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 .
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-13 and 20 in the reply filed on 3/21/2026 is acknowledged.
Claims 14-19 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 3/21/2026.
Priority
The instant application was filed 08/13/2024 and claims priority from provisional application 63532606 , filed 08/14/2023.
Claim Objections
Claims 1-13 and 20 are objected to because of the following informalities:
Claim 1 recites, “the indicator.” The claim previously recite, “indicator molecule.” Claims are clearer and more concise when they use the same terminology throughout. The claims should be amended to provide the same language throughout.
Claim 7 recites, “the indicators.” The claim depends from claim 1 which recites, “indicator molecule” and “indicator.” Claims are clearer and more concise when the claim provides limitations as singular or plural. The claims should be amended to provide either indicator, indicator molecule or indicators.
Appropriate correction is required.
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.
Claims 10-13 and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a mental step or abstract idea without significantly more. The claim(s) recite(s) the abstract idea or mental step of analyzing the change information to detect the target and/or analyzing the change information to detect the targe. These judicial exception are not integrated into a practical application because if there is no steps depend from or otherwise integrate the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no specific steps or reagents which would provide for significantly more.
Claim analysis
The instant claim 10 is directed method for detecting the presence of a target molecule of interest in a sample, comprising the steps of: (a) providing the sample to a chamber; (b) performing the method of claim 1 on the sample by providing at least a first indicator by (1) allowing the indicator to bind specifically to a first region of a target; (2) exciting the indicator to emit a detectable signal; and (3) reporting a change that is detected in a pixel or group of pixels within an array of the TCPA; and (c) analyzing the change information to detect the target; thereby detecting the presence of the target in the sample. The analyzing the change information to detect the target is a mental step or abstract idea.
Claim 11 requires, “method for detecting the presence of a target molecule of interest having a plurality of regions in a sample, comprising the steps of: (a) providing the sample to a chamber; (b) performing the method of claim 1 on the sample by providing at least a first indicator by (1) allowing the indicator to bind specifically to a first region of a target; and providing at least a second indicator that can bind to the first region but having a different binding moiety and a different detectable moiety; (2) exciting the indicator to emit a detectable signal; and (3) reporting a change that is detected in a pixel or group of pixels within an array of the TCPA; (4) removing the detectable moiety while continuing to block another binding moiety from binding to the same region of the target; (c) performing step (b) with a different region of a target; and (d) analyzing the change information to detect the target.” The analyzing the change information to detect the target is a mental step or abstract idea.
Claim 20 is drawn to A computer-performable method for using an artificial intelligence system to sequence a target nucleic acid, comprising the steps of (a) training the system with target nucleic acids of known sequence, primary sequence features, methylation or other epigenetic modifications, or secondary structures in order to obtain a model; and (b) performing the method of claim 12 on a target nucleic acid, wherein the detected changes are characterized by the training model obtained in step (a). The detected changes are characterized by the training model obtained in step (a) is a mental step or abstract idea.
Claim 10 steps (a)-(b) (1), (2), and (3) can be considered positive active steps.
Claim 11 steps (a)-(b) (1), (2), (3), (4) (c) can be considered positive active steps.
Claims 11-13 and 20 depend directly or indirectly from claim 11 and thus have the same active
Dependent claims set forth further limitations to about the sample and outcome of data analysis.
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, abstract idea or mental step.
Claims 10-11 require analyzing the change information to detect the target is a mental step or abstract idea.
Claim 20 depends from claim 11 via claim 12 and requires detected changes are characterized by the training model obtained in step (a) is a mental step or abstract idea. This is also a mental step
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as there are no steps which specifically depend from or otherwise integrate the judicial exceptions.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No, the steps provide no limitations which are specific and provide for significantly more.
The active steps of the claims are routine and conventional over the teachings of over Eid ((Science (2009) volume 323, pages 133-138), Bhan (J. Am. Chem. Soc. 2021, 143, 16630−16640), and Wang (US 20140263961 A1)
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-13 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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.
As set forth in In re Alonso 88 USPQ2d 1849 (Fed. Cir. 2008), at 1851:
The written description requirement of 35 U.S.C. § 112, ¶ 1, is straightforward: “The specification shall contain a written description of the invention ….” To satisfy this requirement, the specification must describe the invention in sufficient detail so “that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date sought.” Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997); see also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 [76 USPQ2d 1724] (Fed. Cir. 2005); Eiselstein v. Frank, 52 F.3d 1035, 1039 [34 USPQ2d 1467] (Fed. Cir. 1995).
Alonso at 1852:
A genus can be described by disclosing: (1) a representative number of species in that genus; or (2) its “relevant identifying characteristics,” such as “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo, 323 F.3d at 964.
In applying the test as set forth in Alonso, it is noted that applicant is claiming Independent claim 1 is drawn to a method for using a temporal contrast pixel array (TCPA) to detect a change in the emission of an indicator molecule that is bound to a target molecule of interest, wherein the indicator comprises detectable moiety and a binding moiety that is capable of binding specifically to a region of the target.
Thus the claim encompass anything which can be considered a temporal contrast pixel array. This is an enormous genus as the specification provides no definition or standard what is required of a TCPA.
Further the claims encompass anything which can be considered target molecule. This is enormous genus as the specification does provide a limiting definition or standard of what is encompassed by a target molecule. Filser (Horizons, The Swiss Research Magazine, 6/9/2018) pages 1-) teaches, “His original ‘Generated Data Base’, GDB-11, held 26.4 million molecules. GDB-17 has 166 billion entries and is unsurprisingly the world’s biggest database for small molecules.” Thus this encompasses an enormous genus.
The claims encompass any indicator molecule which can bind by any means to the target molecule and comprises anything which can be considered a detectable moiety. This is an enormous genus as the specification provides no definition or standard what is required of an indicator molecule or binding or detectable moiety.
The teachings of the specification in view of the title appear to be limited to the detection of nucleic acids. Thus the specification and claims do not provide a representative number of species or structures and relevant characteristics to provide adequate written description for the genus encompassed by the claims.
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 1-13 and 20 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 1 is also indefinite because the claims do not recite the basic steps of the claimed invention in a positive, active fashion (see Ex parte Erlich 3 USPQ2d, 1011). The claim describes a method for using a temporal contrast pixel array (TCPA), but the claim fails to recite any actual steps that define the method. The limitation that the procedure " to detect a change in the emission of an indicator molecule that is bound to a target molecule of interest " is not considered to meet the requirement of a positive process step because no guidance is given as to how to detect a change in the emission of an indicator molecule. Further the specification and claims do not define or provide a standard of what is required of a temporal contrast pixel array (TCPA). Thus the metes and bounds are unclear.
Claim 1 recites, “binding specifically to a target region of the target.” The recitation of binding specifically to a region of the target suggests there is binding non-specifically to a region of the target. The specification does not provide a definition or standard to differentiate binding specifically to a region of the target from binding non-specifically to a target region of the target. Thus the metes and bounds are unclear.
Claim 2 recites, “the first, second, or higher order.” The claim does not previously recite the first, second, or higher order or depend from a claim which provides antecedent basis for the limitation. Thus the metes and bounds are unclear what the recitation is referencing. The rejection can be overcome by amending the claim to have antecedent basis for the limitation or switching the indefinite article to a definite article,
Claim 5 recites, “ wherein step (b).” The metes and bounds are unclear as neither claim 1 or claim 5 provide a step (b). This rejection maybe overcome by amending the independent claim1 to provide active steps including a step (b) which can be performed on a plurality of targets asynchronously.
Claim 8 recites, “wherein the target comprises a plurality of regions, and the regions represent positions of data, whereby the target can be used for data storage and retrieval.” The metes and bounds are unclear as it is unclear what is require of positions of data. Further it is unclear how the target can be used for data storage and retrieval.
Claim 9 recites, “whereby the binding constant of two molecules is determined, wherein one of the molecules is selected from the group consisting of a nucleotide, a polynucleotide, an antibody, a Fab, an aptamer, a fatty acid, a lipid, a carbohydrate sugar, a lectin, and a hormone, or a derivative or an analog thereof.” Claim 9 nor claim 1 from which it depends “binding constant.” Thus the metes and bounds are unclear to what binding the constant is referencing. This rejection can be overcome by providing antecedent basis for this limitation.
Claim 10 recites, “(1) allowing the indicator to bind specifically to a first region of a target;.” The recitation of binding specifically to a region of the target suggests there is binding non-specifically to a region of the target. The specification does not provide a definition or standard to differentiate binding specifically to a region of the target from binding non-specifically to a target region of the target. Thus the metes and bounds are unclear.
Claim 10 recites, “the change information.” Neither claim 10 nor claim 1 from which it depends do not previously recite, “change information.” Thus the metes and bounds are unclear which change information the recitation is referencing.
Claim 11 recites, “(1) allowing the indicator to bind specifically to a first region of a target;.” The recitation of binding specifically to a region of the target suggests there is binding non-specifically to a region of the target. The specification does not provide a definition or standard to differentiate binding specifically to a region of the target from binding non-specifically to a target region of the target. Thus the metes and bounds are unclear.
Claim 11 recites, “(d) analyzing the change information to detect the target.” The claim does not previously recite, “change information.” Thus it is unclear what change information the claim is referencing. Further it is unclear how analyzing the change information is done to allow for detection of target.
Claim 11 recites, “removing the detectable moiety while continuing to block another binding moiety from binding to the same region of the target.” However claim 11 previously recites, “providing at least a second indicator that can bind to the first region but having a different binding moiety and a different detectable moiety.” Thus the claim appears to require at least 2 different detectable moieties. It is unclear which detectable moiety is being removed in step (4).
Claim 12 recites, “method for sequencing a nucleic acid in real time comprising performing the method of claim 11 on unamplified target nucleic acids to detect a nucleotide sequence.” The metes and bounds are unclear how performing the steps of claim 11 which is to detecting a target nucleic acid molecule. Amending the claim to provide steps which would allow for sequencing would address this rejection.
Claim 13 recites, “wherein the detected changes further indicate primary sequence features, methylation or other epigenetic modifications, or secondary structures.” The recitation is confusing and unclear as it is unclear how the detected changes indicate primary sequence features, methylation or other epigenetic modifications, or secondary structures as the claim provides no specific steps.
Claim 20 recites, “A computer-performable method for using an artificial intelligence system to sequence a target nucleic acid, comprising the steps of (a) training the system with target nucleic acids of known sequence, primary sequence features, methylation or other epigenetic modifications, or secondary structures in order to obtain a model; and (b) performing the method of claim 12 on a target nucleic acid, wherein the detected changes are characterized by the training model obtained in step (a).” The metes and bounds of the claim are unclear as the claim is to a computer performable method, then requires , “and (b) performing the method of claim 12 on a target nucleic acid, wherein the detected changes are characterized by the training model obtained in step (a),” which appears to require the steps of claim 11, which do not appear to be computer-performable. Further step (a) appears to be vague , unclear and incomplete how the training is performed.
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.
Claim(s) 1-13, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Eid ((Science (2009) volume 323, pages 133-138), Bhan (J. Am. Chem. Soc. 2021, 143, 16630−16640), and Wang (US 20140263961 A1)
The claims are encompass detection nucleic acids by temporal contrast pixel array. The specification does not provide a definition or standard of what is required of temporal contrast pixel array. The art of record exemplifies use of temporal detection of nucleic acid sequences by pixel analysis was known, as exemplified below. Further the art exemplifies An imaging device has an array with pixels that can image an aspect of an object. In addition, pixels in the array can be used to perform motion detection or edge detection. A first and a second pixel can integrate light non-concurrently, and then their outputs may be compared. A difference in their outputs may indicate an edge in an imaging operation, and motion in a motion detection operation. The motion detection operation may be performed without needing the imaging device to have an additional modulated LED light source, and to spend the power to drive that source.
With regards to claim 1, 10-13 Eid teaches real time sequencing of single polymerase molecules (title)
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Bhan teaches, “we introduce TdT-based Untemplated Recording of Temporal Local Environmental Signals (TURTLES), a polymerase-based molecular recording system that achieves high time resolution in vitro by utilizing post-translational control to change the bases incorporated. First, we describe methods to characterize DNA sequences synthesized by TdT and show that cation concentrations can be encoded in populations of TdT-synthesized DNA using an approach that analyzes the average composition of several bases added at similar times on the same or parallel strands of DNA. We next developed an algorithm to accurately estimate the times of signal changes and show that temporal information can be accurately recovered by using estimates of DNA synthesis rates to map DNA sequences to real time. We also describe an expanded TURTLES system that uses an engineered, allosterically modulated TdT to expand the generalizability and tunability of the system. By inserting an exogenous sensing domain, we show that TURTLES can be adapted to the arbitrary signals of interest. When they are taken together, these results establish the feasibility of DNA synthesis-based encoding systems and demonstrate a recording of cationic environmental signals with minutes resolution for enhanced applications in DNA data storage and DNA recording.” (16631, bottom 1st column-top 2nd column).
Wang teaches, “[0008] In one embodiment, an imaging device has an array with pixels that can image an aspect of an object. In addition, pixels in the array can be used to perform motion detection or edge detection. A first and a second pixel can integrate light non-concurrently, and then their outputs may be compared. A difference in their outputs may indicate an edge in an imaging operation, and motion in a motion detection operation. [0009] An advantage over the prior art is that the motion detection operation may be performed without needing the imaging device to have an additional modulated LED light source, and to spend the power to drive that source. Moreover, motion detection may be performed in a single frame, which does not tax the frame rate.”
Thus it would have been prima facie obvious to one of ordinary skill in the art to use incorporation of nucleotides as indicators for specifically detecting nucleic acid sequences. The artisan would be motivated as Eid teaches it allows for real time sequencing. The artisan would further be motivated as Bhan teaches, “DNA is an attractive medium for both long-term data storage and for in vitro recording of molecular events due to its high information density and long-term stability. Molecular recording strategies write information into DNA by altering existing DNA sequences5 or adding new sequences. “ The artisan would have a reasonable expectation of success as the artisan is merely using known technology.
With regards to claim 2, Eid teaches the detection of intensity (Fig 1 and Fig 2)
With regards to claim 3, Eid teaches the use of waveguide nanostructure arrays (133, abstract) Eid teaches “For the observation of incorporation events, we used a nanophotonic structure, the zero-mode waveguide (ZMW), which can reduce the volume of observation by more than three orders of magnitude relative to confocal fluorescence microscopy (20). This level of confinement enables single-fluorophore detection despite the relatively high labeled dNTP concentrations—between 0.1 and 10 mM—required by DNA polymerase for fast, accurate, and processive synthesis. This range produces average molecular occupancies between ~0.01 and 1 molecules for a ZMW 100 nm in diameter (20, 23), compared with ~3 to 300 molecules for total internal reflection microscopy.”
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims that waveguides use evanescent fields. The artisan would be motivated to use waveguides using evanescent fields as Eid teaches, “This range produces average molecular occupancies between ~0.01 and 1 molecules for a ZMW 100 nm in diameter (20, 23), compared with ~3 to 300 molecules for total internal reflection microscopy.” The artisan would have a reasonable expectation of success as the artisan is merely using known correlation.
With regards to claim 4, Eid and Bhan teach a nucleic acid is the target (titles, figures)
Claim 5 is indefinite as there is no step (b) of the independent claim. Thus claim 5 appears to be at least obvious over the instant claim.
With regards to claim 6, Eid teaches real time. (tile)
With regards to claim 7, Eid teaches, “The average DNA synthesis rate for 740 single-molecule reads was 4.7 T 1.7 bases/s.” Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims incorporation of nucleotides at the recited rate would require a continuous flow of indicators to allow for incorporation.
With regards to claim 8, Bhan teaches, “DNA is an attractive medium for both long-term data storage and for in vitro recording of molecular events due to its high information density and long-term stability. Molecular recording strategies write information into DNA by altering existing DNA sequences or adding new sequences (16630, 1st paragraph, 1st column).
With regards to claim 9, Bhan and Eid teach incorporation of nucleotides.
Bhan teaches, “In Silico Simulations of Recording Faster and Higher Numbers of Input Signal Changes. Using the average dNTP incorporation rate from experiments, and the amount of output signal in the control conditions, we simulated additional experiments in silico. Each simulated experiment had at least 6 signal changes (instances of a single signal change from 0 → 1 or 1 → 0), where each condition was randomly chosen to be 0 or 1. All nucleotides that were added during the 0 or 1 condition had the signal associated with these control conditions. More specifically, to account for the experimental variability in signals within a given control condition, nucleotide signals were sampled from a normal distribution determined by the experimental variability of nucleotide signals within the control conditions. We calculated the variability in two ways, corresponding to the two representative curves in Figure S12A,C. In the first, the variability was calculated across the first 100 nucleotides, in which there were at least 2000 recordings of all base numbers. In the second, the variability was calculated across the first 50 nucleotides, in which there were at least 60000 recordings of all base numbers. Using the output signal of the simulated nucleotides, we used the algorithm we developed from Glaser et al. for decoding binary concentrations.13 The accuracy corresponds to the percentage of conditions correctly classified as 0 or 1 over the duration of the entire recording experiment.” It is routine to use computers to store and analyze large data sets by use an algorithm to further examine feature of the data obtained.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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