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 .
DETAILED ACTION
Status of the Claims
Claims 1-20 are pending. Claims 1-3, 6, 8-10, 14-15 and 17-18 and the subject of this NON-FINAL Office Action. This is the first action on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-18); however they tarverse the species election of PCR primer or extension product1, Maverick Blue, internal attached fluorophore and probe1-fluor1 and probe2-fluor22 in the reply filed on 12/16/2025. First, the election of intercalator is withdrawn. As to the other species, Applicants generally argue, adopting MPEP § 808.01(a) that “where only generic claims are presented, restriction cannot be required unless the generic claims recite or encompass such a multiplicity of species that an unduly extensive and burdensome search would be necessary to search the entire scope of the claim.” As to the first species, Applicants argue that “proper consideration of the term "reporter molecule" in light of the specification supports a conclusion that "an unduly extensive and burdensome search" is not necessary.”3 This is contradicted by Applicants’ own statement before this: “Applicant provisionally elects PCR primer or an extension product of PCR primer as the "reporter molecule" species. Each of claims 1 through 18 are generic with respect to these species.” As explained in the Office Action, claim 1 is so generic that it encompasses any unconventionally-labeled “target-specific reporter molecules,” which is poorly and confusingly defined in the specification as explained below. For example, how is a dNTP “target-specific”? This alone renders the scope of this generic, Applicant-created phrase subject to extensive burdensome searching.
As to the second species, Applicants argue that “the term "probe" used in the requirement only appears in claims 4 and 11 submits that proper consideration of the term "reporter molecule" in light of the specification supports a conclusion that "an unduly extensive and burdensome search" is not necessary.” This conclusion is not warranted by the claims themselves. The claims, and specification, include multiple iterations of the “target-specific reporter molecules” and their labeling: one probe with multiple labels; two separate probes, each with one label that confusingly form a “molecule”; dNTPs, presumably with multiple labels, which is nowhere disclosed; multiple dNTPs, each with a label; covalent attachment during amplification e.g. using cross-linking; etc. In other words, as explained in the Office Action, Applicants’ generic, and confusing, claims render the scope of the labeling scheme broad and uncertain, causing a burdensome search.
Finally, as to the third species of multiplex probe label arrangement, Applicants’ own generic claim in light of the specification render the scope broad and confusing, yielding undue search. For example, as explained above and below, the use of multiple probes is somehow considered a single “target-specific reporter molecule.” This is a different invention from a single probe with multiple labels. And this does not even begin to address how the covalent labels are attached (e.g. during PCR, before PCR, etc.).
Simply put, Applicants’ claims are written in such a way, especially in light of the specification, that they encompass a vast swath of possible combinations of primers, probes, dNTPs or other “molecules” arranged in any of a number of possible ways (e.g. multiple dNTP each labeled, one dNTP with multiple labels, etc.) using any number of possible covalent attachment techniques (e.g. crosslinking during/after PCR, labels attached before amplification, etc.). This alone cause undue search burden.
The elections read on claims 1-3, 6, 8-10, 14-15 and 17-18. Claims 4-5, 7, 11-13, 16 and 19-20 are withdrawn.
Note on Claimed Subject Matter
The claims are directed to the well-known principle that DNA intercalators (here, “double-stranded DNA-binding dye”) such as SYBR can be used with acceptor-fluor-labeled primers, probes, dNTPs, etc. to allow energy transfer, or FRET from the intercalator to the fluor. In other words, this is not allowable subject matter.
Claim Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1-3, 6, 8-10, 14-15 and 17-18 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 pre-AIA the applicant regards as the invention.
In claim 1, at a critical juncture of the claimed subject matter, it is unclear how the fluorophore is covalently attached to the “target-reporter duplex.” Claim 1 recites: “conducting an amplification reaction on the reaction mixture such that when the sample of interest contains the target region, the double-stranded DNA-binding dye binds to a target-reporter duplex formed between the target-specific reporter molecule and the target region, such that the target-reporter duplex has plural copies of a fluorophore covalently attached thereto.” First, it is not clear what causes the covalent attachment: the amplification; the something in the mixture; the “target-specific reporter molecule”; or something else? All that the clause states is to conduct an amplification with the sample, “DNA binding dye” and “target-specific reporter molecule” “such that” the “the target-reporter duplex” has covalently attached fluorophores. And this presumes “thereto” at the end of the clause references the “target-reporter duplex” and not something else. In other words, this critical clause is so unclear that it is impossible to determine the scope of the claim.
The meaning of the unconventional phrase “target-specific reporter molecule” is unclear. The specification indicates that “a reporter molecule includes various constructs as exemplified in FIG. 1C, with the requirement being that, collectively, there are plural copies of an acceptor label within the double helix formed by the reporter molecule” so that “a reporter molecule can be a probe 3 with multiple acceptor labels 6, as depicted at 22, or multiple probes each with at least one label, as depicted at 23” (para. 0022). This is confusing. How does a single molecule (“target-specific reporter molecule”) simultaneously two molecules (“a reporter molecule can be . . . multiple probes each with at least one label, as depicted at 23”). The use of a singular (“molecule”) for the reporter to indicate that two reporters are included is inherently confusing.
Furthermore, the “target-specific reporter molecule” “can also be a probe-target duplex in which the probe . . . may not be labeled provided the target is an extension product 7 labeled by incorporation of a labeled dNTP (plural copies, if probe is not labeled), as depicted at 24” (para. 0022). “A reporter molecular can further be an extension product of a primer with multiple labels, as depicted at 25, a duplex of extension products (also called an amplicon or a PCR product) with multiple labels incorporated during amplification either by a pair of labeled primers, as depicted at 26, or by a plurality of a labeled dNTP, or by a combination of at least one labeled dNTP and a primer with at least one label as depicted at 27” (id.). However, claim 1 contradicts these possibilities when it requires “providing a target-specific reporter molecule in a solution.” In other words, how can an extension product be present before the amplification? In sum, the metes and bounds of the claimed “target-specific reporter molecule” are unclear.
Claim 10 makes no sense. Specifically, it recites a “the single target-reporter duplex,” which not only lacks antecedent basis, it also introduces confusion as to whether amplification occurs. A single “target-reporter duplex” means a single extension occurs. No amplification proceeds. This contradicts claim 1 which requires amplification.
In sum, the claims are confusing at the point of critical subject matter that may help render the claims distinguishable over prior art. However, the Examiner applies prior art that He believes is in-line with the subject matter disclosed in the specification. That is, use of DNA intercalators with multi-acceptor-fluor-labeled primers or dNTPs to generate FRET between the intercalators and the acceptor fluors on the primer or dNTP.
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 –
(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 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by KURATA (US20090233308).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, KURATA teaches amplification with multiple acceptor-labeled dNTPs along with intercalator so that intercalator causes FRET to the labeled dNTPs (Fig. 2).
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Instead of labeled dNTPs, a primer or probe can be used (paras. 0083, 0097-06).
Claims 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by HOSER (US20070148645).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, HOSER teaches amplification with multiple acceptor-labeled dNTPs along with intercalator so that intercalator causes FRET to the labeled dNTPs (Fig. 4).
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Claims 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by SUN (US20070202521).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, SUN teaches amplification with multiple acceptor-labeled dNTPs incorporated into a primer extension, along with intercalator so that intercalator causes FRET to the labeled dNTPs (Claim 1).
Claims 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by DAWSON (US20130116154).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, KURATA teaches amplification with multiple acceptor-labeled probes, along with intercalator so that intercalator causes FRET to the labeled probes (para. 0152).
Claims 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by ABE (US20110059541).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, ABE teaches amplification with probes or primers comprising acceptor-labels, along with intercalator so that intercalator causes FRET to the labeled dNTPs (Fig. 1).
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The probe can have “a group of plural fluorescent dyes including at least an excitation-target fluorescent dye capable of giving excitation energy, which has been obtained by absorption of light, to another fluorescent dye and a detection-target fluorescent dye capable of fluorescing by receiving the excitation energy from the another fluorescent dye” (claim 2; see also para. 0017).
Claims 1-3, 6, 8-10, 14-15 and 17-18 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by HARDIN (WO2009055508).
As to claims 1-3, 6, 8-10, 14-15 and 17-18, HARDIN teaches amplification with probes or primers comprising acceptor-labels, along with intercalator so that intercalator causes FRET to the labeled dNTPs (Fig. 12).
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The probe, primer or dNTPs can have multiple acceptors (para. 0120).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaron Priest whose telephone number is (571)270-1095. The examiner can normally be reached 8am-6pm.
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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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/AARON A PRIEST/Primary Examiner, Art Unit 1681
1 Which is not a proper election because it makes no sense as explained below (two-probe single “molecule” is confusing as explained below).
2 Again, this two-probe single “molecule” is confusing as explained below.
3 “reporter molecule” is inaccurate; the claim recites “target-specific reporter molecule.”