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 .
This action is in response to papers filed 5/27/2026.
Applicant's election with traverse of Group II in the reply filed on 9/23/2025 is acknowledged and has been made final previously.
Claims 16-24, 28-45 are pending. Claims 1-15 and 25-27 are cancelled. Based upon the election made on 9/23/2025 claims 28-45 are withdrawn as being drawn to a nonelected species. It is noted that one the species of ,miR 375 is found in combination for allowance that claims 28-45 will be rejoined.
The following rejections are maintained with response to arguetmsn following.
This action is FINAL.
Withdrawn Objections and Rejections
The claim objections made in the previous office action is withdrawn based upon amendments to the claims.
The 35 USC 112b, 35 USC 112a rejection made in the previous office action is withdrawn based upon amendments to the claims.
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 16-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation (evaluating a NEN cancer) without significantly more. This judicial exception is not integrated into a practical application because no additional steps rely upon or integrate the judicial exceptions of the claims. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no steps that are significantly more or integrate the judicial exceptions.
Claim analysis
The instant claims are directed a method measuring expression of at least two miRNAs and evaluating a NEN cancer.
The correlation is considered a law of nature.
The step of measuring expression level is from a biological sample thus is a physically active step.
Dependent claims set forth further limitations to about the methods used in detecting, and the origin of the sample.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, nature phenomena.
The correlation of expression of miR and NEN evaluating and methylation status is considered a natural phenomenon.
The measuring expression is a positive active step and thus is a physically active step.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no the claim requires no additional steps that integrate the juridical exceptions, rather the active steps are considered general and routine as the steps encompass general methods of determining methylation status and steps of statistical analysis.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No
Arvidsson et al. (Modern Pathology 2018 Vol 31 p. 1302-1317) teaches measuring miR375 expression in a patient with NEN and without cancer (para 1306). Arvidsson et al. teaches that miR-375 is measured relative to a second miR (p. 1311 1st column).As such the only step in the claims are determining a naturally occurring miR expression status using conventional assays.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the claims require normalization expression using RT-qPCR method and that this does not exist in the biological sample (p. 13). The reply asserts that this normalization would e similar to Vanda (Fed Cir 2018) as it comprises additional elements with the normalization (p. 13-14).
These arguments have been reviewed but have not been found persuasive.
The reply points to normalization, however, the claims only requires a comparison to a reference, it does not require any normalization steps. Further even if the claims were modified to normalization, these steps would be considered general routine steps of normalizing data from an expression level of a miRNA using known general steps of normalization. These steps do not provide something additional to the integration step as the claims are using known statistical steps (such as the asserted RT-qPCR).
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 16-18, 20- 22, 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arvidsson et al. (Modern Pathology 2018 Vol 31 p. 1302-1317)..
With regard to claim 16, Arvidsson et al. teaches measuring miR375 expression in a patient with NEN and without cancer (para 1306). Arvidsson et al. teaches that miR-375 is measured relative to a second miR (p. 1311 1st column). Arvidsson et al. teaches that this expression is associated with NEN (p. 1312 2nd column 2nd paragraph).
With regard to claim 17, Arvidsson et al. teaches paired sample determination from the patient (p. 1315 1st column).
With regard to claims 18 and 20, Arvidsson et al. teaches using miR7-5p (p. 1315 2nd column 2nd paragraph).
With regard to claim 21, Arvidsson et al. teaches RT PCR methods and analysis delta Ct (p. 1306 1st paragraph).
With regard to claim 22, Arvidsson et al. teaches a method wherein the samples are tissue samples (p. 1303 2nd column last paragraph).
With regard to claim 24, Arvidsson et al. teaches differentiating between NEN and non-NEN (p 1311 1st column).
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that NEN includes both NET and NEC, however, Arvidsson only teaches NETs (p. 14-15). The reply asserts that Arvidsson et al. does not teach classification across the different types (p. 15). The reply asserts that claim 16 requires normalization against a reference without cancer, however, Arvidsson uses patients with adenocarcinoma (p. 15). The reply asserts that Arvidsson requires a population level statistical comparison whereas Claim 16 requires a patient specific determination (p. 15). Further with regard to claim 17,the reply asserts that the specimens were not serial but at the same time (p. 15).
These arguetmsn have been fully reviewed but have not been found persuasive.
The claims are drawn to neuroendocrine neoplasm cancer, which Arvidsson teaches. The reply appears to assert that both subtypes are not taught, however, the claims are not limited to any particular type of neuroendocrine neoplasm. As Arvidsson et al. teaches at least one subtype, Arvidsson et al. teaches the breadth of the requirement of the claims. There is not requirement via a positive active step to classify across subtypes. The reply asserts that the claims are not limited to references without cancer. However, Arvidsson et al. teaches detection of biopsies of “normal small intestinal mucosa” (p. 1306 1st paragraph) and as such teaches a sample that does not have cancer. The rejection asserts that the specimens were serial, however, figure 10 clears provides a detection of expression at various days (figure 10 and p. 1312) and as such expression was measured at least a first and second time point and the differences provide a change in status (see figure 10).
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.
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.
Claim(s) 19 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arvidsson et al. (Modern Pathology 2018 Vol 31 p. 1302-1317) in view of Litman et al (US Patent Application Publication 2010/0286044 November 11, 2010).
Arvidsson et al. teaches measuring miR375 expression in a patient with NEN and without cancer (para 1306). Arvidsson et al. teaches that miR-375 is measured relative to a second miR (p. 1311 1st column). Arvidsson et al. teaches that this expression is associated with NEN (p. 1312 2nd column 2nd paragraph). However, Arvidsson et al. does not teach measuring miR-159a or measuring expression in a fluid sample.
With regard to claims 19 and 23, Litman et al. teaches screening neuroendocrine fluid samples for miR159a and miR375 (table t and para 18 and para 109, 187, 203 and Table G).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Arvidsson et al. to screen other miR expression levels that are associated with NEN such as the miR taught by Litman et al. The ordinary artisan would be motivated to screen known miR to determine associations of expression in the samples with regard to NEN versus non-NEN samples.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that there is no motivation why to combine Arvidsson RT qPCR normalization approach with the microarray probe catalog (p. 18-19). The reply traverses the rejection. The 35 USC 103(a) is not attempting to modify the method of Arvidsson et al. with the microarray device, but rather to screen other known probes (miR159a and miR375) using the assay techniques of Arvidsson et al. The ordinary artisan would be motivated to screen known miR to determine associations of expression in the samples with regard to NEN versus non-NEN samples.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682
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