DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 31 October 2025 has been entered.
Claims 26, 30-31, 48, and 50 have been amended and claims 27-29 have been canceled. Claims 36 and 49 remain withdrawn, while claims 26, 30-35, 37-48, and 50 remain under consideration herein. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejections set forth in the prior Office action;
The rejection of claim 50 under 35 USC 112(d), in view of Applicant’s amendment of the claim (such that the claim now recites a further limitation of, properly depends from, claim 48);
The rejection of claims under 35 USC 102 as being anticipated by Abbasi et al, in view of the amendment of claim 26 to require the practice of a method in which the FIP or BIP have characteristics relative to the target region (to which they anneal) as set forth in claim 26;
The rejection of claims 48 and 50 as being anticipated by Song et al, in view of the amendment of claim 48 to an FIP and a BIP, wherein either the FIP or BIP has one or more mismatches in relation to a target region as specified in claim 48;
The rejection of claims under 35 USC 103, also in view of the amendment of independent claim 26 noted above; and
The rejection of claim 26 and claims dependent therefrom under 35 USC 101, also in view of the amendment of independent claim 26 noted above.
Claims 26, 30-35, 37-48, and 50 remain rejected for the reasons given below, which include new grounds of rejection necessitated by Applicant’s amendments. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is non-final.
Election/Restrictions
Claims 36 and 49 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 15 November 2023.
Claim Rejections - 35 USC § 112(b)/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 26, 30-35, 37-48, and 50 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.
Claims 26, 30-35, and 37-47 are indefinite over the recitation in independent claim 26 of the limitation “amplifying under isothermal conditions including hybridization, or annealing in isothermal buffer a nucleic acid sequence from a sample, in a reaction mixture comprising” because this language does not make clear what alternative activities are embraced thereby. While it is noted that Applicant has amended the claim in response to a prior indefiniteness rejection, the new claim language is also confusing, as it may be reasonably be interpreted as embracing, e.g., either the entire recited “amplifying” or “annealing” as alternatives (given the language and placement of commas in the claim), with both alternatives requiring the “reaction mixture” but with only the annealing requiring “a nucleic acid from a sample”, or as requiring either an amplifying or an annealing, both of which must employ “a nucleic acid sequence from a sample”. As there are multiple reasonable interpretations of the claim language that impart different boundaries on what is claimed further clarification is required. Additionally, given these different possible reasonable interpretations, it is not clear whether the claims potentially involve two different types of “nucleic acid sequence”, and (to the extent that they may involve two), what nucleic acid sequence constitutes “the nucleic acid sequence” of (a)(i) (although it is noted that the claim does conclude with a requirement for “detecting an amplified nucleic acid sequence, wherein the detection of the amplified nucleic acid sequence indicates the presence of the tandem repeat”, such that the claims are interpreted as requiring detection of an amplified nucleic acid sequence of the type recited in the preamble of the claim. i.e., the claims as written do require “detecting a tandem repeat” that “comprises two or more repeat units…”, although the specific requirements of the “amplifying” or “annealing” are not sufficiently clear).
Claims 48 and 50 remain indefinite over the use of the term “stringent conditions” as a requirement in the claims; see independent claim 48 (from which claim 50 depends). The specification states that (see page 18; see paragraph 70 of US 20210172030 A1):
As used herein, “stringent conditions” are known to those skilled in the art and can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y., 6.3.1-6.3.6, 1991. The stringent conditions may be stringent conditions for hybridization. The stringent conditions may be stringent conditions for annealing. Stringent conditions may be defined as equivalent to annealing in isothermal buffer. Isothermal buffer (lx) may comprise 20 mM Tris-HCl; 10 mM (NH4)2SO4; 50 mM KCl; 8 mM MgSO4; Betaine 0.8M; 0.1% Tween® 20; and may have pH 8.8 at 25° C.
The term “stringent conditions” as employed in the claims is indefinite because the term as defined in the specification could reasonably be interpreted by different persons of skill in the art in multiple different ways. More particularly, some persons of skill in the art might interpret this language as embracing conditions of any type of hybridization/annealing stringency known in the art (including typical low, medium, and high stringency conditions), while others might interpret this term as requiring something more particular/specific (although it is noted that the conditions actually recited above are clearly exemplary, based on the language “conditions may be defined as….”). Accordingly, further clarification is required to ensure that the boundaries of the claims are clear. It is noted that Applicant’s reply of 31 October 2025 (top of page 11) states that the rejection has been overcome by amendment of the claim “to remove the phrase alleged to be indefinite”; however, this is not the case with regard to independent claim 48, and claims 48 and 50 thus remain indefinite for the reasons indicated above.
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 48 and 50 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon/law of nature without significantly more. The claim(s) recite(s) “FIP” and “BIP” primers without clearly specifying any particular required structures/sequences for these primers. As fragments of naturally occurring nucleic acids may function as such primers, these claims recite products of nature that fall under the law of nature/natural phenomenon judicial exception. Nothing recited in the claims necessarily renders the primers of the claims markedly different from their naturally occurring counterparts, nor does their presence together in a kit or “liquid” reaction mixture (as in claim 50) necessarily do so. While it is noted that claim 48 has been amended to require a primer including a region (either F2 of FIP or B2 of BIP) that “anneals to the target region” and has “one or more mismatched nucleotides with respect to the target region”, the “target region” of the claim is merely a target region “comprising one or more nucleotides from each of two repeat units” to which either FIP or BIP ‘is configured to anneal under stringent conditions”. Given the broad definition of “tandem repeat” (both in the specification and in the claim itself), and the lack of clarity with regard to what is encompassed by annealing “under stringent conditions”, the claims continue to embrace – based on at least some reasonable interpretations thereof – fragments of naturally occurring nucleic acids (at least because FIP and BIP are not clearly defined). This judicial exception is not integrated into a practical application because placing a product of nature into a generic container/kit or “medium” does not add a meaningful limitation as it is merely a nominal or token extra-solution component of the claim, and is nothing more than an attempt to generally link the product of nature to a particular technological environment. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the packaging of oligonucleotide primers into kits (or their placement in to a reaction mixture/medium for us, whether inside a kit or not) was well-understood, routine, and conventional in the art before the effective filing date of the claimed invention.
Thus, claims 48 and 50 are not directed to patent eligible subject matter.
It is noted that Applicant’s traversal (Reply pages 11-12) pertains to methods of claim 26 and claims dependent thereof (which were previously rejected under 35 USC 101 on different grounds); while Applicant’s arguments were found persuasive with regard to amended claim 26 and its dependent claims, claims 48 and 50 remain rejected for the reasons given above.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Lee et al (Frontiers in Microbiology 7(Article 2166):1-13 [09 Jan 2017]; cited herein) teach successful RT-LAMP using FIP and BIP primers in which F2 and B2 respectively include 1 mismatch with respect to some target sequences (see Figure 2A and page 5, right column); however, the reference teaches and provides motivation to avoid/minimize (rather than select and incorporate) mismatches (and also does not pertain to the specific objective of tandem repeat detection).
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682