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 without traverse of the following in the reply filed on 07/16/2026 is acknowledged:
Group I, claims 1-3, drawn to a primer set for amplification of a microRNA isoform; and
The species of the first 25 miRNAs and their corresponding 5’ terminus amplification primers SEQ ID NO 1-25.
Claims 4-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/16/2026.
Upon further search and reconsideration, the requirement for the species election is withdrawn.
Status of Claims
Applicant’s amendment filed 07/16/2026 is acknowledged. Claims 2-7 and 11-12 have been amended. Claims 4-20 have been withdrawn. Claims 1-20 are pending in the instant application and claims 1-3 are the subject of this non-final office action.
Specification
The disclosure is objected to because of the following informalities:
The name of the sequence listing file in para [0002] should be the complete file name including the file ending (e.g., “.xml”).
Appropriate correction is required.
Claim Objections
Claim 1-3 is objected to because of the following informalities:
Claim 1 recites “A primer set for amplification of a microRNA isoform (isomiR)”. Claims 2-3 recite “The primer set for amplification of an isomiR”. Each claim should remove the article, i.e., “A primer set for amplification of microRNA isoform (isomiR)” or “for amplification of isomiR”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-3 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 “A primer set … comprising a universal sequence and a 5’-terminus amplification primer linked sequentially to a partial sequence of a 5’ terminus of a …miRNA”.
It is unclear whether the universal sequence is a separate element of the primer set (e.g., “(i) a universal sequence and (ii) a 5’-terminus amplification primer linked sequentially …”) or both elements must be linked sequentially to the 5’ terminus of a miRNA.
Claims 2 and 3 are indefinite for depending from claim 1 and not rectifying the deficiency.
Regarding claim 2, claim 1 recites “A primer set … comprising … a 5’-terminus amplification primer linked … to a 5’ terminus of a…miRNA”. Claim 2 recites “wherein the miRNA comprises at least one selected from … the nucleotide sequences of corresponding 5’ terminus amplification primers are …”.
It is unclear how more than one miRNA is to be selected given the SEQ ID NO that each appears to correspond to a single miRNA. Claim 1 recites a 5’ terminus amplification primer linked to partial sequence of a miRNA.
It is further unclear whether the SEQ ID NO: 1-97, which comprise a common sequence in nucleotides 1-28, and what appears to be a partial sequence of a 5’ terminus of a miRNA 3’ of this region are intended to be the nucleotide sequence corresponding to the 5’ terminus amplification primer or the nucleotide sequence corresponding to the 5’ terminus amplification primer linked sequentially to the partial sequence of the microRNA. That is to say, it is unclear whether claim 2 is intended to further require an additional partial sequence of a 5’ terminus of a microRNA to be linked to SEQ ID NO: 1-97 to meet the limitations.
Applicant may consider amending claim 1 to recite “A primer set … comprising one or more amplification primers comprising …” (see, e.g., para [0044]) and claim 2 to recite “wherein the miRNA of each amplification primer of the one or more amplification primer is selected from the group consisting of …”.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception(s) without significantly more. The claim(s) recite(s) natural product(s). This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter?
Yes, the claim is directed to a product (e.g., manufacture or a composition of matter).
Step 2A, prong 1. Does the claim recite a law of nature, a natural phenomenon, or an abstract idea (recognized judicial exceptions)?
Yes, claim 1 recites a primer set comprising a universal sequence and a 5’ terminus amplification primer linked sequentially to a partial sequence of a 5’ terminus of a microRNA.
Under the interpretation that the universal sequence is sequentially linked, the oligonucleotide of the primer set requires a “universal sequence”, “a 5’ terminus amplification primer” and a “partial sequence of a 5’ terminus of a microRNA”. The claim recites a natural product. The partial sequence of a 5’ terminus of a microRNA is a natural sequence. A 5’ terminus amplification primer, under the broadest reasonable interpretation, may be a short sequence capable of priming (e.g., hexamer primers known in the art), and a universal sequence may likewise be any short sequence. Accordingly, the claimed oligonucleotide reads on, for example, the pre-miRNA comprising the 5’ partial sequence and un-diced upstream sequence that may be considered the primer and a “universal” sequence and/or such the genes that encode such in the genome. Any other unrecited primer required by the “set” may similarly encompass a natural sequence.
Therefore, the nature based product(s) have no markedly different characteristics from the natural sequence(s) that are the appropriate counterparts.
Unter the alternative interpretation that the universal sequence is not sequentially linked, the universal sequence may be any other sequence that is natural sequence. The analysis of above holds for the same reasons, and the nature based product(s) have no markedly different characteristics from the natural sequence(s) that are the appropriate counterpart(s).
See MPEP 2106.04(c)(II)(C)(2) for a discussion of “primers” lacking markedly different characteristics and the appropriate counterparts regardless of the strandedness of the counterpart.
Step 2A, prong 2. Is the judicial exception(s) integrated into a practical application?
No, the claim requires only limitations that read on a natural product. Absent additional limitations that differentiate the natural product from the appropriate counterpart, the judicial exception has not been integrated into a practical application.
Step 2B. Does the claim amount to significantly more?
No, the claim requires only limitations that read on a natural product. Absent additional limitations that differentiate the natural product from the appropriate counterpart, the claim does not amount to significantly more. As discussed in MPEP 2106.05, inventive concept that amounts to significantly more cannot be furnished by the judicial exception itself.
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Lee (US 2017/0335375 A1; published 11/23/2017).
Regarding claim 1, Lee teaches a kit for detecting miRNA (entire document, e.g., Abstract, para [0040-47]) comprising multiple primers (para [0041-47]) comprising:
An extension primer composed of a second hybridizing oligonucleotide and a second adapter oligonucleotide, the second hybridizing oligonucleotide being capable of hybridizing specifically to a portion of single-stranded cDNA reverse transcribed from miRNA, the portion of single-stranded cDNA excluding the portion corresponding to the 3’ end of the miRNA, and the 5’ end of the second hybridizing oligonucleotide (para [0042]), wherein the second adapter comprises a forward primer sequence (para [0043]) that may be a universal forward primer having a constant sequence regardless of the kind of miRNA (para [0045]).
Thus, by excluding the portion corresponding to the 3’ end of the miRNA, Lee teaches that the second hybridizing oligo hybridizes specifically to the 5’ portion of the cDNA, i.e., has the sequence of a 5’ terminus of a miRNA. Further, the second adapter binding site, having the universal forward primer binding site, may be considered a “universal sequence”. See also para [0065].
Said second adapter or universal forward primer may also be considered a “universal sequence” under the alternative interpretation of separate elements.
Thus, as Lee teaches each and every element of claim 1, Lee anticipates claim 1.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Wang (US 2012/0283106 A1; published 11/08/2012).
Regarding claim 1, Wang teaches a set of primers (claims 4-6 and 10; para [0025-0032]), wherein the set of primers comprises an RNA-specific primer that contains sequences from target RNA and the 5’ adapter (claim 4), wherein the RNA is miRNA (claim 10; see also para [0028]).
Wang teaches that the 5’ adaptors may be sequencing primer sequences (para [0030]; see claim 9), i.e., a universal sequence.
Under the alternative interpretation of a “universal sequence” as a separate element, Wang teaches said adapter (claim 1).
Thus, as Wang teaches each and every element of claim 1, Wang anticipates claim 1.
Conclusion
No claims are allowed. No prior art was found teaching:
An amplification primer comprising the particular sequence of SEQ ID NO: 1-97 at nucleotides 1-28 of the 5’ terminus amplification primers, which is common to each of SEQ ID NO 1-97, in combination with the respective partial 5’ miRNA sequence claimed (claim 2); and
A primer set further comprising either the pair SEQ ID NO: 99 and 100 or the pair SEQ ID NO: 101 and 102 (claim 3).
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wang - 2020 (CN 111549110 B; published 06/26/2020) teaches a miRNA quantitative detection kit (Abstract), wherein the kit comprises SEQ ID NO: 2 (para [0034]). Wang – 2020 SEQ ID NO: 2 consists of Instant SEQ ID NO: 102.
Wang – 2020 further teaches SEQ ID NO: 8 and 10-12 which partially comprise the sequence of Instant SEQ ID NO: 99, as shown in the NCBI MSA Viewer below, as aligned by NCBI’s BLAST:
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574
1392
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Greyscale
However, while portions of the apparently stem-loop sequence and of the non-stem loop sequence portions of the oligonucleotide were taught, Wang – 2020 fails to teach or suggest the entire oligonucleotide of Instant SEQ ID NO: 99.
Wang – 2020 fails to teach SEQ ID NO: 100 and 101 and explicitly using a universal sequence with a 5’ sequence for a 5’ terminus of a miRNA.
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/EMMA R HOPPE/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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