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 .
Applicants Amendment
Applicants’ amendment filed 1/21/2026 has been received and entered. Claims 1-20 have been cancelled, claims 21-24, 26-27, 29, 31, 34-41 have been amended.
Claims 21-41 are pending and currently under examination.
Priority
This application filed 3/10/2021 is a continuation of application 15/705079 filed 9/14/2017 now US Patent 10971249, which claims benefit to US provisional application 62/395288 filed 9/15/2016.
There are no comments regarding the summary of priority claim in the instant response.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/21/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The review of the specification has identified a disclosure of a nucleic acid sequence, see specification at paragraph [0160] for sequence disclosed.
Applicants note that in the parent application 15/705079 filed 9/14/2017 now US Patent 10971249, a petition was filed which indicated that no sequence listing was required.
In view of the prior history and decision of the petition office in the parent application and the fact that this is a continuation application with no change in disclosure, the objection is withdrawn.
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 conflicting claims 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); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Response to Applicants arguments
Applicants acknowledge the rejection and argue that in light of the amendments the rejection is no longer appropriate as the claims are not obvious.
In response, no specific arguments or limitations are noted in the arguments. The claims have been amended to indicate the processing is performed in parallel and that matches are analyzed using hierarchical matching rules and the cache is used to store the observed kmer rules. The step of running processes in parallel is only generically provided in the specification and there does not appear to be any evidence that this limitation is not a conventional step of using a computer to perform multi-step processes and appears obvious. With respect to using hierarchically implemented rules, the specification does not appear to support any specific rules or any way of organizing any rules such that this limitation appears to be comprised in the claims of ‘249 for using rules to assess k-mer matches and store the information in a cache.
Given the amendments and guidance and evidence of the specification, the claims appear to be obvious one over the other. It appears that there are embodiments that when practicing one claim that the artisan would necessarily practice embodiments of the claims of the patent. There are no specific embodiments or limitations noted by applicants which are argued not obvious, and given the previous analysis and the rational above, the rejection is maintained.
The rejection has been updated and provided for completeness of the record.
Claims 21-41 stand rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10,971249 (the parent of this continuation). Although the claims at issue are not identical, they are not patentably distinct from each other because each provide broadly for a method of receiving primer sequences and assessing the primers to a reference genomic sequence. The present claim 21 is broader as it does not require assessing or clustering the primers as an initial step of the independent claim but does recite k-mers are ‘present in a cache’, and dependent claims 29 provide for organizing the cache by size and match, which the specification teaches is a means of clustering primers. Subsequently, the cache and matches are assessed by the same series of calculation steps. The independent claims directed to the system and media provide for the same methods.
The pending independent claims for the method are provided for completeness and clarity of the record.
Representative claim 1 of ‘249:
A computer-implemented method of identifying off-target matches from a set of candidate primer sequences on a genome reference sequence, the method comprising:
receiving onto a data storage unit a plurality of candidate primer sequences, wherein some or all of the plurality of candidate primer sequences are organized into clusters, wherein each cluster comprises a respective common region shared by candidate primer sequences within the respective cluster;
populating or updating a cache with one or more respective rule satisfaction calculations for respective common regions when they are initially evaluated as candidate matches or verified matches;
for each candidate primer sequence, calculating using a processor a plurality of candidate matches on the genome reference sequence for the candidate primer sequences, wherein calculating the plurality of candidate matches comprises reusing one or more rule satisfaction calculations for common regions when present in the cache;
calculating, using the processor, verified matches on the genome reference sequence based on the candidate matching locations satisfying a plurality of matching verification rules, wherein calculating the verified matches comprises reusing one or more rule satisfaction calculations for common regions when present in the cache;
performing matching calculations of the verified matches, using the processor, to determine whether the verified matches form an off-target match condition on the genome reference sequence; and
generating a location profile on the genome reference sequence based on the off- target match condition from the verified matches that meet a predetermined off-target threshold.
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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim Rejections - 35 USC § 112
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 21-41 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 pre-AIA the applicant regards as the invention is withdrawn.
In light of the amendments and plain meaning of the claim limitations, it is agreed that the claims are clear and definite.
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 21-41 stand 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
Claim 21 has been amended and still is generally directed to a computer implemented method for identifying the possible location or locations of homology for a primer within a given reference sequence. More specifically, the claims have been amended to indicate the processing is performed in ‘parallel’ and that matches are analyzed using ‘hierarchical’ matching rules and the cache is used to store the observed k-mer rules. The step of running processes in parallel is only generically provided in the specification and there does not appear to be any evidence that this limitation is not a conventional step of using a computer to perform multi-step processes and appears obvious. With respect to using hierarchically implemented rules, the specification does not appear to support any specific rules or any way of organizing any rules such that this limitation appears to be or provide anything but to perform analysis steps in some order. In view of the guidance of the specification, the claims are directed to a method implemented on a computer where the method takes a primer sequence and it is matched to a reference sequence, calculating a verifying the match, performing matching calculations of the verified matches and displaying a location profile within the reference based on the calculations as steps of analysis.
Response to Applicants arguments
Applicants provide guidance for 101 analysis and how it should be applied to the instant claims for each of the steps. Applicants argue that amendments have obviated the 101 rejection because the computer performs the method steps in ‘parallel’ and that there is a multi-level cache.
In response, review of newly added limitations in view of the specification does not appear to support that the limitations obviate the basis of the rejection. While parallel processing is something a computer can provide, the specification supports ‘parallel’ only once and generically supports that ‘In practice, parallel and/or concurrent computation scenarios can be applied.’ (in [075]) and appears to be conventional implementation using a general purpose computer. There is no guidance nor evidence that this integrates or the method as claimed such that it is patent eligible. Similarly, using cache or memory to provide rules or store information during an analysis process appears conventional, and again the specification provides no evidence nor any specific guidance for the claimed method steps affecting the analysis process or processing by the computer.
Applicants cite XY, McRo and Myriad and argue the claims do not preempt others from analyzing kmers in reference sequences.
In response, preemption is just one factor that is considered and by itself is not the basis of patent eligibility. Here, the record has made clear that using kmer searches of a reference sequence were well known and practiced, but importantly given the breadth of the claims the recited steps are considered abstract and steps one can perform using one’s mind. Unlike McRo, there are not specific rules in the specification, nor any support for ‘hierarchal’ application of any rules such the claims in light of the specification provide a fact pattern consistent with McRo. With respect to comparison of XY and the instant claims, the instant claims only require matching ATGC nucleotide bases between a reference and a kmer, and does not appear to be consistent with the fact pattern of molecular structure discussed in XY.
Applicants cite Example 38 and Example 39, and argue that claims do not require any mathematical calculations.
In response, it is acknowledged that the claims do not have specific algorithms recited, but do provide limitations of ‘performing matching calculations’ and for completeness have been interpreted to be mathematical in nature. It is agreed that the claims do not attempt to capture an algorithm by itself, but the analysis of the judicial exception of the claims attempts to describe the nature and requirements of the analysis steps comprised within the claims. With respect to Examples 38 and 39, the fact pattern of analyzing images versus simple linear sequence strings is not found analogous.
Applicants arguments have been fully considered but not found persuasive. Accordingly, the rejection has been maintained.
Updated 101 analysis and rejection for clarity of the record.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
Here, a computer implemented method where the processing instructions of the analysis and data can be stored on a non-transitory medium.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of accessing sequence data for homology of a primer to a reference, and providing calculations based on user input for an ultimate predetermined threshold that results in profile for the locations of primers within the reference. In view of the specification and art of record, the step of aligning and comparing sequence to arrive at the identification of verified matches and the location(s) of the sequences in a given reference are instructional steps. The claim requires computing similarity scores to identify a match/homology. The judicial exception is a set of instructions for analysis of sequence data and appear to fall into the category of Mathematical Concepts in the recitation of that encompasses mathematical calculations, and into the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) as there is no specific requirement for the size or complexity of the data analyzed and no specific rules that appear to require any complex calculations and provide for analysis and display of sequences similar as displayed in figures 14 and 16.
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 the method as a whole appear to be instructions for a computer implemented method of matching shorter primer sequences to larger genomic sequences to determine homology or identity between the two. With respect to computer implementation, this judicial exception requires steps recited at high level of generality and are only implemented on a computer or computer system, and is not found to be a practical application of the judicial exception as broadly set forth but rather analysis performed with the aid of a computer.
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. As such, the claims do not provide for any additional element to consider under step 2B. 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. Based upon an analysis with respect to the claim as a whole, claims 21-41 do not recite something significantly different than a judicial exception which are practiced with the aid of a computer. Claims 21-41 are directed towards a method of receiving sequence data and comparing the data to references sequences, with the broad indication that rules are used and applied to calculations for verification of matches. 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. It is noted that while the claims set forth or imply information about the sequences being analyzed (that they are on specific or represent off-site targets that may be present in a genome), this is only general high level description of the data being analyzed and context and user defined with respect to any genome, any target, any k-mer size. For example, encompassed by the claims is choosing primers to a known genomic region and assessing these to that specific region for homology, then assessment under specific hybridization conditions whether the primer will bind or not. As such, the instant claims set forth an inventive concept that are drawn only to an abstract process that only manipulates data as all this analysis can be visual and/or computational, therefore, are not directed to statutory subject matter. 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 probe that binds a specific sequence within a genomic target) 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.
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 § 103
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 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.
Claims 21-41 rejected under 35 U.S.C. 103 as being unpatentable over Graham et al. (2005), Gardner et al. (2014-of record), Primer-BLAST (2012-of record), NCBI website (of record) and Valimaki et al. (2013-of record) is withdrawn.
Claim 21 broadly provides for a computer implemented method for identifying the possible location or locations of homology for a primer within a given reference genome sequence. However as amended, the art of record does not provide for hierarchical rules in the analysis process.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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, Karlheinz R Skowronek can be reached at 571 272-9047. 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.
/Joseph Woitach/ Primary Examiner, Art Unit 1687
Prosecution Insights