DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I and selected species in the reply filed on March 13, 2026 is acknowledged. The traversal is on the grounds that there is no serious burden of search because of overlapping subject matter, and because electronic search allows for searching of all relevant subclasses without substantial effort. This is not found persuasive because burden of search is not a factor in making a determination of lack of unity in a national stage application. The requirement is still deemed proper and is therefore made FINAL.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [00212] has a sequence of GGGGGGGGGGG which requires a sequence identifier, being more than 10 nucleotides in length. See WIPO Standard ST.26. Appropriate correction is required.
Claims Summary
Claim 1 is directed to a composition for the intended use of detecting a target nucleic acid in a sample, specifically a biological sample, such as a nasopharyngeal swab that is a crude sample derived directly from a subject without being processed (claim 62). The target nucleic acid in the sample has not been subjected to amplification and/or purification (claim 65). Please note the following about claims 62 and 65. With regard to claim 62, the limitation about the sample is part of an intended use recited in claim 1. The composition does not require the presence of the sample. With regard to claim 65, similarly, the limitation about the target nucleic acid in the sample is part of an intended use recited in claim 1. The composition does not require the presence of the sample, thus the target nucleic acid is not required in the composition.
The composition comprises:
An RNase nuclease inhibitor; the inhibitor is protein-based and specifically inhibits an activity of RNase A, B and C (elected species, claim 10); the inhibitor is dithiothreitol (DTT) (elected species, claim 15); the inhibitor is present in a concentration of about 0.01 to about 1 Unit/µl; and
A decoy oligonucleotide comprising tRNAs; the oligonucleotide is present in a concentration of about 0.01 to about 1 Unit/µl; “tRNA” generally refers to a type of RNA molecule that helps decode mRNA into a protein (see paragraph [0131] of the published application US 20240167107A1)
Additional agents:
A reverse transcriptase (claim 22), capable of amplifying a nucleic acid if present in a concentration about 0.01 to about 5 Unit/µl (claim 25)
Isothermal amplification buffer (claim 31)
Surfactant (claim 33), wherein the surfactant is present in a concentration of about 0.01% (v/v) to about 1.5% (v/v) (claim 38)
dNTPs, each dNTP present in a concentration of about 0.5 mM to about 5 mM (claim 41)
One or more primers specific for said target nucleic acid and suitable for said target nucleic acid in an isothermal amplification, LAMP (elected species, claim 44)
The primer contains at most one fragment of 4 consecutive identical single nucleotides, wherein the primer does not form any secondary structure with a ΔG lower than about -4 kcal/mol, and the primer does not comprise a 3’ end region having 6 or more nucleotides that are reverse complementary to a sequence within the same primer or within another primer of said one or more primers (claim 49)
The target nucleic acid is SARS-CoV-2 associated nucleic acid, and the one or more primers comprise primers 1-6 as set forth as SEQ ID NO: 3, 4, 1, 2, 5 and 6, respectively (claim 59)
The concentration of primer 1 is about 1 µM to about 2 µM; primer 2 is about 1 µM to about 2 µM ; primer 3 is about 0.1 µM to about 0.5 µM; primer 4 is about 0.1 µM to about 0.5 µM; primer 5 is 0.3 µM to about 0.8 µM; primer 6 is 0.3 µM to about 0.8 µM (claim 61)
Also claimed is a primer set comprising SEQ ID NO: 1-6 (claim 84), termed the Aptitude N4 primer set, which amplifies the N gene of SARS-CoV-2 (see paragraph [0383] of the published application US 20240167107A1). Claim 92 is directed to a method for detecting a target nucleic acid in a sample, comprising administering the composition of claim 1.
Claim Objections
Claims 15 and 25 are objected to because of the following informalities:
Claim 15, it appears that there should be a comma separating “Protector RNase Inhibitor (Roche, RNAIHN-RO) from β-mercaptoethanol, and a comma separating “(TCEP)” from “glutathione”.
Claim 25, line 2, “is” should be “if”.
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 15 and 92 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.
Claim 15 contains the trademark/trade name RNAsecure™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an RNase inhibitor and, accordingly, the identification/description is indefinite. Similarly, in claim 15, “RNase Inhibitor – Murine (NEB M0314)”, “Protector RNase Inhibitor (Roche, RNAIHN-RO)”. The metes and bounds of the claim cannot be determined.
Claim 92 is directed to a method for detecting a target nucleic acid in a sample, comprising administering the composition of claim 1. However, it is not clear where the composition is being administered. The claim does not have sufficient method steps. While all of the technical details of a method need not be recited, the claims should include enough information to clearly and accurately describe the invention and how it is to be practiced. The metes and bounds of the claim cannot be determined.
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.
Claims 1, 15, 16, 19, 22, 25, 41 and 62 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Craig Richmond, February 1, 2020, RNA probe labeling (E. coli), www.bio.davidson.edu/projects/gcat/protocols/ecoli/GEC%20RNA%20labeling%20(ecoli).pdf, 2 pages, website accessed 5/28/2026). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Craig discloses a method for RNA probe labeling. Following the protocol, at one point, there is a composition comprising the following components:
Sample RNA
2 µL of 5 mg/mL random hexamer (primers)
1 µL of control RNA (yeast tRNA mix, Sigma Cat #R8759) (claims 1 and 19, decoy tRNAs)
18.5 µL of labeling mix which includes
4 µL 0.1M DTT (RNase inhibitor according to instant claim 15, elected species) (claims 1, 15 and 16)
4 µL 10X dNTPs (claim 41), and
1 µL RNAsin® (RNase inhibitor) (claims 1 and 15)
2.5 µL of Reverse transcriptase (claims 22 and 25)
With regard to claim 62, the limitation about the sample is part of an intended use recited in claim 1. The composition does not require the presence of the sample. With regard to claim 65, similarly, the limitation about the target nucleic acid in the sample is part of an intended use recited in claim 1. The composition does not require the presence of the sample, thus the target nucleic acid is not required in the composition. Therefore, the claims are anticipated by the prior art.
Claim 10 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Craig Richmond, February 1, 2020, RNA probe labeling (E. coli), available from www.bio.davidson.edu/projects/gcat/protocols/ecoli/GEC%20RNA%20labeling%20(ecoli).pdf, 2 pages, website accessed 5/28/2026) as applied to claim 1 above, evidenced by Promega (RNasin® Ribonuclease Inhibitor, available from www.promega.com/products/rna-analysis/rnase-inhibitor-rna-protection/rnasin-ribonuclease-inhibitor/?tabset0=0, website accessed 5/28/2026, 9 pages).
Claim 10 is directed to an embodiment wherein the RNase inhibitor is capable of specifically inhibiting an activity of RNase A, B and C (elected species). Richmond does not comment on the spectrum of inhibitory activity of RNasin®, however, Promega is cited as evidence that RNasin® inhibits RNase A, B and C (see Promega, page 4). Therefore, claim 10 is anticipated by the prior art.
Conclusion
No claim is allowed.
Claims 31, 33, 38, 44, 49, 59, 61 and 84 are objected to for being dependent on a rejected claim, or reciting non-elected species.
A set of primers comprising SEQ ID NO: 1-6 is free of the prior art of record.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wei et al. (medRxiv [Preprint], 2020 Jun 16:2020.06.13.20129841, 10 pages). Wei discloses a one-step SARS-CoV-2 detection assay where a saliva sample (crude) is added to a reaction mixture for their high-performance LAMP (which is a variation of RT-LAMP) (see pages 2-3, bridging paragraph). To improve performance of the assay, Wei adds carrier DNA, carrier RNA and RNase inhibitors (see 3-4, bridging paragraph). Wei does not appear to indicate which carrier DNA or which RNase inhibitor(s) are used, thus Wei does not teach or fairly suggest the use of tRNA as a carrier RNA.
Rabe and Cepko (PNAS, September 29, 2020, 117(39):24450-24458) disclose method of isothermal amplification for detection of SARS-CoV-2, in combination with a method for sample inactivation and purification. A crude sample (saliva) is added to a mixture comprising a surfactant detergent, Tween20, for example, TCEP, and EDTA or DTT, to inactivate and lyse virions (see page 24450, right column, first full paragraph, Figure 3, and pages 24451-24452, “Detergent Tolerance” and “Inactivation Protocol” sections). Following inactivation, the sample is added to colorimetric RT-LAMP mix comprising primers to detect SARS-CoV-2 Orf1A (see page 24457, right column, second full paragraph). Rabe and Cepko state that the combination of TCEP and EDTA (or DTT) is sufficient to inactivate RNase activity (see page 24452, left column, top paragraph). Thus, Rabe and Cepko do not teach or fairly suggest the use of another agent to bind to the RNase, such as a decoy oligonucleotide comprising tRNAs.
Morais-Armas et al. (MicroPubl Biol., 9/20/2023, 10.17912/micropub.biology.000979, 6 pages) discloses the use of a carrier yeast tRNA (1 µg/µL) in the detection of SARS-CoV-2 by RT-LAMP.
McLeish et al. (J Clin Microbiol. 2012 Sep;50(9):2910-2917) discloses a composition comprising RNase inhibitors and an RNA carrier, exemplifying herring sperm carrier RNA. Herring sperm RNA is not tRNA. McLeish does not teach or fairly suggest using tRNA as carrier RNA.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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