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 .
Status of the Application
The Amendment and Response filed December 23, 2025 is acknowledged.
Claims 11-16 and 18-21 were pending. Claims 11-16 and 18-19 are being examined on the merits. Claims 20-21 are canceled.
Response to Arguments
Applicant’s arguments filed December 23, 2025 have been fully considered.
The following rejections are WITHDRAWN in view of Applicant’s arguments and claim amendments:
Rejection of claims 11-19 under 35 USC § 112(b), indefiniteness
Prior art rejections
Response to arguments regarding prior art rejections
Applicant argues that the cited art does not teach each limitation of instantly amended claim 11 (Remarks, p. 6).
The Examiner agrees that the cited art does not teach or suggest, at least, clonally amplifying the hairpin-ligated population of single-stranded nucleic acid molecules while they are attached to a support by hybridization with an amplification primer, and where the different single-stranded molecules are amplified in physical isolation.
The prior art rejections are withdrawn.
Claim Interpretation
Claim 11 step (b) recites the limitation “clonally amplifying”, which is being interpreted according to the teachings in the specification. Specifically, the specification teaches …
[t]his continuous process of primer hybridization, extension, displacement and template walking continues for the duration of the amplification reaction …. The product of these amplification and template-walking cycles is the generation of multiple, faithful surface-bound copies of the original seeded LAMPlate [template], as intramolecular concatemeric repetitive duplexes in close spatial proximity to the original seeded LAMPlate [template]. A plurality of such close proximity faithful duplex copies can be referred to as a clone, or a cluster or a colony and as such the original single stranded portion of the seeded LAMPlate [template] can be said to have been “clonally amplified”.
(p. 12, ll. 29-37). Claim 11 additionally recites that the different single strands are amplified in “physical isolation”. Thus, “clonally amplifying” is being construed as generating multiple copies of the original template molecule, with each individual copy being surface bound to a P1 primer, and being in close physical proximity to the original template molecule. Further, each single strand template molecule and its copies are in a physically distinct location relative to every different single strand template molecule and those respective copies. Finally, the copies being in “close … proximity to the original [template]” is being interpreted as each copy being hybridized to a P1 primer adjacent to the P1 primer to which the template is hybridized or adjacent to a P1 primer hybridized to a copy of the same template.
Claim Objections
Claims 11-16 and 18-19 are objected to because of the following informalities:
In claim 11, the phrase “single stranded” in l. 2 of the “wherein in step (b)” clause
should be hyphenated. Also, the phrase “different sequence” in l. 3 of the “wherein in step (b)” clause should be “different sequences”.
Claims 12-16 and 18-19 directly or indirectly depend from claim 11, and thus incorporate its informalities.
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 13-16 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 13 recites the limitation “wherein P1’ hybridizes to the loop of LP1 and extends
…”, the meaning of which is unclear. Specifically, claim 13 indirectly depends from claim 11, which recites primer P1 which also hybridizes to at least a portion of the loop of LP1. Thus, it is unclear how both primers P1 and P1’ participate in the amplification reaction if they both bind to LP1. It is also unclear if P1 and P1’ are intended to be complementary to one another, as the terminology of [X] and [X]’ is conventionally understood to indicate. If so, it is not clear how they could both bind to the same target sequence, LP1. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 14-16 depend directly or indirectly from claim 13, and consequently incorporate
the indefiniteness issues of claim 13.
Prior Art
Independent claim 11 is free of the art. The closest prior art is Wolff1 (WO 2019/073049 A1), Wong2 (WO 2014/071322 A1) and Metzker3 (WO 2015/157747 A1).
The teachings of each of Wolff and Wong are discussed, at least, in the Non-Final Office Action mailed September 26, 2025. However, the teachings of Wolff and Wong, whether considered alone or in combination, do not teach or suggest clonally amplifying the hairpin-ligated population of single-stranded nucleic acid molecules while they are attached to a support by hybridization with an amplification primer, and where the different single-stranded molecules are amplified in physical isolation. Further, while clonal amplification is generally known in the art, e.g., in next-generation sequencing technologies, there would not be any motivation to modify the Wolff method to clonally amplify the substrate-bound single-stranded molecules, nor is it clear that the Wolff detection method would work if the substrate-bound single stranded molecules are clonally amplified.
In addition, Metzker (WO 2015/157747 A1) is directed to methods for amplifying target
nucleic acid molecules comprising ligating hairpin adapters to each end of the target nucleic acid molecule to create a dumbbell structure, and then hybridizing the dumbbell structure to an immobilized primer. The primer is then used in a rolling circle amplification to create clonally-replicated concatemers of the dumbbell structure (paras. 81, 100). However, the Metzker dumbbell is created with a double-stranded fragment, thus creating a “closed” dumbbell structure, while the instant claim 11 dumbbell is created with a single-stranded fragment, thus creating an “open” dumbbell structure. The ordinary artisan would not have been motivated to modify the Metzker dumbbell structure to open it so that the “3’ end of the stem arm of LP1 [can be] extended to make a copy of the single-stranded nucleic acid molecules”, as is required in instant claim 11, nor is it clear that the Metzker method would work is such a modification was made.
Accordingly, independent claim 11 and its dependent claims are free of the art.
Conclusion
Claims 11-16 and 18-19 are being examined. Claims 13-16 are rejected and objected to. Claims 11-12 and 18-19 are objected to, but are otherwise directed to allowable subject matter. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Wolff was cited in the PTO-892 Notice of References Cited mailed May 22, 2025.
2 Wong was cited in the Information Disclosure Statement submitted February 3, 2022.
3 Metzker was cited in the Information Disclosure Statement submitted February 3, 2022.