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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/29/2026 has been entered, thus entering the claims submitted 7/13/2026.
Applicant’s arguments and amendments have been thoroughly reviewed and considered. Claims 2, 6, 8, 12, 18-19, 23, 27, 29, and 31 remain withdrawn. Claims 25 and 36-37 have been canceled. Claims 39-41 have been added. Claims 1, 4, 11, 21-22, 30, 35, and 38-41 are pending and are examined on the merits herein.
Response to Applicant’s Amendments
Claim Objections
Claim 38 was objected to due to minor informalities. In light of Applicant’s amendments to the claims submitted 7/13/2026, this objection has been withdrawn. However, see new grounds of objection below.
35 USC 112(b) Rejections
Claim 37 was rejected due to informality issues. As this claim has been canceled, this rejection has been rendered moot.
35 USC 101 Rejections
Claims 1, 4, 11, 21-22, 30, and 35 were rejected as reciting a natural law. In light of Applicant’s amendments to the claims submitted 7/13/2026, these rejections have been withdrawn.
It is noted that Applicant has not provided substantive arguments regarding any of these previously set forth rejections/objections. See new grounds of rejection below unrelated to Applicant’s amendments.
Claim Objections
Claim 4 is objected to because of the following informality: it is recommended that lines 1-2 read “a decreased amount of said Xloc13 lincRNA transcript, Xloc13 lincRNA intron, or one or more fragments thereof,” similar to the language used in the amended portion of claim 1, to make clear that the Xloc13 lincRNA recited in claim 4 is the same as is used in claim 1. Appropriate correction is required.
Claim 41 is objected to because of the following informality: it is recommended that lines 1-2 read “a decreased amount of said Xloc13 lincRNA transcript, Xloc13 lincRNA intron, or one or more fragments thereof,” as the detection of one of these elements is already described in claim 40, from which this claim depends. Appropriate correction is required.
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 1, 4, 11, 21-22, 30, 35, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Lan et al. (Gene, 2015; cited in Applicant’s IDS), as evidenced by LNCipedia (“Transcript: lnc-TPO-1:2”, 2018), and in view of Yoo et al. (PLoS Genet, 2016), and in view of Cui et al. (J Clin Endocrinal Metab, 2014).
Lan teaches examining the expression profile of long non-coding RNAs (lncRNAs) in human papillary thyroid carcinoma (PTC) samples (Abstract). Each lncRNA examined underwent microarray analysis, where specific probes were used on sample nucleic acids (page 110, Sections 2.1-2.5). Table 3 shows the top 20 upregulated and downregulated lncRNAs, where TCONS_00004663 is shown to be downregulated compared to its expression in noncancerous tissues (and was therefore detected in the sample; instant claim 11). As evidenced by LNCipedia, TCONS_00004663 is another name for a particular XLOC13 transcript (see under “Alternative Transcript Names”).
However, this reference does not discuss follicular thyroid cancer (FTC).
Yoo teaches comparisons of gene expression in FTC, classic PTC, and the follicular variant of PTC (FVPTC; Abstract). PTC, FVPTC, and FTC are the three most common types of thyroid cancer, and FVPTC and FTC are known to harbor similar mutations (page 2, paras. 1-2). Page 3, para. 1 notes further mutational commonality between FVPTC and FTC, and Figure 4C notes more copy number similarities between types of FVPTC (specifically EFVPTC) and FTC than between EFVPTC and PTC. Page 12, para. 1 states, “cPTC and miFTC showed considerably different patterns of genetic alteration to each other. However, FVPTC represented an intermediate mutational status between cPTC and miFTC; EFVPTC and infiltrative FVPTC were similar to miFTC and cPTC, respectively.”
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the guidance provided by Yoo to examine TCONS_00004663, as well as the other biomarkers of Lan, in the context of follicular thyroid cancer. Lan is not specific about the types of PTC samples examined in their method, as the method simply states that PTC tissue was analyzed (page 110, column 1, para. 2). However, the ordinary artisan would recognize that the PTC samples could contain PTC variants, and therefore may encompass FVPTC samples, particularly as this is the most common PTC subtype. As Yoo details the similarities between FVPTC and FTC, the ordinary artisan would therefore be motivated to analyze the biomarkers of Lan in the context of FTC. Lan teaches that measuring the expression of lncRNA biomarkers “may provide new ways for diagnosing and treating PTC,” (page 110, column 1, para. 1), and so by analyzing these biomarkers with FTC samples, similar benefits can be gleaned. As TCONS_00004663 was specifically a top 3 down-regulated lncRNA in Lan, this lncRNA would be of particular interest to examine. There would be a reasonable expectation of success as Lan already shows that their biomarkers can be measured and detected, and this change would still involve analyzing tumor tissue, as is done in Lan, just with a different type of tumor.
However, none of these references teach the treatment limitations of instant claims 1, 35, and 40.
Cui analyzes an EZH2 inhibitor, DZNep, in the context of thyroid cancer cells (“Context”). This included an analysis of FTC cells, FTC133, which are noted to be TP53 mutant-type cells (page E963, column 2, para. 3). DZNep did slightly decrease EZH2 expression in FTC133 cells alone (Figures 1A-1B), but when combined with a PRIMA-1 treatment (which is a p53 reactivator), the viability of cancer cells notably decreased over 72 hours (Figure 2A). Table 1 also shows that with this combination treatment, significantly less FTC133 cells were in mitotic phases compared to controls, and Figure 3 notes that significantly more apoptotic FTC133 cells were present compared to controls with the combination treatment.
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Cui in the method of Lan, as evidenced by LNCipedia, and in view of Yoo to treat patients with FTC with the DZNep EZH2 inhibitor and PRIMA-1 combination described by Cui. Cui shows extremely promising results with the use of this treatment in FTC, including decreased EZH2 expression, slower tumor cell growth, and an increase in tumor cell death. Cui teaches that EZH2 is associated with poor outcomes in cancer (page E968, column 2, para. 2), and concludes that their data “suggest that the combination of DZNep and PRIMA-1 is an effective and relatively selective therapy for thyroid cancer cells (or patients) harboring mutant-type TP53,” (page E970, column 1, para. 1). Thus, perusing this treatment option in FTC, which Cui teaches has mutant-type TP53, would be motivating to the ordinary artisan. Additionally, as this treatment lowers the number and growth of tumor cells in a sample, the ordinary artisan would recognize that this would affect the expression levels of biomarkers associated with FTC expression, such as XLOC13. Thus, as XLOC13 appears to be downregulated in FTC, with this treatment, XLOC13 expression would likely increase. There would be a reasonable expectation of success in using this treatment as Cui already shows its successful use in FTC.
Thus, claims 1, 4, 11, 22, 35, and 40-41 are prima facie obvious over Lan, as evidenced by LNCipedia, in view of Yoo, and further in view of Cui.
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Regarding claims 21 and 30, TCONS_00004663, examined in Lan, is the same sequence as instant SEQ ID NO: 2. See alignment below, using the sequence for the transcript provided by LNCipedia:
Thus, claims 21 and 30 are prima facie obvious over Lan, as evidenced by LNCipedia, and in view of Yoo.
Claims 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Lan et al. (Gene, 2015; cited in Applicant’s IDS), as evidenced by LNCipedia (“Transcript: lnc-TPO-1:2”, 2018), in view of Yoo et al. (PLoS Genet, 2016), Cui et al. (J Clin Endocrinal Metab, 2014), in view of LNCipedia (“Transcript: lnc-TPO-1:2”, 2018), and further in view of Ye et al. (BMC Bioinformatics, 2012).
It is noted that Applicant does not specifically define the terms “primer” or “probe” in the instant specification, and so under the broadest reasonable interpretation of the terms in light of the instant specification, they amount to having very similar scopes, where a primer/probe must be capable of hybridizing to a target sequence, and a primer must be capable of being used for an extension reaction, though a probe may also be used for this purpose.
Lan, as evidenced by LNCipedia, in view of Yoo, and in view of Cui teaches the methods of claims 1, 4, 11, 21-22, 30, 35, and 40-41, as described above, and these teachings involve measuring the amount of XLOC13 in an FTC sample. Lan does teach the use of particular primer sequences (Table 2), but these are not for XLOC13. The probe sequences used in the microarray analysis are not specified in the reference. None of these references teach the primer sequences of the instant claim.
However, aligning the claimed sequences with the XLOC13 sequence shown by LNCipedia reveals the following 100% alignments:
For SEQ ID NO: 6
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For SEQ ID NO: 14
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Ye teaches the use of the publicly available tool Primer-BLAST that allows for design of target specific primers from known sequences (Abstract, page 2, column 2, para. 2, and page 3, column 2, para. 2). Ye teaches that this software is easy to use, flexible, and quicker than other tools (“Conclusions” pages 9-10).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art use the teachings of Ye with Lan, as evidenced by LNCipedia, in view of Yoo, and in view of Cui to arrive at the invention of claims 38-39. Specifically, it would have been prima facie obvious to create the primers of instant SEQ ID NOs: 6, 14, 16, and 18 using the sequence for XLOC13 used in Lan and detailed in LNCipedia with Ye, and these primers could function to detect XLOC13 in the methods of Lan, as evidenced by LNCipedia, in view of Yoo, and in view of Cui. Though Lan does not teach performing PCR methods on XLOC13, the reference does teach PCR generally (page 111, Section 2.9). As XLOC13 shows one of the strongest fold changes for expression in the cancer samples of Lan, it would be obvious to the ordinary artisan that this biomarker would merit additional expression analysis. Figure 5 of Lan also notes that expression levels may differ slightly between microarray results and PCR results for biomarkers, so by utilizing both methods on biomarkers of particular importance, more accurate expression ranges for normal and cancerous samples could be reached, which would improve diagnostic accuracy of the biomarkers. Also, the teachings of Ye indicate that software for PCR primer design is available and can be used by the ordinary artisan to obtain sequences suitable for amplifying a known target. In view of the above, the ordinary artisan would have been motivated to use the publicly available software disclosed in Ye and the known XLOC13 sequences described in the sequences disclosed by LNCipedia to design primers and probes for use in the method of Lan, as evidenced by LNCipedia, and in view of Yoo, and in the absence of unexpected results, the claimed polynucleotides (instant SEQ ID NOs: 6, 14, 16, AND 18) simply represent the result of an obvious series of steps.
Thus, claims 38-39 are prima facie obvious over Lan, as evidenced by LNCipedia, in view of Yoo, in view of Cui, in view of LNCipedia, and further in view of Ye.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA F GIAMMONA whose telephone number is (571)270-0595. The examiner can normally be reached M-Th, 7-5pm.
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/F.F.G./Examiner, Art Unit 1681
/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
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