DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed February 17, 2026. Currently, claims 1-12, 14-21 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
In view of Applicant’s arguments related to the election of species, the requirement is withdrawn.
Priority
This application claims priority to
PNG
media_image1.png
78
622
media_image1.png
Greyscale
Drawings
The drawings are acceptable.
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 1-12, 14-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 1 is directed to “a method of determining microsatellite instability (MSI)” by determining somatic allele lengths in nucleotide repeat tracts, determining somatic mutations outside the nucleotide repeat tracts, determining genomic signature score, determining an MSI score for the sample based on the tract-based score and genomic signature score, and classifying.
The claims are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “determining a genomic signature score” “determining MSI score”, and “classifying the sample”) and a law of nature/natural phenomenon (i.e. the natural correlation between an MSI score and MSI-H or MSS).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 1 involves the patent-ineligible concept of an abstract process. Claim 1 requires performing the step of “classifying the sample as MSI-H or MSS based on MSI score”. Neither the specification nor the claims set forth a limiting definition for "classifying" and the claims do not set forth how “classifying” is accomplished. As broadly recited the determining step may be accomplished mentally by thinking about a subject’s allele and mutation state and making an assessment. Thus, the classifying step constitutes an abstract process idea.
The steps of “determining a genomic signature score” “determining MSI score” are both mathematical concepts such as mathematical relationships, formulas and calculations. The “determining a genomic signature score” “determining MSI score” by definition require an arithmetic or mathematical calculation to generate and apply the rule. These steps fall into the “mathematical concepts” grouping of an abstract idea. The specification states overall MSI score was determined by adding the proportion of unstable tracts multiplied by 200 to the genomic score. This is a calculation. Claim 21 has been added to require the genomic signature score is based on a set of position weigh matrices.
A correlation that preexists in the human is an unpatentable phenomenon. The association between MSI score from somatic allele lengths and somatic mutations and microsatellite instability is a law of nature/natural phenomenon. The "classifying" step which tells users of the process to predict endometrial cancer in the sample, amounts to no more than an "instruction to apply the natural law". This classifying step is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The " classifying" step does not require the process user to do anything in light of the correlation. The " classifying " step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Claim 2 is further directed to preparing a report which is a mental process.
Claims 6-8 recite a step of comparison of nucleotide repeats to reference samples control that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
Claim 9 is directed to determining frequency. Frequency is a mathematical concept and mental process. Frequency is the calculation of number of events over a period of time (i.e. a ratio).
Claim 14 is a method of assigning a genomic signature score to the somatic mutations. Again, the assignment of a score is a mental process, much like classifying.
Claim 21 is directed to position weighted matrixes which is a mathematical calculation.
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites determining the presence of somatic allele lengths in nucleotide repeats and determining somatic mutations, this is not an integration of the exception into a practical application. Instead these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Claims 15-19 are directed to a conditional treatment. For Claim 15, the treatment of selecting or administering a treatment to the patient based on MSI score is not particular. There is no particular treatment administered. Additionally, the selection of a treatment is not an integration, as selection only requires “thinking about” what treatment one might consider administering. Further, the treatment “based on the MSI” score is not required. Claims 16-19 only requires treatment when the MSI-H.
Accordingly, the claims are directed to judicial exceptions.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The measuring allele lengths of nucleotide repeats and somatic mutations in DNA are mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining allele lengths of nucleotide repeats and somatic mutations in DNA was well known in the art at the time the invention was made. The prior art teaches that determining allele lengths of nucleotide repeats and somatic mutations in DNA. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any analysis. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known. Specifically, the specification teaches sequencing may be performed using NGS such as the commercially available Roche 454 sequencer, Life Technologies SOLiD systems etc (see para 27).
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the classifying step is inseparably tied to prior steps that require analyzing DNA sequence data and determining score using lab and computational bioinformatic techniques which can not be performed in the human mind alone. This argument has been considered but is not convincing because the classifying is considered a judicial exception. Once a score is provided the artisan can mentally classify the samples. There is nothing about the classification step that requires more than mental steps. The classification is the conclusion of whether a sample is MSI-H or MSS based upon a score. The classification of a sample as MSI-H or MSS may be performed mentally and does not require more.
The response argues that the claim has been amended to remove the language “fit” and “rule”. This argument has been reviewed but not deemed persuasive because the language has been replaced with “score”. These scores are mathematical concepts. The determination of these scores is not limited to computational bioinformatics. The response clearly states the tract based score is percentage of tracts with a somatic deletion. The calculation of a percentage is a simple mathematical computation which may be performed in the mind. Similarly, the genomic signature score is also as simple mathematical calculation.
The response argues that the MSI score is not a naturally occurring feature. This argument has been considered but is not persuasive. The MSI score is a relationship based upon the somatic allele lengths in a tract of nucleotide repeats and somatic mutation in DNA in regions outside of the plurality of tracts of nucleotide repeats. These are naturally occurring features. The newly issues 101 Examples from July 2024, Example 49, Claim 1 discusses law of nature when the claim describes the naturally occurring relationship between a patient’s genotype (a particular combination of genes giving rise to PI) and phenotype (risk for PI). This relationship is analogous to the relationship describe in the instant claims.
The response cites Vanda Pharmaceutical however the instant claims provide no treatment step and are not narrowly tailored to overcome the patent ineligibility rejection.
The response argues the claims are directed to improvements to technical field of molecular diagnostics and bioinformatics. The response argues the improvements to diagnostic sensitivity, specificity and reliability represent meaningful technical advances in the field and not mere field-of-use limitations. This argument has been reviewed but is not persuasive. Example 49, claim 1 states there is no improvement to the functioning of a computer nor to any other technology. At best, the claimed combination amounts to an improvement to the abstract idea of determining MSI and classifying the sample rather than to any technology. "It is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. For example, in Trading Technologies Int’l v. IBG, 921 F.3d 1084, 1093-94, 2019 USPQ2d 138290 (Fed. Cir. 2019), the court determined that the claimed user interface simply provided a trader with more information to facilitate market trades, which improved the business process of market trading but did not improve computers or technology." See MPEP 2106.05(a).
Thus, there is no integration of the recited exception into a practical application.
The response argues the transformation of a biological article through technical analysis. This argument has been reviewed but it not persuasive. The transformation of a sample from a raw biological material into data is not a transformation of a biological material into a new state or thing. Data is a not an article or a physical object or substance. The MPEP provides that for data, manipulation of basic mathematical constructs has not been deemed a transformation (see MPEPE 2106.05(c)).
Thus, for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112-Description
The following is a quotation 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.
Claims 1-12, 14-21 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to methods which comprise determining a f genomic signature score of the somatic mutations found outside of the nucleotide repeats to genomic signatures of mismatch repair deficiency. The specification does not describe any score. The specification does not provide the method for which the genomic signature score is determined.
The claims further require determining an MSI score and classifying based on the MSI score. The specification does not describe any rule or means to obtain an MSI score or how to classify based on the MSI score. There is no description of which MSI scores classify the sample as MSI-H or MSS.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2b 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed”.
Thus considering the breadth of the analysis, namely determining scores required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claims have been amended to remove the terms fit and rule, and replaced the terms with score. This argument has been considered but is not convincing because the recitation “score” has not provided any particular description of how these values and scores are calculated or obtained. The mere change of recitations does not provide description of the underlying calculations for the values or scores. Thus, for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 112- Second Paragraph
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.
Claims 1-12, 14-21 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 pre-AIA the applicant regards as the invention.
The claims require determining a genomic signature score of the somatic mutations to genomic signatures of mismatch repair deficiency, however it is unclear what the score encompasses. It is unclear how a genomic signature score is performed. Further it is unclear how the score, somatic mutations and lengths of somatic alleles is applied to determine an MSI score. The metes and bounds of how these calculations are performed are unclear and not particular pointed out in the claims. Even more, it is unclear how MSI scores classify MSI-H or MSS. The specification does not provide any guidance for classifying based upon an MSI score. Thus, the metes and bounds of the claimed invention are unclear.
Response to Arguments
The response traverses the rejection. The response asserts the plain meaning of the claim language provides now the scores are determined. The response argues that genomic signature score is determined for the somatic mutation found in step (ii) based on the genomic signatures of mismatch repair deficiency. This argument has been reviewed but is not persuasive. For example, if the artisan determines there are 5 somatic mutations in the DNA in regions outside of the plurality of tracts of nucleotide repeats, it is unclear how this provides how to determine a genomic signature score or how “based on genomic signature of mismatch repair deficiency” is involved. The metes and bounds of the invention are unclear how the presence of somatic mutations in the DNA outside of the plurality of tracts of nucleotide repeats provides a genomic score.
Similarly, it is unclear how an MSI score is determined based on the tract-based score and genomic signature score. While the specific states the scores may be “combined” it is unclear how the scores are combined. Are these scores added? Subtracted? Or otherwise combined? The metes and bounds of how scores are combined is unclear. The specification does not provide a clear guidance how scores are combined. The citation provided in the response does not clearly set forth how the analysis is performed. Further the specification provides that are tow “indeterminate” regions for which there was no data. Thus, the metes and bounds of these terms are unclear. Thus for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Huang et al. (Scientific Reports, Vol. 5, No. 13321, August 26, 2015). Huang teaches assessing microsatellite instability from catalogs of somatic mutations to determining microsatellite instability (MSI). Huang teaches MSI is characterized by somatic mutations that change the length of simple repeats and additional somatic mutation frequencies such as SNS (single nucleotide substitutions mutations)(page 2, para 7). Huang teaches fitting and apply rules to obtain a MSI score (ie. S/T). Figure 1 illustrates variations in T (mutation counts), S (mutation counts in simple sequence repeats) and S/T to classify as MSI-H, MSI-L and MSS.
Vanderwalde et al. (Cancer Medicine, Vol 7, No. 3, pages 746-756, 2018).
Vanderwalde teaches microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and mutational burden. Vanderwalde teaches TMB (total mutation burden) was calculated based on the number of nonsynonymous somatic mutations which encompasses somatic mutations outside of the repeat regions. Vanderwalde teaches the samples were used to calibrate the MSI-NGS assay to classify samples as MSI-H or MSS (page 748, col. 2). Vanderwalde teaches the best option for analysis would be to continue to measure all three TMB, MI, and PD-L1 to ensure that as many patients as possible benefit from drugs.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. 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.
/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
April 7, 2026