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 1-32 are pending and examined herein. No claims are canceled.
Priority
As detailed on the date filing receipt, the application claims priority as early as 23 December 2022. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date except claim 32, which lacks written description support for a system performing immunosuppressive treatment and thus has the filing date of 19 December 2025.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 29 July 2025 and reviewed in the instant office action. The submission was in compliance with the provisions of 37 CFR 1.97. All foreign patent references are instantly considered. Non-patent literature not found in the form are struck through.
The information disclosure statement (IDS) was submitted on 09 January 2026 and reviewed in the instant office action. The submission was in compliance with the provisions of 37 CFR 1.97. Non-patent literature duplicated from the 29 July 2025 are struck through.
Withdrawn Objections and Rejections
In view of the amendments and persuasive argument (remarks: pgs. 12-13), the interpretation of “determination unit” under 35 USC 112(f) and subsequent rejections under 35 USC 112(a) and 112(b) are withdrawn in view of removal of the “unit” nonce term. The non-statutory double patenting rejection is also withdrawn in view of the amendments (pg. 15).
The following rejections are either newly applied or maintained and constitute the complete set of objections and rejections applied to the claims.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 32 recites the processor causes the system to administer, adjust, change, or initiate an immunosuppressive treatment. While the system is disclosed as being used for medical analysis, it is a treating physician or medical expert which uses the medical analysis tool to administer the treatment (pg. 36, paragraph [98]). There is not considered to be written description support for the system, which is recited as comprising an interface configured to receive input and a processor, to perform a treatment.
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 1-32 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea 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 detecting a presence or an absence of a transplant rejection.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong 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 1-15 and 31) and a computer system (claims 16-30 and 32), 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 claims 1 and 16 includes determining and grouping minor allele frequency (claims 1 and 16), generating an amount of nucleic acids derived from the contributors (claims 1 and 16), and detecting the presence or absence of the transplant rejection (claims 1 and 16).
Determining a frequency is interpreted as a verbal description of a mathematical process and is disclosed in the specification as taking the forms of counts, percentages, and ratios (pg. 28, paragraph [72]), which are all mathematical concepts. 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 (MPEP 2106.04(a)(2)).
Generating an amount of nucleic acid derived from each of the three contributors is interpreted as a mathematical and mental step. The specification discloses several mathematical equations required to determine the contributor (paragraphs [73-82]).
Detecting the presence or absence of transplant rejection is based on interpretation of the amounts of nucleic acid from the contributors and thus a data evaluation or judgment, which is a mental process.
Claims 2-3 and 17-18 recite additional information about the determining and grouping of MAFs, which elaborates on the abstract ideas described above.
Claims 5 and 20 recite determining a genotype based on the MAF groupings, which is a mental process.
Claims 6 and 21 recite reordering and grouping information, which are mental processes, and determining MAF information including summary statistics, where determining summary statistics is interpreted as a mathematical concept.
Claims 7-8 and 22-23 recite determining and using a separation point, which is interpreted as an observation and thus a mental process.
Claims 9 and 24 recite generating a waterfall plot and forming groups based on the plot, which are interpreted as mental processes, and calculating mean values, which is a mathematical concept.
Claims 10-12 and 25-27 recite selecting information, determining a separation point, and grouping information, which are mental processes, and determining summary statistics, which is a mathematical concept.
Claims 13 and 28 recite generating a waterfall plot, which is a mental process.
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: 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))?
Claims 1 and 16 recite additional elements that are not abstract ideas: a computer (claims 1 and 16), obtaining a mixed sample (claim 1), assaying the sample to obtain sequence data (claim 1), obtaining sequence data (claim 16), receiving a genomic relationship (claims 1 and 16), an interface (claim 16), and a processor (claim 16).
Claims 4 and 19 recite additional information about the panel of SNPs sequenced.
Claims 14-15 and 29-30 recite additional information about the sample recited in the preamble.
Claims 31-32 recite administering, adjusting, changing, or initiating an immunosuppressive treatment.
The steps of obtaining and/or receiving information to perform the calculations required for determining the allele frequencies are interpreted as data gathering. Data gathering to perform the primary process of the claims is interpreted as insignificant extra solution activity (MPEP 2106.05(g)).
The computer, interface, and determination unit are interpreted as generic computer components. 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)).
The step of administering, adjusting, changing, or initiating an immunosuppressive treatment is not interpreted as a particular treatment (MPEP 2106.04(d)(2)) because the parent claims 1 and 16 recite detecting the presence or absence of transplant rejection and then administering the treatment. That is, the treatment is applied regardless of whether there is a detection of presence or absence and thus is not particular. Therefore, the treatment is considered broadly recited and thus mere instructions to apply the exception (MPEP 2106.05(f)).
None of the dependent claims recite any additional non-abstract elements; they are all directed
to further aspects of the information being analyzed, the manner in which that analysis is performed, or
the mathematical operations performed on the information. [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 16 recite additional elements that are not abstract ideas: a computer (claims 1 and 16), obtaining a mixed sample (claim 1), assaying the sample to obtain sequence data (claim 1), obtaining sequence data (claim 16), receiving a genomic relationship (claims 1 and 16), an interface (claim 16), and a processor (claim 16).
Claims 4 and 19 recite additional information about the panel of SNPs sequenced, where there must be fewer than 500 SNPs analyzed.
Claims 14-15 and 29-30 recite additional information about the sample, including the type of transplant and the sample being a blood sample.
Claims 31-32 recite administering, adjusting, changing, or initiating an immunosuppressive treatment.
Obtaining the data by sequencing and assaying the sample are conventional as the specification discloses “protocols for cell-free DNA extraction, amplification, and sequencing using high-throughput sequencing methods, including next-generation sequencing, are known in the art” (pg. 27, paragraph [70]).
Dengu (Transplantation Reviews 34(3): 8 pgs., 2020; newly cited) teaches transplant rejection prediction based on cfDNA (abstract), with examples of kidney and heart transplant assays based on plasma samples (pg. 2, col. 1, fifth and sixth paragraphs), and the observation that “an increased number of SNPs was used but inferior outcomes were observed” (pg. 2, col. 2, fourth paragraph) and interrogating 50 SNPs or less can be effective (pg. 3, col. 1, penultimate paragraph). Dengu teaches treatment based on the assays (pg. 2, col. 2, first paragraph; pg. 5, col. 2, third paragraph).
Receiving information is a conventional computer function (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014); MPEP 2106.05(d)).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide 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 19 December 2025 Applicant Remarks
Applicant remarks state the instant claims are eligible under 35 USC 101 because the amplification of a mixed sample is unconventional and the abstract ideas have a practical application in the form of detecting transplant rejection (pg. 13).
Taken in reverse order, the remarks state the detection of the presence or absence of a transplant rejection based on assaying the mixed sample is an additional element integrating the abstract ideas into a practical application (pg. 15, second paragraph), thus representing an improvement overcoming the rejection at Step 2A Prong Two. This argument is unpersuasive because the assay, understood as a physical or “wet lab” step, is disclosed as known in the art (pg. 27, paragraph [70]). The disentangling of the three contributor genotypes is provided by a mathematical concept, employs mathematical equations as disclosed in the specification “to infer contributors’ SNP genotypes” (pg. 29, paragraph [75]). Therefore, the improvement is considered to be provided by the abstract idea and not an additional element. Furthermore, the invention culminates in detecting the presence or absence of rejection, but detection is information evaluation based on the math, and thus is a mental process. The claims are amended such that a treatment step occurs, but because the treatment is applied regardless of whether there is a detection of presence or absence, it is not particular. Therefore, the treatment is considered broadly recited and thus mere instructions to apply the exception (MPEP 2106.05(f)), which does not integrate the abstract idea into a practical application.
Applicant remarks state the obtaining nucleic acid sequence data by amplification of the nucleic acids derived from the at least three genetically distinct contributors-which requires physical manipulation of the mixed sample comprising nucleic acids derived from the at least three genetically distinct contributors is an additional element and an unconventional one at that, which thus overcomes the rejection at Step 2B (pg. 14, second and third paragraphs). However, as described above, the obtaining the sequence data by amplification is disclosed as conventional in the specification by virtue of being known in the prior art. The determination of which SNPs belong to which contributors is based on the grouping of SNP signals based on thresholding (pg. 30, paragraph [78]). An inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05), and the equations for determining which contributors are assigned which SNPs comprises mental and mathematical concepts and thus are abstract and cannot provide significantly more at Step 2B.
Therefore, the rejection under 35 USC 101 is 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