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 .
Claim Status
Claims 1-28 are currently pending and under exam herein.
Claims 1-28 are rejected.
Priority
The instant application is a national stage application of PCT/US2021/049289 filed on 09/07/2021, which claims national benefit of U.S. Provisional Patent Application No. 63/075,622, filed on September 8, 2020.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/26/2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of the list of references cited from the IDS is included with this Office Action.
Drawings
The drawings received 03/06/2023 are accepted.
Specification
The disclosure is objected to for the following informalities:
Para [0108] “may contains” should read “may contain”
Para [0160] “This may done” should be “This may be done”
Para [0096] “may rotated” should read “may rotate”
Para [0124] “can appended” should read “can be appended”
Appropriate correction is required.
Claim Objections
Claims 13 and 14 objected to because of the following informalities: in the amended claim set, “of” was crossed out, therefore the claims read, “the method claim 10/ the method claim 1”. Appropriate correction is required.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Claim Interpretation
The term “identifier nucleic acid molecule” is defined in the specification [0061] as “nucleic acid sequences that encode digital information” and will be interpreted as such.
The term “probe” refers to “an agent that binds a target sequence on an identifier nucleic acid molecule” in [0061] of the specification, and will be interpreted as such.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-6, 8-12, 14-16, 19, 20, 24-28 are rejected under 35 U.S.C. 103 as being unpatentable over Roquet et al. (US 20180137418) in view of Reid et al. (US 20170233804).The italicized text corresponds to the instant claim limitations.
As to claim 1, Roquet et al. (Roquet here in) teaches a method and system used to encode computer data or information in a plurality of identifiers, specifically, mapping nucleic acid sequences or nucleic acid molecules to symbols, or bits encoding digital information. ([63], [69];72; mapping the digital information to a target set of identifier nucleic acid sequences; obtaining a plurality of identifier nucleic acid molecules).
Regarding claim 2, Roquet et al reveals that the pattern of black points on the top of FIG 18B is the codebook, and further teaches "the total size of the dataset may be increased to accommodate a codebook that specifies the new mapping instructions" ([184], Fig.18B; wherein said mapping comprises using a codebook that maps a word to a codeword).
With respect to claim 3, Roquet depicts multiple identifier nucleic acid sequences corresponding to a bit value (e.g. “0” or “1”) in a codeword. ([136]FIG 3A and 3B; wherein at least one identifier nucleic acid sequence corresponds to a bit in the codeword.)
Concerning claim 4, Roquet teaches the presence of an identifier at a particular rank specifies a bit-value of '1' and the absence of an identifier at a particular rank specifies a bit-value of '0'. ([82]; wherein if said bit has a bit- value of 1, said bit is represented by a presence of the at least one corresponding identifier nucleic acid sequence in the target set, and if the bit has a bit-value of 0, said bit is represented by an absence of any corresponding identifier nucleic acid sequences in the target set).
Regarding claim 5, Roquet illustrates an example product scheme in Figure 6A and 6B where components are divided into a defined set of layers and identifiers are constructed from assembling one component from each layer. The combinatorial space, or identifier space, is the set of all possible identifiers that can be formed from a particular scheme (Fig. 6A and 6B,[39], [91];wherein said plurality of identifier nucleic acid molecules is obtained by assembling multiple component nucleic acid molecules using a product scheme, wherein the product scheme defines a set of M layers, each layer comprising a set of components, and wherein each identifier nucleic acid molecule contains one component from each layer of the set of M layers.)
Regarding claim 6 , Roquet et al teaches a method for nucleic acid-based computer data storage that may comprise (a) receiving computer data, (b) synthesizing nucleic acid molecules comprising nucleic acid sequences encoding the computer data, he further teaches that this approach to information encoding may use de-novo synthesis of identifiers ([73] [79]; wherein said plurality of identifier nucleic acid molecules is obtained by programmably synthesizing multiple oligonucleotides with de novo synthesis.)
Concerning claim 8, Roquet teaches Identifiers in an identifier library may be constructed to comprise one or more common primer binding sites. (para [0018]; further comprising incorporating common primer binding sites to each identifier molecule of the plurality of identifier nucleic acid molecules.)
With regards to claim 9, Roquet teaches the PCR primers for amplifying identifiers may be designed to prime to the vector such that the barcoded edges are included with the identifier in the amplification product ([127]; further comprising amplifying the plurality of identifier nucleic acid molecules with polymerase chain reaction (PCR) using PCR primers configured to bind to said common primer sites.)
As to claim 10, Roquet reveals the parent identifier is separated by spacer sequences. ([113] further comprising adding a spacer sequence to each identifier nucleic acid molecule of the plurality of identifier nucleic acid molecules.)
Regarding claim 11, Roquet reveals the one or more components (components in this case being the identifier nucleic acid sequences with the spacer sequences) are assembled using overlap-extension polymerase chain reaction (PCR), polymerase cycling assembly, and sticky end ligation ([8]; wherein the spacer sequence is added by one of ligation or overlap extension PCR.)
Regarding claim 12, Roquet teaches the parent identifier comprises a plurality of components flanked by….distinct spacer sequences, indicating that the intervening sequence was successfully integrated into the target insertion site ([9]; wherein the spacer sequence is inserted into a target insertion site within the identifier nucleic acid sequence).
Regarding claim 26, Roquet teaches that the presence of an identifier may indicate a bit value of '1' at the mapped location and the absence of an identifier may indicate a bit value of '0' at the mapped location; therefore, if presence “may” be indicated by a bit value of ‘1’ in one set, then in another set presence of an identifier “may” also be indicated by a value of ‘0’ (wherein if said bit has a bit-value of 1, said bit is represented by a presence of the at least one corresponding identifier nucleic acid sequence in the first target set, and if the bit has a bit-value of 0, said bit is represented by a presence of the at least one corresponding identifier nucleic acid sequence in the second target set.)
Roquet is silent to sequencing an identifier nucleic acid molecule of said plurality of identifier nucleic acid molecules with a nanopore system and accepting or rejecting the identifier nucleic acid molecule into a destination chamber based on whether or not the identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence of the target set in claim 1.
Roquet does not speak to wherein the nanopore system comprises a source chamber, a membrane, a nanopore, and the destination chamber in claim 14.
Roquet is silent to wherein accepting the identifier nucleic acid molecule comprises translocating the identifier nucleic acid molecule from the source chamber to the destination chamber through the nanopore in the membrane in claim 15.
Roquet does not speak to wherein the identifier nucleic acid molecule is accepted or rejected into the destination chamber based on at least one impedance signature to which the identifier nucleic acid molecule matches in claim 19.
Roquet does not teach wherein rejecting the identifier nucleic acid molecules comprises reversing a polarity of an electric field across the nanopore in claim 20.
Roquet does not disclose wherein the destination chamber is a first destination chamber, and the target set is a first target set, and wherein the method further comprises: accepting or rejecting the identifier nucleic acid molecule into a second destination chamber based on whether or not the identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence of a second target set in claim 24.
Roquet is silent to wherein the nanopore system comprises a source chamber, a first membrane, first nanopore in the first membrane, a second membrane, and a second nanopore in the second membrane; and wherein the first membrane separates the source chamber and the first destination chamber, and the second membrane separates the source chamber and the second destination chamber in claim 25.
Roquet does not speak to wherein if said bit has a bit-value of 1, said bit is represented by a presence of the at least one corresponding identifier nucleic acid sequence in the first target set, and if the bit has a bit-value of 0, said bit is represented by a presence of the at least one corresponding identifier nucleic acid sequence in the second target set in claim 26.
Roquet does not explicitly teach further comprising: designating a probe set of component nucleic acid sequences; sequencing a probed identifier nucleic acid molecule from the first destination chamber or the second destination chamber with the nanopore system; and accepting or rejecting the probed identifier nucleic acid molecule into a retrieval chamber based on whether or not the probed identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence containing a component nucleic acid sequence of the probe set in claim 27.
Finally, Roquet is silent to wherein accepting or rejecting the identifier nucleic acid molecule comprises: accepting the identifier nucleic acid molecule into the destination chamber if the identifier nucleic acid molecule has an identifier nucleic acid sequence of the target set; and rejecting the identifier nucleic acid molecule from the destination chamber if the identifier nucleic acid molecule does not have an identifier nucleic acid sequence of the target set in claim 28.
However, these limitations were known in the art at the time of the effective filling date as taught by Reid et al.
With regards to claim 1, Reid teaches a method of sequencing a polymer through a nanopore system (para [0140]; sequencing an identifier nucleic acid molecule of said plurality of identifier nucleic acid molecules with a nanopore system). Additionally, Reid discloses, in dependence on the measure of similarity, selectively completing the translocation of the polymer into the collection chamber or else ejecting the polymer back into the sample chamber (para [0029]; accepting or rejecting the identifier nucleic acid molecule into a destination chamber based on whether or not the identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence of the target set.)
Pertaining claim 14, Reid teaches the method of using a system that comprises a sample chamber containing a sample comprising the polymers, a collection chambers sealed from the sample chamber and a sensor element comprising a nanopore that communicates between the sample chamber and the collection chamber. Reid goes further to explain that each sensor element 30 is made by forming a membrane (31) across a respective well ([25]; [116] wherein the nanopore system comprises a source chamber, a membrane, a nanopore, and the destination chamber.)
As to claim 15, Reid discloses however, the measure of similarity is used to determine whether the polymer is to be collected. If so, then the translocation of the polymer into the collection chamber is completed. Otherwise, the polymer is ejected back into the sample chamber ([30]; wherein accepting the identifier nucleic acid molecule comprises translocating the identifier nucleic acid molecule from the source chamber to the destination chamber through the nanopore in the membrane.)
In regards to claim 16, Reid teaches a series of measurements taken over time once translocation (through the nanopore) is detected. Figure 4 illustrates the resulting measurements in a signal graph, wherein the peaks represent the various impedance signatures. ([180] [386];wherein sequencing the identifier nucleic acid molecule comprises detecting an impedance signal and matching the impedance signal to one of multiple impedance signatures.)
As to claim 17, Reid teaches where the polymer is a polynucleotide there are a
number of methods proposed for controlling the rate of translocation including use of polynucleotide binding enzymes. Signal is measured and affected by the rate of translocation, therefore, if a binding agent can speed up or slow down the rate it would result in a distinct impedance signal ([134]; further comprising binding an agent to each identifier nucleic acid molecule of at least a subset of the plurality of identifier nucleic acid molecules to provide a distinct impedance signal.)
Regarding claim 18, Reid discloses binding the agent (enzyme) to each polynucleotide ([132], [136]; wherein the binding comprises binding the agent to each identifier nucleic acid molecule of the plurality of identifier nucleic acid molecules.)
With respect to claim 19, Reid teaches in step C4, a decision is made responsive to the measure of similarity (i.e. matching to an impedance signature) determined in step C3 either (a) to reject the polymer being measured, (b) that further measurements are needed to make a decision ([199]; wherein the identifier nucleic acid molecule is accepted or rejected into the destination chamber based on at least one impedance signature to which the identifier nucleic acid molecule matches.)
Regarding claim 20, Reid teaches that there are also possibilities (possibilities being rejecting the identifier nucleic acid molecules) for sequencing applications that require strand translocation against an applied potential ([141]; wherein rejecting the identifier nucleic acid molecules comprises reversing a polarity of an electric field across the nanopore.)
As to claim 24, Reid discloses the system may comprise plural collection chambers
and, in respect of each collection chamber, a sensor element comprising a nanopore that provides communication between the sample chamber and the respective collection chamber. This allows the method being performed in respect of plural nanopores in parallel. As well as providing the capability of speeding up the sorting (i.e. accepting or rejecting identifier nucleic acid molecules) that may allow collection of different polymers in different collection chambers. To achieve that, the reference data and criteria for collection are selected accordingly ([34]; wherein the destination chamber is a first destination chamber, and the target set is a first target set, and wherein the method further comprises: accepting or rejecting the identifier nucleic acid molecule into a second destination chamber based on whether or not the identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence of a second target set).
Regarding claim 25, Reid teaches that the method will be performed in plural nanopores, which speaks to a first and second membrane, a first and second nanopore in the membrane, and a first and second membrane that separates the sample (source) chamber from the first and second destination chamber ([34]; wherein the nanopore system comprises a source chamber, a first membrane, first nanopore in the first membrane, a second membrane, and a second nanopore in the second membrane; and wherein the first membrane separates the source chamber and the first destination chamber, and the second membrane separates the source chamber and the second destination chamber.)
With respect to claim 27, Reid discloses wherein a polymer binding moiety (probe or agent), for example an enzyme, is used to control the translocation, this may depend on the polymer binding moiety used. Advantageously, a polymer binding moiety that can control the rate may be selected, meaning it is accepted and will successfully translocate through into the collection chamber—this is only possible when there is a measure of similarity ([246]; further comprising: designating a probe set of component nucleic acid sequences; sequencing a probed identifier nucleic acid molecule from the first destination chamber or the second destination chamber with the nanopore system; and accepting or rejecting the probed identifier nucleic acid molecule into a retrieval chamber based on whether or not the probed identifier nucleic acid molecule corresponds to an identifier nucleic acid sequence containing a component nucleic acid sequence of the probe set.)
As to claim 28, Reid teaches in dependence on the measure of similarity (of a target or reference set), selectively completing the translocation of the polymer into the collection chamber or else ejecting the polymer back into the sample chamber (para [0029]; wherein accepting or rejecting the identifier nucleic acid molecule comprises: accepting the identifier nucleic acid molecule into the destination chamber if the identifier nucleic acid molecule has an identifier nucleic acid sequence of the target set; and rejecting the identifier nucleic acid molecule from the destination chamber if the identifier nucleic acid molecule does not have an identifier nucleic acid sequence of the target set.)
An invention would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention if some motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Roquet teaches that decoding nucleic acid encoded data may be achieved by base-by-base sequencing of the nucleic acid strands, such as Illumina® Sequencing, or by utilizing a sequencing technique that indicates the presence or absence of specific nucleic acid sequences (Roquet et al. [148]). Reid teaches that in this type of measurement system using a nanopore has considerable promise, particularly in the field of sequencing a polynucleotide such as DNA or RNA (Reid et al [2]). Therefore, one of ordinary skill in the art would have recognized a nanopore system could be readily used when dealing with digital data storage in nucleic acid molecules with a reasonable expectation of success, because Reid discloses “such biochemical analysis systems using nanopores can provide significant advantages”(Reid et al. [4]). The invention is therefore prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Roquet et al. (US 20180137418) in view of Reid et al. (US 20170233804) as applied to claims 1-6, 8-12, 14-16, 19, 20, 24-28, and further in view of Choi et al. (Scientific Reports 9:6852 (2019)).
Roquet in view of Reid does not explicitly teach, wherein said plurality of identifier nucleic acid molecules is obtained by synthesizing degenerate oligonucleotide sequences.
However, this limitation was known in the art at the time of the effective filling date of the invention, as taught by Choi et al.
With respect to claim 7, Choi teaches incorporating degenerate bases into oligonucleotide synthesis for DNA-based storage (Figure 1 description, pg. 2 para 2-3; plurality of identifier nucleic acid molecules is obtained by synthesizing degenerate oligonucleotide sequences).
An invention would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention if some motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Roquet teaches that base-by-base synthesis of the nucleic acids can be costly and time consuming and alternative methods may improve the efficiency, improve the commercial viability of digital information storage [70]. Choi discloses that incorporating degenerate bases into oligonucleotide synthesis generates massive variant pools without increasing costs, while halving required DNA length to decrease synthesis expenses. This approach maximizes efficiency by leveraging existing techniques to produce over a billion molecules per design (pg. 2 para 3, pg. 3 para 1). There would be a reasonable expectation of success in making this combination to a person of ordinary skill in the art because they are both analogous in the art of DNA storage; furthermore, Choi reveals that “the proposed method can be integrated with synthetic technologies in the future to reduce the cost of DNA-based data storage by 50%” (Abstract). Therefore the invention is prima facie obvious.
Claims 13, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Roquet et al. (US 20180137418) in view of Reid et al. (US 20170233804) as applied to claims 1-6, 8-12, 14-16, 19, 20, 24-28, and further in view of Ceze et al. (US 2020370111).
Roquet in view of Reid does not disclose wherein the spacer sequence is configured to increase a translocation time of each identifier nucleic acid molecule of the plurality of identifier nucleic acid molecules during sequencing in the nanopore system (of claim 13), nor further comprising sequencing multiple identifier nucleic acid molecules in the nanopore system until the destination chamber comprises a plurality of identifier nucleic acid molecules that is sufficient for representing the digital information with error correction (of claim 21).
Roquet in view of Reid are silent to wherein mapping comprises using forward error correction (of claim 22) and further comprising correcting for any errors that occur during the sequencing step or the accepting or rejecting step by using backward error correction (of claim 23).
However, these limitations were known in the art at the time of the effective filling date of the invention, as taught by Ceze et al.
With respect to claim 13, Ceze teaches a spacer sequence configured to a barcode sequence (identifier nucleic acid) that makes the overall molecule a sufficient length to be read by a sequencing device; a longer sequence equates to increased translocation time (Fig. 1 and [24]; wherein the spacer sequence is configured to increase a translocation time of each identifier nucleic acid molecule of the plurality of identifier nucleic acid molecules during sequencing in the nanopore system. )
Regarding claim 21, Ceze teaches a system that utilizes nanopore sequencing and a plurality of nucleic acid molecules that encode an identifier--once sequencing occurs a destination chamber will comprise the sequenced identifiers that will sufficiently represent the digital information with error correction. Nanopore sequencing devices are well known to have 2 distinct compartments a loading or entry chamber (source chamber) and a receiving (destination chamber) separated by a membrane ( [22], [23], [30], claim 7; further comprising sequencing multiple identifier nucleic acid molecules in the nanopore system until the destination chamber comprises a plurality of identifier nucleic acid molecules that is sufficient for representing the digital information with error correction).
As to claim 22, Ceze discloses mapping with error correcting codes (ECCs) ([67]; wherein mapping comprises using forward error correction.)
With regards to claim 23, Ceze teaches a system of claim 6, wherein determining the digital tag based on the identified molbits includes performing error correction (claim 7, [67]; further comprising correcting for any errors that occur during the sequencing step or the accepting or rejecting step by using backward error correction.)
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion, or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Both Roquet in view of Reid and Ceze are directed to nucleic-acid based storage and nanopore sequencing. An artisan in the field would have recognized that incorporating error-correction mechanisms taught by Ceze would minimize errors and improve accuracy. Ceze teaches “ECCs reduce the possibility of unrecoverable tags” ([67]). One skilled in the field would have had reasonable expectation of success because they are analogous in the art. Therefore, the invention is prima facie obvious.
Conclusion
It is noted that although claims 1-28 contain elements that recite an abstract idea, the additional elements, when considered in combination with the abstract idea integrate the recited judicial exception into a practical application. “Accepting or rejecting the identifier nucleic acid molecule into a destination chamber” utilizes comparisons to affect the function of the particular machine by controlling if the identifier nucleic acid molecule is moved into the destination chamber or not. See MPEP 2106.05(b): “Integral use of a machine to achieve performance of a method may integrate the recited judicial exception into a practical application or provide significantly more.” Therefore, under Step 2A Prong 2, claims 1-28 are integrated into a practical application and are found to be eligible subject matter under 35 U.S.C. § 101.
No claims are allowed.
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/A.A.A./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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