Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Application status
In response to the previous Office action, a non-Final rejection (mailed on 09/15/2025), Applicants filed a response on 12/15/2025. Said amendment canceled Claims 1-55, 66, 71, 73, 77 and 79, and added Claims 80. Thus, Claims 56-65, 67-70, 72 and 80 are at issue and present for examination.
It is noted by the Examiner that Claims 74-76 and 78 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention in the previous Office actions, a non-Final rejection (mailed on 09/15/2025).
Specification – Necessitated by Applicants’ new amendment
The attempt to incorporate subject matter into this instant specification is ineffective because the specification makes a general statement about ‘incorporation by reference’ but there was no suggestion of a clear intent to ‘incorporate by reference’ of this particular reference because the applicant has not identified what is the “essential material” in this reference (see MPEP 608.01(p)(2)) As such, the reference of Vogelstein et al. is not clearly identified as “required” in accordance with 37 CFR 1.57(c)(2). Therefore, the amendment to specification is “NOT ENTERED”.
Claim Rejections - 35 USC § 112 – Necessitated by Applicants’ new amendment
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.
Claim 80 is 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.
Claim 80 was newly added on 12/15/2025, however, there is not a single mention of “β-catenin” in the specification, drawings or claims as originally filed (italicized for added emphasis). The Applicants point out that support can be found in lines 22-33 of page 39. However, this section seems to be what Applicants are trying to incorporate into specification that is “NOT ENTERED” by the Examiner due to the issues with the ‘incorporation by reference’ as explained above (see under Specification). Taken together, claim 80 is rejected as being drawn to a ‘new matter’.
Claim Rejections - 35 U.S.C. § 103 - MAINTAINED
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 56-65, 67-68 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Buscail et al. (First-in-man Phase 1 Clinical Trial of Gene
Therapy for Advanced Pancreatic Cancer: Safety, Biodistribution, and Preliminary Clinical Findings, Molecular Therapy vol. 23 no. 4, 779–789 apr. 2015) in view of Kronke et al. (Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells, Science. 2014 January 17; 343(6168): 301–305), Goding et al. (WO 2007062474 A1) and Stevis et al. (US 20140275489 A1).
The instant claims are drawn to a DNA vector comprising in operable linkage:(a) a promoter;(b) a nucleotide sequence encoding a fusion protein comprising a protein of interest fused to a cytotoxic element selected from the group consisting of deoxycytidine kinase, thymidylate kinase, thymidine kinase-guanylate kinase fusion, and FKBP-Caspase9 fusion;(c) an internal ribosomal entry site (IRES); and(d) a nucleotide sequence encoding a reporter protein.
Buscail et al. teach a DNA vector (CYL-02) comprising in operable linkage: (a) a glucose-responsive promoter (GRP78 or GRP94); (b) a nucleotide sequence encoding a fusion protein comprising a protein of interest (UMK) fused to a cytotoxic element, deoxycytidine kinase (dCK), which is used for a Phase 1 clinical trial for human patients (which encompasses isolated host cell). The Examiner notes that eukaryotic promoters, like GRP78 and GRP94 which work in human cells, are considered an inducible promoter because they are activated or "turned on" by a specific stimulus, i.e., glucose deprivation. Buscail et al. further teach that said fusion protein is separated by a peptide linker, “FMDV 2A peptide” (see page 786, right column, 4th para under “Treatment plan”).
Buscail et al. do not teach a peptide linker comprising one or more iterations of GGS, a reporter protein which is fluorescent, CMV promoter, a protein of interest which is IKZF3.
Kronke et al. teach that an oncoprotein, IKZF3, is one of the essential transcription factors in proliferation of multiple myeloma. Kronke et al. further teach that Lenalidomide is a drug with clinical efficacy in multiple myeloma which causes selective ubiquitination and degradation of IKZF3 (see abstract).
Goding et al. teach that an expression construct, i.e., polycistronic DNV vector, comprising a CMV promoter operably linked to a nucleotide sequence encoding multiple proteins of interest with an IRES inserted in between said proteins or a fluorescent reporter protein, i.e., a green or red fluorescent reporter protein (see pg. 40, line 20; pg. 31, line 1; and claims 10, 11, 13, 23 and 26).
Stevis et al. teach that a fusion protein comprising a reporter protein, which can be Renilla luciferase or green fluorescent protein (see para [0100]), wherein said fusion protein is linked by a peptide linker comprising one or more iterations of Gly-Gly-Ser (see para [0122]).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to make and use the DNA vector taught by Buscail et al. and substitute with the following: a peptide linker comprising one or more iterations of GGS, a reporter protein which is fluorescent, CMV promoter, a protein of interest which is IKZF3 as taught by Kronke et al. Goding et al. and Stevis et al. A person of ordinary skill in the art (POSITA) would have been motivated to make and use such DNA vector because [1] suicide gene such as dCK is routinely fused a gene (UMK) associated with pancreatic cancer for cell survival as taught by Buscail et al., and since IKZF3 is also a known oncogene for multiple myeloma, a POSITA would have been motivated to swap UMK with IKZF3 and express such fusion protein with a reporter protein for cell survival assays; and [2] an IRES allows expressing two or more proteins in a single mRNA transcript, i.e., a fusion protein and a reporter protein as taught by Goding et al.. Furthermore, it would have been a routine experimentation for a POSITA to swap between different but obvious variants of promoters, peptide linkers, and reporter proteins that are present in such DNA vector by using the CMV promoter, a peptide linker comprising GGS, and a reporter protein which is Renilla luciferase or GFP. As discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007), it is considered obvious to combine prior art elements which are obvious variants known to be used in equivalent fields of endeavor together into a single combination. The references of Buscail et al., Kronke et al. Goding et al. and Stevis et al. clearly show that the claimed promoters, peptide linkers, and reporter proteins were known to be used in equivalent fields of endeavor; thus, it is considered obvious to combine them together. A POSITA would have had a reasonable expectation of success to make and use such DNA vectors because all of the required biochemical reagents and techniques were rampantly used as evidenced by Buscail et al., Kronke et al. Goding et al. and Stevis et al. prior to the filing of the instant application. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicants’ Arguments:
"[O]bviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination; rather, obviousness requires the additional showing that a person of ordinary skill at the time of the invention would have selected and combined those prior art elements in the normal course of research and development to yield the claimed invention." Unigene Laboratories, Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011), emphasis added. One of ordinary skill must have 'good reason to pursue the known options within his or her technical grasp."' Rolls-Royce, PLC v. United Techs. Corp., 603 F.3d 1325, 1339 (Fed. Cir. 2010) (quoting KSR, 550 U.S. at 421).
Similarly, the Federal Circuit has distinguished mere feasibility of a combination
with desirability of the combination, and has indicated that motivation to combine requires the latter. Winner Int'l Royalty Corp. v. Wang, 202 F.3d 1340, 1349 (Fed. Cir. 2000) (finding the district court did not err when ruling there was no motivation to combine a second reference with a first reference when such a combination would render the first reference more convenient but less secure). In Winner, the court indicated that the benefits of the combination, "both lost and gained, should be weighed against one another." Id. at 1349. "After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992) (finding that the Board did not meet its burden of proof when it did not explain why a claimed concept was obvious). A person having ordinary skill in the art would not be motivated to modify the DNA vector of Buscail to include a reporter protein as taught by Stevis or Goding because it would not be desirable to add a reporter protein to the DNA vector of Buscail.
The Examiner asserts that Buscail teaches "a DNA vector (CYL-02) comprising in operable linkage: (a) a glucose-responsive promoter (GRP78 or GRP94); (b) a nucleotide sequence encoding a fusion protein comprising a protein of interest (UMK) fused to a cytotoxic element, deoxycytidine kinase (dCK), which is used for a Phase 1 clinical trial for human patients (which encompasses isolated host cell)." Non-final Office Action, page 5. The Examiner does not identify in Buscail "a nucleotide sequence encoding a reporter protein" as recited by independent claim 56. The Examiner acknowledges that Buscail fails to teach "a peptide linker comprising one or more iterations of GGS, a reporter protein which is fluorescent, CMV promoter, a protein of interest which is IKZF3." Non-final Office Action, page 5.
In an attempt to remedy these deficiencies, the Examiner cites Kronke as teaching that IKZF3 is "one of the essential transcription factors in proliferation of multiple myeloma." Non- final Office Action, page 5. The Examiner cites Goding as teaching an expression construct including "a CMV promoter operably linked to a nucleotide sequence encoding multiple proteins of interest with an IRES inserted in between said proteins or a fluorescent reporter protein..." Non-final Office Action, page 5. The Examiner additionally cites Stevis as teaching "a fusion protein comprising a reporter protein, which can be Renilla luciferase or green fluorescent protein." Non-final Office Action, page 6. The Examiner concludes that it would have been obvious to one having ordinary skill in the art to make and use the DNA vector taught by Buscail and substitute, in relevant part, a reporter protein which is fluorescent, stating that the skilled person would have been motivated to make this substitution "for cell survival assays." Non-final Office Action, page 6.
For clarity, independent claim 56 requires only a "reporter protein," while dependent claim 60 recites that the reporter protein may be a fluorescent protein or a bioluminescent protein.
Applicant asserts that a person having ordinary skill in the art would not have been motivated to modify the DNA vector of Buscail to include a nucleotide sequence encoding a reporter protein as taught by Stevis or Goding, at least because a reporter protein would not add any meaningful functionality to the DNA vector of Buscail, and would more likely decrease the sensitivity of a detection assay. Therefore, it would be undesirable to modify the DNA vector of Buscail to include a nucleotide sequence encoding a reporter protein.
Buscail relates to a phase 1 clinical trial of gene therapy for advanced pancreatic cancer. Buscail, Title. Specifically, Buscail characterizes biodistribution of the nonviral gene therapy product CYL-02 in combination with gemcitabine. Buscail, page 779, column 1. The nonviral gene therapy product CYL-02 includes a fusion gene of deoxycytidine kinase (DCK) and uridylate monophosphate kinase (UMK). Buscail, page 779, column 2. Buscail detected presence of CYL-02 in patients, such as in urine, blood, and tumor aspirate, by directly detecting the DNA. Buscail, page 780, column 2. Notably, Buscail relates only to delivery of CYL-02 to human patients, rather than to cultured cells.
The nonviral gene therapy product CYL-02 of Buscail causes cells to express DCK and UMK, the combination of which renders cells sensitive to treatment with gemcitabine. Buscail, page 779, column 2. Buscail teaches that pancreatic cancer cells treated with CYL-02 are expected to die when treated with gemcitabine. Buscail, page 779, column 2.
A person having ordinary skill in the art would thus not be motivated to modify the DNA vector of Buscail (e.g., the nonviral gene therapy product CYL-02) to include a nucleotide sequence encoding a reporter protein because Buscail already provides a method of detecting presence of the DNA vector directly in patient samples. A person having ordinary skill in the art would not recognize any reason why an alternative or additional method of detecting the DNA vector of Buscail would be necessary over Kronke, Goding, and Stevis, as Buscail already teaches a method of detecting the presence of the DNA vector.
The Examiner states that the skilled person would be motivated to "swap UMK with IKZF3 and express such fusion protein with a reporter protein for cell survival assays." Non- final Office Action, page 6. However, the DNA vector of Buscail is cytotoxic, so any cells that receive the DNA vector should theoretically die upon expression of the vector. A person having ordinary skill in the art would recognize that it would not be useful to express a reporter protein as part of a cytotoxic construct because the cell would likely die before the protein could be detected. On the other hand, it would be entirely possible and feasible to detect the residual DNA vector itself after the cell had died. This is likely one reason why Buscail elected to detect the DNA vector directly, rather than detecting any protein expressed from the vector (e.g., DCK or UMK).
Further, modifying Buscail to detect the presence of the DNA vector using a reporter protein, rather than by detecting the DNA directly within a sample, would decrease the sensitivity of detection, at least because cells treated with the DNA vector of Buscail would be expected to die upon administration of the DNA vector. A person having ordinary skill in the art would also recognize that DNA can likely be detected at a much lower level than a reporter protein, especially when the recipient cell dies at around the same time the reporter protein is beginning to be expressed.
Therefore, because modifying the DNA vector of Buscail to include a nucleotide
sequence encoding a reporter protein would have been redundant to the detection method already provided by Buscail and likely would have lower sensitivity, such a modification would not have been desirable the requisite motivation to make the modification is thus absent.
In sum, a person having ordinary skill in the art would not be motivated to modify the DNA vector of Buscail to express a reporter protein over Kronke, Goding, and Stevis. For at least this reason, independent claim 56 and claims 57-65, 67, 68, and 72 dependent therefrom are not obvious over Buscail in view of Kronke, Goding, and Stevis. Reconsideration and withdrawal of the rejection are respectfully requested.
Buscail in view of Kronke, Goding, and Stevis fails to teach or suggest an isolated host cell as recited by dependent claim 72.
Dependent claim 72 recites "An isolated host cell comprising the DNA vector of claim 56." The Examiner states that Buscail teaches "a Phase 1 clinical trial for human patients (which encompasses isolated host cell)." Non-final Office Action, page 5. Applicant asserts that a person having ordinary skill in the art would not recognize an "isolated host cell" within the Phase 1 clinical trial for human patients of Buscail. While human patients may comprise cells, cells within an organism would not fall within the generally recognized meaning of "isolated," at least because they only exist within the context of the whole human. The Examiner does not allege that Kronke, Goding, or Stevis teaches or suggests an isolated cell comprising a DNA vector. Therefore, the Examiner fails to identify within the cited documents all elements of dependent claim 72.
For at least this additional reason, dependent claim 72 is not obvious over Buscail in view of Kronke, Goding, and Stevis. Reconsideration and withdrawal of the rejection are respectfully requested.
Independent claim 56 and claims 57-65, 69, 70, and 72 dependent therefrom are not obvious over Buscail in view of Ochiishi, Goding, and Stevis, at least because the skilled person would not be motivated to modify the DNA vector of Buscail to include a reporter protein as taught by Stevis or Ochiishi.
Examiner’s Explanation:
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Applicants argue that a POSITA would not have been motivated to modify the DNA vector of Buscail et al. because [1] it would not add any meaningful functionality, [2] would likely decrease the sensitivity of a detection assay, and [3] the DNA vector of Buscail et al. is cytotoxic, so any cells that receive the DNA vector should theoretically die upon expression of the vector.
Contrary to Applicants’ allegations, the Examiner notes that the combined teachings of the prior art would provide a meaningful functionally and motivation to make and use the invention as claimed. Especially in the context of the DNA vector of Buscail et al. cells do not immediately die just because the cells comprise the DNA vector of Buscail et al. As explained previously, the DNA vector of Buscail et al. comprise eukaryotic promoters, GRP78 and GRP94, which are an inducible promoter because they are activated or "turned on" by a specific stimulus, i.e., glucose deprivation (see the body of the instant rejection). As such, by having an additional fluorescent reporter protein, a POSITA would be able to determine if the inducible promoters for expression of cytotoxic protein is working properly as a ‘switch’ mechanism in a ‘cell survival assay’ since a POSITA now can monitor the living cells comprising the DNA vectors with fluorescence and determine if the cell death occurs when the ‘switch’ is turned on.
Furthermore, applicants’ allegation that such DNA vector would likely decrease the sensitivity of a detection assay is moot because the claimed invention has no language which requires that the sensitivity of a detection assay must be maintained during the use of the DNA vector.
Lastly, Applicants’ allegation that the cited prior art references fail to teach an “isolated host cell” because a POSITA would not consider a human patient to be encompassed by the definition of “isolated host cell” is moot because the instant specification does not define what the phrase “isolated host cell” encompasses, and a person of ordinary skill in the art, i.e., the Examiner, would interpret a human patient to be encompassed by the meaning of “isolated host cell”.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Claim 56-65, 69-70 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Buscail et al. (First-in-man Phase 1 Clinical Trial of Gene
Therapy for Advanced Pancreatic Cancer: Safety, Biodistribution, and Preliminary Clinical Findings, Molecular Therapy vol. 23 no. 4, 779–789 apr. 2015) in view of Ochiishi et al. (Development of new fusion proteins for visualizing amyloid-β
oligomers in vivo, Scientific Reports volume 6, Article number: 22712, published 03/16/2016), Goding et al. (WO 2007062474 A1) and Stevis et al. (US 20140275489 A1).
The instant claims are drawn to a DNA vector comprising in operable linkage:(a) a promoter;(b) a nucleotide sequence encoding a fusion protein comprising a protein of interest fused to a cytotoxic element selected from the group consisting of deoxycytidine kinase, thymidylate kinase, thymidine kinase-guanylate kinase fusion, and FKBP-Caspase9 fusion;(c) an internal ribosomal entry site (IRES); and(d) a nucleotide sequence encoding a reporter protein.
Buscail et al. teach a DNA vector (CYL-02) comprising in operable linkage: (a) a glucose-responsive promoter (GRP78 or GRP94); (b) a nucleotide sequence encoding a fusion protein comprising a protein of interest (UMK) fused to a cytotoxic element, deoxycytidine kinase (dCK), which is used for a Phase 1 clinical trial for human patients (which encompasses isolated host cell). The Examiner notes that eukaryotic promoters, like GRP78 and GRP94 which work in human cells, are considered an inducible promoter because they are activated or "turned on" by a specific stimulus, i.e., glucose deprivation. Buscail et al. further teach that said fusion protein is separated by a peptide linker, “FMDV 2A peptide” (see page 786, right column, 4th para under “Treatment plan”).
Buscail et al. do not teach a peptide linker comprising one or more iterations of GGS, a reporter protein which is fluorescent, CMV promoter, a protein of interest which is amyloid protein.
Ochiishi et al. teach that the intracellular accumulation of amyloid-β (Aβ) oligomers critically contributes to disease progression in Alzheimer’s disease (AD) and can be the potential target of AD therapy. Ochiishi et al. further teach Aβ-GFP fusion protein for in vivo imaging.
Goding et al. teach that an expression construct, i.e., polycistronic DNV vector, comprising a CMV promoter operably linked to a nucleotide sequence encoding multiple proteins of interest with an IRES inserted in between said proteins or a fluorescent reporter protein, i.e., a green or red fluorescent reporter protein (see pg. 40, line 20; pg. 31, line 1; and claims 10, 11, 13, 23 and 26).
Stevis et al. teach that a fusion protein comprising a reporter protein, which can be Renilla luciferase or green fluorescent protein (see para [0100]), wherein said fusion protein is linked by a peptide linker comprising one or more iterations of Gly-Gly-Ser (see para [0122]).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to make and use the DNA vector taught by Buscail et al. and substitute with the following: a peptide linker comprising one or more iterations of GGS, a reporter protein which is fluorescent, CMV promoter, a protein of interest which is Aβ as taught by Ochiishi et al. Goding et al. and Stevis et al. A person of ordinary skill in the art (POSITA) would have been motivated to make and use such DNA vector because [1] suicide gene such as dCK are routinely fused a gene (UMK) associated with pancreatic cancer for cell survival as taught by Buscail et al., and since Aβ is also a known protein which accumulates intracellularly in Alzheimer’s disease, a POSITA would have been motivated to swap UMK with Aβ and express such fusion protein with a reporter protein for cell survival assays; and [2] an IRES allows expressing two or more proteins in a single mRNA transcript, i.e., a fusion protein and a reporter protein as taught by Goding et al. Furthermore, it would have been a routine experimentation for a POSITA to swap between different but obvious variants of promoters, peptide linkers, and reporter proteins that are present in such DNA vector by using the CMV promoter, a peptide linker comprising GGS, and a reporter protein which is Renilla luciferase or GFP. As discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007), it is considered obvious to combine prior art elements which are obvious variants known to be used in equivalent fields of endeavor together into a single combination. The references of Buscail et al., Ochiishi et al. Goding et al. and Stevis et al. clearly show that the claimed promoters, peptide linkers, and reporter proteins were known to be used in equivalent fields of endeavor; thus, it is considered obvious to combine them together. A POSITA would have had a reasonable expectation of success to make and use such DNA vectors because all of the required biochemical reagents and techniques were rampantly used as evidenced by Buscail et al., Ochiishi et al. Goding et al. and Stevis et al. prior to the filing of the instant application. For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Applicants’ Arguments:
A person having ordinary skill in the art would not be motivated to modify the DNA vector of Buscail to include a reporter protein in view of Ochiishi, Goding, and Stevis, at least because (i) Buscail already provides a method of detecting presence of the DNA vector directly in patient samples and (ii) detecting the presence of the DNA vector using a reporter protein, rather than by detecting the DNA directly within a sample, would decrease the sensitivity of detection, at least because cells treated with the DNA vector of Buscail would be expected to die upon administration of the DNA vector.
Ochiishi fails to cure the deficiencies of Buscail in view of Kronk, Goding, and Stevis as described herein. Specifically, a person having ordinary skill in the art would not be motivated to modify the DNA vector of Buscail to include a nucleotide sequence encoding a reporter protein because such a modification would not add any functionality and would therefore be undesirable. Because it would have been undesirable to modify the DNA vector of Buscail by incorporating the teachings of Ochiishi, Goding, and Stevis as suggested by the Examiner, the claimed DNA vector is not obvious over this combination of documents. Therefore, independent claim 56 and claims 57-65, 69, 70, and 72 dependent therefrom are not obvious over Buscail over Ochiishi, Goding, and Stevis. Reconsideration and withdrawal of the rejection are respectfully requested.
Examiner’s Explanation:
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Applicants argue that a POSITA would not have been motivated to modify the DNA vector of Buscail et al. because [1] Buscail already provides a method of detecting presence of the DNA vector directly in patient samples, and [2] would likely decrease the sensitivity of a detection assay at least because the DNA vector of Buscail et al. is cytotoxic, and cells treated with the DNA vector would die upon administration of the DNA vector.
Contrary to Applicants’ allegations, the Examiner notes that the combined teachings of the prior art would provide a motivation to make and use the invention as claimed. Especially in the context of the DNA vector of Buscail et al. cells do not immediately die just because the cells are treated with the DNA vector of Buscail et al. As explained previously, the DNA vector of Buscail et al. comprise eukaryotic promoters, GRP78 and GRP94, which are an inducible promoter because they are activated or "turned on" by a specific stimulus, i.e., glucose deprivation (see the body of the instant rejection). As such, by having an additional fluorescent reporter protein, a POSITA would be able to determine if the inducible promoters for expression of cytotoxic protein is working properly as a ‘switch’ mechanism in a ‘cell survival assay’ since a POSITA now can monitor the living cells comprising the DNA vectors with fluorescence and determine if the cell death occurs when the ‘switch’ is turned on.
Furthermore, applicants’ allegation that such DNA vector would likely decrease the sensitivity of a detection assay is moot because the claimed invention has no language which requires that the sensitivity of a detection assay must be maintained during the use of the DNA vector.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 56-65, 67-70, 72 and 80 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
THIS ACTION IS MADE FINAL. 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 extension fee 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 JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656