CTNF 17/817,551 CTNF 101435 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority Acknowledgement is made of the provisional application filed on 08/05/2021 and currently considered the effective filing date. Information Disclosure Statement The information disclosure statements received 08/04/2022 and 02/16/2024 have been considered. 12-151 AIA 26-51 12-51 Status of Claims Claims 11-13, 23-24, and 26-71 are cancelled. Claims 1-10, 14-22 and 25 are currently pending and being examined on the merits. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claims 1-10, 14-22 and 25 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. Claims 1 and 14, recite “a desired edit of a sequence segment” in lines 3-4, respectively. The term “desired” is a relative term and indefinite. The specification is silent regarding a clear and precise definition of “desired edit”. One skilled in the art would not recognize the metes and bounds of the limitation. Claim 9 recites “the selected at least one of the multiple guide nucleic acid sequences” in the last line. The limitation “the selected…sequences” lacks antecedent basis. Claim 1 does not have an active step of selecting a multiple guide nucleic acid sequence, but merely an intent for such selection, i.e. “permitting selection, from the report, of at least one of the multiple guide nucleic acid sequences” in the penultimate and last lines. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more. Step 2A, Prong 1 In accordance with MPEP § 2106, claims found to recite statutory subject matter (claim 1-10 are drawn to a method; claims 14-22 and 25 are drawn to a system) ( 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: Claims 1 and 14 recite: “…identifying…one or more characteristics of the guide nucleic acid sequence and/or sequence segment…”, mental step, i.e. can be done with pen or paper “…assigning…a score to the guide nucleic acid sequence for each of the identified one or more characteristics…”, mental step “…aggregating…the assigned scores into an edit score for the guide nucleic acid sequence…”, mental step, or mathematical concept of addition “…compiling…a report…”, mental step Claims 2 and 15 recite: “…receiving a request for the desired edit…”, mental step “…identifying the multiple guide nucleic acid sequences based on the desired edit of the sequence segment of the target organism and/or a location in the sequence segment” , mental step Claim 3 recites: “…the request includes a defined effectivity rate for the desired edit of the sequence segment.”, which limits claim 2. Claims 4 and 17 recite: “…identifying the one or more characteristics, based on a scoring data structure, in the guide nucleic acid sequence …” , mental step Claims 5 and 18 recite: “…identifying the one or more characteristics, based on a scoring data structure, in the sequence segment…” , mental step Claims 7 and 20 recite: “…summing the scores assigned to the guide nucleic acid sequence for each of the identified one or more characteristics…” , mental step Claims 8 and 21 recite: “…identifying the at least one of the multiple guide nucleic acid sequences… based on the associated edit score…”, mental step “…determining…a number of experiments and/or samples for the at least one of the multiple guide nucleic acid sequences, based on the edit score and a defined effectivity rate from the request and/or based on an effectivity rate of the at least one of the multiple guide nucleic acid sequences Claim 9 recites: “…editing the sequence segment of the target organism using the selected at least one of the multiple guide nucleic acid sequences…” , mental step Claim 25 recites: “…compile a report including the multiple guide nucleic acid sequences and the edit score for each of the multiple guide nucleic acid sequences…” , mental step The claims recite an abstract idea of analyzing and modifying genomic sequences (See MPEP 2106.07(a)). These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. While claims 14, 15, 17, 18, 20, 21, and 25 recite performing some aspects of the analysis using a “system”, there are no additional limitations that indicate that this model requires anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1-10 recite(s) an abstract idea/law of nature/natural phenomenon ( 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 to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements: Claims 1 and 14 recite: “…a genome editor computing device…” “…memory…” (clm. 14, ln. 9) Claims 2 and 15 recite: “…receiving a request for the desired edit…” There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. As such, claims 1-25 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 recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The instant claims recite the following additional elements: Regarding claims 1-25 , the steps of outputting sequencing data, aggregating scores related to said sequencing data, and the receiving of a request (which amounts to input of information) do not integrate the abstract idea into a practical application and constitutes an insignificant extra-solution activity (i.e., data gathering and presentation), which does not impose a meaningful limit on the abstract idea (see MPEP 2106.05 (g). Additionally, as discussed above, there are no additional limitations to indicate that the claimed analysis requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. Furthermore, the additional elements recited in the claims amount to well-understood, routine and conventional activity, as evidenced by Gooden et al. (Nucleic Acids Res. 2021 Jan 8;49(D1):D871-D876) and Chen et al. (Nucleic Acids Res. 2019 Jan 8;47(D1):D63-D68.) The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself ( Step 2B : No ). As such, claims 1-25 is/are not patent eligible. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 07-15 AIA Claim (s) 1-6, 8, 14-19, 21 and 25 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Gooden et al (Nucleic Acids Res. 2020 Oct 13;49(D1):D871–D876) . Gooden et al. is directed to a database of functionally validated guide RNAs for genome editing in human and mouse cells. In regard to claims 1 and 14 , Gooden et al. teaches dbGuide, a database of functionally validated guide RNA sequences for CRISPR/Cas9-based knockout in human and mouse (Intro, pg. D871, re: clm. 1, A computer-implemented method for use in identifying one or more mechanisms for editing a genome sequence…) . Gooden teaches a manually curated database of guide RNA sequences from over 1000 peer-reviewed articles with each sequence having direct reference to the original publication, with the results of targeted amplicon sequencing for ∼ 2000 unique sgRNA sequences tested individually in human (293T) or mouse (NIH-3T3 or P19) cultured cells publicly searchable in the database for “a total of nearly 6000 unique guide RNA sequences for which some level of validated activity exists.” (Intro, pg. D871, re: clm. 1, …for each of multiple guide nucleic acid sequences, for a desired edit of a sequence segment of a target organism: identifying, by a genome editor computing device, one or more characteristics of the guide nucleic acid sequence and/or sequence segment…) . Gooden et al. further teaches a user interface allowing a user to search for and obtain a report of information about guide RNA sequences, including scoring metrics associated with base editing specificity. Gooden et al. specifically cites the use of sgrnascorer on pg. D875, a design tool listed on Table 1, which delivers “predicted activity using the sgRNA Scorer 2.0 algorithm (−3 to 3). Higher the value, greater the predicted activity…” ( re: clm. 1, clm. 14, A computer -implemented method/A system for use in identifying one or more mechanisms for editing a genome sequence, the method comprising…one or more characteristics of the guide nucleic acid sequence and/or sequence segment… assigning, by the genome editor computing device, based on a scoring data structure, a score to the guide nucleic acid sequence for each of the identified one or more characteristics; and aggregating, by the genome editor computing device, the assigned scores into an edit score for the guide nucleic acid sequence;) . The “activity”, in this case, refers to the ability of guide RNAs to direct a chosen base editing system (such as CRISPR) to splice genomic region, as disclosed on pg. D872: “Quantitative editing data for nearly 2000 sgRNA sequences were generated internally from either transfection of Cas9 / sgRNA plasmids or Cas9 protein…” and on pg. D875, “Downloading sequences for use in experiments”, stating: “It is highly recommended to select and download multiple guide RNA sequences when performing knockout experiments to ensure any functional consequences observed may not be due to spurious off-target activity from a single guide RNA…” Therefore, Gooden et al. teaches on the limitations of identifying one or more mechanisms for editing a genome sequence (pg. D874-D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: clm. 1, clm. 14, A computer -implemented method/A system for use in identifying one or more mechanisms for editing a genome sequence, the method comprising…one or more characteristics of the guide nucleic acid sequence and/or sequence segment; assigning, by the genome editor computing device, based on a scoring data structure, a score to the guide nucleic acid sequence for each of the identified one or more characteristics; and aggregating, by the genome editor computing device, the assigned scores into an edit score for the guide nucleic acid sequence; and then compiling, by the genome editor computing device, a report, wherein the report includes the multiple guide nucleic acid sequences and the edit score for each of the multiple guide nucleic acid sequences, thereby permitting selection, from the report, of at least one of the multiple guide nucleic acid sequences based on the associated edit score.) As Gooden et al. teaches a database of functionally validated guide RNA sequences from which a user may generate a report containing specificity scores, Gooden anticipates claims 1 and 14. In regard to claims 2 and 15 , Gooden et al. teaches receiving user requests for a desired edit of a sequence segment via input of a sgRNA spacer sequence into a query, and returns guide sequences based upon the limitations set by the user’s query (pg. D873-D875, “Opening user interface”, Fig. 2, re: clm. 2 and 15 , …receiving a request for the desired edit; and identifying the multiple guide nucleic acid sequences based on the desired edit of the sequence segment of the target organism and/or a location in the sequence segment…) . As Gooden et al. teaches receiving user requests for a desired edit of a sequence segment via input of a sgRNA spacer sequence into a query, Gooden et al. anticipates claims 2 and 15. In regard to claim 3 and 16 , the applicant’s disclosure in the specification, “effectivity rate” is defined by the user and/or the desired edit. Gooden et al. teaches a report of the specificity of the guide nucleotide sequence via a guidescan off-target score, which inherently accompanies the effectiveness of a guide sequence (pg. D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: clm. 3 and 16, ...wherein the request includes a defined effectivity rate for the desired edit of the sequence segment ). As Gooden et al. teaches a report of the specificity of the guide nucleotide sequence, Gooden et al. anticipates claims 3 and 16. In regard to claims 4 and 17 , Gooden et al. teaches guide sequence search results based on a scoring data structure (pg. D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: clm. 4 and 17, … wherein identifying one or more characteristics includes identifying the one or more characteristics, based on a scoring data structure, in the guide nucleic acid sequence ). As Gooden et al. teaches guide sequence search results based on a scoring data structure, Gooden et al. anticipates claims 4 and 17. In regard to claims 5, 18, and 25 Gooden et al. teaches a report of the chromosome position associated with the guide sequence as well as scores associated with the guide sequence (pg. D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: clm. 5 and 18 , … wherein identifying one or more characteristics includes identifying the one or more characteristics, based on a scoring data structure, in the sequence segment, re: clm. 25, wherein the genome editor computing device is further configured to compile a report including the multiple guide nucleic acid sequences and the edit score for each of the multiple guide nucleic acid sequences ). As Gooden et al. teaches a report of the chromosome position associated with the guide sequence, Gooden et al. anticipates claims 5, 18 and 25. In regard to claims 6 and 19, Gooden et al. teaches predicted mutational outcomes associated with application of the guide sequence via Favored Outcomes of Repair Events at Cas9 targets (FORECasT) score, and a report of calculations of non-homologous end joining (NHEJ) mutation frequencies (pg. D873-D875, “Analysis of targeted amplicon sequencing data”, “Search results when searching by gene/coordinate/accession”, Fig. 2, re: clm. 6 and 19 , … wherein the one or more characteristics are independently selected from: …DNA modifications… ). As Gooden et al. teaches predicted mutational outcomes associated with guide RNAs, Gooden et al. anticipates claims 6 and and 19. In regard to claims 8 and 21, Gooden et al. teaches an exportable PDF of experimental applications for guide RNA sequences of interest post-user query (pg. D875, “Downloading sequences for use in experiments”, re: clm. 8 and 21, … the genome editor computing device is further configured to: identify the at least one of the multiple guide nucleic acid sequences, from the memory, based on the associated edit score; and/or determine a number of experiments and/or samples for the at least one of the multiple guide nucleic acid sequences, based on the edit score and a defined effectivity rate from the request and/or based on an effectivity rate of the at least one of the multiple guide nucleic acid sequences …). As Gooden et al. teaches a method to identify a number of experiments and/or samples for the at least one of the multiple guide nucleic acid sequences , Gooden et al . anticipates claims 8 and 21 . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim (s) 7 and 20, are rejected under 35 U.S.C. 103 as being unpatentable over Gooden et al. (Nucleic Acids Res. 2020 Oct 13;49(D1):D871–D876) as applied to claims 1-6, 8, 14-19, 21 and 25 above, in view of Tycko et al. (Mol Cell. 2016 Aug 4;63(3):355-70.) . Claims 7 and 20 are directed to aggregating the assigned scores into the edit score for the guide nucleic acid sequence and summing the scores assigned to the guide nucleic acid sequence for each of the identified one or more characteristics. Gooden et al. is applied to claims 1-6, 8, 14-19, 21 and 25 above. In regard to claims 7 and 20 , Gooden et al. teaches a computer-implemented method of identifying characteristics of guide nucleic acid sequences and assigning scores to said sequences (pg. D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: clms. 7 and 20, The computer-implemented method…wherein aggregating the assigned scores into the edit score for the guide nucleic acid sequence… ). Gooden et al. does not teach summing the scores assigned to the guide nucleic acid sequence for each of the identified one or more characteristics. Tycko et al. teaches scoring guides based on a weighted sum of the mismatches in their off-target sites, with weights experimentally determined to reflect the effect of the mismatch position on cleavage efficiency, via a specificity score (pg. 5, “Computational guide RNA selection and predictive models”, Table 1, Table 2, re: clms. 7 and 20, … summing the scores assigned to the guide nucleic acid sequence for each of the identified one or more characteristics … in order to aggregate the assigned scores into the edit score for the guide nucleic acid sequence, to sum the scores assigned to the guide nucleic acid sequence for each of the identified one or more characteristics. ). In KSR Int 'l v. Teleflex, the Supreme Court, in rejecting the rigid application of the teaching, suggestion, and motivation test by the Federal Circuit, indicated that “The principles underlying [earlier] cases are instructive when the question is whether a patent claiming the combination of elements of prior art is obvious. When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR Int'l v. Teleflex lnc., 127 S. Ct. 1727, 1740 (2007). Applying the KSR standard to Gooden et al. and Tycko et al. the examiner concludes that the combination of the computer-implemented method of identifying characteristics of guide nucleic acid sequences and assigning scores to said sequences according to Gooden et al. with scoring guides based on a weighted sum of the mismatches in their off-target sites as disclosed by Tycko et al. represents some teaching, suggestion or motivation in the prior art that would have lead one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to predictably lead to a computational method of aggregating scores for guide nucleic acid, including summing at least one score associated with a characteristic for the guide nucleic acid (in this case, the score would be the specificity score as disclosed by Tycho et al. ) Gooden et al. discloses in their abstract that their framework will allow for continual addition of experimentally validated guide RNA sequences, inviting collaboration from those skilled in the art to contribute. Given Gooden et al. states in their results and discussion on pg. D873 that their database: “…uses a simple HTML interface which utilizes the datatables and highcharts javascript libraries for displaying data in tabular and graphical formats, respectively (Figure 1A). The application is built in python using django with a MySQL database used for data storage and retrieval.” And Gooden et al states in their abstract that the framework will “…allow for continual addition of newly published and experimentally validated guide RNA sequences for CRISPR/Cas9-based knockout as well as incorporation of sequences from different gene editing systems, additional species and other types of site-specific functionalities such as base editing, gene activation, repression and epigenetic modification.”, one skilled in the art could add Tycho et al’s summation teaching to Gooden et al.’s database as an additional method of scoring guide sequences with no change to the function of either art, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of the invention. One of ordinary skill in the art of sequence analysis before the effective filing date of the claimed invention would have had a reasonable expectation of success because contributing Tycho et al’s summation teaching to Gooden et al.’s database as an additional method of scoring would have made Gooden et al’s database stronger in that it would provide more accessible avenues to collect, gauge the effectiveness and specificity of, and otherwise analyze guide nucleic acid sequences that could be compared with to other sequences from external experimental sources, enhancing the volume and significance of data collected. Therefore, the invention would have been prima facie obvious to one of skill in the art at the time of filing of the application, absent evidence to the contrary . 07-21-aia AIA Claim s 9, 10, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Gooden et al. (Nucleic Acids Res. 2020 Oct 13;49(D1):D871–D876), as applied to claims 1-6-8, 14-20, 21 and 25 above, in view of Liang et al (Sci Rep. 2016 Feb 19;6:21451.) . Gooden et al. is directed to a database of functionally validated guide RNAs for genome editing in human and mouse cells. Liang et al. is directed to methods of evaluating the design and efficiency of sgRNAs in plants. Claim 9 is directed to editing the sequence segment of the target organism using the selected at least one of the multiple guide nucleic acid sequences. Claims 10 and 22 are directed to a plant being a target organism for a guide nucleic acid sequence. Gooden et al. is applied to claims 1-6, 8, 14-19, 21 and 25 as taught in the aforementioned 35 U.S.C. 102 claim rejection. Gooden et al. is applied to claims 7 and 20 as taught in the aforementioned 35 U.S.C. 103 claim rejection. In regard to claims 9, 10, and 22 , Gooden et al. teaches a computer-implemented method of identifying characteristics of guide nucleic acid sequences and assigning scores to said sequences (pg. D875, Fig. 2, “Search results when searching by gene/coordinate/accession”, re: cls. 9, The computer-implemented method… ). Gooden et al. does not teach editing the sequence segment of the target organism using one of the multiple selected guide nucleic acid sequences nor does their teaching include a plant as stated in claims 10 and 22. Liang et al. teaches a method to develop CRISPR/Cas9-sgRNA system for multiplex editing in plants, collected and analyzed those sgRNAs which have been validated in plants in the process, and performed experimental testing in rice plants (pg. 2, supplemental Table 1, Results, pg. 4, “Highly efficient genome editing.”, pg. 5, Table 1, re: clm. 9, …editing the sequence segment of the target organism using the selected at least one of the multiple guide nucleic acid sequences, clms. 1 and 22, …wherein the target organism includes a plant. ) Applying the KSR standard to Gooden et al. and Liang et al. the examiner concludes that the combination of the computer-implemented method of collecting and displaying guide nucleic acid sequences for a user, identifying characteristics of said guide nucleic acid sequences and assigning scores to said sequences according to Gooden et al. with the CRISPR/Cas9-sgRNA system for multiplex editing in plants as disclosed by Liang et al. represents some teaching, suggestion or motivation in the prior art that would have lead one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to predictably lead to a computational method of aggregating scores for guide nucleic acids, including those that are validated to effectively target and edit plant nucleic acid sequences. Gooden et al. discloses in their abstract that their framework will allow for continual addition of experimentally validated guide RNA sequences, inviting collaboration from those skilled in the art (Liang et al., in this case) to contribute. Additionally, Gooden et al.’s database of guide nucleic acid sequences was sourced from published scientific articles containing experimentally validated sequences, such that Liang et al. may have been included had it not been published prior to Gooden et al. Additionally, Gooden et al. ’s database is available for modification (pg. D875, “…a link to an excel spreadsheet template is provided for researchers wishing to contribute to the database.”). Finally, Liang et al. disclose a desire to contribute to plant sequence editing efficiency, stating on pg. 2: “Although several online tools were developed for highly specific sgRNA selection, the tools for the evaluation of sgRNA editing efficiency in plants are still lacking. Unlike the screening libraries in animal cell lines, genome editing in plants takes long time to obtain transgenic products. Thus, criteria that can be used to distinguish efficient and inefficient sgRNAs are of great utility for avoiding generation of non-edited transgenic plants resulting from inefficient sgRNAs.” As Gooden et al.’s database serves as a repository of guide sequences accessible to a public user, one skilled in the art could add Liang et al.’s teaching to Gooden et al.’s database as an additional method of scoring guide sequences with no change to the function of either art, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of the invention. One of ordinary skill in the art of sequence analysis before the effective filing date of the claimed invention would have had a reasonable expectation of success because Gooden et al. and Liang et al. disclose collections of guide sequences for use in living organisms, and one skilled in the art of sequencing and bioinformatics could reasonably contribute Liang et al.’s CRISPR/Cas9-sgRNA system for multiplex editing in plants and plant-validated guide nucleic acids teaching to Gooden et al.’s database as an additional source of experiments and experimentally validated guide nucleic acid sequences to generate a stronger database of guide sequences and examples of how to use them. Therefore, the invention would have been prima facie obvious to one of skill in the art at the time of filing of the application, absent evidence to the contrary. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN T STUBBS whose telephone number is (571)272-0340. The examiner can normally be reached M-F 8-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry Riggs can be reached at 571-270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /J.T.S./Examiner, Art Unit 1686 /LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686 Application/Control Number: 17/817,551 Page 2 Art Unit: 1686 Application/Control Number: 17/817,551 Page 3 Art Unit: 1686
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