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 .
The claims dated 11/10/2025 are under consideration.
Election/Restrictions
Applicant’s election of Group I, claims 1 and 4-14, in the reply filed on 11/10/2025 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 § 818.01(a)).
Claims 15 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/10/2025.
Priority
This application is a 371 national stage entry of PCT/GB2021/052339 (filed 9/9/2021), and claims benefit to UNITED KINGDOM 2014190.9 (filed 9/9/2020).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 § 609.04(a) 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 or on a submitted IDS, they have not been considered.
Specification
The use of terms that are trade names or marks used in commerce has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The reference to a website appears on p. 11, lines 20-21.
Claim Objections
Claim 13 is objected to because of the following informalities: the claim recites “milk” twice. Appropriate correction is required.
Claim Interpretation
Claim 1 recites “a plurality of miRNAs”, which is interpreted as requiring at least one of the miRNAs recited in the last “wherein” clause of the claim.
In claim 9, the “off-species control miRNA molecule” is interpreted in view of p. 8, lines 7-8 of the instant specification as being “an miRNA from another species, i.e. not dogs, cats or humans”.
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 and 4-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The claim(s) recite(s):
“determining the level of expression of each of a plurality of miRNAs within a sample from a subject” (claim 1); and
“using one or more Artificial Intelligence (AI) model to predict the disease condition of the subject; wherein the one or more Al model compares the level of expression of each miRNA molecule with at least one pre-determined reference level characteristic of a non-diseased subject for each one of the plurality of the miRNA molecules of step (a), wherein a deviation of the level of expression of said miRNA molecules from step (a) in comparison with the at least one reference level allows for the diagnosis and/ or prognosis of the disease” (claim 1).
The “determining” step broadly encompasses data processing as described on pages 11 and 12 of the specification. The processing of data regarding “a plurality of miRNAs”, e.g., two miRNAs, is of a limited amount that can be processed by the human mind and/or with the aid of pen and paper. See MPEP 2106.04(a)(2).III.
The process performed with an AI model is one that may be performed by the human mind, but for the recitation of “using one or more Artificial Intelligence” in the step. That is, other than reciting “using one or more Artificial Intelligence” nothing in the step preclude the step from practically being performed in the human mind. For example, but for the “using one or more Artificial Intelligence” language, the step in the context of the claim encompasses a user manually analyzing data organized in a table regarding only 2 miRNAs. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic AI steps, i.e., “using one or more Artificial Intelligence”, then it falls within the “Mental Processes” grouping of abstract ideas. Accordingly, these steps recites an abstract idea. See MPEP 2106.04(a)(2)III.C.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions. The claimed limitations are mere data gathering steps. MPEP 2106.05(g).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because: 1) they do not include additional elements; and 2) the claims encompass the use of commercially available reagents that are well-known and used in a conventional manner as described on p. 11 of the instant specification.
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 1 and 4-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The specification, while being enabling for the methods of claims 1 in which the sample is heart tissue, blood, urine, saliva and milk, does not reasonably provide enablement for using any type of samples. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The claims broadly encompass determining the expression of miRNAs within any type of sample, skin, hair, fingernail, etc. Some of the claimed miRNAs, including cfa-miR-133a and cfa-miR-133b, are expressed specifically in muscle tissue. See Care (Nature Medicine. 2007. 13(5):613-618). The measured levels are used to predict a “disease condition” of the subject, e.g., heart disease.
It is known that bodily fluids, such as blood, urine, milk, saliva, milk and cerebrospinal fluid, contain circulating nucleic acids for various tissues, including miRNAs.
Because the miRNAs recited in the claimed method include those that are tissue specific, it is unpredictable that one would be able to measure tissue specific miRNAs in other solid biological samples. One would not reasonably expect to measure all of the recited miRNAs in non-heart sample or biofluid sample because at least cfa-miR-133a in not expressed in non-muscle tissue.
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 1 and 4-14 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.
Regarding claim 1, the claim recites “the disease condition”, “the diagnosis and/or prognosis” and “the disease”. The recitations lack proper antecedent basis.
Furthermore, it is unclear the reference to “the disease condition” is in reference to “heart disease” as set forth in the preamble.
Claims 4-14 depend from claim 1 and are rejected for the same reason.
Regarding claim 12, the claim recites a Markush group and uses the conjunction “or” to separate out options. It is unclear if the options prior to the “or” are the Markush group, and those after the “or” are separate options and outside of the Markush group.
The claims recites “related conditions”. It is unclear what constitutes a condition that is “related” to another condition.
Regarding claim 13, the claim recites a Markush group and uses the conjunction “or” to separate out options. It is unclear if the options prior to the “or” are the Markush group, and those after the “or” are separate options outside of the Markush group.
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.
(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.
Claim(s) 1, 6-8, 10 and 12 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ikeda (US 2009/0306181 A1) as evidenced by Wagner (Frontiers in Genetics. 2013. 4:46, 9 pages).
Regarding claim 1, Ikeda teaches determining the expression pattern of a set of (e.g., at least one, two or more) microRNAs in a test myocardium sample obtained from an individual, the microRNA in the set of microRNAs includes miR-30b, miR-133b, miR-320, miR-423*, miR-499, let-7b and let-7c (para. 13).
It is noted that Wagner demonstrates that human miRNA reagents also detect related canine miRNAs and vice versa (p. 2). For Example, hsa-miR-30b and cfa-miR-30b, hsa-miR-133b and cfa-miR-133b, hsa-miR-320a and cfa-miR-320 and cfa-miR-320, hsa-miR-423-5p and cfa-miR-423a, hsa-miR-499a-5p and cfa-miR499, hsa-let-7b and cfa-let-7b and hsa-let-7c and cfa-let-7c are all related. Thus, the determining done by Ikeda would also determine the expression of at least some of the recite miRNAs of claim 1.
Ikeda further teaches comparing the expression pattern determined above with one or more reference expression patterns, wherein each reference expression pattern is determined from the set of microRNAs in a reference myocardial sample obtained from an individual whose heart disease type is known (para. 13). Ikeda further teaches the comparison is done using AI models, including using Support Vector Machine, to determine a subset of miRNAs and using Naive Bayes and Logistic regression to build a model for heart disease class prediction (para. 44).
Regarding claim 6, Ikeda teaches using a Support Vector Machine as noted above, which is a machine learning algorithm for predictive modelling.
Regarding claim 7, Ikeda teaches using a Support Vector Machine and Naive Bayes and Logistic regression as noted above.
Regarding claim 8, Ikeda teaches using U6 or GAPDH as a normalizer (par. 20, 21, 24).
Regarding claim 10, Ikeda teaches the use of miR-17-5p (para. 10 and 11), miR-20a (para. 10, 11), and miR-23a (para. 10, 12). It is noted that the claim does not specify how the “normalizer” is used.
Regarding claim 12, Ikeda teaches the heart disease is dilated cardiomyopathy, mitral stenosis, pulmonary stenosis and/or tricuspid stenosis (para. 13).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 4, 5 and 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ikeda (US 2009/0306181 A1) in view of Jung (AJVR. 2018. 79(2):163-169) and as evidenced by Wagner (Frontiers in Genetics. 2013. 4:46, 9 pages).
Regarding claims 4 and 5, Ikeda teaches determining the expression pattern of a set of (e.g., at least one, two or more) microRNAs in a test myocardium sample obtained from an individual, the microRNA in the set of microRNAs includes miR-30b, miR-133b, miR-320, miR-423*, miR-499, let-7b and let-7c (para. 13).
It is noted that Wagner demonstrates that human miRNA reagents also detect related canine miRNAs and vice versa (p. 2). For Example, hsa-miR-30b and cfa-miR-30b, hsa-miR-133b and cfa-miR-133b, hsa-miR-320a and cfa-miR-320 and cfa-miR-320, hsa-miR-423-5p and cfa-miR-423a, hsa-miR-499a-5p and cfa-miR499, hsa-let-7b and cfa-let-7b and hsa-let-7c and cfa-let-7c are all related. Thus, the determining done by Ikeda would also determine the expression of at least some of the recite miRNAs.
Ikeda further teaches comparing the expression pattern determined above with one or more reference expression patterns, wherein each reference expression pattern is determined from the set of microRNAs in a reference myocardial sample obtained from an individual whose heart disease type is known (para. 13). Ikeda further teaches the comparison is done using AI models, including using Support Vector Machine to determine a subset of miRNAs and using Naive Bayes and Logistic regression to build a model for heart disease class prediction (para. 44).
While Ikeda teaches the subject may be a dog (para. 66), Ikeda does not specifically teach determining the expression of miRNAs in a dog sample as encompassed by claims 4 and 5, a blood sample as encompassed by claim 13, and the use of cell-free miRNA.
However, Jung teaches measuring miRNA in the context of heart failure.
Regarding claims 4-5, Jung teaches that cfa-miR-133 and cfa-miR-423 are relevant to canine heart failure (Table I).
Regarding claim 13, Jung teaches the sample is blood (p. 164, Isolation of microRNAs).
Regarding claim 14, Jung teaches the use of cell-free miRNAs isolated from a blood sample (p. 164, Isolation of microRNAs).
It would have been prima facie to have modified the method of Ikeda by at least screening for cfa-miR-133 and cfa-miR-423 in a dog sample. The modification has a reasonable expectation of success as it simply replaces one source of miRNA with another source of miRNA and using reagents that detect miRNAs of interest to Ikeda.
Claim(s) 9 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ikeda (US 2009/0306181 A1) in view of Croce (US 2006/0105360 A1) and as evidenced by Wagner (Frontiers in Genetics. 2013. 4:46, 9 pages).
Regarding claims 9 and 11, Ikeda teaches determining the expression pattern of a set of (e.g., at least one, two or more) microRNAs in a test myocardium sample obtained from an individual, the microRNA in the set of microRNAs includes miR-30b, miR-133b, miR-320, miR-423*, miR-499, let-7b and let-7c (para. 13).
It is noted that Wagner demonstrates that human miRNA reagents also detect related canine miRNAs and vice versa (p. 2). For Example, hsa-miR-30b and cfa-miR-30b, hsa-miR-133b and cfa-miR-133b, hsa-miR-320a and cfa-miR-320 and cfa-miR-320, hsa-miR-423-5p and cfa-miR-423a, hsa-miR-499a-5p and cfa-miR499, hsa-let-7b and cfa-let-7b and hsa-let-7c and cfa-let-7c are all related. Thus, the determining done by Ikeda would also determine the expression of at least some of the recited miRNAs.
Ikeda further teaches comparing the expression pattern determined above with one or more reference expression patterns, wherein each reference expression pattern is determined from the set of microRNAs in a reference myocardial sample obtained from an individual whose heart disease type is known (para. 13). Ikeda further teaches the comparison is done using AI models, including using Support Vector Machine to determine a subset of miRNAs and using Naive Bayes and Logistic regression to build a model for heart disease class prediction (para. 44).
While Ikeda teaches the above methods, Ikeda does not specifically teach the additional elements of claims 9 and 11.
However, Croce teaches the use of the use of Arabidopsis sequences based on the absence of any homology with known miRNAs from other species, and used as controls for non-specific hybridization (para. 206). Croce teaches the use of three Arabidopsis sequences: ath-miR156a, ath-miR157a and ath-miR180a (Table 8).
It would have been prima facie obvious to have modified the method of Ikeda at the time of filing by incorporating the use of the non-specific hybridization controls of Croce. In particular, it would have been obvious to use the Arabidopsis sequence taught by Croce because Ikeda is not interested in measuring Arabidopsis miRNA levels.
The use of ath-mir167d of claim 11 is an obvious variant of the use of ath-miR156a, ath-miR157a and ath-miR180a sequences taught by Croce. The claimed Arabidopsis miRNA and those of Croce are obvious variants because the each represent miRNA sequences not found in the mammals of interest to Ikeda.
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 1 and 4-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19/043,498 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim sets encompass overlapping subject matter. For example, “predictive classification models” in the ‘498 claims overlaps with the broader “AI model” of the present claims. Both claim sets measure miRNAs. In the ‘498 claims, the miRNAs are identified by SEQ ID NOs and in the present claims that are identified by their name. However, a comparison between the sequences of the ‘498 claims and the sequences given in the specification for the claimed miRNAs, demonstrates they are the same miRNAs.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 4-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/817,580 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim encompass overlapping subject matter. For example, “predictive classification models” in the ‘580 claims overlaps with the broader “AI model” of the present claims. Both claim sets measure miRNAs. In the ‘580 claims, the miRNAs are identified by SEQ ID NOs and in the present claims they are identified by their name. However, a comparison between the sequences of the ‘580 claims and the sequences given in the specification for the claimed miRNAs, demonstrates they are the same miRNAs.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682