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 .
Election/Restrictions
Applicant's election with traverse of Group II in the reply filed on June 15, 2026 is acknowledged. The traversal is on the ground(s) that unity of invention is present when a single inventive concept is fulfilled where there is a technical relationship within the claimed subject matter involving one or more of the same corresponding technical features that define a contribution over the prior art (page 7, Response) and that the instantly claimed subject matter of Groups I-V possess a common feature that makes contribution over the prior art (page 8, 1st paragraph, Response) as Shi et al. do not teach any discussion relating to TROLL-2 or TROLL-3 lncRNA (page 8, Response). This is not found persuasive and Applicants’ characterization of the restriction is entirely misleading. The restriction mailed out on December 15, 2025 clearly states that TROLL-1 was disclosed by Shi et al. (see below):
PNG
media_image1.png
562
1006
media_image1.png
Greyscale
Applicants, in response to this restriction requirement, canceled TROLL-1 from the claims.
Therefore, the restriction as mailed was proper but nevertheless may presently be negated by Applicants’ amendment. Regardless of this fact, the restriction is maintained because: 1) the elected markers shared by the groups of inventions lack a special technical feature that contribute over the prior art as evidenced by the below prior art rejection; and 2) the unity of invention is applied to a single category of inventions (see 37 CFR 1.475(b)). Because the present groups of inventions are multiple methods, additional methods are outside of such a category and therefore lack unity of invention.
With regard to Applicants’ election of species TROLL-2, KRAS, and expression level of the genes with traverse, Applicants’ arguments lack merit as these genes are not shared by a special technical feature as they are recited as an alternative species, with each of the markers not sharing a sequence identity. As well, the localization of an expression product versus the amount of expression of a product are completely different observance and therefore they do not share a common feature in their characteristics that relates to a correlation. Nevertheless, the withdrawn species will be examined to the extent that the elected species is free of prior art with generic/genus claims not being subject to a substantial rejection.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 5, and 10-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 15, 2026.
Information Disclosure Statement
The IDS received on July 10, 2025 is proper and is being considered by the Examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because the texts of the Figures are unclear and are illegible (see Figure 1A-H, for example, also Fig. 2H, etc.). Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. Applicants are required to peruse the entire set of drawings and provide drawings with clear texts and information that are legible. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Objections
Claims 2, 3, and 6 are objected to because of the following informalities:
Claims 2 and 3 recite, “ofWDR26”. There should be a space between the words, “of” and “WDR26.”
Claim 6 recites the phrase, “NCOA5 is is i) higher”. The second instance of the word, “is” should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 2-4, 8, 9, 22, 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.
Claim 2 is indefinite because the claim preamble recites that the method is for assessing the efficacy of a cancer treatment, but the claim only recites active steps of obtaining a sample and measuring the levels of TROLL-2, TROLL-3, WDR26, and/or NCOA5, or the localization of WDR26 or NCOA5, failing to recite a final step that agrees with the preamble. As well, the claim recites the step of obtaining a tissue sample from “a” subject, but this subject is not necessarily limited to the subject of the preamble receiving the cancer treatment regimen.
Claim 3 is indefinite because the limitations recited in the wherein clause is not an active step, but rather recitation of a natural correlation that exists as the claim does not contain an active comparison step to the controls.
Claim 4 is also indefinite by way of its dependency on claim 1 and 4.
Claim 8 recites the limitation, “the anti-cancer agent.” There is an insufficient antecedent basis for this limitation in the claim. For the purpose of prosecution, the claim has been construed to depend from claim 7 that provides a proper antecedent basis.
Claim 9 is indefinite by way of its dependency on claim 8.
Claim 22 is indefinite for the same reason as claim 2.
Claim 24 is indefinite because a positive control cannot be from a subject whose cancer treatment regimen that is “being assessed.” Rather, a positive control must have an outcome that has been pre-established so that a test sample can be measured against that pre-established outcome from the positive control.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 23 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 23 is dependent on claim 22. Claim 22 requires the assay of TROLL-2 or TROLL-3. Claim 23, however recites that the method now assays TROLL-2, TROLL-3 “and/or” WDR26 “and/or” NOCA5, which effectively negates the requirement of TROLL-2 or TROLL-3 assay, thus falling outside of the scope established by the parent claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2-4, 6, and 22-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally existing phenomenon without significantly more. The claims recite the level of TROLL-2, TROLL-3, WDR26 and/or NCOA5; and cytoplasmic (intracellular) localization of WDR26 and NCOA5 and the predisposition of a subject’s implication to poor cancer treatment prognosis. This judicial exception is not integrated into a practical application because the additional steps are recited in high level of generality without significantly applying the judicial exception into a practical application.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. The subject claims satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon. As stated above, the claims recite a law of nature/natural phenomenon that exists between the levels of long non-coding RNAs, namely, TROLL-2 and TROLL-3, WDR26, or NCOA5; or the cytoplasmic localization (i.e., intracellular localization) of WDR26 or NCOA5 in cells and the subject’s predisposition to respond to a cancer treatment.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
Claims 2-4:
Claim 2 recites additional steps in the form of “obtaining a tissue sample from a subject” who has received a cancer treatment regimen and measuring the expression level of TROLL-2, TROLL-3, WDR26, or NCOA5, or observing the intracellular localization of WDR26/NCOA5 in cells. However, these steps are deemed insufficient to meaningfully apply the judicial exception because obtaining a tissues sample from a subject who received an anticancer therapy is an insignificant pre-solution activity and no different than the steps of administering a thiopurine drug to a patient and measuring the drug metabolite levels (see Mayo) to which Supreme Court determined was insignificant.
Claims 3 and 4 fail to integrate the judicial exception into a practical application that imposes a meaningful limit because the additional element recited in the form of comparing the subject marker levels to that of a control is deemed to reveal the amount of level that is associated with a predisposition to subject’s predisposition to cancer in the form of anti-cancer drug efficacy, offering no more than a pre-solution activity, recited in a highly general way.
Claim 6:
Claim 6 recites additional steps in the form of “obtaining a tissue sample from a subject” who is receiving a cancer treatment regimen and measuring the expression level of TROLL-2, TROLL-3, WDR26, or NCOA5, or observing the intracellular localization of WDR26/NCOA5 in cells. However, these steps are deemed insufficient to meaningfully apply the judicial exception because obtaining a tissues sample from a subject who received an anticancer therapy is an insignificant pre-solution activity and no different than the steps of administering a thiopurine drug to a patient and measuring the drug metabolite levels (see Mayo) to which Supreme Court determined was insignificant.
As well, the wherein clause that further recites the naturally existing correlation based on the level of expression to controls, they fail to integrate the judicial exception into a practical application that imposes a meaningful limit because the additional element recited in the form of comparing the subject marker levels to that of a control is deemed to reveal the amount of level that is associated with a predisposition to subject’s predisposition to cancer in the form of anti-cancer drug efficacy, offering no more than a pre-solution activity, recited in a highly general way.
Claims 22-24:
Claim 22 recites additional steps in the form of “obtaining a tissue sample from a subject” who is receiving a cancer treatment regimen and measuring the expression level of TROLL-2, TROLL-3; and claim 23 recites an addition step of measuring the expression levels of WDR26, or NCOA5, or observing their intracellular localization in cells. However, these steps are deemed insufficient to meaningfully apply the judicial exception because obtaining a tissues sample from a subject who received an anticancer therapy is an insignificant pre-solution activity and no different than the steps of administering a thiopurine drug to a patient and measuring the drug metabolite levels (see Mayo) to which Supreme Court determined was insignificant.
As well, the wherein clause that further recites the naturally existing correlation based on the level of expression to controls (claims 23 and 24), they fail to integrate the judicial exception into a practical application that imposes a meaningful limit because the additional element recited in the form of comparing the subject marker levels to that of a control is deemed to reveal the amount of level that is associated with a predisposition to subject’s predisposition to cancer in the form of anti-cancer drug efficacy, offering no more than a pre-solution activity, recited in a highly general way.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
Presently, the additional elements discussed above that utilizes a highly general language of “measuring” the levels of the markers, or their localization, as well as the well-known means of comparing against a known control of predetermined outcome to ascertain significance of difference in expression levels (between test and control), are recognized in the art as being commonly employed, routine and conventional.
Therefore, these elements are not deemed significantly more than inclusion of means which are commonly used, routine and conventional.
Therefore, the present claims lack patent eligibility.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 2-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Napoli et al. (Nature Communications, Published October 14, 2020, vol. 11, pages 1-16).
For the instant rejection, “subject” in the step of the phrase, “obtaining a tissue sample from a subject” is not afforded the antecedent basis by the preamble phrase, “cancer treatment regimen administered to a subject1.”
With regard to claim 2, Napoli et al. teach a method which comprises the steps of: a) obtaining a tissue sample from a subject (“we performed in situ (ISH) for TROLL-2 and TROLL-3 in a breast cancer tissue microarray (TMA) with 45 samples including normal breast tissue, lobular hyperplasia, DCIS, and invasive breast cancer biopsies”, page 4, 1st column); and b) measuring the expression level of TROLL-2 and TROLL-3 (“expression of TROLL-2 and TROLL-3 … levels of both lncRNAs were higher in grade 3 compared to grade 1 and 2 tumours …”, page 4).
As well, Napoli et al. teach that intracellular localization of WDR26 correlates with breast cancer (“we found that cellular localization of WDR26 was mainly nuclear in normal breast tissue and lobular hyperplasia, while in the advanced phases of the disease … WDR26 localization was almost exclusively cytoplasmic …”, page 5).
With regard to claims 3 and 4, the claims do not set forth any active step of comparison, but recites inherent characteristics associated with the levels of TROLL-2, TROLL-3, and/or intracellular localization of WDR26.
For claims 3 and 4, Applicants should consider reciting an active step of “comparing the expression level of TROLL-2 or TROLL-3” with the expression levels of TROLL-2 or TROLL-3 in a negative control (or positive control), to make the comparison step a positive action.
Therefore, Napoli et al. anticipate the invention as claimed.
Claim Rejections - 35 USC § 103
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.
Claims 2-4, 6-9, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Napoli et al. (Nature Communications, Published October 14, 2020, vol. 11, pages 1-16).
For the instant rejection, “subject” in the step of the phrase, “obtaining a tissue sample from a subject” construed to reference the subject recited in the preamble (“cancer treatment regimen administered to a subject”).
With regard to claim 2, Napoli et al. teach a method which comprises the steps of: a) obtaining a tissue sample from a subject (“we performed in situ (ISH) for TROLL-2 and TROLL-3 in a breast cancer tissue microarray (TMA) with 45 samples including normal breast tissue, lobular hyperplasia, DCIS, and invasive breast cancer biopsies”, page 4, 1st column); and b) measuring the expression level of TROLL-2 and TROLL-3 (“expression of TROLL-2 and TROLL-3 … levels of both lncRNAs were higher in grade 3 compared to grade 1 and 2 tumours …”, page 4).
As well, Napoli et al. teach that intracellular localization of WDR26 correlates with breast cancer (“we found that cellular localization of WDR26 was mainly nuclear in normal breast tissue and lobular hyperplasia, while in the advanced phases of the disease … WDR26 localization was almost exclusively cytoplasmic …”, page 5).
Napoli et al. explicitly teach and suggest that the increased levels of TROLL-2 and TROLL-3, the intracellular localization of WDR26, are observed in samples of breast cancer tissues when compared to levels found in the normal sample (“we found that levels of both lncRNAs [TROLL-2 and TROLL-3] were undetectable in normal breast tissue and increased with breast cancer progression with the highest levels observed in invasive breast cancer samples”, page 3; “we assessed the expression levels of their 2 interacting proteins, WDR26 and NCOA5, in a TMA of breast cancer progression with 45 samples, comprising normal breast tissue, lobular hyperplasia, DCIS, and invasive breast cancer biopsies. Interestingly, we found that the cellular localization of WDR26 was mainly nuclear in normal breast tissue and lobular hyperplasia, while in advanced phases of the disease (i.e., DCIS and invasive-ductal carcinoma samples) WDR26 localization was almost exclusively cytoplasmic … also found that the expression of WDR26 and NCOA5 increased over the progression of breast cancer”, page 5).
While Napoli et al. explicitly teach that TROLL-2 and TROLL-3 are absent in normal breast cancer and their expression levels (along with WDR26 and NCOA5) increase as breast cancer progresses and WDR26’s intracellular localization, the artisans do not explicitly teach that this correlation should be utilized in determining whether an anti-cancer therapy is efficacious or not (claim 2, in-part and claim 6, in-part), treat a subject having TROLL-2, TROLL-3, WDR26, and/or NCOA5 expression profile indicative of breast cancer (claims 7-9), or assessing whether an anticancer drug prescribed to a subject is effective (claims 22-24)
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the teachings of Napoli et al. for determining whether a cancer drug given to a subject experiencing breast cancer is efficacious or providing treatment to a subject anticancer therapy to a subject for the following reasons.
The motivation to apply the correlation that exists between the level of TROLL-2, TROLL-3, WDR26, and/or NCOA5 is based on the teachings of Napoli et al. who expressly teach that the level of these markers found in a subject was correlated to the progression of the disease2, and that TROLL-2 and TROLL-3 were not found in normal tissue samples whereas they were found and expressed in greater amounts in cancerous samples3. Therefore, one of ordinary skill in the art would have been motivated to apply the findings to determine: 1) whether an anticancer therapy is efficacious by determining whether the amount of the subject-markers are decreasing (or not increasing), an indication of drug’s effectiveness, and when the levels the markers do not indicate effectiveness, provide alternative treatment; and 2) whether a subject is positive for cancer (by presence of TROLL-2 and/or TROLL-3) and provide a treatment thereof.
As to comparing the levels of the markers to a control sample in the form of positive or negative when comparing a test sample, doing so have been an industry standard and therefore, would have been an obvious application of the means which are well-established, and fully within the purview of the ordinarily skilled artisan.
In addition, Napoli et al. teach that lowering the amount of TROLL-2 and TROLL-3 resulted in reduction of tumour formation and progression, wherein these findings were made via use of shRNA and siRNA:
“results prompted us to verify whether TROLL-2 and TROLL-3 are required for the formation and progression of these tumour types in vivo … TROLL-2 and TROLL-3 were downregulated via doxycycline-inducible shRNAs … downregulation of either TROLL-2 or TROLL-3 strongly impaired the formation of both [primary lung adenocarcinomas and secondary lung colonies] … downregulation of either lncRNA significantly reduced the tumorigenic … and metastatic … potential of both melanoma cell lines … these results demonstrate that TROLL-2 and TROLL3 are markers of cancer progression and are necessary for tumour and metastasis formation in multiple cancer types” (page 6, 2nd column)
Therefore, one of ordinary skill in the art would have been motivated to provide an anti-sense therapy means, such as siRNA/shRNA to lower the expression of TROLL-2 and/or TROLL-3 in a subject who has been diagnosed with cancer, with a reasonable expectation of success that doing so would reduce/impair the formation, progression, and metastasis of cancer.
The legal standard for “reasonable expectation of success” is provided by case law and is summarized in MPEP 2144.08, which notes “obviousness does not require absolute predictability, only a reasonable expectation of success; i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”
Therefore, for these reasons, the invention as claimed is deemed prima facie obvious.
Claims 2-4, 6-9, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira et al. (Nature Communications, vol. 10, pages 1-18).
Table 1 of the specification (page 55) discloses that TROLL-2 for human subject is RPSAP52 transcript.
With regard to claim 2, Oliveria et al. teach a method comprising: a) obtaining a tissue sample from a subject (“[t]otal RNA, including miRNA, was extracted …”, page 15, 1st column, 2nd paragraph); and b) measuring the expression level of TROLL-2 (or RPSAP52 transcript, “TROLL-2,” herein) (“Real-time PCR reactions were performed”, page 15, 2nd paragraph; also “absolute amounts of RNAs were obtained by comparison with in vitro transcribed RNA standards of known concentration … RNA standards correspond to the sequences amplified in RT-qPCR in the analysis of RPSAP52 …”, page 15, 2nd column, 5th paragraph).
Oliveira et al. explicitly teach and suggest that the increased levels of TROLL-2 is observed in samples of breast cancer when compared to levels found in the normal sample (“RPSAP52 transcripts are overexpressed in a variety of human cancers compared with normal controls”, Fig. 1)
While Napoli et al. explicitly teach that the expression level of TROLL-2 is observed in breast cancer as well as “cancers” (see above),the artisans do not explicitly teach that this correlation should be utilized in determining whether an anti-cancer therapy is efficacious or not (claim 2, in-part and claim 6, in-part), treat a subject having TROLL-2 expression profile indicative of cancer (claims 7-9), or assessing whether an anticancer drug prescribed to a subject is effective (claims 22-24).
Oliveira et al. do employ cell lines of a subject sample, and not a tissue sample.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the teachings of Oliveira et al. for determining whether a cancer drug given to a subject experiencing breast cancer is efficacious or providing treatment to a subject anticancer therapy to a subject for the following reasons.
The motivation to apply the correlation that exists between the level of TROLL-2 is based on the teachings of Oliveira et al. who expressly teach that the level of the marker found in a subject was correlated to cancer.
Therefore, one of ordinary skill in the art would have been motivated to apply the findings to determine: 1) whether an anticancer therapy is efficacious by determining whether the amount of the subject-markers are decreasing (or not increasing), an indication of drug’s effectiveness, and when the levels the markers do not indicate effectiveness, provide alternative treatment; and 2) whether a subject is positive for cancer (by presence of TROLL-2) and provide a treatment thereof.
As to comparing the levels of the markers to a control sample in the form of positive or negative when comparing a test sample, doing so have been an industry standard and therefore, would have been an obvious application of the means which are well-established, and fully within the purview of the ordinarily skilled artisan.
In addition, Oliveira et al. teach that lowering the amount of TROLL-2 resulted in reduction of tumorigenesis, wherein these findings were made via use of shRNA:
“Upon RPSAP52 knockdown, all three breast cancer cell lines tested … proved to be significantly less proliferative … and had a significantly lower percentage colony formation density than control cells … RPSAP52 depletion was also associated with a decreased migration potential … next used tumor formation assays in nude mice. MCF10A and Hs578T cells stably expressing either scrambled shRNAs or shRNAs against RPSAP52 were subcutaneously injected into mice, and the tumor formation and volume was monitored. Tumors originating from RPSAP52 knockdown cells had a significantly lower volume and weight at end point than control tumors, both for the on-tumorigenic and the tumorigenic cells” (page 4)
Therefore, one of ordinary skill in the art would have been motivated to provide an anti-sense therapy means, such as siRNA/shRNA to lower the expression of TROLL-2 in a subject who has been diagnosed with cancer, with a reasonable expectation of success that doing so would reduce/impair the formation, progression, and metastasis of cancer.
As well, one of ordinary skill in the art would have had a reasonable expectation of success that the correlation discovered in the cell-lines of breast cancer would have been observable in a tissue sample, as such findings find relevance from cell-lines to tissue samples themselves4.
The legal standard for “reasonable expectation of success” is provided by case law and is summarized in MPEP 2144.08, which notes “obviousness does not require absolute predictability, only a reasonable expectation of success; i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”
Therefore, for these reasons, the invention as claimed is deemed prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2-4, 6-9, and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 6, 7, 8, 17, and 18-23 of copending Application No. 17/791,706 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims of the reference application is also directed to a method of assessing the efficacy of a cancer treatment administered to a subject wherein the method relies on the measurement of the expression of TROLL-3 in a tissue sample of said subject and its comparison against that of a control (see claim 2), as well as determining the intracellular localization of WDR26 and/or NCOA5 (see claim 2), as well as administering an inhibitor agent (additional) when the initial cancer treatment is not found to be efficacious (see claim 2). The claims of the reference application also are directed to a method of treating a cancer in a subject by measuring the expression level of TROLL-3 (see claim 6).
Therefore, claims of the instant application are obvious over the claims of the reference patent.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YOUNG J KIM/Primary Examiner
Art Unit 1637 August 20, 2026
/YJK/
1 The deliberate usage of “a subject” and not “the subject” renders the subject in the obtainment step, embrace any subject.
2 “the expression of TROLL-2 and TROLL-3 are elevated in breast tumours and correlate with breast cancer progression” (page 4, 1st column, 2nd paragraph)
3 “we performed in situ hybridization (ISH) for TROLL-2 and TROLL-3 in a breast cancer tissue microarray (TMA) with 45 samples including normal breast tissue, lobular hyperplasia, DCIS, and invasive breast cancer biopsies. Notably, we found that the levels of both lncRNAs were undetectable in normal breast tissue and increased with breast cancer progression with the highest levels observed in invasive breast cancer samples” (page 4, 1st column, 1st paragraph)
4 “[w]e have previously uncovered positive impact of the expression of the pseudogene RPSAP52 … genes are generally expressed at low levels in differentiated normal tissue and overexpressed in a number of human cancers, including breast cancer” (page 2, 1st column, bottom paragraph, Oliveira et al.)
Prosecution Insights