DETAILED CORRESPONDENCE
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 the papers filed February 17, 2026. Currently, claims 1-18 are pending. Claims 11-18 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election of Group I in the paper filed February 17, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 11-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/EP2021/087806, filed December 29, 2021 and claims priority to EPO 20217509.7, filed December 29, 2020.
Drawings
The drawings are acceptable.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The list of references on pages 30-37 has not been considered as an IDS.
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 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claims 1-10 are directed to “a method for detecting or diagnosing a neurological and/or neuropsychological condition” “wherein the detection of the biomarkers in the sample indicates the presence of the neurological and/or neuropsychological condition” or a risk thereof. Claim 5 further requires wherein a differential level of the biomarker “compared to a control” “indicates the presence of the neurological and/or neuropsychological condition”.
Claims 1-10 are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “indicates that the subject has neurological and/or neuropsychological condition” and “a differential level of the biomarker compared to a control or reference”) and a law of nature/natural phenomenon (i.e. the natural correlation between the presence of miRNA and neurological and/or neuropsychological conditions).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 1 involves the patent-ineligible concept of an abstract process. Claim 1 requires “wherein the detection of the biomarkers in the biological sample indicates the presence of neurological and/or neuropsychological conditions”. Neither the specification nor the claims set forth a limiting definition for “detecting or diagnosing” neurological and/or neuropsychological condition and the claims do not set forth how “detecting” is accomplished. As broadly recited the detecting step may be accomplished mentally by thinking about a subject’s biomarkers and assessing whether the subject has neurological and/or neuropsychological condition. Thus, the determining step constitutes an abstract process idea.
Claim 5 further recites a comparison between the biomarker level and a control or reference that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
A correlation that preexists in the human is an unpatentable phenomenon. The association between the presence and level of miRNA biomarkers and neurological and/or neuropsychological conditions is a law of nature/natural phenomenon. The wherein clause which tells users of the process to predict neurological and/or neuropsychological condition in the sample, amounts to no more than an "instruction to apply the natural law". The wherein clause is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The wherein clause does not require the process user to do anything in light of the correlation. The wherein clause fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and determining the presence or level of miRNA, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The detecting the presence of biomarkers is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining the biomarkers was well known in the art at the time the invention was made (see 102 rejections below). The steps are recited at a high level of generality. The claim merely instructs a scientist to use any assay to determine the presence or amount of miRNA biomarkers. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known. The specification teaches the amount of microRNA may be measured using qRT-PCR, qPCR, droplet digital PCR, next generation sequencing or hybridization such as Southern blot. All of these methods are extremely well known at the time the invention was made.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112- Second Paragraph
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 1-10 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 pre-AIA the applicant regards as the invention.
Regarding claims 1-10, the claims are replete with the phrases “preferably”, "such as" and “for example.” These recitations render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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 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.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hornstein et al. (WO2020/230133, November 19, 2020).
Hornstein teaches cell-free miRNA markers for prognosis and diagnosis of neurodegenerative diseases. In particular Hornstein teaches the neurodegenerative disease is frontotermal dementia or FTD (abstract). Hornstein teaches analysis of level of mi-R-181a-5p (see Figure 7, 8, 10, 14, for example). Hornstein further teaches specific embodiments with miR-181a-5p, miR-146a-5p (page 20, lines 25), miR-148a-3p (page 21, lines 12-13). Hornstein teaches combination of any two or more of the above describe miRNAs is considered (page 21, lines 21-23).
With respect to Claim 2, the collection of blood, plasma or serum is not a surgical method (page 21, lines 23-25).
With respect to Claim 3, Hornstein teaches the subject is a human being (page 6, line 27).
With respect to Claim 4, Hornstein teaches the biological sample is a fluid or tissue such as blood, plasma, serum, cerebrospinal fluid (page 21, lines 23-25).
With respect to Claims 5-6, Hornstein teaches performing quantification using next generation sequencing (page 39).
With respect to Claims 7-10, FTD is a dementia and Amyotrophic lateral sclerosis is a neurodegenerative disease that destroys motor neurons in the brain and spinal cord.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Hill et al. (US 2022/0017962, January 20, 2022, PCT filed December 2019).
Hill teaches methods of diagnosing a disease, where the disease is a neurodegenerative disorder such as Parkinson’s disease, Alzheimer’s disease and prion disease. Hill analyzes each of miR-181a-5p, miR-146a-5p, miR-148a-3p in neurodegenerative diseases. Table 10 provides has-miR-181a-5p is significantly downregulated in in PD patients (page 27). Table 10 provides has-miR-146a-5p is significantly upregulated in Creutzfeldt-Jakob disease/CJD patients. Table 11 provides has-miR-148a-3p is differentially expressed in AD vs Healthy controls (page 27).
With respect to Claim 2, the collection of blood, plasma or serum is not a surgical method (par 51).
With respect to Claim 3, Hill teaches the subject is a human being (para 66).
With respect to Claim 4, Hill teaches the biological sample is a fluid or tissue such as blood, plasma, serum (para 51).
With respect to Claims 5-6, Hill teaches performing quantification of level of expression of the small non-coding RNA compared to a reference level (para 17, 23, 53). Hill teaches the levels are detected using qRT-PCR.
With respect to Claims 7-10, dementia, Parkinson’s, Alzheimer’s and CJD are each cognitive disorders that reduce learning capability and reduce neuronal plasticity.
Conclusion
No claims allowable over the art.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bianco et al. (WO 2017/085287, May 26, 2017) teaches analysis of miRNAs for monitoring neurological, neurogdegenerative and inflammation-based diseases (abstract). Bianco lists each of miR-181a, miR146a-5p and 148a-3p.
Xu (US 2015/0275299, October 1, 2015) teaches miRNAs as markers for Parkinson’s disease. Each of the miRNA claimed are recited in Table 39, page 3, as differentially expressed and/or correlated with clinical/pathological findings.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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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 on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
April 3, 2026