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
Election Restrictions
1. Applicant’s election without traverse of Group I and species (RNA; Reverse Transcriptase; Protoscript II Reverse Transcriptase; SARS-CoV-2; saliva) in the reply filed on 12/16/2025 is acknowledged.
Claims 35, 47, 54, 55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/16/2025.
Claims 1-5, 8, 10, 11, 13, 16, 18, 19, 24, 26-29 are under consideration.
Information Disclosure Statement
2. The information disclosure statements (IDS) were submitted on 10/5/2022; 11/28/2023; 5/22/2024; 9/3/2024; 5/9/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
3. The drawings are objected to because: Figure 2 recites “red” and “colored regions”.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
4. Claim 19 is objected to because of the following informalities:
For consistency with the other claims, claim 19 should recite a comma after reciting dependency (“The method of claim 1, further comprising …”).
Appropriate correction is required.
Claim Rejections - 35 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.
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.
5. Claims 1-5, 8, 10, 11, 13, 16, 18, 19, 24, 26-29 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.
See claims 1-5, 8, 10, 11, 13, 16, 18, 19, 24, 26-29 as submitted 11/27/2023.
As to claim 1, the claim recites “a target at least partially single-stranded viral genome”. It is not clear what the recitation means, such as if the claim intends to recite “a target comprising at least a partially single-stranded viral genome” or “a target of at least a partially single-stranded viral genome” or similar.
Further as to claim 5, the elected embodiment of “Protoscript II Reverse Transcriptase” recites a trademark, which is indefinite (See MPEP 2173.05(u): If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parteSimpson, 218 USPQ 1020 (Bd. App. 1982). See also Eli Lilly & Co. v. Apotex, Inc., 837 Fed. Appx. 780, 784-85, 2020 USPQ2d 11531 (Fed. Cir. 2020)).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
6. Claim 19 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
See claim 19 as submitted 11/27/2023.
The instant claim is drawn to a method of detecting a target comprising providing sample, providing an oligonucleotide molecule complementary to a selected portion, contacting the sample with the oligonucleotide molecule, contacting hybridization product with polymerase and dNTP mixture, subjecting mixture to conditions in which hybridization product is extended, producing adenosine triphosphates, metabolizing the adenosine triphosphates, and quantifying readout signal, which is a statutory category of invention (Step 1: YES).
The instant claim is directed to a method of detection, further reciting a quantifying step, which also reads on mathematical calculations or mental processes, or abstract ideas. As such, the instant claims recite judicial exceptions (JE) in the form of an abstract idea (Step 2A, Prong One: YES).
The crux of the instant claim is the quantification of the readout signal from the method of detection. The instant claims do not recite any particular treatment or prophylaxis. As such, the instant claim does not recite additional elements that integrate the JE into a practical application (Step 2A, Prong Two: NO).
As discussed in detail below, it was well-understood, routine, and conventional at the time of filing to detect viral nucleic acid in a sample. Further, the claim does not recite additional elements that amount to significantly more than the judicial exception. As such, the instant claims do not recite significantly more than the JE (Step 2B: NO).
Accordingly, the instant claim does not constitute patent eligible subject matter under 35
U.S.C § 101.
Claim Rejections - 35 USC § 103
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 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.
7. Claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Eckert et al. (US20120003661)(See PTO-892: Notice of References Cited) in view of Gandelman et al. (“Novel Bioluminescent Quantitative Detection of Nucleic Acid Amplification in Real-Time,” PLoS One, Vol.5, Issue 11; e14155: 1-13)(2010))(cited in applicant’s IDS submitted 10/5/2022).
See claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 as submitted 11/27/2023.
See also the 35 U.S.C. 112(b) rejection above.
Eckert et al. teaches: methods for rapid and specific detection of target microorganisms (abstract)(as recited in claim 1); including viruses [0040](as recited in claim 1); wherein enzyme is provided on solid support [0011](as recited in claims 8, 11); saliva sample [0013](as recited in claims 1, 27)(interpreted as the providing a sample step as recited in claim 1); bioluminescent assay for real time (BART)[0099]; wherein PPi produced during amplification is converted to ATP by the action of ATP sulphurylase [0099](as recited in claim 16); this ATP is then used in a reaction by luciferase and luciferin to produce a light output permitting real time analysis of amplification kinetics (as recited in claim 10); a unique feature of BART is an initial burst of light; this light peak is a function of the amount of target (nucleic acid) in the sample [0099].
Eckert et al. does not teach: partially single-stranded viral genome; RNA; method steps (as recited in claim 1).
Gandelman et al. teaches: RT-LAMP-BART for the detection of CSFV (p. 9); CSFV as detection target (p. 9)(single stranded RNA virus as recited in claims 1, 3); use of reverse transcription, LAMP amplification and BART detection reagents (p. 9); reverse transcriptase (p. 11)(as recited in claim 4); pGEM construct containing DNA fragments complementary to CSFV RNA (p. 12); wherein sequences of the CSFV target and five oligonucleotides including two LAMP, two loop and one displacing primer designed against the sequence are shown in Table 4 (p. 12)(interpreted as “providing an oligonucleotide molecule complementary to a selected portion of the target at least partially single-stranded viral genome adjacent to a single-stranded template region of the target at least partially single-stranded viral genome” as recited in claim 1); RNA was in vitro transcribed from the pGEM construct using AmpliScribe T7 High Yield Transcription Kit (p. 12) interpreted as “contacting the sample with the oligonucleotide molecule so that the oligonucleotide molecule hybridizes to the selected portion of the target at least partially single-stranded viral genome and forms a hybridization product comprising a double-stranded nucleic acid start portion in the viral genome at a location corresponding to the selected portion and the single-stranded template region is adjacent to the double-stranded nucleic acid start portion” as recited in claim 1); RT-LAMP-BART reagent contained displacing primer, loop primer, LAMP primer, dNTP, DNA polymerase large fragment, reverse transcriptase, ATP sulfurylase (p. 13); BART reactions were run in 20µl total volume containing 15µl reagent mix with added template solution (p. 13)(interpreted as “contacting the hybridization product with a polymerase and a dNTP mixture to form a polymerase extension mixture and subjecting the polymerase extension mixture to conditions under which the hybridization product from the double-stranded nucleic acid start portion is extended by addition of nucleotides complementary to the single-stranded template region” as recited in claim 1).
Gandelman et al. also teaches: designing LAMP primers complementary sequence and assayed using a template; reactions were conducted in a closed one-tube format that contained all enzymes and reagents necessary for DNA amplification and ELIDA and incubated at 55 degrees C, suitable for annealing, DNA synthesis, conversion of PPi to ATP and light emission, as well as ATP sulfurylase and luciferase stability; such assays are preferred to as LAMP-BART assays (p. 2)(as recited in claim 1).
Gandelman et al. also teaches: PPi can be converted into ATP and quantitatively detected using firefly luciferase in ELIDA and in pyrosequencing; ELIDA is used to detect the instantaneous production of PPi as each single nucleotide base is added step-wise to a polynucleotide chain as it is synthesized base-by-base on a template molecule; for each position on the chain, addition of each of the four bases is attempted until successful addition is determined by PPi production, measured by light output through ELIDA” (p.2)(interpreted as “thereby releasing free phosphates” as recited in claim 1; as recited in claim 19); “during nucleic acid amplification, enzymatic conversion of PPi released during DNA synthesis into ATP is continuously monitored through the bioluminescence generated by thermostable firefly luciferase. The assay shows a unique kinetic signature for nucleic acid amplifications with a readily identifiable light output peak, whose timing is proportional to the concentration of original target nucleic acid. This allows qualitative and quantitative analysis of specific targets, and readily differentiates between negative and positive samples” (abstract)(considered to correlate with steps “producing adenosine triphosphates from the released free phosphates; and metabolizing the adenosine triphosphates produced from the free phosphates to produce a readout signal, indicating the presence of the target at least partially single-stranded viral genome in the sample” (p.1)(as recited in claims 1, 19); wherein reaction mixtures were covered with mineral oil to prevent evaporation (p. 11)(as recited in claim 28).
One of ordinary skill in the art would have been motivated to use method and detect target as taught by Gandelman et al. with the method as taught by Eckert et al. Eckert et al. teaches detection of virus and use of BART, and Gandelman et al. also teaches detection of virus, use of BART, and such a method of BART and target (See MPEP 2144.06: Substituting equivalents known for the same purpose).
As to claims 2, 24, 26, Gandelman et al. teaches wherein contamination with abundant quantities of dATP during amplification leads to high backgrounds, since dATP is an alternative substrate for firefly luciferase (p. 2); wherein high background in BART is due to high content of dATP (p. 5). In view of such teachings or suggestions, one of ordinary skill in the art would have been motivated to target uracil/thymine-free region (as recited in claim 2) and minimize presence of dATP (as recited in claims 24, 26) in order to reduce background and enhance sensitivity and efficiency of assay (See MPEP 2144.05: II. ROUTINE OPTIMIZATION: A.Optimization Within Prior Art Conditions or Through Routine Experimentation: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. [W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
One of ordinary skill in the art would have had a reasonable expectation of success for using method and detecting target as taught by Gandelman et al. with the method as taught by Eckert et al. There would have been a reasonable expectation of success given the underlying materials and methods (BART as taught by Eckert et al. and Gandelman et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
8. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Eckert et al. in view of Gandelman et al. as applied to claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 above, and further in view of Potapov et al. (“Base modifications affecting RNA polymerase and reverse transcriptase fidelity,” Nucleic Acids Research, Vol. 46, No. 11: 5753-5763 (2018))(See PTO-892: Notice of References Cited).
See claim 5 as submitted 11/27/2023.
See also the 35 U.S.C. 112(b) rejection above.
See the teachings of Eckert et al. in view of Gandelman et al. above.
Eckert et al. in view of Gandelman et al does not teach: wherein the reverse transcriptase is Protoscript® II Reverse Transcriptase (Protoscript II RT).
Potapov et al. teaches: RNA polymerases and reverse transcriptases (p. 5753); converting RNA to DNA by reverse transcriptases (p. 5753); using ProtoScript II kit (p. 5754); ProtoScript reverse transcriptase (p. 5756).
One of ordinary skill in the art would have been motivated to use reverse transcriptase as taught by Potapov et al. with the method as taught by Eckert et al. in view of Gandelman et al. Eckert et al. in view of Gandelman et al. teaches the use of reverse transcriptase, and Potapov et al., which also teaches the use of reverse transcriptase, teaches such a transcriptase known and used in the art (See MPEP 2144.06: Substituting equivalents known for the same purpose)
One of ordinary skill in the art would have had a reasonable expectation of success for using reverse transcriptase as taught by Potapov et al. with the method as taught by Eckert et al. in view of Gandelman et al. There would have been a reasonable expectation of success given the underlying materials (reverse transcriptase as taught by Potapov et al. and Eckert et al. in view of Gandelman et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
9. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Eckert et al. in view of Gandelman et al. as applied to claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 above, and further in view of Marques et al. (“A Nitric Oxide Quantitative Assay by a Glyceraldehyde 3-Phohsphate Dehydrogenase/Phosphoglycerate Kinase/Firefly Luciferase Optimized Coupled Bioluminescent Assay,” Analytic Method 6(11): 3741-3750 (2014))(cited in applicant’s IDS submitted 10/5/2022).
See claim 13 as submitted 11/27/2023.
See the teachings of Eckert et al. in view of Gandelman et al. above.
Eckert et al. in view of Gandelman et al. does not teach: wherein said producing adenosine triphosphates comprises: subjecting the released free phosphates to a coupled glyceraldehyde 3-phosphate dehydrogenase-phosphoglycerate kinase enzymatic reaction to produce adenosine triphosphate.
Marques et al. teaches: bioluminescent assay (title); wherein GADPH is a substrate for phosphoglycerate kinase to generate ATP, which is an essential cofactor for the firefly luciferase bioluminescent reaction (abstract).
One of ordinary skill in the art would have been motivated to use enzyme as taught by Marques et al. with the method as taught by Eckert et al. in view of Gandelman et al. Eckert et al. in view of Gandelman et al. teaches bioluminescent assay for generating ATP and producing a signal, and Marques et al., which also teaches bioluminescent assay for generating ATP and producing a signal, teaches such an enzyme for use in such processes (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using enzyme as taught by Marques et al. with the method as taught by Eckert et al. in view of Gandelman et al. There would have been a reasonable expectation of success given the underlying materials and methods (generating ATP in bioluminescent assays as taught by Marques et al. and Eckert et al. in view of Gandelman et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
10. Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Eckert et al. in view of Gandelman et al. as applied to claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 above, and further in view of Minekawa et al. (WO2005001097A1)(See PTO-892: Notice of References Cited)(See also the WIPO description of WO2005001097A1)(See PTO-892: Notice of References Cited) and Wu et al. (“A new coronavirus associated with human respiratory disease in China,” Nature, Vol. 579: 265-270 (2020))(See PTO-892: Notice of References Cited).
See claim 18 as submitted 11/27/2023.
See the teachings of Eckert et al. in view of Gandelman et al. above.
Eckert et al. in view of Gandelman et al does not teach: SARS-CoV-2.
Minekawa et al. teaches: detecting SARS coronavirus (title); using LAMP methods for amplification of SARS coronavirus-specific nucleotide sequence [0021]. Wu et al. teaches 2019-nCov (abstract)(also known as SARS-CoV-2).
One of ordinary skill in the art would have been motivated to detect SARS-CoV-2 as taught by Minekawa et al. and Wu et al. with the method as taught by Eckert et al. in view of Gandelman et al. Eckert et al. in view of Gandelman et al. teaches detection of virus using nucleic acid amplification methods, and Minekawa et al., which also teaches detection of virus using nucleic acid amplification methods, teaches SARS coronavirus, and Wu et al., further teaches such a known species of SARS coronavirus (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for detecting SARS-CoV-2 as taught by Minekawa et al. and Wu et al. with the method as taught by Eckert et al. in view of Gandelman et al. There would have been a reasonable expectation of success given the underlying materials and methods (detecting virus as taught by Minekawa et al. and Wu et al. and Eckert et al. in view of Gandelman et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
11. Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Eckert et al. in view of Gandelman et al. as applied to claims 1-4, 8, 10, 11, 16, 19, 24, 26-28 above, and further in view of Carlson et al. (US20190376131)(cited in applicant’s IDS submitted 10/5/2022).
See claim 29 as submitted 11/27/2023.
See the teachings of Eckert et al. in view of Gandelman et al. above.
Eckert et al. in view of Gandelman et al does not teach: wherein multiple oligonucleotide molecules are provided for hybridizing to different complementary portions of the target at least partially single-stranded viral genome adjacent to different single-stranded template regions of the target at least partially single-stranded viral genome.
Carlson et al. teaches: in vitro nucleic amplification and detection methods for detecting virus in samples (abstract); detecting hepatitis A virus (HAV, which is a single stranded RNA virus); including using multiple oligomers for amplifying viral target regions [0010]; including different combinations of amplification oligomers to serve as primers for different target regions in the HAV genome [0058].
One of ordinary skill in the art would have been motivated to use multiple oligonucleotide molecules as taught by Carlson et al. with the method as taught by Eckert et al. in view of Gandelman et al. Eckert et al. in view of Gandelman et al. teaches nucleic acid amplification and detection methods for detecting virus, including single stranded RNA virus, in samples, and Carlson et al., which also teaches nucleic acid amplification and detection methods for detecting virus, including single stranded RNA virus, in samples, teaches the advantage of using multiple oligomers for amplifying viral target regions for improved detection and effectiveness overall.
One of ordinary skill in the art would have had a reasonable expectation of success for multiple oligonucleotide molecules as taught by Carlson et al. with the method as taught by Eckert et al. in view of Gandelman et al. There would have been a reasonable expectation of success given the underlying materials and methods (nucleic acid amplification and detection methods as taught by Carlson et al. Eckert et al. in view of Gandelman et al.) and are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
12. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to M FRANCO G SALVOZA whose telephone number is (571)272-4468. The examiner can normally be reached M-F 8:00 to 5:00.
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/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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