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 .
Status of the Claims
Claims 1-4, 6-9, 11-14, and 16-26 are examined herein.
Claim 5, 10, 15, and 27 are canceled.
Priority
As detailed on the 07 August 2020 filing receipt, the application claims priority as early as 27 June 2017. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Withdrawal / Revision of Objections and/or Rejections
The objection to claim 1, element (A)(iii) is withdrawn in view of amendment adding a space.
The objection to claim 22 is withdrawn in view of standardization of "MHC-1 presentation score" and "MHC-presentation score."
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
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 1-4, 6-9, 11-14, and 16-26 are rejected under 35 USC § 101 because the claimed inventions are directed to non-statutory subject matter without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of "determining the likelihood of a subjecting having or developing a cancer or autoimmune disease."
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prone One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of
Matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is
the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-4, 6-9, 11-14, and 16-21) and a computer system (claims 22-26), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in independent claim 1 include "calculating the predicted binding affinity," "using the predicting binding affinity to produce a rank score," and "identifying the subject" as having an increased or decreased likelihood of having or developing cancer or autoimmunity based on comparison to the rank threshold score. Calculating the predicted binding affinity, using the affinity to produce a rank score which are numerical, and identifying using a comparison of values are interpreted as a verbal description of a mathematical concept. Furthermore, the calculating step is described in mathematical terms in claim 6. A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation (MPEP 2106.04(a)(2)).
Mental processes, defined as concepts practically performed in the human mind such as steps of evaluating, analyzing or organizing information, recited in independent claim 1include "generating" peptide sequences, "producing the MHC-I presentation score, comprising selecting the lowest rank score," and "comparing the MHC-I presentation score with a rank threshold score." Generating sequences is interpreted as selecting sequences with certain mutations in preferred positions; producing the score by selecting the lowest score is interpreted on selecting and thus also a mental process; and comparing values is interpreted as data evaluation and thus a mental process. Furthermore, the step of "identifying a subject" may also be a mental process, as it is an evaluation or judgment based on the numerical comparison.
Independent claim 22 recites similar abstract ideas.
Claims 6-8 and 23-25 recites further mathematical steps for calculating the affinity scores and ranks.
Claims 9 and 26 recite further information about the sequence data, which is selected as part of the mental process.
Claims 11-14 and 16-21 recite further information about the cancer and related peptides.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
At Step 2A Prong Two of 101 analysis, it is determined whether the judicial exceptions determined at Step 2A Prong One are integrated into a practical application by additional elements, where the additional elements are elements of the claims which are not abstract.
Claims 1 and 22 recite "obtaining" sequences from a library using a computer system, which is interpreted as an element in addition to the abstract ideas. Claim 2 recites "obtaining a biological sample from the subject" and "assaying the sample for the presence" of a mutation. Claim 3 recites the origin of the biological sample. Claim 4 recites whole genome sequencing and whole exome sequencing. Claims 1 and 22 recite a computing/computer system comprising "a processor," and "a communication system."
The step of obtaining a sequence from a library and detecting CAM based on the library are steps required for generation of the presentation score. Therefore, these steps are interpreted as data collection required to carry out the abstract ideas and thus insignificant extra-solution activity (MPEP 2106.05(g)). Similarly, the sequencing steps, whether it is whole genome or whole exome sequencing, are steps for populating the libraries, which is used to generate the presentation threshold score which is compared with the subject score. Thus, the sequencing is also a data gathering step and insignificant extra-solution activity (MPEP 2106.05(g)).
The "computing system," "processor," and "communication system" refer to a general purpose computer. The claims do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)). [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Claims 1 and 22 recite "obtaining" sequences from a library using a computer system, which is interpreted as an element in addition to the abstract ideas. Claim 2 recites "obtaining a biological sample from the subject" and "assaying the sample for the presence" of a mutation. Claim 3 recites the origin of the biological sample. Claim 4 recites whole genome and whole exome sequencing. Claims 1 and 22 recite a computing/computer system comprising "a processor," and "a communication system."
Obtaining data using a computer amounts to receiving data on a computer, where receiving data on a computer is a well-understood, routine, and conventional task (MPEP 2106.05.(d)). Steps of obtaining a sample from the subject, assaying for the presence of a cancer-associated peptide, the type of sample, and origin of the library are taught at least by the review of Li (Cancers 3: 4191-4211, 2011; newly cited) as "massively parallel DNA sequencing" on "blood" (pg. 4199, paragraph 1), "whole-genome sequencing" (pg. 4194, last paragraph), and “examination of all exons (exome)” (pg. 4194, first paragraph), with discussion of affinity prediction (pg. 4200, paragraph 1) including "MHC class I" (pg. 4197, last paragraph). Therefore, it appears that knowledge of this additional elements are known together in the prior art and are considered conventional.
Thus, the additional elements do not amount to an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 04 December 2025 Applicant Remarks
Applicant remarks state that at Step 2A Prong One, the claims do not recite abstract ideas (pg. 14, fourth paragraph). Applicant remarks state that because the steps are directed to a computer-implemented bioinformatic method, they are not directed to an abstract idea. This argument is not persuasive because the claims recite calculating a score and performing comparisons, which are interpreted as at least mathematical concepts and mental processes respectively, performed in a computational environment. Implementing a mathematical principle, for instance, on a computer is not a patentable application of the principle (Gottschalk v. Benson; MPEP 2106.04(d)). Upon determination that the claims recite abstract ideas, they are further analyzed to determine if the abstract steps are integrated into a practical by application by the additional elements (MPEP 2106.04(d)(I)).
Applicant remarks state, relevant to Step 2A Prong Two, that the instant invention applies computational steps in a specific bioinformatic workflow to produce a concrete result (pg. 15, first paragraph) and the steps are limited to a technological field rather than being field-neutral (pg. 15, second paragraph), which constitute an improvement to technology. The steps are interpreted as abstract – generating sequences from a sequence set obtained from a library, calculating a score based on said generated sequences, and comparing said score to a threshold – which are implemented using a general purpose computer comprising a processor and communication system which are interpreted as general computer components. This is then interpreted as instructions to apply the abstract idea using a computer (MPEP 2106.05(f)). The concrete result is a comparison of values indicating a likelihood of developing or having a disease, and thus a metric of diagnosis, which is abstract. That is, the steps are interpreted as obtaining sequences, generating CAM-centric sequences, using the CAM-centric sequences to mathematically calculate a score, and determine a diagnosis based on the score. Therefore, it is unclear how the result is concrete. The field of technology is similarly unclear. Generating a diagnosis based on the computations is not interpreted as a technology, and even if it was, it still culminates in data where the elements in addition to the abstract ideas are collecting data either from a library or generating the library by sequencing and performing analysis on a computer. The remarks state an improvement is provided (pg. 16, fourth paragraph), but it is not clear how the additional elements – obtaining sequences from a library and performing analyses on a computer – are providing the alleged improvement.
Applicant remarks state the claimed method modifies the sequences obtained from the library and generates new sequences which are CAM-centric and of equal length (pg. 15, third paragraph). It is unclear how this is not a mental process of modifying the sequences, performed using a computer. Because it is a mental process, whether such a step is routine or conventional is not a criterion for overcoming the rejection as with additional elements at Step 2B.
Applicant remarks state the method produces a newly computed metric which enables classification of likelihood of having a cancer or autoimmunity, and that this is not a calculation (pg. 15, fourth paragraph). However, claim 6 recites a mathematical concept used for producing scores using a logistic regression model, which is implemented using a computer system.
Applicant remarks state the claimed methods do not recite mental processes because generating CAM-centric peptides of different lengths, predicting binding affinities for each, and ranking them is computationally intensive and not practicable (pg. 15, last paragraph to pg. 16, first paragraph). Calculating the binding affinity is, for the reasons previously discussed, at least a mathematical concept. Generating CAM-centric peptides and ranking the peptides by score is understood as a repetitive task. While it is acknowledged that such computations performed mentally, or with paper and pencil, would take considerable time and effort, the singular purpose of computers and computer networks, to perform large numbers of calculations via algorithms, rapidly, and without error (assuming no error in user input). Although a general-purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same. and constitutes an abstract idea. See Bancorp Serves., L.L.C. v. Sun life Assur. Co. of Canada (U.S.), 687 F.3d 1266, 1278 (Fed. Cir. 2012) (holding that "the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter"); see also SiRF Tech., Inc. v. lnt'I Trade Comm'n, 601 F.3d 1319,1333 (Fed. Cir. 2010) (holding that: In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations). Here, the repetitive nature of generating equal length peptide sequences and ranking them by affinity score does not cause it to graduate from being mental processes into a non-abstract element.
Applicant remarks state the claims recite an improvement to detection of cancer or autoimmunity based on the calculated presentation score, which provides significantly more than the abstract idea (pg. 16, last paragraph and pg. 17, first paragraph). At Step 2B, it is determined whether the claims contain additional elements that amount to an inventive concept. It is also noted that an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05). The limitations of the computed score for identifying the likelihood of having a disease is therefore not considered at Step 2B because it is a judicial exception. The additional elements are obtaining the sequences either from a library or by sequencing and using a computer to perform the mathematical and mental steps. These elements are taught by Li, and automating an abstract process and/or performing the steps in a computational environment would have been prima facie obvious to a person having ordinary skill in the art (MPEP 2114(III)). For that reason, the elements in addition to the abstract ideas are interpreted as conventional and thus do not provide significantly more than the abstract ideas.
The rejection under 35 USC 101 is therefore maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685