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 .
Priority
This application filed 6/4/2021 is a continuation of 14/710229 now US Patent 11,053548 which claims benefit to US Provisional application 61/991839 filed 5/12/2014;
and is related to PCT/US15/30366 filed 5/12/2015.
Claim Status
Original claims 1-12 filed 6/4/2021 are pending and are currently under examination.
Information Disclosure Statement
The two information disclosure statements (IDS) submitted on 11/30/2022 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered 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.
Claim analysis
Claims 1 is directed towards a method for detecting copy number states of chromosomes. More specifically claim 1 has a step of ‘extracting DNA from a tumor-derived sample’ with the subsequent step which requires ‘sequencing’ and fragmenting the DNA into sequences of at least 300 base pairs to provide for sequence reads, and steps that provide obtaining read counts, calculating fractions from the read counts, multiplying each read fraction by a scaling factor to normalize and calling copy number with the ‘normalized scaled read fractions’.
Dependent claims have been amended and set forth further details on how each of the steps are performed and indication of application of the determination like diagnosing aneuploidy and for the source of the DNA and that the DNA is isolated as part of the extraction process.
In view of the guidance of the specification there is no new sequencing technologies provided, and for the breadth of resulting data the step of sequencing can be performed by any means known in the art that generates sequence reads. For the newly added step of extracting, the guidance of the specification provides a general overview of possible techniques that could be used. Further, the specification teaches sequencing itself is contemplated and within the scope of the claims in that certain next generation sequencing methods/technologies use capture as part of the sequencing process; see for example the teaching of 454 sequencing which “involves two steps. In the first step, DNA is sheared into fragments of approximately 300-800 base pairs, and the fragments are blunt ended. Oligonucleotide adaptors are then ligated to the ends of the fragments. The adaptors serve as primers for amplification and sequencing of the fragments (specification at page 34).
The steps that follow the generation of reads have not been amended, and still require ‘obtaining read counts’, ‘calculating read fractions’, multiplying each chromosomal read fraction by a scaling factor’ to normalize and ‘calling copy number’ based on these steps. Though broadly set forth in the claims for any means of capturing and sequencing, apparently implied in the physical steps of capturing and sequencing is that they are performed in a manner that the resulting reads when analyzed would be informative in calling copy number, otherwise the calculations would not result in accurate correlation of the reads and chromosome being analyzed.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a method. Specifically, the claims require a physical step of capturing and sequencing to produce reads.
For step 2A of the 101 analysis, the judicial exception of the claim is taking data of ‘read counts’ and using it to calculate a fractions and by multiplying it by a ‘scaling factor’ provide a normalization and make a correlation of the read count to copy number of a chromosome as the calculated chromosome state. In review of the guidance of the specification these steps are considered abstract instructional steps for analyzing sequence read data that is obtained from sequencing. The judicial exception is a set of instructions for analysis of sequence read data and appears to fall into the category of mathematical concepts for the use of mathematical relationships and/or the use of mathematical calculations as using a ‘scaling factor’ to make a correlation between read counts and chromosome ploidy; and also to the category of mental processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion). In this case each of the steps can be performed on paper or in one’s mind (depending on the amount of read data that needs to be evaluated from sequencing), where here providing the number of read counts in a sample versus an expected control could easily be evaluated to be the same or higher/lower representing duplication/deletion of the read represented by the read count.
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 have an additional element of obtaining read data, and appears that it can be separated from the analysis and does not appear to be an integrated practical application of the judicial exception that follows the data capture. This judicial exception requires steps recited at high level of generality and does not recite or require the use of a computer, and is not found to be a practical application of the judicial exception as broadly set forth even if implemented with the aid of a computer.
For step 2B of the 101 analysis, the claim includes additional steps considered additional elements in the claim which are directed to isolating DNA from a sample and using sequencing to obtain a read and read numbers. In review of the specification and art of record obtaining sequence data from the DNA isolated from a sample are considered conventional steps of obtaining data of DNA sequences from a sample (see for example Xie et al CNV-seq, a new method to detect copy number variation using high-throughput sequencing BMC Bioinformatics 2009) for methods taught and discussed in who teach the use of 454 sequencing to determine changes in chromosomal copy number/variability and FAST-SeqS: A Simple and Efficient Method for the Detection of Aneuploidy by Massively Parallel Sequencing Isaac Kinde, 2012). However, the claim have been amended to require a step of fragmenting into 300 base pairs as part of the sequencing step, which is not found in the relevant art and art of record to be a conventional step of sequencing to generate reads. The steps of the claim now require several steps considered additional elements that are not found to be conventional when analyzed under step 2B.
Accordingly, the claims are found to be patent eligible.
It is noted that the 101 analysis has been done for completeness and clarity of the record to provide interpretation and rational of the claim limitations.
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 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,053548. Although the claims at issue are not identical, they are not patentably distinct from each other because each method comprises the same active steps and source material and only differ in the interpretation of the data. No specific patient or type of individual is required of the claims, so practicing the steps are the same with the indication that the resulting analysis would or might indicate the aneuploidy is from cancer but could not distinguish if this were actually from an embryo or fetus, in particular for sources such as those listed in claims 8-9. A copy of the allowed independent claim of ‘548 is provided for comparison to instant pending claims.
A method for determining copy number states of chromosomes in a sample, the method comprising the steps of:
extracting DNA from an embryo-derived sample suspected to include at least one chromosome with an altered copy number;
sequencing the DNA to generate sequence reads, wherein sequencing includes fragmenting the DNA into sequences of at least 300 base pairs to generate the sequence reads;
obtaining read counts as a number of the sequence reads that map to each chromosome;
calculating chromosomal read fractions as the fraction per chromosome of a total of the read counts;
correcting an error caused by interdependence in the chromosomal read fractions by multiplying each chromosomal read fraction by a scaling factor that arithmetically minimizes a sum of distances between the read fractions and respective nearest whole number multiples of control euploid read fractions to obtain scaled read fractions;
normalizing the scaled read fractions by estimating the exact number of each chromosome in a given sample; and
calling a copy number for the embryo-derived sample using the normalized scaled read fractions from each chromosome.
Conclusion
No claim is allowed.
The closet art of record is Isaac Kinde, (7/2012), ‘Affiliation The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland, United States of America ⨯ FAST-SeqS: A Simple and Efficient Method for the Detection of Aneuploidy by Massively Parallel Sequencing’ and Sebastian M. Waszak ET AL: "Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity", PLoS Computational Biology, vol. 6, no. 11, 11 November 2010. It is noted that independent claim 1 relates to a method for detecting copy number states of chromosomes in a sample based on read counts , in which a scaling factor is used to minimize the distance between the observed read fraction for a chromosome and the nearest whole number multiple of a control euploid read. Each chromosomal read fraction is multiplied by the scaling factor. Claim 1 does not describe how the scaling factor is derived, nor does claim 1 describe at which stage and how a comparison between the sample chromosome(s) and the control chromosome(s) is performed. While the art of record appears to appreciate that read data can be used to correlate chromosome abnormality, none of the reference of record provide for the steps of calculating, generating and multiplying read fraction data as generally required of the claim.
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