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 9/23/2025 is acknowledged. The traversal is on the ground(s) that that Panarelli et al. does not teach classifying cancer (p. 2). This is not found persuasive because the technical feature that relate all three inventions is expression of miRNA and as Panarelli et al. taches such expression the technical feature is taught.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-27 are pending. Claims 1-15 and 25-27 are withdrawn as being drawn to a nonelected invention.
An action on the merits for claims 16-24 is set forth below.
Claim Objections
Claims 16-24 are objected to because of the following informalities: The phrase “NEN” should be spelled out for clarity. Claims 17-24 are objected to as depending on the objected claim. 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 16-24 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 16-24 are indefinite over the step of determining expression of at least two miRNAs obtained from subjects without cancer in claim 16. This step is indefinite as it does not appear that it is required for the evaluation of NEN cancer. As such it is not clear how the step modifies the claims and how it effects the metes and bounds of the claims.
Claim 18-19 are indefinite over “at least a second miRNA is added to the biological sample(s)” in claims 18. It is not clear how to add a miRNA to a sample and therefore the metes and bounds of the claims are unclear.
Claim Rejections - 35 USC § 112
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 16-24 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.
The claims are drawn to evaluating NEN based upon expression level of miR-375 expression. The claims are drawn to any subject, any sample and any expression level of mir375. Further, the claims are limited to NEN cancer status being one or more of differentiating between NEN and non-NEN, diagnosing a NEN pathological type, monitoring any disease state and subject condition, determining prognosis, evaluating response to a treatment, and evaluating effectiveness of a treatment.
The specification teaches clinical samples from humans with NEN and without NEN (p. 18). The specification teaches that miR 375 was increased in patients with NENE versus non-NEN (p. 22). However, the specification does not provide functionality to any species. Further, the claims are drawn to functionally correlating miR375 expression with NEN pathological type, monitoring diseases state and subject condition, determining prognosis, evaluating response to treatment and effectiveness of a treatment. Although the specification provides expression of miR375 was increased in patients with NEN versus non-NEN, the specification has not described any of the evaluation and levels of expression needed to functionally correlating miR375 expression with NEN pathological type, monitoring diseases state and subject condition, determining prognosis, evaluating response to treatment and effectiveness of a treatment. The specification does not describe any treatments or anticancer therapies nor how the selection or evaluation are performed for selection.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. However, as discussed above, the specification provides on particular species and does not provide critical structures for the breadth of the claims.
Further, the art, as recited below, teaches that expression of biomarkers differ in different species. However, the specification has not provided identifying characteristics or functional attributes that would distinguish different members of the claimed genus. Rather, the art teaches that changes in the structure of nucleic acids between species can have an effect on expression. Enard et al. (Science 2002 Vol 296 p. 340) teaches that even between closely related species gene expression patterns differ (abstract). Enard et al. teaches that mRNA expression levels are different between humans, chimpanzees, orangutans and rhesus marcques (p. 340 1st column last sentence-2nd column 1st paragraph). Enard et al. teaches that there are a large number of quantitative differences in gene expression in closely related mammals (p. 342 2nd column last paragraph).
In the instant case the specification does not provide the skilled artisan with an adequate written description of particular nucleic acids suitable for performing the claimed method as generically encompassed in the claims.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that "Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed." (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.) In the instant case, the specification fails to teach the necessary common attributes or features of the miR-375 across species and samples and functionally determining in of the encompassed “evaluating NEN cancer” state in view of the species disclosed. As such, one of skill in the art would not recognize that applicant was in possession of the genus encompassed by the broadly claimed invention.
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.
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).
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.
Conclusion
No claims are allowed.
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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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682