Notice of Pre-AIA or AIA Status
The present application, filed on 17 February 2023 and claiming a foreign (Australian) priority (18 August 2020), is being examined under the first inventor to file provisions of the AIA (effective 16 March 2013).
The Office actions (OA), as detailed below, are provided on the basis that all claimed inventions receive the broadest reasonable interpretation for a person having ordinary skill in the art.
Objection to Informalities in Claims
In claim 25 (amended), “at leaset” should be “at least.”
One Rejection under 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.
Claim 18, which defines one aqueous solution in a lateral flow assay (LFA), is rejected under 35 USC §112(b) or pre-AIA 35 USC 112, 2nd paragraph as being indefinite for failing to point out and distinctly claim the concentration of DNA aptamers bound to nanoparticles suitable for the LFA: the claimed recitation of “a concentration in the range of 200 to 500” requires a unit measure (nM or µM, etc.) to make sense. For the purpose of compact prosecution, the concentration here is assumed to be measured in nM, as disclosed in a related document (WO 2022/038521, p. 48).
Rejections under 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.
1. Claims 1-3 and 10 are rejected under 35 USC §103 as being unpatentable over Song et al June 2020 (Cite No. 2 of record in the IDS filed 2/17/2023) and in view of Yu et al January 2020 (Development of a lateral flow aptamer assay strip for facile identification of theranostic exosomes isolated from human lung carcinoma cells. Analytical Biochemistry 594: 113591):
Song et al 2020 taught the “discovery of DNA aptamers targeting the receptor-binding domain of the SARS-CoV-2 spike glycoprotein” (Abstract, p. 9895), including eight aptamers (Table S1 in Supporting Information, https://pubs.acs.org/doi/10.1021/acs.analchem.0c01394?goto=supporting-info, 2020) that match exactly the aptamer sequences of SEQ ID NOs. 1-8 as currently claimed, although they did not teach about using these novel aptamers in any assay involving nanoparticles;
Yu et al 2020 developed an “aptamer assay … using nanogold particles as visualization probes”, stressing that DNA aptamers conjugated with gold nanoparticles (AuNP) can offer “a low cost lateral flow aptamer assay” for diagnostic use.
Based on the teaching by Song et al 2020 and Yu et al 2020, a person having ordinary skill in the art (PHOSITA) would, at the effective filing date of claims 1-3 and 10, be able to combine gold nanoparticles (AuNP) and SARS-CoV-2 spike protein-specific aptamers toward an assay for diagnosing SARS-CoV-2 infection, especially because Song et al 2020 explicitly taught that their DNA “aptamers present an opportunity for generating new probes for recognition of SARS-CoV-2…” (Abstract), including the use in a lateral flow assay (LAF) like the one developed by Yu et al 2020. Thus, claims 1-3 are rejected for their obviousness.
2. Claims 7-8 (dependent on claim 1) are rejected under USC §103 as being unpatentable over its inherited issues above (claim 1 being obvious from prior art) and further in view of Schuling et al 2018 (Aptamer-based lateral flow assays. AIMS Bioengineering 5(2): 78-102):
Schuling et al 2018 teaches that “biotinylated complementary oligonucleotide” interacts with “aptamer fragment-AuNPs conjugates” in a “control zone” of LFA to generate a “red band” (p. 83, last paragraph) for visualization.
Using the collective teaching by Song et al. 2020, Yu et al. 2020 and Schuling et al 2018, a PHOSITA would, at the effective filing date of claims 7-8, be able to apply biotinylated oligonucleotide and AuNP for the detection of SARS-CoV-2 spike protein because LFA has “advantages including low costs, easy operation by non-specialized users and low analyte volumes needed” (Abstract).
3. Claims 11-13, 17-19, and 21 (also dependent on claim 1) are rejected under USC §103 as being unpatentable first over issues inherited from claim 1 above and further in view of Schüling et al 2018:
Schüling et al 2018 also teaches that “the introduction of linker, fluorophores and different functional groups fused to either the 3’ or the 5’ end of the aptamer represent possible modifications, which can be introduced during the chemical synthesis to enhance the stability of the aptamers or (to) simplify detection,” with “high reproducibility” (p. 81, 1st paragraph) and “a dynamic range from 50–1000 nM” (p. 84, last paragraph).
Thus, a PHOSITA would, at or even before the effective filing date of claims 11-13, 17-19 and 21, be able to follow the methods taught by Song et al 2020, Yu et al. 2020 and Schüling et al 2018 toward a SAR-CoV-2-specific LFA because similar assays have proved to be “easy,” with several “unique” elements thar are flexible and desirable “for the detection of small molecules, proteins and whole cells or viruses” (Schüling et al 2018, p. 81, first two paragraphs).
4. Claim 23 is rejected under USC §103 as being unpatentable over Song et al June 2020 in view of Yu et al January 2020 and further in view of Chen et al May 2020 (A DNA Aptamer Based Method for Detection of SARS-CoV-2 Nucleocapsid Protein. Virologica sinica 35: 351-154):
As cited for the rejection of claim 1 above, Song et al 2020 and Yu et al 2020 teach the discovery and use of SARS-CoV-2-specific DNA aptamers in “a low cost lateral flow aptamer assay… using nanogold particles as visualization probes” (Yu et al 2020);
Chen et al 2020 discloses a method for evaluating the suitability of DNA aptamers, including the use of “5’ biotinylated aptamer 1 and its derivatives” for the “detection of SARS-CoV-2… protein” (p. 352) by LFA.
Thus, a PHOSITA would, at or even before the effective filing date of claim 23, be able to adopt and combine the prior art by Song et al, Yu et al and Chen et al to develop a test kit similar to claim 23 with a reasonable success rate, especially when such assay is desirable for a timely diagnosis of SARS-CoV-2 infection.
5. Claim 25, which has all the limitations of claim 1, is rejected under USC §103 as being unpatentable over Song 2020 and Yu 2020 and further in view of Ilett et al 2020 (Application of automated electron microscopy imaging and machine learning to characterise and quantify nanoparticle dispersion in aqueous media. Journal of Microscopy, 279 (3): 177–184):
As set forth above for the rejection of claim 2, Song and Yu teach the use of DNA aptamers conjugated with AuNP for disease diagnosis or biomarker detection, including optical methods for quantification of signals in solutions, although they fall short of teaching machine learning procedures as instantly claimed;
Ilett et al 2020 (available online December 2019) taught that “machine learning using two free open-source software tools” enables “accurate nanoparticle agglomerate analysis of particles suspended in aqueous media containing other potential confounding components such as salts, vitamins and proteins” (p. 179).
The techniques disclosed by Ilett et al 2020 are sufficiently detailed enough that a PHOSITA would be able to combine these methods with the teaching by Song 2020 and Yu 2020 toward a diagnostic assay similar to the invention shown in claim 25, especially when the needs for reliable SARS-CoV-2 diagnosis are unmet.
6. Claim 28 and 30 are rejected under USC §103 as being unpatentable over Song et al June 2020 as set forth for claims 1 above and in view of Ranganathan et al 2020 (An aptamer-based colorimetric lateral flow assay for the detection of human epidermal growth factor receptor 2 (HER2). Analytical Biochemistry 588: 113471):
As set forth above for claim 1 and claim 25, Song et al 2020 found that, after optimization for hairpin structures, two of their “DNA aptamers targeting the receptor-binding domain of the SARS-CoV-2 spike glycoprotein” have sensitivity levels at 5.8 nM and 19.9 nM, respectively, being slightly better than the values cited in claim 28 (20 nM) and claim 30 (20 nM), although their experimental conditions did not explicitly cite wavelength for measuring target signal’s optical density (OD);
Ranganathan et al 2020 (available in October 2019), on the other hand, presented “an aptamer-based colorimetric lateral flow assay” in which two sets of OD signals were measured at the wavelength of “620 nm” and “525 nm”, respectively, before plotting the numbers against target concentrations (Fig. 1) to establish “calibration curves.”
In light of the teaching by Song et al. 2020 and Ranganathan et al 2020, a PHOSITA would be able to properly calibrate an aptamer-based LFA for optimal outputs -- using known procedures to achieve expected results.
7. Claim 32 is rejected under USC §103 as unpatentable over all the limitations for claim 23 and further in view of Choi et al 2014 (Real-time measurement of human salivary cortisol for the assessment of psychological stress using a smart phone. Sensing and Bio-sensing Research 2: 8-11) and Justino et al 2017 (Effect of saliva collection methods and oral hygiene on salivary biomarkers. Scandinavian Journal of Clinical and Laboratory Investigation 77: 415-422):
Choi et al 2014 established that detection of biomarkers in human saliva using “lateral flow immune strip” can yield desirable output when “saliva sample’s viscosity was decreased… in a dilution buffer” (p. 11), although they did not evaluate the effects of mouthwash on assay results;
Justino et al 2017 noted that “oral hygiene decreased salivary flow” and cautioned the “effect of saliva collection methods and oral hygiene on salivary biomarkers” (p. 415).
The teaching by Choi et al 2014 and Ranganathan et al 2017 would sufficiently enable a PHOSITA to properly calibrate an aptamer-based LFA (as taught by Song et al 2020 and Yu et al 2020) for optimal outputs, because saliva samples are readily available bodily fluids that are broadly used for the detection of biomarker or infection – another example of using known procedures to achieve expected results.
8. Claims 40 and 41 are rejected under USC §103 as being unpatentable over Song et al 2020 and Yu et al 2020 and in further view of aforementioned Ranganathan et al 2020 :
As set forth above for claim 1, Song et al 2020 and Yu et al 2020 jointly teach the use of DNA aptamers conjugated with AuNP for disease diagnosis or biomarker detection, although they did not specify materials required for LFA;
Ranganathan et al 2020, on the other hand, cites the use of “cationic charged PDDA polymer at the control zone” for LFA (Scheme 2), and they further defined control zone (p. 6) and test zone (p. 2) required for LFA (Fig. 5).
Based on the teaching by Song et al. 2020, Yu et al 2020 and Ranganathan et al 2020, a PHOSITA would be able to combine the specific methods to design a diagnostic device similar to the invention in claims 40 and 41, for the purpose of diagnosing SARS-CoV-2 infection.
Conclusion
No claim is allowed.
Additional Prior Art Cited but Not Applied
In addition to the prior art cited above and provided on Form 892, the following non-patent literature has been deemed as relevant to the instant application:
Dalirirad and Steckl 2019 (Aptamer-based lateral flow assay for point of care cortisol detection in sweat. Sensors and Actuators B: Chemical 283: 79-86): these authors use “aptamer-conjugated AuNPs” a “strip biosensor for the detection of cortisol in sweat (and other biofluids).”
Mirkin et al 2003 (patent application published as US 2003/0087242 A1): these inventors disclose the preparation of two single-stranded DNA linkers (16 nucleotides each) (Figure 1) “attached to nanoparticles” and the use of “oligonucleotides attached to the gold nanoparticles” (Abstract).
Mak et al. 2016 (Lateral-flow technology: From visual to instrumental. Trends in Analytical Chemistry 79: 297-305): these investigators reviewed the history and technical details of lateral flow assays.
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/JANET L ANDRES/Supervisory Patent Examiner, Art Unit 1671