Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/20/2025 has been entered.
Applicant’s amendment
Applicant’s response filed 6/20/2025 has been received and entered. As requested, the amendment filed after final 5/27/2025 has been entered. Claims 21, 23, 27, 29, 30-32, 34 and 39 have been amended, claims 1-20 were previously cancelled.
Claims 21-43 are pending.
Election/Restriction
Applicant's election with traverse of Group II in the reply filed on 2/15/2024 was acknowledged. Upon review and initial search of the two groups do not appear to be a serious burden to examine together, and the restriction requirement was withdrawn.
Claims 21-43, drawn to a method of sequencing a polynucleotide using flows and a system comprising a chamber and detectors for sequencing are pending and currently under examination.
Priority
This application filed 6/5/2020, is a continuation of 13/599876 filed 8/30/2012, now US Patent 10704164, which claims benefit to provisional applications 61/545290 filed 10/10/2011, 61/529687 filed 8/31/2011; and related to through claim of priority to 13/599876 as the parent of continuation in part of 14/505636 filed 10/3/2014 (now ABN), which is the parent to continuation 16/433380 filed 6/6/2019, which is the parent to continuation 18/949259 filed 11/15/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/20/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that both citations are international search reports. It is noted that for review of these, the pending claims that were reviewed in these actions were not provided, but for completeness and clarity of the record the cited references when provided in this prosecution were not considered in light of the instant claims. The foreign statutes and comments of the reviewers were not clearly in context of the pending claims and were not considered for their logic nor factual accuracy of comments in actions from other foreign offices.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Response to Applicants Arguments
Applicant indicates that they do not concede to the rejection and request an abeyance until allowable subject matter is identified.
In response, Applicant’s comments are noted however a rejection cannot be held in abeyance. No specific arguments are provided; therefore, the rejections are maintained for the reasons of record.
The rejections are reiterated below for completeness of record.
Claims 21-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10,704164 (US Application 13/598876, parent related as continuation of instant application). Although the claims at issue are not identical, they are not patentably distinct from each other because the methods and systems of each of the applications are drawn to the same method of use of a barcode sequence in a sequencing method as well as the system and barcode used and claimed. Independent claim 19 provides for the system in which the method is implemented.
A copy of the independent method claim of ‘164 is provided:
A method for sequencing a polynucleotide, the method comprising:
introducing, into a polynucleotide, a barcode sequence to create a polynucleotide sample, wherein the barcode sequence is a series of nucleotide bases determined by a predetermined flowspace vector corresponding to a predetermined order of nucleotide flows used for sequencing, wherein the predetermined flowspace vector is a string of characters with each character representing an expected number of nucleotide incorporations resulting from a nucleotide flow of the predetermined order of nucleotide flows;
inserting the created polynucleotide sample into a flow chamber of a sequencing instrument comprising the flow chamber, a sensor in the flow chamber, and a fluidics controller configured to control the flow of nucleotides into the flow chamber;
exposing the created polynucleotide sample in the flow chamber to the series of nucleotides in a presence of a polymerase and a primer by individually flowing the series of nucleotides into the flow chamber according to the predetermined order of nucleotide flows using the fluidics controller, wherein incorporation of nucleotides of the series of nucleotides into the created polynucleotide sample produces a synthesized polynucleotide complementary to the polynucleotide sample;
obtaining, using the sensor, a series of signals resulting from the exposing of the created polynucleotide sample to the series of nucleotides, the series of signals indicating one or more nucleotide incorporations or one or more nucleotide non-incorporations for each nucleotide flow;
outputting the series of signals as data to a computing unit in communication with the sensor, the computing unit comprising a processor and a memory configured to receive and store the data;
resolving, using the processor, the series of signals to generate a rendered, wherein each character represents a number of nucleotide incorporations resulting from a respective nucleotide flow of the predetermined order of nucleotide flows;
comparing, using the processor, the rendered flowspace string of characters to predetermined flowspace strings of characters corresponding to a set of barcode sequences comprising the introduced barcode sequence, wherein the predetermined flowspace strings of characters are codewords of an error-tolerant code, the error-tolerant code is an error-correcting code configured to correct one or more errors present in the rendered flowspace string of characters based on differences between the rendered flowspace string and the predetermined flowspace strings of characters; and identifying, by the processor, the polynucleotide of the polynucleotide sample based on the comparison.
Claims 21-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-40 of copending Application No. 16/433380 (RCE filed). Although the claims at issue are not identical, they are not patentably distinct from each other because the methods and systems of each of the applications are drawn to the same method of use of a barcode sequence in a sequencing method as well as the system and barcode used and claimed. Claim 40 provides for the system in which the method is implemented.
A copy of the instantly pending method claim of ‘380 is provided:
21. (Currently Amended) A method for sequencing a polynucleotide, the method comprising:
inserting a polynucleotide sample into a flow chamber of a sequencing instrument, the sequencing instrument comprising the flow chamber, a sensor in the flow chamber, and a fluidics controller configured to control flow of nucleotides into the flow chamber, and the polynucleotide sample comprising the polynucleotide and a barcode nucleotide sequence comprising a series of nucleotide bases determined by a predetermined flowspace vector corresponding to a predetermined order of nucleotide flows, wherein the predetermined flowspace vector is a string of characters which each character representing an expected number of nucleotide incorporations resulting from a nucleotide flow of the predetermined order of nucleotide flows;
using the fluidics controller of the sequencing instrument, exposing the polynucleotide sample in the flow chamber of the sequencing instrument to a series of nucleotides in presence of a polymerase and a primer by individually flowing the series of nucleotides into the flow chamber
according to a predetermined order of nucleotide flows that corresponds to the predetermined flowspace vector using the fluidics controller;
obtaining, using the sensor, a series of signals resulting from the exposing of the polynucleotide sample to the series of nucleotides, the series of signals indicating an incorporation event or a non-incorporation event for each nucleotide flow of the series of nucleotides according to the predetermined order;
outputting the series of signals as data to a computing unit in communication with the sensor, the computing unit comprising a processor and a memory configured to receive and store the data;
resolving, using the processor, the series of signals to generate a rendered flowspace string of characters defining a rendered flowspace vector, each character of the rendered flowspace string of characters corresponding to a number of nucleotide incorporations resulting from the exposing;
comparing, using the processor, the rendered flowspace vector comprising the rendered flowspace string of characters to a plurality of predetermined flowspace vectors comprising predetermined flowspace strings of characters corresponding to a set of barcode nucleotide sequences comprising the barcode nucleotide sequence of the polynucleotide sample, wherein the predetermined flowspace strings of characters are codewords of an error-tolerant code, the codewords configured to be distinguishable from one another in the presence of zero, one, or two errors in the rendered flowspace string of characters; and
transforming, based on results of the comparing, the rendered flowspace string of characters into a sequence of bases to identify a sequence of the polynucleotide.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 21-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/949259 filed 11/15/2024 (not docketed).
Although the claims at issue are not identical, they are not patentably distinct from each other because the methods and systems of each of the applications are drawn to the same method of use of a barcode sequence in a sequencing method as well as the system and barcode used and claimed. Claims directed to the system in which the method is implemented are obvious need to practice the method.
A copy of the instantly pending method claim of ‘259 is provided:
A method for sequencing a polynucleotide, the method comprising: inserting a polynucleotide sample into a flow chamber of a sequencing instrument, the sequencing
instrument comprising the flow chamber, a sensor in the flow chamber, and a fluidics controller configured to control flow of nucleotides into the flow chamber, and the polynucleotide sample comprising the polynucleotide and a barcode nucleotide sequence comprising a series of nucleotide bases determined by a predetermined flowspace vector corresponding to a predetermined order of nucleotide flows, wherein the predetermined flowspace vector is a string of characters which each character representing an expected number of nucleotide incorporations resulting from a nucleotide flow of the predetermined order of nucleotide flows;
using the fluidics controller of the sequencing instrument, exposing the polynucleotide sample in the flow chamber of the sequencing instrument to a series of nucleotides in presence of a polymerase and a primer by individually flowing the series of nucleotides into the flow chamber according to a predetermined order of nucleotide flows that corresponds to the predetermined flowspace vector;
obtaining, using the sensor, a series of signals resulting from the exposing of the polynucleotide sample to the series of nucleotides, the series of signals indicating an incorporation event or a non-incorporation event for each nucleotide flow of the series of nucleotides according to the predetermined order;
outputting the series of signals as data to a computing unit in communication with the sensor, the computing unit comprising a processor and a memory configured to receive and store the data;
resolving, using the processor, the series of signals to generate a rendered flowspace string of characters defining a rendered flowspace vector, each character of the rendered flowspace string of characters corresponding to a number of nucleotide incorporations resulting from the exposing;
comparing, using the processor, the rendered flowspace vector comprising the rendered flowspace string of characters to a plurality of predetermined flowspace vectors comprising predetermined flowspace strings of characters corresponding to a set of barcode nucleotide sequences comprising the barcode nucleotide sequence of the polynucleotide sample, wherein the predetermined flowspace strings of characters are codewords of an error-tolerant code, the codewords configured to be distinguishable from one another in the presence of zero, one, or two errors in the rendered flowspace string of characters; and
transforming, based on results of the comparing, the rendered flowspace string of characters into a sequence of bases to identify a sequence of the polynucleotide.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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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 21-43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim Analysis
The claims have been amended and still generally are directed towards a method of sequencing a polynucleotide using a barcode by introducing a series of nucleotides, obtaining a signal and resolving the signal to determine if an error exists, as well as a system to perform the method. Claim 21 has been amended to more clearly indicate that the incorporations are ‘into the synthesized barcode polynucleotide’ which has been the implied interpretation as it is the only means of obtaining the sequence data or as claimed the signals that result in introducing flows and incorporation of nucleotides according to what is present in the nucleotide being sequenced as a method of sequencing set forth in the preamble. As amended, the signals for the portion of nucleotide which is a barcode is representative of a codewords or an error-tolerant code, and which barcode clearly represents a code or representation of what was sequenced and what the data represents, and effectively the claims require that the analysis steps result in a series of ‘characters’ which are the bases that are introduced during the sequencing and then the string of sequence information is compared to a reference or predetermined expected sequence and identifying final step has been amended to be ‘transforming’ which is still based on the comparing step analysis. As amended, the reasonable interpretation of these amended steps are evaluating sequence reads generated by sequencing and comparing the resulting sequence to a reference. The sequencing process requires flows and flowspace which appears to be directed to sequence by synthesis process platform of sequencing.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a method and product used to implement the method.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of obtaining, resolving and comparing sequence read data represented in the initial sample barcode sequences. The step of aligning and comparing sequence to arrive at the identification of malicious sequences are instructional steps. In light of the guidance of the specification, the claim requires computing similarity with the broad steps of receiving data, determine a potential sequence and resolving what the sequence represents. The judicial exception is a set of instructions for analysis of sequence data and appears to fall into the category of mental processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion). Here once the sequence data is obtained from a sequencing process assessing the obtained sequence with an expected sequence and possibly correlating a nucleic acid sequence with a coded set of characters are considered broad generic instructional steps. The breadth of “obtaining”, “resolving”, and “comparing” encompasses non-transformative visual assessment of sequence, coupled with prior knowledge of the correlation of said sequence might represent. This breadth does not impose a meaningful limit on the claim scope, such that all others are not precluded from using the natural principle of encoding a message in a nucleic acid sequence, and more broadly is similar to the naturally occurring codons which provide for a protein sequence. Although the claims recite obtaining signals, the courts have also identified limitations that did not integrate a judicial exception into a practical application; for example, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f).
As the steps of “obtaining”, “resolving”, and “comparing” are very generally recited, the combination together reasonably is interpreted as mere data gathering. Computing, constructing datasets and using statistical models was well understood, conventional, and routinely performed in the art at the time the application was filed. See MPEP § 2106.05(g) for a discussion on adding insignificant extra-solution (both pre-solution and post-solution) activity to the judicial exception. See also MPEP § 2106.05(h) for a discussion on generally linking the use of a judicial exception to a particular technological environment or field of use. The claims appear to fall into the category of Mathematical Concepts, as it applies the use of statistics and mathematical relationships in analyzing encoded sequences, and also into the category of mental processes, as concepts performed in the human mind (including an observation, evaluation, judgment, opinion) because there is no apparent complexity to or amount of data that is collected and analyzed as presently claimed.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the analysis is applied, and simply provides an assessment of the read data provided in the first step. With respect to the sequencing steps and sequence read data gathering, Guo et al who teaches a system for DNA Sequencing by Synthesis (2010) provided evidence that sequencing with flows was known. This judicial exception requires steps recited at high level of generality and are only stored on a non-transitory, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of obtaining sequence data suc as that provided by Guo et al. As such, the claims do not provide for any additional element to consider under step 2B that appear to provide for significantly more as a whole. For the analysis steps, it is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process."
As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence data. While the instruction are stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception. Without additional limitations, a process that employs mathematical algorithms (aligning sequences) to manipulate existing information (identify a barcode) to generate additional information is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract idea (designing probes to a target sequence) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
Response to Applicants arguments
Applicants summarize the basis of the rejection noting the amendments to the claims and argue that the claims are directed to a concrete improvement and provides an improvement of accuracy of the sequencing process by identification of a target. More specifically applicants indicate the string represents ‘an expected number of nucleotide incorporations into the synthesized barcode’ and not the bases themselves.
In response, the amended claims have been evaluated above. In review of the evidence there does not appear to be any improvement to the sequencing process as claimed. The basis of the argument is unclear, because all that is provided in the specification with respect to ‘flow’ as it relates to sequencing is to provide nucleotides for possible incorporation in the polynucleotide sequence and resulting in sequence read data of the linear sequence. There does not appear to be anything unique required of the claim, nor requirements of the specification beyond known methods of sequencing and providing a linear sequence representation of the read data based on the incorporation(s) of a nucleotide. In prosecution known methods such as evidenced by Guo et al. demonstrate sequencing by synthesis appears to anticipate the process of obtaining the sequence reads. What is left is the judicial exception which appears to be broadly directed at comparing the sequence read such as a barcode to a reference to identify the target. The use of barcodes to identify targets is well known and does not appear to provide an improvement to the technology as asserted by Applicants.
Applicants argue that the design of the barcode is error tolerant, and such specific design provide for a verifiable incorporation expectation and in addition to requirement of incorporation which is not abstract provides a non-naturally occurring embodiment making the claim patent eligible.
In response, a description of the sequences being sequenced does not appear to provide any meaningful limitation to make the claims patent eligible, in particular in view that the method of sequencing envisioned and encompassed by the claim was well known. At best, the argument appears to be directed to interpreting data and possibly designing sequences which can be interpreted in some particular fashion, none of which is required of the claims. Furthermore, while the art rejections have been withdrawn, the references of record clearly demonstrate that ‘error resistant’ sequence strings as provided by Hamady and Goolay were known, sequenced and as a whole not sufficient enough to provide considerations of any practical application or unique combination of elements such that the claims would be considered patent eligible.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claims 21-27, 29-34, 37-43 rejected under pre-AIA 35 U.S.C. 102a and e as being anticipated by Hamady et al (US 2010/0323348 pub Dec 23, 2010, efd Jan 31, 2009) is withdrawn.
Upon review, examiner agrees that while Hamady et al teach to use Hamming and Golay codes and provide for specific barcodes of nucleic acid sequences that can be used, it fails to provide for each of the method steps set forth in the amended claims.
Conclusion
No claim is allowed.
In prosecution, Hamady et al. (US patent 7323309), Mirkin et al. (US patent 7323309), Rothberg et al. (US pub 2009/0127589), Hoffman et al. (1991) and Lin et al. (1983) have been noted as relevant art of record. Generally, they provide that at the time of filing, inserting and using barcodes inserted into a nucleic acid sequence, and using said sequence to detect errors and correcting such error during nucleic acid amplification (see paragraph [0005] for example) were known as evidenced by the teaching of Hamady et al. which teaches the use of variety of correctable codes (paragraph [0021]) including Hamming and Golay codes (paragraph [0097] for example). Citation of Rothberg et al. is to demonstrate that performing sequencing or during the incorporation of nucleotide into a sequence to obtain signals of what the read represents was known. Hoffman et al. (1991) and Lin et al. (1983) were provided for further evidence of the teaching of codes that can be provided in a variety of ways including using Hamming and Golay codes which were well known at the time of filing (see citation in specification paragraph [0073]) and context of the level and knowledge of the skilled artisan.
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/Joseph Woitach/Primary Examiner, Art Unit 1687