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 .
Status of the Claims
Claims 1-6 are pending and examined herein. No claims are canceled.
Priority
As detailed on the 21 March 2022 filing receipt, the application claims priority as early as 12 September 2019. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Withdrawn Rejections and Objections
The objections related to the typographical errors are withdrawn in view of amendment. The objection to the presence of hyperlinks in the specification is withdrawn in view of the amendments. Claim objections are withdrawn in view of amendments. The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
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 1-6 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 1, element (3), recites two options in a list relating to the outcome of determination whether the expression vector sequence is known or not. The list elements are not joined by a conjunction, making their requirements unclear. The claims are amended to recite “or” after element (3), which makes it unclear whether determining known and unknown vectors are required in element (3) but also whether the step is optional altogether with respect to element (4). For compact examination, it is assumed that the conjunction "or" will be added between the two parts of element (3) and removed from the end of element (3).
Claim 1, element (4) recites three sub-steps – one if the expression vector is known, one if the expression vector is unknown, and determining copy number. Elements (4-1) and (4-2) are joined by an “or” clarifying that one or the other is required based on whether the expression vector is known or unknown, but there is no conjunction joining element (4-3), making it unclear if it is also optional or required regardless of whether (4-1) or (4-2) is selected. For compact examination, it is assumed element (4-3) should be preceded by an “and” to make it clear that while step (4-1) and (4-2) are options based on whether the vector sequence is known or unknown respectively, (4-3) is required in either situation.
Dependent claims 2-6 do not remedy this lack of clarity and so are similarly rejected.
Response to Applicant Remarks regarding 35 USC 112(b)
Applicant remarks state the amendments providing missing conjunctions clarify the indefiniteness claim 1. The remarks are not entirely persuasive because the claim now recites “or” after element (3), which makes it unclear whether determining known and unknown vectors are required in element (3) but also whether the step is optional altogether with respect to element (4). Furthermore, while it is appreciated that the applicant remarks state elements (4-1) and (4-2) are options and (4-3) is required for both, this is not clearly reflected by the conjunctions in the claim. Therefore, the rejection under 35 USSC 112(b) are maintained.
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 1-6 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of identifying clean transgenic or gene-edited material and insertion sites.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-6), which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in claim 1 include the mathematical calculations based on the counts, such as determining the number of reads matching the vector sequence or library and determining the copy number. These are mathematical operations based on the collected data. Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, recited in claims 1 include "extracting… qualified paired-end reads” which is interpreted as data evaluation or judgment based on the matching patterns to the reference.
Dependent claim 2 recites additional steps related to quality control following the re-sequencing that is interpreted as performed on the data, including removing adapters and low quality reads, and as such is interpreted as reciting mental processes.
Dependent claims 3-5 recites additional data analysis steps involving evaluation of insertion sites and so is interpreted as including mental steps.
Dependent claim 6 recites designing pre-primer and post-primer sites, which is interpreted as data manipulation and thus a mental process.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Claim 1 recites additional elements that are not abstract ideas: “extracting genomic DNA,” “whole genome re-sequencing,” and “determining whether an expression vector sequence containing T-DNA sequence” by mapping sequence data to a reference genome. These steps are interpreted as data collection steps for the mathematical steps of determining whether there are transgenic or gene editing events, and thus are insignificant extra-solution activity (MPEP 2106.05(g)).
Dependent claim 6 also recites “verifying the integrated sites using a PCR assay,” which is interpreted as insignificant extra solution activity because performing PCR to verify the insertion sites is not impacted by the judicial exception (MPEP 2106.05(g)).
Therefore, the additional elements are not interpreted as integrating the abstract ideas into a practical application. [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
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 of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05). The claims recite additional elements that are not abstract ideas: “extracting genomic DNA” (claim 1), “whole genome re-sequencing” (claim 1), “determining whether an expression vector sequence containing T-DNA sequence” by mapping sequence data to a reference genome (claim 1), and “verifying the integrated sites using a PCR assay” (claim 6). Yang (Scientific Reports 3(2839): 9 pgs., 2013; previously cited on the 02 June 2025 IDS form) teaches extraction of total genomic DNA (pg.8, col. 2, fifth paragraph), “paired-end re-sequencing” (abstract), determining “T-DNA insertions” (pg. 4, col. 1, first paragraph), and “the insert is verified using common PCR and Sanger sequencing analysis” (pg. 2, col. 1, fifth paragraph). Park (Genomics and Informatics 13(3): 81-85, 2015; previously cited on the 02 June 2025 IDS form) teaches examination of “transgenic insertion sites using paired-end whole genome re-sequencing data” (pg. 82, col. 1, paragraph 2) including extraction of total genomic DNA (pg. 82, col. 2, paragraph 2) and “polymerase chain reaction (PCR) test to identify T-DNA” (pg. 84, Fig. 4 caption). Hammoudi (Plant Signaling & Behavior 12(3): 6 pgs., 2017; previously cited on the 02 June 2025 IDS form) teaches re-sequencing a whole genome to identify insertions which were confirmed with PCR (abstract). Therefore, these additional elements are considered well-understood, routine, and conventional at the effective filing date of the invention. The recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 02 September 2025 Applicant Remarks Related to 35 USC 101
Applicant remarks assert that claim 1 “only uses these calculation steps… within a larger framework that amounts to a practical application” and said calculations are merely “incidental” (pg. 10, last paragraph), and thus the analysis should be concluded at Step 2A. This argument is unpersuasive. At Step 2A Prong One, it is determined whether a judicial exception is recited (MPEP 2106.04). Based on the analysis above and in the applicant remarks, mental processes and mathematical concepts are claimed. At least mathematical concepts are recited in the claims, such as the copy number calculations, and not merely involved. The MPEP gives an example of the machine in the form of a teeter totter which recites physical structures which are governed by, or involved with, mathematical concepts to move but math is not claimed whatsoever (MPEP 2106.04(II)(1)). This is contrasted with the instant claims where a mathematical relationship or operation is required in the forms of counts and copy number determination. Therefore, analysis is continued at Step 2A Prong Two, in which it is determined whether the judicial exception(s) is/are integrated into a practical application by an additional element (MPEP 2106.04(d).
Applicant remarks further assert that physical steps are recited, including extracting DNA, re-sequencing, assembly, and ligation (pg. 11, first paragraph). As explained in the rejection above, these steps are interpreted as elements in addition to the abstract ideas and not abstract ideas. However, at Step 2A Prong Two, it is determined whether the judicial exception(s) is/are integrated into a practical application by an additional element (MPEP 2106.04(d). These steps are data collecting steps required to perform the abstract steps of determining copy number for the purpose of producing data in the form of site identification. As such, these elements in addition to the abstract ideas are considered insignificant extra-solution activity and thus do not integrate the abstract ideas in a practical application. Consequently, they are further analyzed for conventionality at Step 2B and found to be conventional in view of Yang, Park, and Hammoudi, as explained above.
Therefore, the rejection under 35 USC 101 is maintained.
Claims Free of the Art
The claims recite calculations for determining read counts for known or unknown expression vector sequences based on sequencing depth, read length, coverage. Similar art, such as Park (BMC Biotechnology 17(67): 8 pgs., 2017; previously cited on the 27 October 2021 PTO-892 form) and Yang (Scientific Reports 3(2839): 9 pgs., 2013; previously cited on the 02 June 2025 PTO-892 form) teach mapping vectors with similar methods, they do not teach the recited reference mapping based on single-end reads which may or may not match the vector, wild-type, both, or neither. Yang teaches a single end strategy and situations in which one end matches the host (or wild-type) and vector, but not further inclusion of multiple such reads as indicators of insertion site starts. Therefore, the instant claims are not interpreted as fairly taught or suggested by the prior art, and thus are considered free of the prior art.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685