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 .
Priority
This application filed 08/17/2023 claims priority from Provisional Application 63371942, filed 08/19/2022. The claims are therefore examined as filed on 08/19/2022, the effective filing date. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further review of the priority application(s).
Claim Status
Claims 1-20 are pending.
Claims 1-20 are examined.
Claims 1-20 are rejected.
Information Disclosure Statement
The Information Disclosure Statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, all references have been considered.
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 5-6 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 5 states that one or more of the operations (of claim 1) comprise analyzing the sample to determine genetic sequences, epigenetic data or a transcriptional state associated with the genetic molecules and the tumor genetic molecules, while claim 6 further states that the analysis comprises whole exome sequencing or whole genome sequencing. These are unclear with respect to claim 1, which recites a general computer system for performing the operations. Claim 1 does not recite any kind of sequencing device for determining genetic sequences/performing whole exome or whole genome sequencing, and only describes a computer system capable of receiving and analyzing sequenced data, while claims 5 and 6 imply that the computer itself is performing the sequencing operations. It is unclear if claims 5 and 6 are meant to describe the data received (implying that the data had been previously sequenced prior to being received by the computer) or if the computer system of claim 1 was meant to also include a sequencing device coupled to the computer system for performing sequencing operations. Therefore claims 5 and 6 are indefinite due to lack of clarity.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental processes and mathematical concepts, without significantly more.
The MPEP at MPEP 2106 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of matter?
(2A)(1) Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea?
(2A)(2) Do the claims recite additional elements that integrate the judicial exception into a practical application?
(2B) If the claims recite a judicial exception and do not integrate the judicial exception, do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?
With regard to step (1) (Are the claims directed to a process, machine, manufacture or composition of matter?): Yes. The claims are directed to one of the statutory classes. Claims 1-13 are directed to a product (a computer system comprising an interface circuit, computation device and memory), claims 14-16 are also directed to a product (a non-transitory computer readable storage medium), and claims 17-20 are directed to a process (a method that uses a computer system).
With regard to step (2A)(1) (Do the claims recite a judicially recognized exception?): Yes. The claims recite the abstract ideas of processing data using mental steps and mathematical concepts. Claims that recite nothing more than abstract ideas, natural phenomena, or laws of nature are not eligible for patent protection (see MPEP 2106.04).
Abstract ideas include mathematical concepts, (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (See MPEP 2106.04(a)(2)). In particular, these abstract ideas include but are not limited to:
Determining a sample-specific dynamic quality metric based on a type of cancer, sequencing coverage of one or more cancer-specific genomic targets associated with the type of cancer, and a first ratio of the number of tumor genetic molecules to a sum of the number tumor genetic molecules and the number of genetic molecules or a second ratio of the number of tumor genetic molecules to the number of genetic molecules (mental process/mathematical concept; the human mind is capable of determining a quality metric based on data, and determining a metric from data is equivalent to performing a calculation; claims 1, 14, 17)
Selectively providing an indication of whether a mutation or the type of cancer is present in the sample based on a comparison of the sample-specific dynamic quality metric and a threshold (mental process/mathematical concept; the human mind is capable of providing an indication based on a comparison of a numerical value to a threshold, comparing a numerical value to a threshold is a mathematical concept; claims 1, 14, 17)
Providing one or more treatment recommendations based at least in part on the indication (mental process; the human mind is capable of providing a recommendation based on data/an indication; claim 4)
Dependent claims 2-3, 10-13, 15-16 and 19-20 further limit the abstract ideas recited in the independent claims, and do not change their characterization as abstract ideas.
Therefore, the claims recite elements that constitute one or more judicial exceptions.
With regard to step (2A)(2) (Do the claims recite additional elements that integrate the judicial exception into a practical application?): No. Claim 1 and its dependents recite the additional element of a computer system comprising an interface circuit, computation device and memory for performing the claim steps. Claim 14 and it’s dependents recite the additional element of a non-transitory computer readable storage medium, and claim 17 and its dependents also recite the additional element of performing the method steps using a computer system. The claims also all recite the additional element of receiving information corresponding to the sample that is associated with a tissue biopsy or a liquid biopsy. Claims 5 and 6 further describe sequencing operations performed on a sample, claim 7 further describes receiving the information by accessing the information in memory, and claims 9 and 18 further describe the data received.
While the claims recite the additional element of receiving data, such steps that only amount to necessary data gathering , without any technical details of how the data is obtained that integrate the judicial exception, are insignificant extrasolution activities that do not add a meaningful limitation to the claims (see MPEP 2106.05(g)). As a result, the judicial exception is not integrated into a practical application. In addition, while the claims recite additional elements related to the use of computers, they do not provide any specific details by which the computer system comprising an interface circuit, computation device, memory, or computer readable storage medium performs or carries out the judicial exception listed in step (2A)(1), nor do they provide any details of how specific structures of the computer are used to implement these functions. The judicial exception is therefore not integrated into a practical application because the generically recited computer elements do not add a meaningful limitation to the abstract idea, as they amount to simply implementing the abstract idea on a computer (see MPEP 2106.05(f)). Because the claims do not recite any additional elements that integrate the judicial exception into a practical application, the claims as a whole are directed to an abstract idea.
With regard to step (2B) (Do the claims recite additional elements that provide an inventive concept and amount to significantly more than the judicial exception?): No. The claims recite an abstract idea with additional elements; however, these additional elements are general computer elements added to abstract ideas, and non-particular instructions to apply the abstract idea by linking it to a field of use or extrasolution activity (see MPEP 2106.05(f-h)). General computer elements used to perform an abstract idea do not provide an inventive concept, and similarly, non-particular instructions to gather or produce data do not provide an inventive concept. Non-particular instructions to gather data, by receiving data using computer elements or by sequencing, are also considered well-understood, routine and conventional activities (see MPEP 2106.05(d), which indicates that limitations such as “Receiving or transmitting data over a network” from Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362, “Storing and retrieving information in memory” from Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, and “Amplifying and sequencing nucleic acid sequences”, from University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014) are recognized as conventional activities). The claims therefore do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As a result, the claims as a whole do not provide an inventive concept.
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.
Claim Rejection
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over FINKLE 2021 “Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA”.
Claim Interpretation and Scope and Contents of Prior Art
Claims 1, 14 and 17 recite a computer system, non-transitory computer-readable storage medium, and method using a computer system, respectively, with operations/steps that comprise receiving information corresponding to a sample that is associated with a tissue biopsy or a liquid biopsy, wherein the sample comprises a number of genetic molecules associated with normal tissue, and a number of tumor genetic molecules associated with a tumor.
With respect to these limitations, FINKLE teaches methods and systems for validating a liquid biopsy of circulating tumor DNA, comprising sequencing tissue and liquid biopsy samples and analyzing them in a bioinformatics pipeline using general computer elements (pg 8-9), where the sample comprises a number of genetic molecules (cell-free DNA) associated with a tumor and with normal tissue (tumor fraction; pg 10).
Claims 1, 14 and 17 further recite determining a sample-specific dynamic quality metric based at least in part on: a type of cancer, sequencing coverage of one or more cancer-specific genomic targets associated with the type of cancer, and a first ratio of the number of tumor genetic molecules to a sum of the number tumor genetic molecules and the number of genetic molecules or a second ratio of the number of tumor genetic molecules to the number of genetic molecules and based at least in part on a comparison of the sample-specific dynamic quality metric and a threshold, selectively providing an indication of whether a mutation or the type of cancer is present in the sample.
With respect to these limitations, FINKLE teaches filtering variants based on a set of quality metrics including coverage, VAF, strand bias, and genomic complexity (pg 9 col 1) and also teaches determining a sample-specific dynamic quality metric based on individual cancer cohorts and individual genes which is compared to a dynamic threshold (pg 10 col 1), combined with sequencing coverage metrics and tumor fraction estimations to determine if a variant is present/accurate (pg 10). FINKLE does not teach using a single dynamic quality metric for making variant determinations, however it would be obvious to one of ordinary skill that any/all of the metrics of FINKLE can be combined to produce the same result of validating the determined mutation/variant.
Claim 2 recites the limitation wherein the mutation comprises: a single nucleotide variation (SNV), a copy number variation, a fusion, an insertion, a deletion or an epigenetic change. With respect to this limitation, FINKLE teaches that the mutations can comprise SNVs, Indels, copy number variations, and fusions (Table 1).
Claim 3 recites the limitation wherein the genetic molecules comprise deoxyribonucleic acid (DNA). With respect to this limitation, FINKLE teaches that the genetic molecules are DNA (pg 2, pg 8).
Claim 4 recites the limitation wherein the one or more operations comprise providing one or more treatment recommendations based at least in part on the indication. With respect to this limitation, FINKLE teaches that its method can be used to support oncologic treatment decisions (pg 1 col 2) and for monitoring disease progression and assessing treatment outcomes (pg 8 col 1).
Claim 5 recites the limitation wherein the one or more operations comprise analyzing the sample to determine genetic sequences, epigenetic data or a transcriptional state associated with the genetic molecules and the tumor genetic molecules. With respect to this limitation, FINKLE teaches analyzing the sample to determine genetic sequences (pg 8).
Claim 6 recites the limitation wherein the analysis comprises whole exome sequencing or whole genome sequencing. With respect to this limitation, FINKLE teaches using whole genome sequencing to analyze samples (pg 8 col 2, pg 10 col 2).
Claim 7 recites the limitation wherein receiving the information corresponding to the sample comprises accessing, in the memory, the information corresponding to the sample.
With respect to this limitation, FINKLE teaches accessing the sequencing information in a bioinformatics pipeline/analysis server (pg 8 col 2) which would include accessing the information in memory.
Claim 8 recites the limitation wherein the first ratio or the second ratio corresponds to a tumor fraction. With respect to this limitation, FINKLE teaches the ratio is tumor fraction (pg 4).
Claims 9 and 18 recite the limitation wherein the number of tumor genetic molecules in the sample is based at least in part on histology, liquid biopsy data, pathology information, a simulation or an output of a pretrained predictive model. With respect to this limitation, FINKLE teaches determining tumor fraction from the liquid biopsy data (pg 10).
Claims 10, 15, and 19 recite the limitation wherein the sample-specific dynamic quality metric is a function of the first ratio or the second ratio when the number of genetic molecules is between 30 and 150. With respect to this limitation, FINKLE teaches determining a limit of detection (LOD) used in determining the quality metric and removing variants below the LOD (pg 2 last par, pg 10 col 1), but does not teach that the metric is a function of the ratio when the number of genetic molecules is between 30-150. However, it would be obvious to one of ordinary skill in the art that an adequate amount of tumor genome copies to DNA molecules are needed in a sample for accurate analysis, so specifying 30-150 molecules would be a matter of routine optimization.
Claim 11 recites the limitation wherein, when the type of cancer comprises lung cancer, the genomic region of interest comprises chromosome 7, region p 11.2 or a region that comprises an epidermal growth factor receptor. With respect to this limitation, FINKLE teaches that when the cancer is lung cancer (pg 10 col 2) the genomic region of interest can include EGFR, the epidermal growth factor receptor gene (pg 4 col 2, Fig 3).
Claim 12 recites the limitation wherein, when the type of cancer comprises breast cancer, the genomic region of interest comprises chromosome 6, region q25.1-q25.2 or a region that comprises an estrogen receptor 1. With respect to this limitation, FINKLE teaches that when the cancer is breast cancer (pg 10 col 2) the genomic region of interest can include ESR1, which is the estrogen receptor 1 gene (pg 4 col 2, Fig 3).
Claims 13, 16, and 20 recite the limitation wherein the threshold is based at least in part on one or more of: the type of cancer, the sequencing coverage, or both. With respect to this limitation, FINKLE teaches that the threshold is based at least on individual cancer cohorts/cancer type (pg 10 col 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY C LEVERETT whose telephone number is (571)272-5494. The examiner can normally be reached 8:00am - 5:00pm M-Th.
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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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/MARY C LEVERETT/Examiner, Art Unit 1687
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