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 .
Claims 1-2, 4-7, 10, 15-21, 23-26, 29, 34, 37-40 and 43 are pending. Claims 1-2, 4-7, 10 and 15-17 are being examined on the merits. Claims 18-21, 23-26, 29, 34, 37-40 and 43 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2, 4-7, 10 and 15-17) in the reply filed on July 10, 2026 is acknowledged.
Claims 18-21, 23-26, 29, 34, 37-40 and 43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 10, 2026.
Information Disclosure Statement
The Information Disclosure Statement submitted September 16, 2024 has been considered.
Specification
The use of the terms for various nucleic acid assay reagents and components, which are trade names or marks used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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.
Specifically, the following trademarks appear in the specification at pp. 34-37 and 43: Phusion, NanoDrop, HiScribe, RNaseOUT, Tween, ATTO, Alexa Fluor and CutSmart.
Claim Objections
Claims 1-2 are objected to because of the following informalities:
In claim 1, the limitation “single stranded” in l. 1 should be hyphenated.
In claim 2, the limitation “the targeting payload sequence” in ll. 1-2 should be “the
target payload sequence” to keep the language consistent with claim 1.
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 1-2, 4-7, 10 and 15-17 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.
Indefiniteness rejections
Claim 1 recites the limitation a “single stranded nucleic acid construct”, the meaning of which is unclear. Specifically, it is unclear what structure the construct is intended to have, for several reasons:
First, the claim recites that the single-stranded construct comprises a targeting domain,
a signaling domain, and at least one splint oligonucleotide that hybridizes to the targeting domain and the signaling domain. A construct comprised of these three components is shown in instant Fig. 1A, as follows:
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However, Fig. 1A shows that such a construct is (partially) double-stranded. It is not clear how that construct would have to be modified to generate a single-stranded construct, as recited in claim 1. Is the splint oligonucleotide actually attached to the 3’ end of the signaling domain, and then folds back and forms some sort of hairpin structure?
Second, the claim recites numerous instances of “orthogonal ligation adapter sequence”, and recites that each of the at least one programmable unit in the targeting domain have first and second such adapter sequences, and that each of the at least two programmable units in the signaling domain have first and second such adapter sequences. Then in the “at least one splint oligonucleotide” clause, the claim recites that the splint oligonucleotide hybridizes to the orthogonal ligation adapter sequences. Which of the numerous orthogonal ligation adapter sequences does the splint oligonucleotide hybridize to? In embodiments with more than one splint oligonucleotide, does each splint oligonucleotide have the same sequences? Do all the first (5’?) orthogonal ligation adapter sequences have the same sequence? Do all the second (3’?) orthogonal ligation adapter sequences have the same sequence? In embodiments where the signaling domain has more than two programmable units, perhaps three, does the splint oligonucleotide still hybridize the second unit of the signaling domain?
Third, it isn’t clear what the “final construct product” (in the last line) refers to. Is the “final construct product” different from the “single stranded nucleic acid construct”?
Fourth, it isn’t clear what is meant by “the construct is amplified to produce the final construct product”. Claim 1 is a product claim. The “construct is amplified” limitation is a statement of intended use of the product. Is this intended to be a product by process limitation? If so, is the claim intended to be directed to the “final construct product” or the “single stranded nucleic acid construct” (if there is any difference between them).
Fifth, the claim recites that the construct comprises “a [single] targeting domain”, “a [single] signaling domain” and “at least one splint oligonucleotide”, and that a “functional unit” is formed by hybridizing those three components together. Then, the “wherein” clause recites that “the construct” can have two or more functional units comprising the targeting domain and at least one signaling domain”. How many signaling domains does a functional unit have – is it limited to one (as recited in the “at least one clause”) or is it one or more (i.e., at least one, as recited in the “wherein the construct” clause)?
Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 2, 4-7, 10 and 15-17 depend from claim 1, and consequently incorporate the indefiniteness issues of claim 1.
Claim 16 recites the limitation “wherein the nucleic acid of interest comprises DNA and/or RNA”, the meaning of which is unclear. Specifically, it is unclear how a single nucleic acid can comprise both DNA and RNA. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claim 17 recites the limitation “wherein the imaging oligonucleotide of interest is a fluorophore”, the meaning of which is unclear. Specifically, while an oligonucleotide can have a fluorophore attached to it, it is not clear how an oligonucleotide itself can be a fluorophore; that is, oligonucleotides do not fluoresce. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Lack of antecedent basis rejections
Claim 16 recites the limitation "the nucleic acid of interest" in ll. 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claim 16 depends, does not recite a “nucleic acid of interest”.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-2, 4-7, 10 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Kool1 (US Patent No. 6,077,668) and Daugharthy2 (US Patent App. Pub. No. 2021/0340621; effectively filed April 22, 2020).
Regarding independent claim 1, as noted above, there are numerous indefiniteness
issues in the claim. Nevertheless, Kool teaches a single-stranded nucleic acid construct with a predetermined number of binding sites, the construct comprising: a targeting domain, comprising at least one programmable unit with each unit comprising from a 5’ end to a 3’ end, a target payload sequence comprising a predetermined number of binding sites; a signaling domain, comprising at least two programmable units with each unit comprising from a 5’ end to a 3’ end, a signaling payload sequence comprising a predetermined number of binding sites; and at least one splint oligonucleotide, wherein the construct can have two or more functional units comprising the targeting domain of interest and at least one signaling domain of interest, and wherein the construct is amplified to produce the final construct product (col. 4, ll. 31-33; col. 15, ll. 23-25; col. 16, ll. 21-31; col. 53, ll. 49-58; col. 12, ll. 13-22, col. 3, ll. 55-58; col. 4, ll. 56-57). In addition, Daugharthy teaches various adapter sequences (paras. 65, 74).
Regarding dependent claims 2 and 16-17, Kool additionally teaches that the targeting payload sequence hybridizes to a target sequence in a target nucleic acid, optionally DNA or RNA, and that the signaling payload sequence hybridizes to an imaging oligonucleotide, optionally comprising a fluorophore (col. 4, ll. 31-43; col. 17, ll. 26-59).
Regarding dependent claims 4-7 and 10, Daugharthy teaches various additional components associated with the adapters, including various linkers, domains comprising primer binding sequences, at least two signal domains where the binding sites are different, and teaches that the adapters can have different sequences (Fig. 1; paras. 7, 42).
Regarding dependent claim 15, Kool additionally teaches that the nucleotides in the construct can comprise various modifications, including, e.g., phosphorothioate modifications, which protect from exonuclease digestion (col. 13, ll. 56-67 through col. 14, ll. 1-11).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Kool construct components with the Daugharthy adapter sequences and other components and to optimize the binding sites, modifications and components, to arrive at the recited construct through routine optimization. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Conclusion
Claims 1-2, 4-7, 10 and 15-17 are being examined and are rejected. Claims 1-2 are objected to. No claims are allowed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Kool was cited in the Information Disclosure Statement submitted September 16, 2024.
2 Daugharthy was cited in the PTO-892 Notice of References Cited mailed May 14, 2026.
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