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 statement(s) (IDS) filed 8 July 2024 is considered, initialed, and attached hereto.
Claim Status
Claims 1-5, 8-9, 20-21, 24-26, 32-33, 37, and 39 are pending and under examination.
Claims 6-7, 10-19, 22-23, 27-31, 34-36, 38, and 40-43 are canceled.
Specification
The disclosure is objected to because of the following informalities: Page 58 line 14 of the specification filed 11 December 2024 includes “was” in superscript where it should not be in superscript.
Appropriate correction is required.
The use of terms such as Cy, Gibco, and Invitrogen, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they 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.
Claim Objections
Claim 9 is objected to because of the following informalities:
Claim 9 recites “wherein said nucleic acid comprised by said probe compound comprises DNA”. The nucleic acid of the underlined portion is interpreted as referring to the nucleic acid recited in line 2 of claim 8 upon which claim 9 depends. However, the wording of claim 9 appears to suggest that the nucleic acid comprises the probe compound, rather than the probe compound comprising the nucleic acid as in claim 9. Examiner suggests that an amendment to clarify this meaning could be either changing claim 9 to recite “wherein said nucleic acid of said probe compound comprises DNA” or changing claim 8 to recite “said probe compound comprises a complementary nucleic acid having a sequence complementary to at least a portion of said target nucleic acid” and claim 9 to recite “wherein said complementary nucleic acid comprises DNA”.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites in lines 4-5 “said probe compound comprises a complementary sequence”. Because the claim does not limit what sequence the complementary sequence is complementary to, the recited complementary sequence is interpreted as encompassing any sequence that is complementary to another sequence.
Claim Rejections - 35 USC § 112(b) - 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.
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 3, 21, and 39 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 3 recites the limitation "said change" in line 3. There is insufficient antecedent basis for this limitation in the claim. Because claim 2 provides antecedent basis for said change, claim 3 is interpreted as depending upon claim 2 instead of depending upon claim 1.
Claim 21 recites the limitation “said probe compound” in line 2. There is insufficient antecedent basis for this limitation in the claim because it may refer to either the “control probe compound” recited in line 3 of claim 20 upon which claim 21 depends or the “probe compound” recited in line 4 of claim 1 upon which claim 21 depends via claim 20.
Claim 39 recites the limitation “said biological sample” in line 4. There is insufficient antecedent basis for this limitation in the claim.
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 –
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4-5, 8-9, and 37 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Chen et al. (US Patent Document Cite No 1 in IDS filed 8 July 2024)(US 2015/0322499, published 12 November 2015, effectively filed 12 May 2014), herein Chen.
Regarding claim 1, Chen teaches a method of determining a presence of at least one target nucleic acid in a sample (“the method of the invention can be used to detect nucleic acids” [0074]), the method comprising:
contacting a nucleic acid-containing fraction of said sample with at least one probe compound capable of binding to said target nucleic acid, said probe compound comprises a complementary sequence (“The method comprises (1) providing a solution comprising samples, labeled molecules, and probe particles in an accommodating space” [0007]; “The “sample” of the invention refers to any sample containing nucleic acids” [0044]; “Referring to FIG. 4 […] The probe 11 and the labeled molecule 13 can bind to the target molecule (nucleic acids) 15” [0064] and FIG. 4, note that the labeled molecule 13 is equivalent to the claimed probe compound, this is also referred to as DNA2 in Examples 1+2 of [0075]-[0083], see specifically the mixing step in [0078]);
exposing said probe compound to a temperature gradient (“(2) providing a temperature control system in a control region of the accommodating space to create a temperature gradient within the solution” [0007]; “A temperature gradient was provided by near infrared laser light” [0081] of Examples 1+2); and
detecting a signal of said probe compound during said exposing to said temperature gradient (“(3) detecting the expression level of the labeled molecules in a predetermined area and a contrast area” [0007]; After laser exposure, the fluorescent DNA (DNA2) was not uniformly distributed around the heated region because of thermophoresis. Fluorescence was observed” [0081] of Examples 1+2),
said signal being indicative of a presence or absence of the target nucleic acid in the sample (“(4) analyzing the difference in the expression level of the labeled molecules between the predetermined area and the contrast area. The probe particles can bind to the target molecules. If the sample contains target molecules, then the probe particles, the target molecules, and the labeled molecules can form “probe particle-target molecule-labeled molecule” complexes. The direction or speed of the motion of the molecular complexes in a temperature gradient is different from that of the free labeled molecules” [0007]; see also [0064]), and
the method further comprising contacting said nucleic acid-containing fraction of said sample with an additional compound capable of binding to nucleic acids (“(1) providing a solution comprising samples, labeled molecules, and probe particles in an accommodating space” [0007]; “Referring to FIG. 4 […] The probe 11 and the labeled molecule 13 can bind to the target molecule (nucleic acids) 15” [0064] and FIG. 4, note that the probe 11 is equivalent to the claimed additional compound, this is also referred to as gold nanoparticles bound to DNA1 in Examples 1+2 of [0075]-[0083], see specifically the mixing step in [0078]). Note with regard to FIG. 4 as described in [0064] that 15 is the target nucleic acid of the sample, 13 are the probe compounds that have label G that produces a signal, and 10 are probe particles that are the additional compound, comprised of the probe 11 and particle P).
Regarding claim 4, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), wherein said target nucleic acid is a single-stranded nucleic acid (FIG. 4, 15 is the target nucleic acid and is single stranded).
Regarding claim 5, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), wherein said target nucleic acid comprises RNA (“In one embodiment, the target molecule is […] a RNA molecule” [0013]).
Regarding claim 8, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), wherein said probe compound comprises a nucleic acid having a sequence complementary to at least a portion of said target nucleic acid (“Referring to FIG. 4 […] The probe 11 and the labeled molecule 13 can bind to the target molecule (nucleic acids) 15 to form the complex C1” [0064], see in FIG. 4 the hybridization by complementary sequences of target molecule 15 with probe compound 13 to connect them with the probe particle in C1; note in Example 1 [0075]-[0079] that DNA3 is the target nucleic acid and DNA2 is the probe compound, which [0077] teaches are complementary).
Regarding claim 9, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), wherein said nucleic acid comprised by said probe compound comprises DNA (“In one embodiment, the labeled molecule is a DNA molecule” [0014]; see also Example 1 [0075]-[0079] DNA2).
Regarding claim 37, Chen teaches a method of determining a presence of a target nucleic acid in a subject, comprising detecting a presence of said target nucleic acid according to claim 1 (see 35 U.S.C. 102 rejection of claim 1 above) in a sample obtained from a subject (“The “sample” of the invention refers to any sample containing nucleic acids. The biological sample of the invention is not limited and includes any material containing nucleic acids, chromosomes, and/or plasmids. In one embodiment, the biological sample of the invention can be a fungus, a virus, a microorganism, a cell, a blood sample, an amniotic fluid, a cerebrospinal fluid, or a tissue sample from skin, muscle, buccal, conjunctival mucosa, placenta, or gastrointestinal tract” [0044], recited biological samples such as blood samples and tissue samples are examples of samples obtained from subjects because there is no limiting definition of “subjects” in the instant specification).
Therefore, claims 1, 4-5, 8-9, and 37 are anticipated by Chen.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US Patent Document Cite No 1 in IDS filed 8 July 2024)(US 2015/0322499, published 12 November 2015, effectively filed 12 May 2014), herein Chen, as applied to claims 1, 4-5, 8-9, and 37 above.
Regarding claim 24, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above). Though Chen does not specifically teach that said contacting with said additional compound is effected subsequently to said contacting with said probe compound, this limitation is merely a change in the sequence of mixing ingredients from mixing the probe compound (DNA2) and additional compound (DNA1) first to produce a mixture that is then mixed with the nucleic-acid containing sample (DNA3), as taught by Chen in [0077], to first mixing the probe compound and sample to produce a mixture that is then mixed with the additional compound. MPEP §2144.04(IV)(C), citing In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930), states that “Selection of any order of mixing ingredients is prima facie obvious”. As the difference between Chen and claim 24 is merely the selection of an order of mixing ingredients, the invention as a whole of claim 24 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 2-3 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US Patent Document Cite No 1 in IDS filed 8 July 2024)(US 2015/0322499, published 12 November 2015, effectively filed 12 May 2014), herein Chen, as applied to claims 1, 4-5, 8-9, and 37 above, and in view of Duhr et al. (Foreign Patent Document Cite No 2 in IDS filed 8 July 2024)(WO 2009/098079), herein Duhr.
Regarding claim 2, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above). However, Chen does not teach the method wherein said detecting comprises determining a change in said signal with respect to a signal of said probe compound in the absence of said target nucleic acid. This deficiency is made up for in the teachings of Duhr.
Regarding claim 2, Duhr teaches a similar method of determining a presence of a target nucleic acid (“The measurement of thermo-optical properties can be applied for detection of a specific DNA sequence” page 139 lines 4-5) by contacting the target nucleic acid with a complementary probe compound (“Here, an assay is shown where a short fluorescently labeled DNA probe hybridizes with a complementary DNA strand. Upon hybridization the probe adopts the thermo-optical properties of the target molecule” page 139 lines 7-9; “For the experiment shown in Fig. 38 (a) samples with a constant amount of labelled probe DNA (400 nM) were mixed with varying amount of unlabeled target DNA” page 140 lines 29-30), exposing the probe compound to a temperature gradient (“The infrared laser heating is turned on. The immediately established local spatial temperature distribution causes the labeled primers and elongated primers (as well as internal reference standards) to drift to lower or higher temperatures” page 142 lines 18-20), and detecting a signal of said probe compound during said exposing to said temperature gradient (“During the laser heating an image of the fluorescence distribution is recorded” page 142 line 28). Furthermore, Duhr teaches determining changes in the signal with respect to the signal of the probe compound with varying amounts of target nucleic acid, including in the absence of target nucleic acid (“For the experiment shown in Fig. 38 (a) samples with a constant amount of labelled probe DNA (400 nM) were mixed with varying amount of unlabeled target DNA. In this case target concentrations of 0nM, 100nM, 200 nM, 400 nM, 800nM, 1200 Nm and 1600 nM were measured” page 140 lines 29-32; Fig. 38a, note the comparison in the graph between fraction double stranded DNA when the concentration of unlabeled DNA is 0 nM with other concentrations). Note that the recitation in claim 2 “said change that is beyond a predetermined threshold of said probe compound in the absence of said target nucleic acid is indicative of a presence of the target nucleic acid in the sample” is not a required active step of the claimed method, but rather a statement of how an a result of the claimed method may be interpreted. Because this statement does not recite an active step of a method or further limit any component of the method, it does not further limit the subject matter encompassed by the claim. Therefore, the method of Duhr modified with the teaching of a similar method of Chen that utilizes an additional compound (the probe particle of Chen) teaches all limitations of claim 2.
Regarding claim 3, the combination of Chen and Duhr teach the method of claim 2 (see 35 U.S.C. 103 rejection of claim 2 above; note that claim 3 is interpreted as depending upon claim 2 rather than claim 1 as discussed in the 35 U.S.C. 112(b) rejection of claim 3 above), and Duhr further teaches the method wherein said determining of said change is executed quantitatively (“The thermo-optical properties (i.e. concentration change) of the free probe molecule is known from an independent experiment” page 142 lines 14-15, note that the “free probe” is the probe in the absence of target nucleic acid that it hybridizes to; “The relative amount of hybridized strands (as shown in Figure 38 (a)) can be determined, by (1) subtracting the signal of the free probe molecule from all other signals followed by (2) a division of the subtracted signals by the saturation value (i.e. concentration change determined in saturation) determined at an excess of target” page 143 lines 9-12).
Regarding claims 20-21, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), and Duhr teaches a similar thermo-optical method (see 35 U.S.C. 103 rejection of claim 2 above). Additionally, Duhr teaches that a different method of detecting a target nucleic acid, RT-PCR can enable quantification of a relative amount by normalizing results to the results of additional normalizing genes (“In real-time polymerase chain reaction […] is a laboratory technique based on polymerase chain reaction, which is used to amplify and simultaneously quantify a targeted DNA molecule. It enables both detection and quantification (as absolute number of copies or relative amount when normalized to DNA input or additional normalizing genes) of a specific sequence in a DNA sample” page 39 lines 23-28). Because both RT-PCR and the thermo-optical method taught by Duhr are both taught as being used for the detection of target nucleic acids and Duhr teaches the detection of multiple sequences simultaneously (“By using multiple fluorescence labels it is possible to detect several sequences simultaneously” page 140 lines 18-19), one of ordinary skill in the art would be able to extend the teaching of using a different normalizing gene (the control nucleic acid) in RT-PCR to the thermo-optical method by using a different fluorescently labeled probe for the normalizing gene and then normalizing the signal of the probe compound complementary to the target nucleic acid to the signal of the probe compound complementary to the control nucleic acid.
Regarding claim 33, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above), and Duhr teaches a similar method (see 35 U.S.C. 103 rejection of claim 2 above) comprising concomitantly determining a presence of a first target nucleic acid in the sample using a first probe compound and a presence of a second target nucleic acid in the sample using a second probe compound (“By using multiple fluorescence labels it is possible to detect several sequences simultaneously” page 140 lines 18-19).
In view of Chen’s teaching that their method of analyzing a target molecule provides an improvement of other thermophoresis-based methods by overcoming the challenge of detecting binding events that only cause a small change in thermophoresis by including an additional compound ([0005]-[0006]), it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention combine the method of thermo-optical analysis (based on thermophoresis) of Duhr with the teachings of Chen (MPEP §2143(I)(G)). One of ordinary skill in the art would have a reasonable expectation of success in this combination because the methods of both Chen and Duhr are based upon the changes in thermophoretic movement of a probe when it is free and when it is bound to a target. Therefore, the invention as a whole of claims 2-3 and 33 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US Patent Document Cite No 1 in IDS filed 8 July 2024)(US 2015/0322499, published 12 November 2015, effectively filed 12 May 2014), herein Chen, as applied to claims 1, 4-5, 8-9, and 37 above, and in view of Deng et al. (“Rapid One-Step Detection of Viral Particles Using an Aptamer-Based Thermophoretic Assay” J Am Chem Soc 143(19), pages 7261-7266 (2021)), herein Deng Main, as evidenced by Deng et al. (“Rapid One-Step Detection of Viral Particles Using an Aptamer-Based Thermophoretic Assay” J Am Chem Soc 143(19), Supplementary Information (2021)), herein Deng Supplementary.
Regarding claim 32, Chen teaches the method of claim 1 (see 35 U.S.C. 102 rejection of claim 1 above). However, Chen does not teach exposing said probe compound to a temperature of at least 80 °C prior to said contacting with said nucleic acid-containing fraction of said sample. This deficiency is made up for in the teachings of Deng Main as evidenced by Deng Supplementary.
Regarding claim 32, Deng Main teaches a similar thermophoretic assay to that of the method of Chen using a fluorescently labeled aptamer, similar to the claimed probe compound and the labeled molecule of the method of Chen, though it differs in that it binds to a viral particle rather than a complementary nucleic acid in order to detect the viral protein rather than a target complementary nucleic acid (“Here, we describe a one-step thermophoretic assay that integrates aptamer binding to the SARS-CoV-2 S protein and PEG-enhanced thermophoretic accumulation, allowing for rapid and quantitative detection of pseudotyped SARS-CoV-2 viral particles (Figure 1). By directly mixing viral particles with PEG molecules (8000 Da, 6%) and Cy5-conjugated aptamers, two processes occur in parallel in an infrared laser induced temperature gradient: high-affinity binding between aptamers and the S protein on the surface of viral particles and rapid accumulation of particles toward the laser spot through the PEG-enhanced thermophoresis” page 7261 right column paragraph 2). Deng Supplementary provides evidence that the assay of Deng Main further comprises exposing the fluorescently labeled aptamer (equivalent to the probe compound) to a temperature of at least 80 °C prior to contacting the sample containing the target of the aptamer (“Annealing of the DNA probes. DNA oligonucleotides were dissolved in the buffer (0.55 mM MgCl2 in PBS) with the final concentration of 10 μM. The solution was heated at 95 °C for 5 min and then immediately cooled at ice for 5 min. The DNA probes were stored at -20 °C until usage” page 2 paragraph 2).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of the manner of preparing DNA probes for use in a thermophoresis-based assay taught by Deng Main and as evidenced by Deng Supplementary for the less specific manner of preparing DNA probes for use in the thermophoresis-based assay taught by Chen (see Chen Example 1 paragraph [0076] not teaching any specific temperature-related steps of preparing the probe compound, DNA2, prior to contacting it with the additional compound (particle bound to DNA1) in [0076] and the target-containing sample DNA3 in [0078]) (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because heating DNA probes prior to incubating them with samples that contain complementary target nucleic acids is common practice in DNA probe hybridization-based technologies. For example, a similar heating step is done in the fluorescent in situ hybridization assay taught by Alamri et al. (“Fluorescence In Situ Hybridization of Cells, Chromosomes, and Formalin-Fixed Paraffin-Embedded Tissues” Methods Mol Biol 1606, pages 265-279 (2017)) in section 3.1.5 on page 273 and 3.2.3 on page 275. Therefore, the invention as a whole of claim 32 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US Patent Document Cite No 1 in IDS filed 8 July 2024)(US 2015/0322499, published 12 November 2015, effectively filed 12 May 2014), herein Chen, as applied to claims 1, 4-5, 8-9, and 37 above, and in view of Rogers et al. (US 2018/0267048, published 20 September 2018, effectively filed 30 July 2015), herein Rogers.
Regarding claim 39, Chen teaches a method comprising determining a presence of at least one target nucleic acid according to claim 37 (see 35 U.S.C. 102 rejection of claim 37above). However, Chen does not specifically teach a method of diagnosing at least one disease or disorder that comprises the method of claim 37 wherein the at least one target nucleic acid is associated with said disease or disorder. This deficiency is made up for in the teachings of Rogers.
Regarding claim 39, Rogers teaches a method for diagnosis of a disease comprising determining the presence of a target nucleic acid using microscale thermophoresis wherein a presence of said target nucleic acid in said biological sample is indicative of a presence of said disease (“Methods for detecting the presence or absence of target nucleic acid suitable for use in steps (b) and (c) include […] or microscale thermophoresis” [0115]; “In some embodiments the method of the present invention may be used to detect or diagnose infection with a pathogenic disease. Suitably the method of the present invention may be used to detect or diagnose infection with a pathogenic disease is which a target nucleic acid sequence characteristic of the pathogenic microorganism can be identified” [0130]).
In view of Chen’s teaching that their method of analyzing a target molecule provides an improvement of other thermophoresis-based methods by overcoming the challenge of detecting binding events that only cause a small change in thermophoresis by including an additional compound ([0005]-[0006]), it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention combine the improved method of detecting a target molecule by thermophoresis taught by Chen with the method of diagnosing an infection using microscale thermophoresis to detect a target nucleic acid characteristic of the infection taught by Rogers (MPEP §2143(I)(G)). One of ordinary skill in the art would have a reasonable expectation of success in this combination because the method of Chen and the method of Rogers using microscale thermophoresis are both based upon the principles of thermophoresis and therefore would not expect the use of the specific thermophoresis-based assay of Chen in the method of diagnosis of Rogers to prevent the method of Rogers from functioning. Therefore, the invention as a whole of claim 39 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Allowable Subject Matter
Claims 25-26 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: though the method of claim 24 is obvious in view of the prior art of Chen (see 35 U.S.C. 103 rejection of claim 24 above), Chen does not teach or make obvious a modified version of the method of claim 24 wherein the additional compound capable of binding to nucleic acids comprises at least one intercalating agent, as required by claim 25. The nearest prior art is Chen (as previously discussed), Maeda et al. (“Effects of long DNA folding and small RNA stem–loop in thermophoresis”, Proc Natl Acad Sci U S A 109(44), pages 17972-17977 (2012)), herein Maeda, and Sass et al. (“Binding affinity data of DNA aptamers for therapeutic anthracyclines from microscale thermophoresis and surface plasmon resonance spectroscopy” Analyst 144(2), pages 6064-6073 (2019)), herein Sass.
While Maeda teaches using thermophoresis to analyze nucleic acids and teaches using intercalating dyes in this method (“For thermophoresis experiment, we visualized T4 DNA, small RNA, and small DNA with SYBR gold fluorescent dye” page 17977 left column paragraph 2, note that SYBR gold is an intercalating agent; “We tracked single T4 DNA stained by YOYO-1 instead of SYBR gold” page 17977 left column paragraph 3; “YOYO-1 fluorescent dye that intercalates into base pairs in DNA” page 17977 right column paragraph 2), Maeda only teaches using these intercalating agents as dyes for visualizing the nucleic acid for which the thermophoretic properties are being analyzed. Maeda lacks using a probe compound to detect a target using thermophoresis. As the method of Chen already has a fluorescent label on the probe compound (the labeled molecule) and the additional compound of Chen does not function as a dye, but rather to increase differences in molecular weight between free and bound probe, one of ordinary skill in the art would not have a reason to use the intercalating dyes of Maeda to replace the additional compound of the method of Chen.
Sass teaches using thermophoresis to assess the affinity of DNA probes (aptamers) binding to the intercalating agents daunorubicin (DRN) and doxorubicin (DOX) (Abstact). However, in Sass the intercalating agents are the target being detected by the probe compound (DNA probe/aptamer), rather than being an additional compound included in an assay detecting the binding of a probe compound with a target nucleic acid. Therefore, one of ordinary skill in the art would not have a reason to use the intercalating agents taught by Sass as replacements for the additional compound of the method of Chen.
Therefore, claim 25 is free of the prior art. Claim 26 is free of the prior art because claim 26 depends upon claim 25. Therefore, claims 25-26 are directed to allowable subject matter and would be allowable if rewritten into independent form.
Conclusion
Claims 25-26 are objected to as dependent upon rejected claims. Claims 1-5, 8-9, 20-21, 24, 32-33, 37, and 39 are rejected. Claims 6-7, 10-19, 22-23, 27-31, 34-36, 38, and 40-43 are canceled.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
