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 claims / Response to Amendment
This office action is in response to an amendment filed on May 12, 2026.
Claims 71 and 76-85 were previously pending. Applicant amended claims 71 and 78-79; cancelled claims 76-77; claim 86 is newly added.
Claims 71 and 78-86 are currently pending and under consideration.
All of the previously presented objection and rejections have been withdrawn as being obviated by the amendment of the claims.
The previously set forth prior art rejections have been withdrawn in view of the recent claim amendment filed on May 12, 2026, which added new limitations to the claims (i.e., the newly amended method in claim 1 now recites "wherein the quinone compound is present in the composition at a concentration of about 1 mM to about 100 mM"). Thus, the scope of the claims has been changed in a manner that were not considered in the previous rejections.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Priority -- Updated
The priority date of the instant claims 71 and 78-86 is 04/16/2021, filling date of the US provisional application NO. 63/175,656.
New Grounds of Rejections - 35 USC § 112(b)
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 71 and 78-86 are rejected under 35 U.S.C. 112(b), 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 1 has been amended to recite "wherein the quinone compound is present in the composition at a concentration of about 1 mM to about 100 mM," which is indefinite for its recitation of "about," without clearly defining the term in the specification.
The lack of definition of "about" makes the scope of the claim unclear because the term introduces ambiguity in the meets and bounds of the claimed concentration. It is unclear to what extent a concentration may vary to still be considered "about" a specific number.
Claims 78-86 are rejected for depending from claim 71 and not remedying the indefiniteness.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The following are new grounds of rejections necessitated by Applicant's amendments. Although the claims were previously rejected as being unpatentable over the same reference(s), Applicant's amendments have necessitated the inclusion of new grounds of rejections in this Office action. It is noted that, to the extent that they apply to the present rejection; Applicant's arguments are addressed in the "Response to Arguments" section following the rejections.
Claims 71 and 78-86 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hainfeld (Hainfeld et al. ; US20070224625A1 - Site-specific enzymatic deposition of metal in situ; published on 2007-09-27; cited as U.S. Patent document # 018 in IDS filed 05/07/2025), as evidenced by
Wikipedia (Hydroquinone - Wikipedia; Archived Apr 12, 2020 on WaybackMachine) and
Owsik (Owsik,et al. "The oxidation of hydroquinone to p-benzoquinone catalysed by Cu (II) ions immobilized on acrylic resins with aminoguanidyl groups: Part 1." Journal of Molecular Catalysis A: Chemical 178.1-2 (2002): 63-71).
Regarding claim 71, Hainfeld teaches a method comprising
contacting the biological sample with a composition comprising a quinone compound selected from the group consisting of p- benzoquinone and hydroquinone ([0189]; [0068]),
wherein the quinone compound is present in the composition at a concentration of about 1 mM to about 100 mM (e.g., [0068] lines 19-20, treating sample with a solution comprising 2.5 mg/ml hydroquinone, which is 22.7mM with mW of 110.11 g/mol, see Wikipedia),
wherein the biological sample is a tissue specimen ([0189]; [0068]).
Hainfeld anticipates the single claimed step of contacting a biological sample with a composition within the claimed concentration range. Thus, the method steps in Hainfeld is identical to claim 1, except that Hainfeld is silent as to the inherent characteristic that the composition reduces autofluorescence.
MPEP 2112 states:
“III. A REJECTION UNDER 35 U.S.C. 102 AND 103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. “There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102.” In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims. “
“II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. “The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.”).”
Here, the functional property of reducing autofluorescence is inherently taught by Hainfeld because the reference teaches the identical step using identical chemical and compositional features required by the claim, thus the reduction of autofluorescence necessarily results from practicing the disclosed method.
Regarding claim 78, Hainfeld teaches a formalin fixed paraffin embedded tissue specimen ([0190])
Regarding claim 79, Hainfeld teaches performing a deparaffinization step prior contacting the sample with the quinone compound ([0190-0191]).
Regarding claim 80, Hainfeld teaches detecting one or more targets in the biological sample ([0036], in situ hybridization of target gene).
Regarding claim 81, Hainfeld teaches detecting a nucleic acid target in the biological sample, wherein the nucleic acid is selected from an RNA and a DNA ([0040]).
Regarding claim 82, Hainfeld teaches in situ hybridization methods for detecting target molecules, including gene products (see, [0040]; [0131]). Hainfeld also teaches that in situ hybridization detects RNA sequences ([0131] lines 1-6).
Therefore, a skilled artisan would understand that Hainfeld's in situ hybridization methods of detecting gene products and RNA targets include the detection of mRNA, as mRNA is transcription product of a gene and a type of RNA1.
Regarding claim 83, Hainfeld teaches the nucleic acid target is DNA ([0040]).
Regarding claim 84, Hainfeld teaches detecting a target protein in the biological sample ([0044]).
Regarding claim 85, Hainfeld teaches detecting multiple nucleic acid targets ([0183]” Multiple probes can be utilized for detecting multiple SNPs in a population of target polynucleotides in parallel”).
Regarding claim 86, it recites “wherein the quinone compound is p-benzoquinone,” this limitation is anticipated by Hainfeld.
Hainfeld teaches contacting the biological sample with p-benzoquinone by teaching treating the sample with hydroquinone and hydrogen peroxide (For example in para. [0068] Hainfeld teaches treating FFPE human colon carcinoma tissue section with 2.5 mg/ml hydroquinone (22.7 mM) and hydrogen peroxide), such an reaction yields p-benzoquinone (see [0233] in Hainfeld; see also Owsik, Fig. 1).
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As noted in Owsik: “[t]he oxidation of hydroquinone (H2Q) to p-benzoquinone (Q) is well known for a long time,” which has been reported to proceed with high efficiency, e.g., 98% yield (see Owsik Abstract, Fig. 1; page 64,left-hannd col, para1). Accordingly, a person of ordinary skill in the art would have readily understood that oxidation of hydroquinone at 22.7mM, as disclosed in Hainfeld, would produce at least 1mM p-benzoquinone, thereby contacting the biological sample with p-benzoquinone in an amount within the claimed range.
Response to Arguments
Applicant's arguments filed on May 12, 2026 have been fully considered.
Claim Rejections - 35 USC§ 102
Applicant argues Hainfeld does not focus on fluorescence measurement and does not teach reducing autofluorescence (Remarks, page 6-8).
This argument has been fully considered but is not persuasive.
As discussed in the rejection above, Hainfeld still anticipates claim 71 because the reduction of autofluorescence is an inherent result of the claimed contacting step, which Hainfeld teaches.
It is noted that the claim, as currently written, does not require any active step that applies or makes use of this inherent, autofluorescence-reducing property. Applicant is advised that amending the claim to better reflect Example 4 of the instant application, which describes a method performing RNA ISH to evaluate signal-to-noise ratio in fluorescent imaging analysis for nucleic acid targets, may overcome the art rejections over Hainfeld, set forth in this office action.
Prior Art
Below are relevant prior art not used in rejection but pertinent to the claims or disclosure.
The quenching property of quinone compound that reduces background fluorescence is known in the art:
See Valeur (Molecular Fluorescence: Principles and Applications. Bernard Valeur 2001; Wile y-VCH Verlag GmbH) at page 84-85: "Quinones, hydroquinones, purines and pyrimidines are well-known examples of molecules responsible for static quenching." ;
See Ma (Ma, Wei. "Redox-Mediated Quantum Dots as Fluorescence Probe and Their Biological Application." Nonmagnetic and Magnetic Quantum Dots (2018): 133) at page 139: "… by taking advantage of the effective quenching ability of benzoquinone for QDs and natural ligand-receptor pairing on the cell surface (that recovers the signal), paves the way for the development of highly specific and low-background techniques for bioimaging of cancer cells as well as probing of unknown cell-surface receptors. "
The high background noise in florescence detection is a known issue, performing treatment steps to a biological sample to reduce autofluorescence is also known in the art:
See Luo (Luo et al., US20130023433A1 - Methods of detecting nucleic acid sequences with high specificity ; Published on: 2013-01-24; cited as U.S. Patent document # 022 in IDS filed 05/07/2025) in Abstract, [0019], [0767] for examples.
See also Sun (Sun et al. Simple Elimination of Background Fluorescence in Formalin-Fixed Human Brain Tissue for Immunofluorescence Microscopy. J Vis Exp. 2017 Sep 3;(127):56188. doi: 10.3791/56188. PMID: 28892031; PMCID: PMC5614400.).
Iwaki (Iwaki et al. , US20030044830A1 - Method of reducing background in florescence detection ; Published on 2003-03-06) specifically teaches methods of reducing background in fluorescence detection in nucleic acid hybridization assays, wherein background is reduced by using a quenching agent (Abstract; [0091]; [0093]), such as benzoquinone ([0039]).
Conclusion
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.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 It is well-known in the art that In situ hybridization is used for detection of mRNA. See Wikipedia (In situ hybridization - Wikipedia; Archived April 04, 2020 on WaybackMachine)
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