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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 2/24/2026 is acknowledged.
Claim Objections
Claims 5 and 21 are objected to because of the following informalities: there is a typographical error in line 4 of the claim where the roman numeral three is typed as “Ill.” Appropriate correction is required.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/106980, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional application does not provide support for:
wherein the virus is human adenovirus (HAdV) or herpes simplex virus (HSV) or
wherein the isothermal amplification is warm-start LAMP or RT-LAMP.
Claims which recite any of these elements are entitled the prior art date of the international application, 10/28/2021.
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.
Claims 1, 2, 5-8, 13-17, and 21-30 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.
The phrase “nucleic acids-based masking construct” indefinite because this is not a term of art and its meaning is not defined in the specification. It is not clear what it means to be “nucleic acids based”- it is not clear how this differs from being a nucleic acid or what the scope of this phrase is, and it is not clear what the construct is “masking” or what it means to be a “masking” construct. The term is used throughout the disclosure, and an example of a “quenched fluorescent nucleic acids probe” is given, but the metes and bounds of the term and what else may or may not be encompassed is unclear, and thus the claims are all indefinite for this recitation.
Regarding claims 6 and 22, it is unclear how the recited amplification choices are related to the recited Cas effector since there is no conjunction between the elements within (a) or the elements within (b).
Regarding claims 8, 17, 25, 26, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 14 and 29, the phrase “warm-start” is indefinite because “warm” is a matter of opinion or a relative term and no basis for determining what is “warm” versus “hot” or “cold” is given in the disclosure.
In claims 14, 15, and 29, The phrase “RT-LAMP” is indefinite because it is not clear if “RT” here means reverse transcriptase or real time, both of which are common meanings for RT in the art.
Regarding claim 15, it is unclear how the recited amplification choices are related to the recited Cas effector since there is no conjunction between the elements within (a) or the elements within (b).
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.
Claim(s) 8, 14, 15, 26, and 29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ding et al. (Biosensors and Bioelectronics 184 (2021) 113218; 27 pages).
Ding teaches forming a mixture comprising sample nucleic acids, isothermal amplification reagents for amplifying one or more target nucleic acid sequences, Cas12a, a guide polynucleotide designed to form a complex with Cas12a, and a nucleic acids-based masking construct comprising a non-target sequence (see at least figure 1(a) where the masking agent is called ssDNA-FQ, the guide polynucleotide is crRNA).
Ding teaches partitioning the mixture into a plurality of compartments (see Figure 1A).
Ding teaches incubating the partitioned mixture at a temperature for isothermal amplification and Cas effector cleavage of an amplified DNA strand, wherein the Cas effector exhibits collateral nuclease activity and cleaves the non-target sequence of the nucleic acid based masking construct once activated by the target sequences (See Figure 1B).
Ding teaches detecting signal from cleavage of the non-target sequence, thereby detecting the one or more target sequences in the sample (See Figure 1A and B), and
Ding teaches determining the copy number of the target nucleic acid based on a Poisson distribution of the proportion of positive to negative compartments (See p. 5, 1st column and Fig. S10).
Ding teaches that the positive compartments indicate the presence of SARS-CoV-2 (i.e. disease) in a subject. Ding teaches comparing the quantity of virus to a control, see. 3, 2nd column and Figure 2.
With regard to claim 8, the masking construct comprises a quenched fluorescent nucleic acid probe (Figure 1).
With regard to claims 14 and 29, the assay employs warm-start LAMP and an RT-LAMP, see section 3.2 noting that DAMP is a species of LAMP.
With regard to claims 15 and 26, the target nucleic acids are SARS-CoV-2, see title and throughout.
This reference is available as prior art because the rejected claims are not entitled to benefit of priority to the provisional application.
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.
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(s) 1, 2, 5-8, 13-14, 16, 17, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (ACS Synth. Biol. 2019, 8, 2228−2237) in view of Ronaldo et al. (Anal. Chem. 2019, 91, 1034−1042).
Li teaches forming a mixture comprising sample nucleic acids, isothermal amplification reagents for amplifying one or more target nucleic acid sequences, Cas12b, a guide polynucleotide designed to form a complex with Cas12b, and a nucleic acids-based masking construct comprising a non-target sequence (p. 2236, first column where the masking agent is called “fluorescent probe”, the guide polynucleotide is sgRNA).
Regarding claims 2 and 17, the Cas effector is 12b.
Li teaches incubating the mixture at a temperature for isothermal amplification and Cas effector cleavage of an amplified DNA strand, wherein the Cas effector exhibits collateral nuclease activity and cleaves the non-target sequence of the nucleic acid-based masking construct once activated by the target sequences (See p. 2236, first column and also p. 2232 and Figure 2).
Regarding claims 5, 6, 21, 22 the amplification is loop-mediated isothermal amplification and the Cas effector is Cas12b (p. 2231).
Regarding claims 7 and 23 and 24, the masking construct suppresses generation of a detectable positive signal until cleaved (see p. 2235, 2nd column).
Regarding claim 13, Li teaches guide RNA with mismatches relative to target and still provided detection, depending on the length of the sgRNA (p. 2231).
Regarding claims 14 and 29, Li teaches warm-start LAMP (p. 2235).
With regard to claim 25, Li teaches both DNA and RNA targets.
With regard to claim 26, the claim further defines “virus DNA” which was not required in claim 25, and remains optional in claim 26 so the teachings of Li address this claim since the limitations are not clearly required but defined as part of a “such as” clause.
Li teaches detecting signal from cleavage of the non-target sequence, thereby detecting the one or more target sequences in the sample (See Figure 2).
Regarding claim 16 and dependents, Li teaches generating curves for different control, known amounts of target and then generating a standard curve for quantifying target, thus, teaches comparing to a control. Li teaches that the one-step system is convenient for target detection, including point of care testing, demonstrating the LAMP plus cas12b system for the detection of viral disease targets.
Li does not teach partitioning the mixture into a plurality of compartments, and determining the copy number of the target nucleic acid based on a Poisson distribution of the proportion of positive to negative compartments.
Rolando teaches real-time digital LAMP and teaches that the approach can be adapted to quickly study and optimize assays using precise, real-time digital quantification, accelerating development of critically needed diagnostics. In the method taught by Rolando, reaction mixtures containing reagents for LAMP are loaded into individual wells of a chip and incubated for amplification (See Figure 1; p. 1036, 2nd column). The reference teaches determining the concentration of the target nucleic acid based on a Poisson distribution of the proportion of positive to negative compartments, and which is determining the copies per uL (p. 1038, 1st and 2nd column). Rolando teaches that using “digital” approaches provide absolute quantification with high resolution, and that digital isothermal approaches have been used to quantify viral load for HCV, HIV, influenza (p. 1035, 1st column). Rolando also teaches comparing the sample signal to a negative control (see figure 2f, for example).
Regarding claims 8 and 28, Rolando teaches that the mixture is partitioned into about 18,000 partitions (p. 1036, 2nd column).
With regard to claim 27, the chip taught by Rolando is considered a “microfluidic” chip (p. 1036, 2nd column).
Regarding claim 29, the detection occurs in real-time, so the lamp is RT-LAMP, where RT stands for real-time (p. 1036, 2nd column).
Therefore, it would have been obvious before the effective date to have modified the method taught by Li et al so as to have partitioned the mixture into a plurality of compartments and to have quantified the target using a Poisson distribution, as taught by Rolando. One would have been motivated to do so to take advantage of the digital nature of the method taught by Rolando, including the ability to quantify a desired target. Regarding claims 16 and7, it would have been obvious to use the digital method to detect the presence of a viral disease in the subject as suggested by both Li and Rolando in order to provide diagnostic information for a virus such as the encephalitis virus taught by Li or the HCV, HIV, or influenza mentioned by Rolando. Furthermore, upon determining that a patient has a virus such as one causing encephalitis or HCV or HIV or influenza, it would have been obvious to one having ordinary skill in the art to administer an appropriate treatment to the subject based on the severity of the disease of the subject, as was well established in the medical arts at the time of the invention. The examiner takes Official notice that treatment of disease appropriate to severity was routine in the medical field before the effective filing date.
Claim(s) 15 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Rolando as applied to claims 1, 2, 5-8, 13-14, 16, 17, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30 above, and further in view of Augustine et al. (Biology 2020, 9(8), 182; https://doi.org/10.3390/biology9080182; 17 pages).
The teachings of Li in view of Rolando as they apply to claims 1 and 16 and 26, from which claims 15 and 26 depend are given previously in this Office action and are fully incorporated here.
Neither Li nor Rolando teach a method wherein the target for amplification is SARS-CoV-2.
Augustine teaches that due to the global pandemic the development of tests for the detection of SARS-CoV-2 is essential, and teaches that LAMP is one technique that is being used for the detection of the virus. (Abstract and throughout).
Therefore, it would have been obvious to have modified the method taught by Li in view of Rolando by using it to detect SARS-CoV-2. As both references teach methods for detection of targets, and both suggest the appropriateness of the methods for viral targets in particular, one would have been motivated to use one-step test taught by Li in view of Rolando for the detection of SARS-CoV-2 in order to provide a test for detecting and quantifying infection of the global pandemic causing agent.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Ding 2020 teaches a one-pot isothermal detection assay that employs recombinase polymerase amplification followed by detection via collateral cleavage of a probe by Cas12a.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682