DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The examiner reviewing your application at the PTO has changed. To aid in correlating papers in this application, all further correspondence regarding this application should be directed to examiner Carla Myers.
Continued Examination Under 37 CFR 1.114
3. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15 May 2026 has been entered.
4. Applicant's arguments and amendments to the claims presented in the reply of 15 May 2026 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
In particular, the previous objection to claim 12 has been obviated by the amendment to the claim.
The previous rejection of the claims under 35 U.S.C. 112(b) has been obviated by the amendments to the claims.
The previous rejection of claims 21-23 as reciting an improper Markush grouping has been obviated by the cancellation of claims 21-23. This rejection does not apply to the present claims because the claims require each of the recited acinar cell-derived signature genes and ductal cell-derived signature genes. That is, the genes are not recited in the alternative but rather each of the recited genes is required by the claims.
The prior rejections of the claims under 35 U.S.C. 103 over Bailey et al in view of Brunton; alone or in combination with Grandjean et al, or in combination with Maynard et al or in combination with Woll et al have been obviated by the amendments to the claims. In particular, the rejections have been obviated by the amendment to the claims to require performing targeted RNA sequencing or targeted microarray analysis using primers or baits that target each of the listed acinar cell-derived signature genes and each of the listed ductal cell-derived signature genes; assessing the transcript expression data to determine a molecular signature enrichment score from the transcript expression data, wherein the molecular signature enrichment score differentiates whether the tumor is of acinar cell origin or of ductal cell origin based on a comparison of expression between the acinar cell-derived signature genes and the ductal cell-derived signature genes; and treating the individual having a molecular signature enrichment score that indicates that the tumor is of acinar cell origin with an inhibitor of AKT kinase, and treating the individual having a molecular signature enrichment score that indicates that the tumor is of ductal cell origin by targeting the
glycolysis pathway.
Claim Status
5. Claims 1, 4-8, 12, 15 and 24 are pending and have been examined herein.
New Claim Objections
6. Claims 1, 4-8, 12, 15 and 24 are objected to because of the following informalities:
In claim 1, “method for treating pancreatic ductal adenocarcinoma
(PDAC) subtype” should read “method for treating a pancreatic ductal adenocarcinoma
(PDAC) subtype.
In claim 1, “from tumor sample of the individual affected with PDAC sample” should read “from a tumor sample of an individual affected with PDAC”
Appropriate correction is required.
New Claim Rejections - 35 USC § 112(b) - Indefiniteness
7. 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, 4-8, 12, 15 and 24 are 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.
Claims 1, 4-8, 12, 15 and 24 are indefinite over the recitations of “performing a targeted microarray”, “the targeted microarray consists of targeting,” and “the targeted microarray comprises use of” (recited in claim 1) because these phrases are not clear since a “targeted microarray” is a product and not an assay/process. Similarly, claim 5 is indefinite over “the transcriptomic analysis comprises the targeted microarray.” This rejection may be obviated by amendment of claim 1 to recite ““performing a targeted microarray analysis”, “the targeted microarray analysis consists of targeting,” and “the targeted microarray analysis comprises use of”; and amendment of claim 5 to recite ““the transcriptomic analysis comprises the targeted microarray analysis.”
Claims 6-8 are indefinite over the recitation that the method further comprises determining a treatment response in claim 6 and the method further comprises treating the individual affected with PDAC based on the response to the treatment. Claim 1, from which claims 6-8 depend, already requires performing a step of treating the individual and it is unclear as to the relationship between the treatment in claims 6-8 and the treating in claim 1. For instance, it is unclear as to whether the methods of claim 6-8 are intended to determine a treatment response to the treatment comprising inhibiting AKT kinase or treatment comprising targeting the glycolysis pathway and it is unclear as to whether the “determining a treatment response” is performed before and/or after the treating step of claim 1. It is further unclear as to how claim 8 is intended to further limit claim 1 if the treatment in claim 8 is the same as that in claim 1 since claim 1 already requires performing the treating step.
Claim 7 is indefinite over the recitation of “incubating the cell culture” because it is not clear as to whether this phrase is intended to refer to the cell culture that is produced by culturing the cell or the cell culture to which the treatment is provided or both. This rejection may be obviated by amendment of claim 7 to recite “culturing a cell isolated from the tumor to obtain a cell culture; providing a treatment to the cell culture; incubating the cell culture to which the treatment has been provided”.
Claim 24 is indefinite and vague over the recitation of “performing immunohistochemistry on a tumor sample” because it is not clear as to how this recitation relates back to the remainder of the claim and to the method of treating a PDAC subtype. It is unclear as to whether “a tumor sample” is intended to encompass any tumor sample from any source or a tumor sample from the individual affected with PDAC.
New Claim Rejections - 35 USC § 112(a) - New Matter
8. 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, 4-8, 12, 15 and 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. This is a new matter rejection.
The disclosure as originally filed does not provide basis for the amendment to claim 1, and thereby dependent claims 4-8, 12, 15 and 24, to recite that the method comprises performing targeted RNA sequencing or targeted microarray (analysis) and does not provide basis for methods wherein the targeted RNA sequencing or the targeted microarray (analysis) comprises use of primers or baits that target the acinar cell-derived signature genes and the ductal cell-derived signature genes.
In the reply of 15 May 2026, Applicant states that support for the amendments to the claims is found in the originally filed claims and at paragraphs 0014, 0039, 0061, 0062, 0065 and Table 1 of the specification. In the reply of 29 May 2025, Applicant states that support for the amendment to add previous clams 21-23 is found at paragraphs 0014, 0039, 0061, 0062, 0065.
However, the cited portions of the specification do not provide support for the concepts of performing targeted RNA sequencing or targeted microarray analysis wherein the targeted RNA sequencing and targeted microarray analysis specifically target / detect the recited acinar and ductal cell-derived signature genes, particularly using primers or bait that target the recited acinar and ductal cell-derived signature genes.
Rather, the disclosure as originally filed teaches methods of RNA sequencing and microarray analysis per se and teaches whole transcriptome analysis. For instance, para [0007] of the specification states “the transcriptomic analysis is selected from bulk RNA analysis, spatial transcriptomic analysis, and single cell RNA sequencing; the transcriptomic analysis uses a microarray.” Para [0039] of the specification states “Further embodiments perform single cell RNA sequencing to assess the transcriptome of a cell or multiple cells within the tumor.”
The disclosure does not specifically disclose the use of primers or baits and does not teach primers or baits that target the acinar cell-derived signature genes and the ductal cell-derived signature genes. Note that the term “bait” implies the use of a nucleic acid to capture and enrich for a target nucleic acid prior to performing RNA sequencing or microarray analysis and is not equivalent to a probe present on a microarray. Even if the claims were limited to microarray methods that use probes that target only the acinar cell-derived signature genes and ductal cell-derived signature genes, the disclosure as originally filed does not appear to provide support for this concept since the information provided in the disclosure appears to be limited to whole transcriptome analysis and not the use of a microarray that detects only the acinar cell-derived signature genes and ductal cell-derived signature genes.
Additionally, the disclosure as originally filed does not appear to provide basis for the step in claim 1 of “wherein the molecular signature enrichment score differentiates whether the tumor is of acinar cell origin or of ductal cell origin based on a comparison of expression between the acinar cell-derived signature genes and the ductal cell-derived signature genes.” The genes in the acinar cell-derived signature genes are distinct from the genes in the ductal cell-derived signature and it is unclear as to why the expression level of the genes in the two signatures would be compared to one another. The cited portions of the specification do not teach comparing the expression of the acinar cell-derived signature genes with the ductal cell-derived signature genes.
If Applicant maintains that the originally filed disclosure provides basis for the amended claims, Applicant should point to specific teachings (e.g., by paragraph number) in the present application to establish basis for each of the recitations set forth in the claims.
Priority
9. The present claims are not entitled to priority to provisional application 63/155,156, filed 01 March 2021.. It is noted that a claim as a whole is assigned an effective filing date rather than the subject matter within a claim being assigned individual effective filing dates. The ‘156 application does not provide support for each of the embodiments in independent claim 1 and each of the embodiments in the dependent claim. For example, the ‘156 application does not teach the limitation of performing targeted RNA sequencing or targeted microarray (analysis). The ‘156 application also does not teach that the targeted RNA sequencing or the targeted microarray (analysis) comprises use of primers or baits that target the acinar cell-derived signature genes and the ductal cell-derived signature genes. The ‘156 application also does not provide basis for the step in claim 1 of “wherein the molecular signature enrichment score differentiates whether the tumor is of acinar cell origin or of ductal cell origin based on a comparison of expression between the acinar cell-derived signature genes and the ductal cell-derived signature genes.”
If Applicant asserts that the present claims are entitled to priority to the provisional applications, Applicant should point to specific teachings (e.g., by page and line number) in the priority applications to establish priority for each of the recitations set forth in the claims.
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” states “To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” which states:
“To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Flowers et al (Cancer Discovery. “Cell of Origin Influences Pancreatic Cancer Subtype” 02 March 2021. 11(3) 660-677 and Supplemental Table S4 p. 1-50; available via URL: < aacrjournals.org/cancerdiscovery/article/11/3/660/2776/Cell-of-Origin-Influences-Pancreatic-Cancer>) teaches methods for distinguishing between acinar cell-derived PDAC and ductal cell-derived PDAC based on differences in gene expression levels in these two subtypes of PDAC (e.g., p. 668 “Acinar Cell– and Ductal Cell–Derived Tumors Are Transcriptionally Distinct”). It is stated that “analysis of differentially expressed genes by DESeq2 revealed that 1,075 genes are more highly expressed in acinar cell–derived tumors than in ductal cell–derived tumors and that 417 genes are more highly expressed in ductal cell–derived tumors than in acinar cell–derived tumors (log2 fold change > 1.0, P-adjusted value < 0.05; Fig. 5B; Supplementary Table S4). Supplementary table S4 provides the data for expression levels of 18,526 genes that were analyzed for their expression levels in acinar cell-derived and ductal cell-derived PDAC” (p. 698, col. 2 to p. 699, col. 1. Note that only the first 50 pages of Supplementary Table S4 are provided. It is stated that “our ductal cell–derived
signature displays a striking enrichment of genes involved in glycolysis, and, accordingly, some patient-derived cell lines of the squamous subtype are sensitive to glycolysis inhibition” (p. 674, col. 1)
Flowers further teaches that “496 genes were more highly expressed in acinar cell–derived tumors than in ductal cell–derived tumors, and 77 genes were more highly expressed in ductal cell–derived tumors than in acinar cell–derived tumors” (p. 670, col. 1). However, the reference does not appear to teach the specific identity of the 496 genes that were more highly expressed in acinar cell–derived tumors than in ductal cell–derived tumors, and the specific identity of the 77 genes that were more highly expressed in ductal cell–derived tumors than in acinar cell–derived tumors. Accordingly, Flowers does not teach or suggest the presently claimed methods that require (in part) performing targeted RNA sequencing or targeted microarray analysis using primers or baits that target the particular 496 genes expressed at higher levels in acinar cell-derived tumors and the particular 77 genes expressed at higher levels in ductal cell-derived tumors and assessing the resulting transcript expression data to determine determining a molecular signature enrichment score from the transcript expression data, wherein the molecular signature enrichment score differentiates whether the tumor is of acinar cell origin or of ductal cell origin based on a comparison of expression between the acinar cell-derived signature genes and the ductal cell-derived signature genes.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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