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 1-11, 13-14, 16-19 and 21-22, in the reply filed on 03/31/2026 is acknowledged.
Claim 26 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-11, 13-14, 16-19, 21-22, and 26 are pending.
Claims 1-11, 13-14, 16-19 and 21-22 are under examination on the merits.
Priority
This application 18/566,369 filed on 12/01/2023 is a 371 national phase of PCT/ US2022/047600 filed on 10/24/2022, and claims the benefit of provisional U.S. Patent Application No. 63/277,043, filed on 11/08/2021.
The priority date of claim 1 and its dependent claims 2-11, 13-14, 16-19 and 21-22 is determined to be 11/08/2021, the filing date of provisional U.S. Patent Application No. 63/277,043.
Specification
The use of terms which are trade names or marks used in commerce (including IIlumina® has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it 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 Rejections - 35 USC § 112(b)
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 16 and 17 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 16 recites the limitation “wherein the electrodes are spaced apart from one another by about 100 nm or less”. The term about is indefinite in the context of “100 nm or less”. It is unclear what the bounds of spacing are required to be.
Claim 17 recites the limitation “wherein tips of the electrodes have widths of about 1 nm to about 100 nm”. The term about is indefinite. It is unclear what the lower and upper bounds of widths are required to be.
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 1-11, 13-14, 16-19 and 21-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 1 is directed to a method comprising “using the sequential alterations in the impedance to respectively identify the nucleotides”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the step encompasses the mental step of looking at a readout or report of sequential alterations in impedance and making mental judgements.
Claims 2-11, 13, 14, 16-19, and 21-22 depend from claim 1, and require the same using…to identify step.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites ”sequentially passing, through a space between electrodes, labels respectively corresponding to the nucleotides” and “sequentially altering an impedance between the electrodes using the labels”, these are not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to passing nucleotides through electrodes and altering impedance are techniques that are routine, conventional, and well-known in the art as demonstrated in the 103 rejection documented below.
Furthermore, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activities in the life science arts when they are claimed in a merely generic manner or as insignificant extra-solution activity:
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
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.
Claims 1-6, 8, 10-11, 13-14, 16-19 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Predki et al. (WO2019213437, on IDS dated 03/14/2024) in view of Turner et al. (WO2014182630A1, on IDS dated 03/14/2024).
Regarding claim 1, Predki teaches a method for identifying sequence information, the method comprising: providing an LC resonator having an effective impedance, a cell having a nanopore, and a polymer that can translocate through the nanopore, such translocation affecting the effective impedance (claim 1). Predki teaches the polymer comprises at least two nucleotides, each type of nucleotide providing a unique frequency response at the probe frequency (claim 12), which reads on labels respectively corresponding to the nucleotides; and sequentially altering an impedance between the electrodes using the labels. Predki teaches the cell comprises at least a top electrode and a bottom electrode, the nanopore or nano-channel being disposed between the electrodes, and the polymer passes through the nanopore or nano-channel (claim 7) and that nucleotides may pass through the nanopore sequentially (paras 12, para 181), which reads on sequentially passing, through a space between electrodes. Predki further teaches as the polymer passes through the nanopore, the electrodes can measure the change in electric potential across the nanopore so as to identify the sequence of monomers in the polymer (para 143) and that The change in capacitance is measured as the polymer, e.g. DNA, passes through the nanopore, using high frequency impedance spectroscopy (para 34), which reads on using the sequential alterations in the impedance to respectively identify the nucleotides.
Predki teaches using different probe frequencies of different nucleotides to provide a unique frequency response (claim 12), and that enhancing the differences in current, resistance or capacitance between different bases, e.g., by using non-natural bases which have a greater difference in size or are otherwise modified to give different signals (para 160) but does not teach labels corresponding to the nucleotides.
Turner teaches a method for nucleic acid sequencing. Turner teaches the use of nanoscale electronic elements comprising electrodes to provide sequence information using nucleotide analogs having impedance labels and identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Predki and Turner to arrive at the instantly claimed invention. The modification would have entailed adding the label of Turner to the nucleotides of Predki. One would have been motivated by the ability of labels to enhance the differences between different bases and provide more accurate identification of nucleotides. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 2, Predki teaches use of an LC resonator (resonating circuit) (claim 1) that has a resonant frequency when there is no DNA in the nanopore (para 205), i.e. based upon the impedance between the electrodes, and reading the sequence of a charged polymer, e.g., DNA, by measuring capacitive or impedance variance, e.g., via a change in a resonant frequency response, as the polymer passes through the nanopore (Abstract).
Regarding claim 3, Predki teaches use of an LC resonator (tank circuit) (claim 1).
Regarding claim 4, Predki teaches measuring capacitive or impedance variance, e.g., via a change in a resonant frequency response, as the polymer passes through the nanopore (Abstract).
Turner teaches that a capacitive label on the nucleotide analog produces a measurable change in the capacitance at the nanoscale electrodes (para 18).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Predki and Turner to arrive at the instantly claimed invention. The modification would have entailed adding the label of Turner to the nucleotides of Predki. The labels of Turner accomplish the function of altering capacitance as needed to perform the method of Predki. One would have been motivated by the ability of labels to enhance the differences between different bases and provide more accurate identification of nucleotides. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 5, Turner teaches polymerase mediated nucleic acid synthesis, providing a substrate comprising a nanoscale electrode, a polymerase enzyme and a template nucleic acid; exposing the polymerase to a plurality of types of nucleotide analogs, each comprising a different capacitive label… and using the monitored electrical signal at the electrode over time to determine a sequence of the template nucleic acid (para 14).
Regarding claim 6, Turner teaches the capacitive label on the nucleotide analog produces a measurable change in the capacitance at the nanoscale electrodes (para 14), which reads on the labels are coupled to the nucleotides.
Regarding claim 8, Predki teaches a method using an exonuclease to cleave each base as it passes through the nanopore.
Predki teaches using different probe frequencies of different nucleotides to provide a unique frequency response (claim 12), and that enhancing the differences in current, resistance or capacitance between different bases, e.g., by using non-natural bases which have a greater difference in size or are otherwise modified to give different signals (para 160) but does not teach labels corresponding to the nucleotides.
Predki does not teach labels, and does not teach the labels pass through the space between the electrodes after the nucleotides are cleaved from a polynucleotide.
Davis teaches a tag coupled to an incorporated nucleotide is detected with the aid of a nanopore (para 245)
Turner teaches nucleotide analogs having impedance labels that pass through a nanopore (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Predki and Turner to arrive at the instantly claimed invention. The modification would have entailed using the labeled nucleotides of Turner in the method of Predki. One would have been motivated by the ability of labels to enhance the differences between different bases and provide more accurate identification of nucleotides.
There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 10, Turner teaches each label type comprising a different impedance label attached to the phosphate portion of the nucleotide analog (para 6).
Neither Predki nor Turner specifically teach the labels are coupled to gamma phosphates of the nucleotides.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Turner to arrive at the instantly claimed invention. The modification would have entailed attaching the labels specifically to the gamma phosphates of the nucleotides. Determining the appropriate phosphate to attach a label to would have been merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 11, Predki teaches a nanopore disposed between the electrodes (claim 7, para 321).
Regarding claim 13, Predki teaches making hybrid nanopores comprising a pore-forming protein (portion of a nanopore) in synthetic material such as a metal surface or electrode (para 135).
Regarding claim 14, Predki teaches using a nanofluidic device, comprising channels allowing for fluid flow (para 132). Predki further teaches embodiments with top and bottom electrodes that are fluid-filled (Figs. 48A-C and Fig. 85), which reads on at least one of the electrodes comprises a surface of a fluidic channel.
Regarding claim 16, Predki teaches a nanopore or nanochannel disposed between the electrodes (claim 7, para 321), and a nanochannel width of about l0nm to 1000 nm (para 367).
Regarding claim 17, neither Predki nor Turner teach the size of electrode tips.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Predki and Turner to arrive at the instantly claimed invention. The modification would have entailed designing the electrode tips to an appropriate size in the context of the entire nanochip. Determining the appropriate electrode tip size would have been merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 18, Predki teaches the polymer is moved through a nanopore via a DC steering voltage applied to the electrodes (claim 9)
Regarding claim 19, Predki teaches the transfer of monomers (nucleotides) through the nanopore at the rate of 1 million nucleotides per second (para 34).
Regarding claims 21 and 22, Turner teaches capacitive labels such as polystyrene spheres (beads), and attached to each of the nucleotide analogs is a sphere of a different size (para 221).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Predki et al. (WO2019213437, on IDS dated 03/14/2024) in view of Turner et al. (WO2014182630A1, on IDS dated 03/14/2024) as applied to claims 1-6, 8, 10-11, 13-14, 16-19 and 21-22 above, and further in view of Davis et al. (USPGPub 20140134616).
Neither Predki nor Turner teach the labels pass through the space between the electrodes after the labels are cleaved from the nucleotides
Davis teaches nucleic acid sequencing using tags, the method comprising providing tagged nucleotides into a chamber comprising a nanopore (Abstract).
Regarding claim 7, Davis teaches the tag can be detected with the aid of the nanopore when the tag is released from the nucleotide (Abstract).
Davis teaches that methods of nucleic acid sequencing that pass a single stranded nucleic acid molecule through a nanopore may have insufficient sensitivity (para 4).
Davis teaches that tags can be driven through the nanopore repeatedly, thus increasing the time period in which the tag can be detected (para 79).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Predki and Turner with Davis to arrive at the instantly claimed invention. The modification would have entailed using the labeled nucleotides of Turner in the method of Predki and cleaving the labels from the nucleotides before passing through the nanopore as taught by Davis. One would have been motivated by the improved control of time reading signal through the nanopore with the goal of increased accuracy. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Predki et al. (WO2019213437, on IDS dated 03/14/2024) in view of Turner et al. (WO2014182630A1, on IDS dated 03/14/2024) as applied to claims 1-6, 8, 10-11, 13-14, 16-19 and 21-22 above, and further in view of Kokoris et al. (US PGPub 20180334729).
Regarding claim 9, neither Predki nor Turner teach the labels are coupled to one another in a surrogate polymer passed through the space between the electrodes.
Kokoris teaches encoding nucleic acid information on a surrogate polymer (para 17) that is conveyed through a nanopore (para 226, Fig. 4).
Kokoris teaches that surrogate polymers have the advantage of preserving the original genetic information of the target nucleic acid, while also increasing linear separation of the individual elements of the sequence data (para 17),
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Predki and Turner with Kokoris to arrive at the instantly claimed invention. The modification would have entailed generating a surrogate polymer as taught by Kokoris using the labeled nucleotides of Turner in the method of Predki. One would have been motivated by the ability to improve resolution of nucleotides moving through the nanopore by increasing separation between nucleotides. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Conclusion
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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