be successfully detected in order to determine CEACAM5 promoter activity (pg. 478).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the cancer-specific KIF20A promoter operably linked to GFP rendered obvious by Williams in view of Zhang and Shi for a cancer-specific CEACAM5 promoter that can be operably linked to GFP, as described by Zhou and Baczynska. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that a cancer-specific promoter may be utilized in order to drive expression of a GFP reporter protein while Zhou and Baczynska teach that CAECAM5 was a known cancer-specific promoter that could be utilized to drive expression of GFP.
Claim(s) 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Williams (PG Pub No. US 2015/0275221 A1) in view of Zhang (PloS one 11.12 (2016): e0167449) and Shi (Oncotarget 7.18 (2016): 26206) as applied to claims 9, 25-28, and 36 above, and further in view of Fernandez-Retana (Tumor Biology 39.6 (2017): 1010428317711895) and
Regarding claim 35, Williams in view of Zhang and Shi render obvious claims 9 and 25-28 as described above.
Williams in view of Zhang and Shi does not teach or suggest that at least one of the two promoter elements is obtained from FAM111B (Claim 35).
Fernandez-Retana is drawn towards a study concerned with the analysis of degradome-related genes and how they can predict metastasis in cervical cancer patients (Abstract). Fernandez-Retana teaches that FAM111B is expressed in cancerous cells (i.e., a FAM111B promoter element expresses FAM111B in cancerous cells) and not expressed in cells that had a complete response to treatment (i.e., non-cancerous cells) (pg. 6-7; see Figure 3). Fernandez-Retana teaches that FAM111B is a gene that is associated with prostate cancer risk and plays a role in tumorigenesis (pg. 8).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the cancer-specific KIF20A promoter operably linked to GFP rendered obvious by Williams in view of Zhang and Shi for a cancer-specific FAM111B promoter, as described by Fernandez-Retana. A person of ordinary skill in the art would have had a reasonable expectation of success because Williams in view of Zhang and Shi teaches that a cancer-specific promoter may be utilized in order to drive expression of a GFP reporter protein while Fernandez-Retana teaches that FAM111B is a gene (i.e., a gene comprising a promoter element) that is only expressed in cancerous cells.
Response to Arguments
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Applicant alleges that Williams, Zhang, and Shi, when considered alone or in combination, fail to teach or suggest the use of two or more promoter elements wherein the promoter induces increased expression of said gene expression product in said cancer cell as compared to a non-cancer cell.
This argument is not found persuasive because, as discussed above in the currently pending 35 USC 103 rejection of record, Williams teaches that the vectors may use combination promoters such as a human or murine CMV-derived enhancer elements combined with the elongation factor 1α (EF1α) promoters (i.e., promoters comprising two or more promoter elements), or the diversity of tissue specific or inducible promoters known in the art such as the muscle specific promoters muscle creatine kinase (MCK), and C5-12 or the liver-specific promoter apolipoprotein A-I (ApoAI) (i.e., Williams teaches that two separate promoters may be utilized to express the vector in a specific tissue) ([0185]). Therefore, as discussed above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute at least one of the two promoter elements of Williams with a promoter element obtained from KIF20A, as described by Zhang and Shi.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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