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 .
Applicant's Amendment/Request for Reconsideration-After Non-Final Rejection, filed 21 October 2025, has been entered and fully considered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application 62/418,639 filed 11/7/2016 is acknowledged.
Status of Claims
Claims 1-132 are cancelled;
Claims 133-153 are pending and are examined on the merits.
Withdrawn Rejections/Objections
The rejection to claims 133-153 35 U.S.C. 112(b) in the Office action mailed 20 May 2025 are withdrawn in view of claims amendments filed 21 October 2025.
Claim Rejections - 35 USC § 112
This is a new rejection necessitated by claim amendments.
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 133-153 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 133 recites the limitation "the second somatic mutational profile" in page 2, 3rd step line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
This rejection is maintained from the previous Office Action. Modifications are necessitated by claim amendments.
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 133-153 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 133-153 are directed to a process, here a "method," for determining cancer status in a human patient, with a series of functional steps.
Step 2A Prong One: Identification of Abstract Ideas
Claim 133 recites:
Identifying one or more somatic mutations associated with cancer in the first biological test sample.
----this step does not specify how exactly to identify somatic mutations. Under a broadest reasonable interpretation (BRI), this step encompasses a judgement/decision-making activity, which equates to an abstract idea of mental processes.
Creating a first somatic mutational profile as input to a trained machine learning model, the first somatic mutational profile comprising the one or more somatic mutations.
----this step recites a data manipulation/re-organization activity, which equates to an abstract idea of mental processes.
Generating, by inputting the first somatic mutational profile into the trained machine learning model, a first set of reconstructed latent mutational signatures for the one or more somatic mutations in the first somatic mutational profile, and an associated exposure weight for each reconstructed latent mutational signature in the first set.
----The machine learning model is not specified. Under a BRI, the machine learning model can be based on a mathematical algorithm such as linear regressions. Therefore the first set of reconstructed latent mutational signatures and the associated exposure weight for each reconstructed latent mutational signature are the results of mathematical calculations, and this step recites abstract ideas of mathematical concepts.
Wherein the machine learning model is trained by deconvoluting the first somatic mutational profile based on a signature matrix generated using a training set comprising patient samples from patients with known cancer status.
----How exactly “deconvoluting” is performed is not specified. Under a BRI, the deconvolution process is interpreted as identifying a shared/common signature matrix among samples of the same cancer status. And such a process encompasses mathematical calculations. Therefore this step recites abstract ideas of mathematical concepts.
Generating, by inputting the second somatic mutational profile into the trained machine learning model, a second set of reconstructed latent mutational signatures for the one or more somatic mutations in the second somatic mutational profile, and an associated exposure weight for each reconstructed latent mutational signature in the second set
---- The machine learning model is not specified. Under a BRI, the machine learning model can be based on a mathematical algorithm such as linear regressions. Therefore the second set of reconstructed latent mutational signatures and the associated exposure weight for each reconstructed latent mutational signature are the results of mathematical calculations, and this step recites abstract ideas of mathematical concepts.
Monitoring the effectiveness of the therapeutic regimen based on the first set of reconstructed latent mutational signatures and the second set of reconstructed latent mutational signatures.
----This step does not specify how exactly “monitoring the effectiveness of the therapeutic regimen” is performed. Under a BRI, this step encompasses observation, comparison of the two reconstructed latent mutational signatures (first and second) and judgement. Therefore this step equates to an abstract idea of mental processes.
Because the steps above do recite elements that, individually and in combination, constitute abstract ideas. The claim must therefore be examined further to determine whether the claims integrate the above-identified abstract ideas into a practical application (MPEP 2106.04(d)).
Step 2A Prong Two: Consideration of Practical Application
The claims result in a process of monitoring the effectiveness of the therapeutic regimen based on the first set of reconstructed latent mutational signatures and the second set of reconstructed latent mutational signatures (claim 133), and selecting an appropriate treatment for the human patient based on the environmental exposure and associated exposure weight (claim 152). These two steps both read on abstract idea of mental processes, or more specifically generating information from existing data. The claims do not recite any additional elements that integrate the abstract idea/judicial exception into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
Obtaining a biological test sample from the human patient (claim 133----this step recites the acquiring of samples, which equates to an additional element of sample gathering);
Sequencing a plurality of nucleic acids in the biological test sample to obtain a plurality of sequence reads (claim 133----this step recites the acquiring of sequencing reads, which equates to an additional element of data gathering);
Obtaining a second biological test sample from the human patient at a second time point post administration of the therapeutic regimen (claim 133----this step recites the acquiring of samples, which equates to an additional element of sample gathering);
Sequencing a plurality of cell-free nucleic acids in the second biological test sample to obtain a second plurality of sequence reads (claim 133----this step recites the acquiring of sequencing reads, which equates to an additional element of data gathering); and
The claims do not include additional elements that are sufficient to amount of significantly more than the judicial exception because it is routine and conventional to perform the acts of gathering samples and gathering sequencing data. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself.
As evidenced by the following references, acquiring next generation sequence data from cancer patients is commonly used to build up mutational signatures. Attempts to use the signature to diagnose/prognose cancers are also discussed in these references before the effective filing date of current invention (emphasis added):
Kandoth, Cyriac, et al. "Mutational landscape and significance across 12 major cancer types." Nature 502.7471 (2013): 333-339. Previously Cited.
Waddell, Nicola, et al. "Whole genomes redefine the mutational landscape of pancreatic cancer." Nature 518.7540 (2015): 495-501. Previously Cited.
Nik-Zainal, Serena, et al. "Landscape of somatic mutations in 560 breast cancer whole-genome sequences." Nature 534.7605 (2016): 47-54. Cited on the 2/8/2023 IDS: C59.
Alexandrov, Ludmil B., et al. "Signatures of mutational processes in human cancer." Nature 500.7463 (2013): 415-421. Cited on the 2/8/2023 IDS: C8
Olivier, Magali, et al. "Modelling mutational landscapes of human cancers in vitro." Scientific reports 4.1 (2014): 4482. Previously Cited.
Alexandrov, Ludmil B., et al. "A mutational signature in gastric cancer suggests therapeutic strategies." Nature communications 6.1 (2015): 8683. Cited on the 2/8/2023 IDS: C10.
Hence the JEs are not integrated into something significant more in Step 2B.
As a summary, instant claims 133-153 are not 101 eligible.
Response to Applicant’s Argument
In the Remarks filed 21 October 2025, Applicant argued (page 3, 2nd para through page 4, 2nd para) that “the additional elements are directed to this improvement to technology, in that the analytical workflow is applied to obtainment and sequencing of biological samples before and after administration of therapeutic regimen”. Applicant’s argument refers to Step 2A/Prong Two in the 101 analysis, relating to whether claims are integrated into a practical application or not.
The argument is not persuasive. The argued additional elements, are classified as insignificant extra-solution activities (MPEP §2106.05(g)). The technical merits rooted in the judicial exceptions (here the comparison of the 1st and 2nd reconstructed latent mutational signatures) are not applied by, captured in, or reflected in any additional elements. “Monitoring the effectiveness of the therapeutic regimen” is classified into an abstract idea of mental processes. An abstract idea cannot integrate claims into a practical application.
In the Remarks, Applicant argued (page 4, 4rd para through page 5, 1st para) that “the additional elements are non-routine, unconventional, and not well understood activity in the technological field, thereby amounting to an inventive concept supporting eligibility under Step 2B”.
Applicant’s argument is not persuasive. The argued additional elements, sampling and sequencing a patient before and after administering a therapeutic regimen, is a well-known and routine practice in clinical researches, especially in monitoring treatment effectiveness.
Hence, the 101 rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GL/
Patent Examiner
Art Unit 1686
/Anna Skibinsky/
Primary Examiner, AU 1635