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 June 22, 2026. Currently, claims 1-19, 22-24 are pending. Claims 22-24 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of Group I, Claims 1-19 in the paper filed June 22, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/GB2022/052352, filed September 16, 2022 and claims priority to UK 2113344.2, filed September 17, 2021.
Drawings
The drawings are acceptable.
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 1-19 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 1-19 are directed to “a method for predicting the location and/or viability of an early pregnancy in a subject by determining the level of has-miR-411-5p”.
Claim 3 is directed to detecting a ratio which is a mathematical calculation that may be performed in the mind.
Claim 4-8 each recite correlations between levels of miRNA and phenotypes. The claims are also directed to a comparison, i.e. increased or decreased level, which is an abstract idea.
Claim 9 requires comparing the miRNA with a control which is an abstract idea.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “predicting the location and/or viability of an early pregnancy”, “determining a ratio”, “referring a subject for further medical examination or diagnosis”, “wherein the subject is instructed to follow procedural guidance”) and a law of nature/natural phenomenon (i.e. the natural correlation between the level of has-miR-411-5p and the location and/or viability of an early pregnancy).
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, the claims involve the patent-ineligible concept of an abstract process. The claims require predicting the location and/or viability of an early pregnancy. Neither the specification nor the claims set forth a limiting definition for “predicting" and the claims do not set forth how “predicting" is accomplished. As broadly recited the “predicting" may be accomplished mentally by thinking about a subject’s miRNA level and predicting the location and/or viability of an early pregnancy. Thus, the predicting constitutes an abstract process idea.
Claims 5-9 further recite a comparison between the expression level and a control 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 expression levels of miRNA and the location and/or viability of an early pregnancy is a law of nature/natural phenomenon. The predicting step which tells users of the process to the location and/or viability of an early pregnancy in the sample, amounts to no more than an "instruction to apply the natural law". This recitation 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 predicting does not require the process user to do anything in light of the correlation. The predicting 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 does not recite any additional elements that integrate the exception into a practical application of the exception. While the claims recite determining the level of miRNA in a sample from the subject, 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.
Claim 10-11, 13-14-19 are directed treating or managing a subject. The claims are not directed to particular treatments. Instead, the claims are directed to referring and instructing which is not an administration step. Referring and instructing do not integrate the abstract predicting or the natural phenomenon because it is merely an instruction regarding therapy but does not require the therapy be delivered or administered.
Accordingly, the claims are directed to judicial exceptions.
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 measuring expression 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 claims do 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 expression levels was well known in the art at the time the invention was made. The prior art teaches that expression analysis using commercially available biochips and arrays that comprise the claimed genes. The miR-411-5p and miR-21-5p may be detected using the Toray and the Agilent miRNA arrays. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any expression analysis assay to determine the expression. 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.
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.
Claims 1-19 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.
The claims are indefinite. It is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of Claim 2 is directed to a method for predicting the location and/or viability of an early pregnancy. However, the claim only provides for comprising determining the level of has-miR-411-5p. Thus, it is not clear if applicant intends to cover any method for determining the level of has-miR-411-5p, or if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If the claim requires something more, it is unclear what additional active process step the method requires and it appears that the claims are incomplete. The claims fail to provide any active steps that clearly accomplish the goal set for the by the preamble of the claims. Claims 2-19 are similarly indefinite. Claim 13 does not require any method for determining an appropriate medical management or treatment protocol.
Regarding claims 9-10, and 19 the phrase “preferably”, “optionally”, and "such as" render the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 16 is directed to a method of Claim 14 comprising the steps as defined in Claim 8. Claim 8 does not require any steps not already required for Claim 14. In fact, claim 14 requires additional combinations and ratios not required by Claim 8. It is unclear what step is required for Claim 16 to further limit Claim 14. Correction is required.
Claim 18 is directed to a method carried out on “samples”. Samples is plural. The multiple samples lacks proper antecedent basis. Claim 14 is directed to a single sample. Clarification is required.
Claim 19 is indefinite over the recitation “the miRNA molecules” because Claim 14 does not recite any miRNA molecules in several embodiments. Clarification is required.
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.
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) 1-2, 4-11, 13-16, 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wen et al. (Molecular Medicine Reports, Vol. 16, pages 6650-6673, 2017).
Wen teaches microRNA expression profiling in placentas complicated with selective intrauterine growth restrictions. Wen teaches determining the level of has-miRNA-411-5p in a biological sample from the subject. miR-411-5p is specifically identified in Table III, 4th miRNA from the bottom.
With respect to Claim 2, Wen teaches analysis of miRNA on Affymetrix microRNA 4.0 array system. As noted in GEO GSE98146, miR-21-5p is analyzed on this array. Thus, Wen teaches determining the level of both miR-441-5p and miR-21-5p.
With respect to Claim 4-8 are directed to wherein clauses that recite intended uses. The Claims do not require any additional method steps to distinguish the claims or require anything more than determining the level miRNAs.
With respect to Claim 9, Wen teaches a method of determining differentially expressed miRNAs (page 6654, col. 2). Wen also teaches samples were analyzed and normalized to U6 expression (end of Table V).
With respect to Claims 10, 14 the claims require the subject is referred for further medical examination only if determination of an increased risk of ectopic pregnancy is determined. Thus, this is a conditional recitation.
With respect to Claim 11, the claim does not require any additional steps in situations where the pregnancy is uncomplicated.
With respect to Claims 13, 16, the only active method steps are determining expression levels of miRNA-411-5p in a biological sample from the subject. Wen teaches this, as discussed above.
With respect to Claim 19, the analysis on arrays requires hybridization. Wen also teaches quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
Claim(s) 1-2, 4-17, 19 is/are rejected under 35 U.S.C. 102(a)( as being anticipated by Zhao et al. (Clinical Biochemistry, Vol. 46, pages 953-960, 2013- cited in IDS March 13, 2024).
Zhao is a review article about diagnostic potential for miRNAs as biomarkers for pregnancy specific disease. Zhao teaches the level of miR-411 was determined on an array (see Table 1, references 12)
Zhao teaches miR-21 was determined in SGA and controls from the placenta using real-time PCR (Table 2).
With respect to Claim 4-8 are directed to wherein clauses that recite intended uses. The Claims do not require any additional method steps to distinguish the claims or require anything more than determining the level miRNAs.
With respect to Claim 9, Zhao teaches a method of determining differentially expressed miRNAs using controls.
With respect to Claims 10, 14 the claims require the subject is referred for further medical examination only if determination of an increased risk of ectopic pregnancy is determined. Thus, this is a conditional recitation.
With respect to Claim 11, the claim does not require any additional steps in situations where the pregnancy is uncomplicated.
With respect to Claim 12, Zhao teaches that when studying ectopic pregnancy, hCG monitoring may be performed.
With respect to Claims 13, 16, the only active method steps are determining expression levels of miRNA-411-5p in a biological sample from the subject. Zhao teaches this, as discussed above.
With respect to Claim 17, Zhao teaches plasma, serum may be used to analyze miRNA for miRNA analysis of pregnancy -associated conditions (Table 2).
With respect to Claim 19, the analysis on arrays requires hybridization. Zhao also teaches quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)(see Table 1 and 2).
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kyriacou et al. (Non-coding RNA Research, Vol. 13, pages 162—173, 2025) teaches maternal plasma microRNAs as potential biomarkers for triaging pregnancies of unknown location and ectopic pregnancy diagnosis. This is applicant’s post filing date work.
Bennett et al. (WO2021/160978 (August 19, 2021)) teaches miR-21-5 is increased expression levels in ectopic pregnancy (Figure 2).
c) Goren et al. (WO 2009/093254, July 30, 2009). Goren teaches method and compositions for diagnosing complications of pregnancy including ectopic pregnancy. As seen in Figure 9, hsa-miR-411 (SEQ ID NO: 15) is underexpressed in PET samples. SEQ ID NO: 15 is has-miR-411-5p sequence. Goren teaches analysis of microRNAs in serum (page 29).
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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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
August 10, 2026
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