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 Amendments
Applicants’ amendment filed 6/11/2026 has been received and entered. Claims 1-30, 32-39, 41-44, 48, 49 have been cancelled, claim 46 has been amended, and claims 50-64 have been added.
Claims 31, 40, 45-47, 50-64 are pending.
Election/Restriction
Applicant’s election without traverse of Group 1 in the reply filed on 6/11/2026 is acknowledged.
Claims from the non-elected groups have been cancelled in the instant response.
Newly added claims 50-64 are dependent on the elected independent and consistent with the elected group.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claims 31, 40, 45-47, 50-64 are pending and currently under examination.
Priority
This application filed 5/24/2021 is a continuation of 15/313705, filed 11/23/2016, now US Patent 11,047002, which a national stage filing of PCT/GB2015 filed 5/22/2015; and claims benefit to foreign application GB1409282.9 filed 5/23/2014 in United Kingdom.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The two information disclosure statement (IDS) submitted on 2/10/2022 and 7/28/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
It is noted that the IDS contain office actions related to foreign applications, but do not provide a context or specific claims or references that are discussed in the actions (see for example 8#s 38-42 of 7/28 IDS). These have been reviewed for what is provided within them, but the relevant application material such as specification, claims and cited references have not been used for the review.
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).
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.
Claims 31, 40, 45-47, 50-64 rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11,047002 (parent 15/313705 of this continuation). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims provide for the same steps with slightly different steps for introducing versus tagging, but use the same molecular tag configuration limitations, and a variation of the final requirement as optional for the second sequence generated.
Claim 1 of ‘002 is provided for comparison.
A method for generating sequences of at least one target template nucleic acid molecule comprising:
a) providing at least one sample of nucleic acid molecules comprising at least two target template nucleic acid molecules;
b) tagging each of the at least two target template nucleic acid molecules with a unique first molecular tag and a unique second molecular tag, wherein tagging each of the at least two target template nucleic acid molecules comprises introducing a unique first molecular tag and a stub sequence into one end of each of the at least two target template nucleic acid molecules and a unique second molecular tag and a stub sequence into the other end of each of the at least two target template nucleic acid molecules, thereby to provide at least two tagged template nucleic acid molecules wherein each of the at least two tagged template nucleic acid molecules is tagged with a unique first molecular tag and a unique second molecular tag;
c) amplifying the at least two tagged template nucleic acid molecules using primers which comprise a region which is capable of hybridizing to the stub sequence at each end of the tagged template nucleic acid molecules to provide multiple copies of the at least two tagged template nucleic acid molecules, wherein each of the copies of the at least two tagged template nucleic acid molecules comprises a first molecular tag and a second molecular tag;
d) sequencing regions of the multiple copies of the at least two tagged template nucleic acid molecules comprising the first molecular tag and the second molecular tag, wherein sequencing regions of the multiple copies of the at least two tagged template nucleic acid molecules comprises sequencing the first molecular tag and sequencing the second molecular tag of each of the multiple copies of the at least two tagged template nucleic acid molecules; and
e) reconstructing a consensus sequence for at least one of the at least two target template nucleic acid molecules; wherein step e) comprises
(i) identifying clusters of sequences of the multiple copies of the at least two tagged template nucleic acid molecules which are likely to correspond to the same target template nucleic acid molecule by assigning sequences comprising first molecular tag sequences which are homologous to one another and second molecular tag sequences which are homologous to one another to the same cluster;
(ii) selecting at least one cluster of sequences wherein the sequences within the selected cluster comprise a first molecular tag and a second molecular tag which are more commonly associated with one another than with a different first molecular tag or second molecular tag;
(iii) reconstructing a consensus sequence of a target template nucleic acid molecule by aligning sequences in the cluster selected in step (ii), and
defining a consensus sequence from the aligned sequences; and
optionally (iv) performing steps (ii) to (iii) in respect of a second and/or further template nucleic acid molecule.
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.
For completeness of the record, claims 31, 40, 45-47, 50-64 were analyzed under the 101 framework and found patent eligible. The analysis and logic is provided for clarity of the record of the Examiners analysis.
Claim analysis
Claims 31, 40, 45-47, 50-64 are generally drawn to a computer implemented method to generate consensus sequences of a target template and to a computer implemented method to generate sequences of a target template. Independent claim 31 requires providing a nucleic acid and introducing two unique molecular tags to two target templates, amplifying the tagged templates and sequencing the regions to provide read data and from the read data produced reconstructing and ‘defining a consensus sequence’ by identifying sequence regions by the tags and aligning sequences to arrive at a consensus sequence. The method of claim 31 is directed to a method that did not specifically require or recite the use of a computer to perform the analysis of step e) for reconstruction, however in light of the guidance of the specification the method also will be interpreted to be performed on a computer for the purposes of the 101 analysis.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of analyzing and accessing sequence data obtained from amplification and sequencing of a target template to reconstruct a consensus sequence of the template. In view of the guidance of the specification, the steps of reconstructing a consensus sequence require aligning and comparing sequence to arrive at the identification of overlapping ‘consensus’ sequences appear to be instructional steps for sequence analysis. The claim requires computing similarity scores of homologous reads. The judicial exception is a set of instructions for analysis of sequence data and appear to fall into the category of mental processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion). In this case there is no required complexity of the data being analyzed, only requiring analysis of one of two targets that were tagged and sequenced. Given the guidance of the specification the alignment and evaluation of sequences that share homology and evaluating end tags to sort/cluster the sequences into groups based on the presences of the tag ends, and appears that it can be practiced on paper or in one’s mind.
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 that follows the judicial exception, and the additional elements of the claim preceding the judicial exception appear to only provide the read data for analysis. However, claim 31 has physical steps considered additional elements, which as amended provide for a uniquely tagged sequence and unique read data reflecting the step of tagging. The analysis steps provided appear to be a practical application for evaluating the newly created sequences and read data provided. Under this step, it appears that the claims are patent eligible.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of tagging constructs and then obtaining sequence data for further analysis. However, as amended the claims require a non-conventional primer and sequence data obtained through the steps considered additional elements. While a search of the relevant art for PCR using multiple tagged primers identifies Eggert et al. who provides guidance for multiplex-PCR-based methodology as a reference where they purposely use multiplex to make overlapping constructs and have to analyze/cluster various constructs during the analysis, the claims as amended provide for a unique tag and means that differentiates it from Eggert et al. Further, while Schloss et al. is more on point with the guidance of the present specification recognizing problems based on targets with variability associated with them and discuss using and excluding artifacts from PCR amplification, and provide specifically for the use of ‘clustering’ programs to analyze the read data of 16S, the steps and primers required of the claims are not taught and do not appear to be conventional elements based on the art of record.
Accordingly, under this step the claims appear to be patent eligible for providing a combination of non-conventional steps and elements based on the art of record.
Conclusion
No claim is allowed.
The closest art of record is Schloss et al. (2011) and Armougom et al. (2009). It is noted that while Schloss et al. do teach clustering based on using pairwise sequence alignments instead of a multiple sequence alignment and that primer design for analysis of 16 can result in chimera formation, it fails to teach the combination of elements required of the instant tags or primer design as a means to identify 5’ and 3’ ends of a target sequence that is subsequently used in the methods of analysis presently claimed. With respect to Eggert et al. cited in the basis of the 101, it was noted for teaching a multiplex polymerase chain reaction (multiplex-PCR) generates gene fragments that contain preformed point mutations. In addition to the chimeras observed by Schloss et al. created as an artifact, Eggert et al. demonstrates directly that chimera can be generated by multiplex amplification protocols and is a source of error/artifact.
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.
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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.
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/Joseph Woitach/ Primary Examiner, Art Unit 1687
Prosecution Insights