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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/07/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims
Claims 71 and 76-85 are pending.
Priority
The priority date of the instant claims 71 and 76-85 is 04/16/2021, filling date of the US provisional application NO. 63/175,656.
Claim Objections
Claim 79 is objected to because of the following informalities:
In claim 79, lines 2-3, "performing a deparaffinization step prior contacting the sample with the quinone compound" should read "performing a deparaffinization step prior to contacting the sample with the quinone compound."
Claim 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 76-85 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.
A) Claim 71 recites in the preamble a "method of reducing autofluorescence in a biological sample," followed by a single step of "contacting the sample with an effective amount of a quinone compound."
This claim language is indefinite because it is unclear whether the preamble imposes a meaningful limit on the claimed method step, and if so, how.
MPEP§ 2111.02 states:
"During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. "
"If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. "
However, in the present case, the indefinite claim language prevents such a determination from being made with reasonable certainty.
First, if the "biological sample" recited in the preamble defines what is used in the method step, then the preamble could provide a manipulative difference by defining the type of sample required. However, there is inconsistency between the term "biological sample" in the preamble and the term "sample" in the body of the claim. It is unclear whether "the sample" in the contacting step refers to "a biological sample" mentioned in the preamble or if it is intended to encompass a broader scope by using the general term "sample."
Second, while the preamble recites an intended result ꟷ "reducing autofluorescence in a biological sample" ꟷ it is unclear how this applies to the claimed step. The contacting step, in contrast, does not reference autofluorescence or any measurement thereof. As written, the step does not specify any characteristic of the sample (e.g., whether it is a biological sample, or whether it exhibits autofluorescence), nor does it define how reduction of autofluorescence is achieved or measured. While the step recites "contacting the sample with an effective amount of a quinone compound," it does not clarify what the compound is "effective" for ꟷ whether it is effective in reducing autofluorescence or in achieving some other undefined purpose (e.g., improving signal-to-noise ratio, which can be achieved by increasing level of detected signal and/or reducing background noise). As further discussed below, the scope of "effective amount" is itself unclear.
Thus, it is unclear whether and how the claimed step is operationally tied to the preamble.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, "the sample" is interpreted to encompass any sample. And any prior art reference that fully teach the contacting step in the claimed method is considered to meet all the limitations in the claim.
B) Claim 71 also recites "an effective amount of a quinone compound," which is indefinite because the scope of "an effective amount" is unclear.
The specification does not define any specific quantity, concentration, or range for the recited quinone compounds that would qualify as an "effective amount." It is unclear how an "effective amount" is determined or what qualifies as "effective." Specifically, it is unclear whether this term encompasses specific concentrations, threshold, quantity, or other parameters, as well as the corresponding measurement approach.
Take concentration for example, in example 4, para [0159], the specification describes experiments conducted to optimize treatment conditions for hydroquinone and p-benzoquinone, testing factors such as concentration and incubation time.
Example 4 explores effectiveness of various conditions, in the specific context of improving signal-to-noise ratio in fluorescent microcopy imaging. The reported results (Table 2) are qualitative in nature, describing signal/noise ratio for each experimental condition as follows:
"For the signal/noise ratio, --- indicates no change compared to control, --+ indicates slight improvement compared to control, -++ indicates improvement compared to control, and +++ indicates the condition was most effective." ([0159], lines 6-9)
However, the specification does not clarify which of these outcomes meet the threshold of being "effective." For instance, it is unclear whether a "slight improvement compared to control" qualifies as "effective" within the scope of the claim.
In addition, the specification discloses that multiple factors influence the observed signal-to-noise ratio. For example, in the experiments with p-benzoquinone (pBQ), as shown in Table 2, 2mM pBQ concentration with overnight incubation yielded the "most effective" result, while a much higher concentration ꟷ 20mM with 30 minutes incubation ꟷ resulted in only "slight improvement." This variation indicates that effectiveness in improving signal-to-noise ratio depends on multiple interrelated factors, not just amount of quinone compound.
The specification also appears to contain internal inconsistencies. For example, para. [0158] states that p-benzoquinone is at maximum solubility at 100mM, yet Table 2 reports testing the same compound at 200mM ꟷ twice the stated solubility limit. The contradiction further clouds the meaning and metes and bounds of an "effective amount."
Moreover, claim 71 also recites compounds 2,3-dichloro-5,8-dihydroxy-1,4- napthoquinone; 2-methoxybenzo-1,4-quinone; 2-chloro-1,4-benzoquinone; 2,5-dichloro-1,4- benzoquinone; 2,6-dichloro-1,4-benzoquinone; and 2,5-dimethyl-1,4-benzoquinone; however, the specification does not disclose any specific treatment conditions for these compounds, with any specific amounts.
As such, the determination of an "effective amount" for the above compounds is entirely undefined, as the disclosure fails to provide any information regarding the quantities of these compounds used in the experiments.
For the reasons discussed above, the scope of the claim is indefinite.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, an "effective amount" is interpreted as any amount.
Claims 76-85 are rejected for depending from claim 71 and not remedying the indefiniteness.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 71 and 76-85 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 71, it recites:
“contacting the sample with an effective amount of a quinone compound selected from the group consisting of p-benzoquinone, hydroquinone, 2,3-dichloro-5,8-dihydroxy-1,4- napthoquinone, 2-methoxybenzo-1,4-quinone, 2-chloro-1,4-benzoquinone, 2,5-dichloro-1,4- benzoquinone, 2,6-dichloro-1,4-benzoquinone, and 2,5-dimethyl-1,4-benzoquinone. “
The recited "effective amount" for quinone compounds 2,3-dichloro-5,8-dihydroxy-1,4- napthoquinone; 2-methoxybenzo-1,4-quinone; 2-chloro-1,4-benzoquinone; 2,5-dichloro-1,4- benzoquinone; 2,6-dichloro-1,4-benzoquinone; and 2,5-dimethyl-1,4-benzoquinone lack written description support.
While Table 3 of the specification indicates that these compounds exhibit "Autofluorescence quenching effect," the disclosure does not provide any specific test conditions for the compounds 2,3-dichloro-5,8-dihydroxy-1,4- napthoquinone; 2-methoxybenzo-1,4-quinone; 2-chloro-1,4-benzoquinone; 2,5-dichloro-1,4- benzoquinone; 2,6-dichloro-1,4-benzoquinone; and 2,5-dimethyl-1,4-benzoquinone, at any concentration or amount ꟷ let alone disclose what would qualify as an "effective amount."
Therefore, the claims encompass subject matters that extend beyond the content disclosed in the application, failing to meet the written description requirement of 35 U.S.C. 112(a).
Claims 76-85 are rejected because they depend from claim 71 and inherit the deficiencies of the base claim.
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.
Claims 71 and 76 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsien (Fluorophores for confocal microscopy: photophysics and photochemistry. In: Pawley JB, editor. Handbook of biological confocal microscopy. Springer Science+Buisness Media; New York, NY: 2006. pp. 174. )
Regarding claims 71 and 76, Tsien teaches contacting a sample with hydroquinone (page 174, left-hand col, para 1, lines 7-10, “In dead, fixed samples, it has become common to add antioxidants such as propyl gallate (Giloh & Sedat, 1982), hydroquinone, p-phenylenediamine, etc., to the mounting medium.”)
Claims 71, 76-85 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).
Regarding claims 71 and 76, Hainfeld teaches contacting a sample with hydroquinone ([0190-0191]; [0128]; [0119]; [0006]).
Regarding claim 77, Hainfeld teaches the sample is a tissue specimen ([0190] human breast cancer biopsies).
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 RNA 1.
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”).
Prior Art
Other prior art also contacting a quinone compound to biological sample:
Goldberg et al., US20050048599A1 - Sensitive and rapid determination of antimicrobial susceptibility; published 2005-03-03;
Ma et al. Target-specific imaging of transmembrane receptors using quinonyl glycosides functionalized quantum dots. Analytical Chemistry. 2014;86(11):5502-5507;
Iwaki et al.; US20030044830A1 - Method of reducing background in florescence detection ; Published on 2003-03-06; cited as U.S. Patent document # 016 in IDS filed 05/07/2025.
Conclusion
Claim 79 is objected to; claims 71 and 76-85 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/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)