DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Claim status
2. Claims 1-7 are currently pending and under exam herein.
Claims 1-7 are rejected.
Priority
3. This application is a divisional of U.S. Application No. 16/968576. The claimed benefit of U.S. Provisional Application 62/628,079, filed on February 8, 2018 and 62/656,796, filed on April 12, 2018, are acknowledged. In this action, all claims are examined as though they had an effective filing date of 8 February 2018. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
Information Disclosure Statement
4. The information disclosure statements (IDSs) submitted on 03 October 2023 and 13 March 2024 are being considered by the examiner. The IDS of 03 October 2023 includes some non-patent literature attached to a parent application 16/968,576 that are being considered by the examiner.
Drawings
5. The drawings submitted on 03 October 2023 are accepted by the examiner.
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.
7. Claims 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 2A, Prong 1
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1 recites: a method of detecting a sequencing error in a barcode among a population of unique barcodes wherein each unique barcode is designed to comprise a plurality of barcode reads comprising identifying a first unique barcode among the population of unique barcodes
Claim 1 recites: wherein the first unique barcode comprises only one barcode read
Claim 1 recites: comparing the sequence of the first unique barcode with the population of unique barcodes
Claim 1 recites: identifying a second unique barcode among the population of unique barcodes
Claim 1 recites: wherein the second unique barcode differs from the first unique barcode with less than four degenerate base mismatches and wherein the second unique barcode comprises a plurality of barcode reads
Claim 2 recites: the method of claim 1, wherein the second unique barcode differs from the first unique barcode in less than three degenerate base mismatches
Claim 3 recites: the method of claim 1, wherein the second unique barcode differs from the first unique barcode in less than two degenerate base mismatches
Claim 4 recites: the method of claim 1, further comprising correcting the mismatches in the first unique barcode.
Claim 5 recites: the method of claim 1, wherein each barcode read is associated with a barcode
Claim 6 recites: the method of claim 1, wherein the barcode read is in the form of information other than sequence, so long as the information is associated with the barcode
Claim 7 recites: the method of claim 6, wherein the information is selected from the list consisting of color, index, ID, cluster, location, container, compartment information, and a combination thereof
The limitations directed to ‘identifying a first unique barcode’, ‘comparing the sequence of the first unique barcode with the population’, ‘identifying a second unique barcode’ and ‘correcting the mismatches’ are generically recited data analysis steps that can be practically performed in the human mind because the human mind is capable of identifying relevant information, comparing values, and determining information from other values. Therefore, these limitations fall under the "Mental processes" groupings of abstract idea.
The limitations directed to ‘wherein the first unique barcode comprises only one barcode read’, ‘wherein the second unique barcode differs from the first unique barcode with less than two, three or four degenerate base mismatches’, ‘wherein the second unique barcode comprises a plurality of barcode reads’, ‘wherein each barcode read is associated with a barcode’, ‘wherein the barcode read is in the form of information other than sequence’ and ‘wherein the information is selected from the list’ further limit the barcodes that are identified, compared or corrected. Therefore, they merely further limit the judicial exception but do not change their positions as abstract ideas.
As such, claims 1-7 recite an abstract idea (Step 2A, Prong 1: YES).
Step 2A, Prong 2
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception in some other meaningful way because the claims do not recite any additional elements.
As no additional elements that provide a practical application of the recited judicial exception, claims 1-7 are directed to an abstract idea (Step 2A, Prong 2: NO).
Step 2B
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite additional elements. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-7 are not patent eligible.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
8. Claim 1-7 is rejected under pre-AIA 35 U.S.C. 102(a)(1) as being unpatentable over Quail et al. (BMC Genomics, 2014, Vol. 15, p. 1-13 ). The italicized text corresponds to the instant claim limitations.
Regarding claim 1, Quail et al. teaches designing a set of 384 eleven-base Illumina barcode sequences (i.e. a population of unique barcodes) that are at least 5 changes apart from each other, to be added to samples destined for sequencing, which allow for single-error correction and result in very low levels of barcode misallocation due to sequencing error. Quail et al. discloses that the method is called SASI-Seq (sample assurance spike-in sequencing) wherein uniquely barcoded DNA fragments are spiked into samples at the onset. A given SASI tag will stay associated with a sample as it is processed through library preparation and sequencing set-up (Figure 1). The sequence of that tag will be read at the same time that a sample is sequenced, thus allowing unambiguous identification of a sample by virtue of its reported SASI tag sequence. The spike-in can be done at low levels that would nonetheless generate a large enough number of reads to enable identification of minor contaminants. Therefore, there are a plurality of barcode reads (abstract, p. 2, col. 1, para. 2 – col. 2, para. 2; a method of detecting a sequencing error in a barcode among a population of unique barcodes wherein each unique barcode is designed to comprise a plurality of barcode reads.
Regarding claim 1, Quail et al. teaches Illumina barcodes were designed using a Hamming script with an edit distance of 4 (i.e. such that no barcode sequence was less than 4 changes away from its closest sequence match). Quail et al. further teaches that, in theory, this allows single nucleotide errors to be corrected, and two errors to be detected, without reporting the wrong barcode. Quail et al. further discloses a set of 384 barcodes with an edit distance of 5 between any two members, allowing single base error correction, three base error detection and requiring at least 4 sequencing errors in the barcode read before being mistaken for an alternative barcode. In the case of single base error correction, the first unique barcode is the single base error-containing barcode and the second unique barcode is the same barcode without the error and the two barcodes have less than 4 degenerate base mismatches. Quail et al. teaches testing the method using PhiX 174 spike-in barcoded fragments in to a human library preparation and sequencing experiment using an Illumina MiSeq instrument. A spreadsheet showing a portion of Table S5 shows 68 of the 384 barcodes in the experiment along with the proportion of barcode molecules analyzed wherein one mismatch was detected and corrected (p. 2, col. 1, para. 2; Fig. 1; p. 3, col. 1, para. 2 – p. 5, col. 1, para. 1; Table S5; identifying a first unique barcode among the population of unique barcodes, wherein the first unique barcode comprises only one barcode read; comparing the sequence of the first unique barcode with the population of unique barcodes; and identifying a second unique barcode among the population of unique barcodes, wherein the second unique barcode differs from the first unique barcode with less than four degenerate base mismatches and wherein the second unique barcode comprises a plurality of barcode reads).
Regarding claim 2, Quail et al. teaches a set of 384 barcodes with an edit distance of 5 between any two members, allowing single base error correction, three base error detection and requiring at least 4 sequencing errors in the barcode read before being mistaken for an alternative barcode. In the example of single base error correction, the first unique barcode is the single base error-containing barcode and the second unique barcode is the same barcode without the error and the two barcodes have less than three degenerate base mismatches (i.e. 1 mismatch). Quail et al. further discloses using spike-in fragments containing barcodes in an Illumina library preparation and sequencing run of human DNA. A spreadsheet showing a portion of Table S5 shows 68 of the 384 barcodes in the experiment along with the proportion of barcode molecules analyzed wherein one mismatch was detected and corrected (p. 2, col. 2, para. 3 – p. 3, col. 1, para. 1; p3, col. 1, para. 2 - p. 5, col. 1, para. 1; Table S5; the method of claim 1, wherein the second unique barcode differs from the first unique barcode in less than three degenerate base mismatches).
Pertaining to claim 3, Quail et al. teaches a set of 384 barcodes with an edit distance of 5 between any two members, allowing single base error correction, three base error detection and requiring at least 4 sequencing errors in the barcode read before being mistaken for an alternative barcode. In the example of single base error correction, the first unique barcode is the single base error-containing barcode and the second unique barcode is the same barcode without the error and the two barcodes have less than two degenerate base mismatches (i.e. 1 mismatch); this design was put into practice in using spike-in fragments containing barcodes into an Illumina library preparation and sequencing run of human DNA. A spreadsheet showing a portion of Table S5 shows 68 of the 384 barcodes in the experiment along with the proportion of barcode molecules analyzed wherein one mismatch was detected and corrected (p. 2, col. 2, para. 3 – p. 3, col. 1, para. 1; p3, col. 1, para. 2 - p. 5, col. 1, para. 1; Table S5; the method of claim 1, wherein the second unique barcode differs from the first unique barcode in less than two degenerate base mismatches).
Pertaining to claim 4, Quail et al. discloses that it is the barcode with the single base error that is corrected (i.e. with one mismatch). Quail et al. further discloses that that the major error mode of Illumina sequencing is substitution errors (p. 3, col. 1, para. 3; Table S5; the method of claim 1, further comprising correcting the mismatches in the first unique barcode).
Regarding claim 5, Quail et al. discloses that a set of 384 barcodes with an edit distance of 5 between any two members, allowing single base error correction, three base error detection and requiring at least 4 sequencing errors in the barcode read before being mistaken for an alternative barcode Quail et al. further discloses the sequences of each barcode. Therefore, each barcode read is associated with a barcode (Table S5; p. 3, col. 1, para. 1; the method of claim 1, wherein each barcode read is associated with a barcode).
Regarding claim 6, Quail et al. discloses that there are a total of 384 highly discriminative barcodes that can have a background rate of false attribution of less than 0.005%. Quail et al. further discloses that their method called SASI-Seq is for sample assurance and that uniquely barcoded DNA fragments are spiked into samples at the onset and a given SASI tag will stay intimately associated with a sample as it is processed through library preparation and sequencing set-up. Quail et al. further teaches that the sequence of that tag will be read at the same time that a sample is sequenced, thus allowing unambiguous identification of a sample by virtue of its reported SASI tag sequence. Quail et al. further discloses that Ideally each and every sample would have a uniquely barcoded SASI fragment set (Fig. 1; p. 2, col. 1, para. 2; p. 8, col. 1, para. 4; p. 8, col. 2, para. 2; the method of claim 1, wherein the barcode read is in the form of information other than sequence, so long as the information is associated with the barcode).
Pertaining to claim 7, Quail et al. disclose that the information represented by each unique barcode is sample ID. Quail et al. discloses that The sequence of that tag will be read at the same time that a sample is sequenced, thus allowing unambiguous identification of a sample by virtue of its reported SASI tag sequence (p. 2, col. 1, para. 2; the method of claim 6, wherein the information is selected from the list consisting of color, index, ID, cluster, location, container, compartment information, and a combination thereof).
Conclusion
9. No claims are allowed.
E-mail Communications Authorization
10. Per updated USPTO Internet usage policies, Applicant and/or applicant's representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300): "Recognizing that Internet communications are not secure, / hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. / understand that a copy of these communications will be made of record in the application file."
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273- 8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Inquiries
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER J SMITH whose telephone number is (571)272-7801. The examiner can normally be reached Monday-Friday 7:00 AM - 3:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.J.S./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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