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 .
This office action is in response to the claimed amendment filed on April 21, 2026, in which claims 1-45, 51-52, 55-62, 65-67, 71-77, 79, 81-82, 84 and 87 were canceled and claims 46-50, 53-54, 63-64, 68-70, 78, 80, 83, 85-86 and 88-89 are presented for further examination.
Response to Arguments
Applicant’s arguments with respect to claims 46-50, 53-54, 63-64, 68-70, 78, 80, 83, 85-86 and 88-89 have been considered in view of a new ground of rejection necessitated.
After further reviewed applicant’s arguments in light of the original specification, it is conceivable the claimed amendment filed on April 21, 2026, the 102 rejection set forth in the last office action has been withdrawn.
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 46-50, 53-54, 63-64, 68-70, 78, 80, 83, 85-86 and 88-89 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The claimed invention is involved in hierarchical machine learning techniques for identifying molecular categories from expression data. The independent claims 46, 88 and 89 fail to deal anything with identifying molecular categories from expression data based on hierarchical machine learning techniques. The omitted steps are: “identifying a candidate molecular category for a biological sample obtained from a subject for analyzing DNA and/or RNA expression data obtained from the subject”.
Claims 47-50, 53-54, 63-64, 68-70, 78, 80, 83 and 85-86 are also rejected under the same rationale.
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 46-50, 53-54, 63-64, 68-70, 78, 80, 83, 85-86 and 88-89 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract without significantly more.
Step 1, Statutory Category:
Claims 46-50, 53-54, 63-64, 68-70, 78, 80, 83 and 85-86 are directed to a method
Claim 88 is directed to a system.
Claim 89 is directed to a non-transitory computer readable storage medium.
Therefore, claims 46-50, 53-54, 63-64, 68-70, 78, 80, 83, 85-86 and 88-89 fall into at least one of the four statutory categories of invention, i.e., process, machine, manufacture, or composition of matter.
Step 2A, Prong One (Judicial exception recited)
The limitation “obtaining RNA expression data previously obtained by processing the biological sample obtained from the subject, wherein the RNA expression data comprises first RNA expression data for a first set of genes and second RNA expression data for a second set of genes different from the first set of genes; processing the RNA expression data using a hierarchy of RNA-based machine learning classifiers corresponding to a hierarchy of molecular categories to obtain RNA-based machine learning classifier outputs including a first output and a second output, the hierarchy of molecular categories including a parent molecular category and first and second molecular categories that are children of the parent molecular category in the hierarchy of molecular categories, the hierarchy of RNA-based machine learning classifiers comprising first and second RNA-based machine learning classifiers corresponding to the first and second molecular categories, the processing comprising: processing the first RNA expression data using the first RNA-based machine learning classifier to obtain the first output indicative of whether the first molecular category is a candidate molecular category for the biological sample” in claims 46, 88 and 89, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement, but for the recitation of generic computer components. One can manually compare the clinical diagnosis received from the clinician to the clinical diagnosis associated with at least one candidate molecular category identified for the biological sample, wherein if the diagnoses do not match, then the clinical diagnoses associated with the at least one candidate molecular category may be provided to the clinician to inform treatment selection
At Step 2A, Prong Two:
The claim recites the following additional elements: That the method is "implemented by a computing system" is a high-level recitation of a generic computer components and represents mere instructions to apply on a computer as in MPEP 2106.05(f), which does not provide integration into a practical application.
The limitation “processing the first DNA expression data using the first DNA-based machine learning classifier to obtain the first output indicative of whether the first molecular category is a candidate molecular category for the biological sample; and
processing the second DNA expression data using the second DNA-based machine learning classifier to obtain the second output indicative of whether the second molecular category is a candidate molecular category for the biological sample” represents an extra-solution activity because it is a mere nominal or tangential addition to the claim, a mere generic transmission and presentation of collected and analyzed data. (See MPEP 2106.05 (g)).
The limitation “at least one computer hardware processor, and at least one non-transitory computer-readable storage medium” are recited at a high level of generality such that they amount to on more than mere instructions to apply the exception using a generic component. (see MPEP 2106.05(f)). These limitations can also be viewed as nothing more than an attempt to generally link the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(h)). Note, the mere instructions to apply an exception on a generic computer cannot integrate a judicial exception into a practical application.
Step 2B (claim provides an inventive concept):
The conclusions for the mere implementation using a computer, mere field of use, and using generic computer components (machine learning i.e. ML) as a tool are carried over and do not provide significantly more.
With respect to the “processing ….” identified as insignificant extra-solution activity above when re-evaluated this element is well-understood, routine, and conventional as evidenced by the court cases in MPEP 2106.05(d)(II), " iv. Presenting offers and gathering statistics, OIP Techs., 788 F.3d at 1362-63, 115 USPQ2d at 1092-93" and "i. … transmitting data over a network, …Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information); … OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015) (sending messages over a network); buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network)".
With respect to the “at least one computer hardware processor, and at least one non-transitory computer-readable storage medium” amount to elements that have been recognized as well-understood, routine, and conventional activity in particular fields, as demonstrate by: Relevant court decision: the followings are examples of court decisions demonstrating well-understood, routine and conventional activities, see e.g., MPEP 2106.05(d)(II) and MPEP 2106.05(f)(2): Computer readable storage media comprising instructions to implement a method, e.g., see Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements when considered both individually and as an ordered combination do not amount to significantly more than the abstract idea.
Looking at the claim as a whole does not change this conclusion and the claim appears to be ineligible.
Accordingly, claim 46 is directed to an abstract idea. The remaining independent claim 88 and 89 fall short the 35 USC 101 requirement under the same rationale.
The dependent claims 46-50, 53-54, 63-64, 68-70, 78, 80, 83 and 85-86 when analyzed and each taken as a whole are held to be patent ineligible under 35 USC 101 because the additional recited limitations fail to establish that the claims are not directed to an abstract idea.
Claim 47 recites “wherein the DNA expression data further comprises third DNA expression data, wherein the hierarchy of molecular categories further comprises a third molecular category that is a child of the parent molecular category in the hierarchy of molecular categories, wherein the hierarchy of DNA-based machine learning classifiers further comprises a third DNA-based machine learning classifier corresponding to the third molecular category, and wherein the processing further comprises processing the third DNA expression data using the third DNA-based machine learning classifier to obtain a third output indicative of whether the third molecular category is a candidate molecular category for the biological sample”. This additional element is recited at a high level of generality and would function in its ordinary capacity for processing the third DNA expression data using the third DNA-based machine learning classifier, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 48 recites “wherein the DNA expression data further comprises fourth DNA expression data, wherein the hierarchy of molecular categories further comprises a fourth molecular category that is a child of the first molecular category in the hierarchy of molecular categories, wherein the hierarchy of DNA-based machine learning classifiers further comprises a fourth DNA-based machine learning classifier corresponding to the fourth molecular category, and wherein the processing further comprises processing the fourth DNA expression data using the fourth DNA-based machine learning classifier to obtain a fourth output indicative of whether the fourth molecular category is a candidate molecular category for the biological sample”. This additional element is recited at a high level of generality and would function in its ordinary capacity for processing the fourth DNA expression data using the fourth DNA-based machine learning classifier, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 49 recites “wherein the DNA expression data further comprises fifth DNA expression data, wherein the hierarchy of molecular categories further comprises a fifth molecular category that is a child of the first molecular category in the hierarchy of molecular categories, wherein the hierarchy of DNA-based machine learning classifiers further comprises a fifth DNA-based machine learning classifier corresponding to the fifth molecular category, and wherein the processing further comprises processing the fifth DNA expression data using the fifth DNA-based machine learning classifier to obtain a fifth output indicative of whether the fifth molecular category is a candidate molecular category for the biological sample”. This additional element is recited at a high level of generality and would function in its ordinary capacity for processing the fifth DNA expression data using the fifth DNA-based machine learning classifier, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 50 recites “wherein the parent molecular category is a solid neoplasm molecular category, the first molecular category is an adenocarcinoma molecular category, and the second molecular category is a sarcoma molecular category”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 53 recites “wherein processing the first DNA expression data using the first DNA-based machine learning classifier comprises: obtaining one or more first DNA features from the first DNA expression data; and applying the first DNA-based machine learning classifier to the first DNA features to obtain the first output”. This additional element is recited at a high level of generality and would function in its ordinary capacity for applying the first DNA-based machine learning classifier to the first DNA features to obtain the first output, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 54 recites “wherein the one or more first DNA features comprise: one or more features indicating, for each gene of a respective set of one or more genes, whether the DNA expression data indicates presence of a pathogenic mutation for the gene; one or more features indicating, for each gene of a respective set of one or more genes, whether the DNA expression data indicates presence of a hotspot mutation for the gene; a feature indicating tumor mutational burden for the biological sample; one or more features indicating a normalized copy number for each chromosome segment of a respective set of one or more chromosome segments for which expression data is included in the DNA expression data; one or more features indicating loss of heterozygosity (LOH) for each chromosome segment of a respective set of one or more chromosome segments for which expression data is included in the DNA expression data; one or more features indicating whether the DNA expression data indicates presence of one or more protein coding genes; one or more features indicating, for each gene of a respective set of one or more genes, whether the DNA expression data indicates presence of a fusion with another gene of the respective set of one or more genes; a feature indicating ploidy for the biological sample; and/or a feature indicating whether the DNA expression data indicates presence of microsatellite instability (MSI)”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 63 recites “wherein the one or more first DNA features comprise at least 10 features corresponding to the first molecular category”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 64 recites “ wherein processing the first DNA expression data using the first DNA-based machine learning classifier to obtain the first output comprises processing the first DNA expression data to obtain a first probability that the first molecular category is a first candidate molecular category for the biological sample, wherein processing the second DNA expression data using the second DNA-based machine learning classifier to obtain the second output comprises processing the second DNA expression data to obtain a second probability that the second molecular category is a second candidate molecular category for the biological sample”. This additional element is recited at a high level of generality and would function in its ordinary capacity for processing the first DNA expression data to obtain a first probability that the first molecular category is a first candidate molecular category for the biological sample, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 63 recites “wherein the first molecular category is a molecular category selected from among the following molecular categories: Molecular category, Neoplasm, Solid Neoplasm, Hematologic Neoplasm, Melanoma, Non-Uveal Melanoma, Uveal Melanoma, Non-Cutaneous Melanoma, Cutaneous Melanoma, Sarcoma, Soft Tissue Sarcoma, Osteosarcoma, Mesothelioma, Peritoneal Mesothelioma, Pleural Mesothelioma, Neuroendocrine, Neuroendocrine Small Cell, Small Cell Prostate Cancer, Large Cell Neuroendocrine Carcinoma, Small Cell Lung Carcinoma, Squamous Cell Carcinoma, Colorectal Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Adenocarcinoma, Adrenocortical Carcinoma, Glioma Adenoid Cystic Carcinoma, Adenoid Cystic Carcinoma of the Uterine Cervix, Adenoid Cystic Carcinoma of the Breast, Salivary Gland Adenoid Cystic Carcinoma, Testicular Germ Cell Tumor Pheochromocytoma, Cervical Squamous Cell Carcinoma, Liver Neoplasm, Hepatocellular Carcinoma Cholangiocarcinoma, Lung Adenocarcinoma, High Grade Glioma IDH Mut, Thyroid Neoplasm, Merkel Cell Carcinoma, Paraganglioma, Gastrointestinal Neuroendocrine Neoplasm, Squamous Cell Lung Carcinoma, Thymoma, Prostate Adenocarcinoma, Urinary Bladder Urothelial Carcinoma, Oligodendroglioma, Squamous Cell Carcinoma of the Head and Neck, Gastrointestinal Adenocarcinoma, Gynecological Renal Cell Carcinoma, Astrocytoma, Pancreatic Adenocarcinoma Stomach Adenocarcinoma, Pancreatic Adenocarcinoma, Colorectal Adenocarcinoma of the Breast Breast Cancer, Ovarian Cancer, Uterine Corpus Endometrial Carcinoma, Non-Clear Cell Carcinoma, Clear Cell Carcinoma, Basal Breast Cancer, and Non-Basal Breast Cancer”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 69 recites “wherein the first molecular category is associated with at least one international classification of diseases (ICD) code”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 70 recites “obtaining RNA expression data previously obtained by processing the biological sample obtained from the subject; processing the RNA expression data using a hierarchy of RNA-based machine learning classifiers corresponding to the hierarchy of molecular categories to obtain RNA-based machine learning classifier outputs, wherein the hierarchy of RNA-based machine learning classifiers is different from the hierarchy of DNA-based machine learning classifiers; and wherein the identifying the at least one candidate molecular category for the biological sample using at least some of the RNA-based machine learning classifier outputs and at least some of the DNA-based machine learning classifier outputs”. This additional element is recited at a high level of generality and would function in its ordinary capacity for processing the RNA expression data using a hierarchy of RNA-based machine learning classifiers corresponding to the hierarchy of molecular categories, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 78 recites “receiving an indication of a clinical diagnosis of the biological sample; and determining an accuracy of the clinical diagnosis based on the at least one candidate molecular category identified for the biological sample”. This additional element is recited at a high level of generality and would function in its ordinary capacity for receiving an indication of a clinical diagnosis of the biological sample, this additional element does not integrate the integrate the judicial exception into a practical application and does not amount to significantly more.
Claim 80 recites “wherein the first molecular category of the hierarchy of molecular categories is one of neoplasm, hematologic neoplasm, melanoma, sarcoma, mesothelioma, neuroendocrine, squamous cell carcinoma, adenocarcinoma, glioma, testicular germ cell tumor, pheochromocytoma, cervical squamous cell carcinoma, liver neoplasm, lung adenocarcinoma, high grade glioma isocitrate dehydrogenase (IDH) mutant, thyroid neoplasm, squamous cell lung adenocarcinoma, thymoma, prostate adenocarcinoma, urinary bladder urothelial carcinoma, oligodendroglioma, squamous cell carcinoma of the head and neck, gastrointestinal adenocarcinoma, gynecological cancer, renal cell carcinoma, astrocytoma, pancreatic adenocarcinoma, stomach adenocarcinoma, pancreatic adenocarcinoma, breast cancer, ovarian cancer, uterine corpus endometrial carcinoma, non-clear cell carcinoma, clear cell carcinoma, basal breast cancer, non-basal breast cancer, papillary renal cell carcinoma, and chromophobe renal cell carcinoma”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 83 recites “wherein each DNA-based machine learning classifier of the hierarchy of DNA-based machine learning classifiers is a gradient-boosted decision tree classifier, a neural network classifier, or a logistic regression classifier”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 85 recites “wherein the biological sample is a sample of a cancer of unknown primary (CUP) tumor”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Claim 86 recites “identifying at least one anti-cancer therapy for the subject based on the identified at least one molecular category; and administering the at least one anti-cancer therapy”. This limitation, as drafted, is a process that, under its broadest reasonable interpretation, covers a mental process as a form of evaluation or judgement. There is no additional elements recited which tie the abstract idea into a practical application and does not amount to significant more than the identified judicial exception.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 10,311,967 (involved in visualizing and classifying molecular functional profile based on machine learning model).
US 200030129660 (involved in defining a matrix of distances between molecules or sets of molecules that incorporate both the relation of corresponding expression profiles and information on their relation within a biological network; and clustering the molecules based on said distance)
US 20160378914 (involved in defining a matrix of distances between molecules or sets of molecules that incorporate both the relation of corresponding expression profiles and information on their relation within a biological network; and clustering the molecules based on said distances).
US20140278131 (involved in constructing an initial graph by combining gene expression data with image data with each node in a graph associated with gene and by drawing edges between nodes, where the edges based on membership of gene clusters or morphological distance for corresponding gene knockdown image stacks.)
US20140180599 (involved in receiving primary expression data of a group of normal people and secondary expression data of a subject with respect to gene expression patterns of genes included in a gene network. An estimate of a representative expression pattern summarizing a distribution of the gene expression patterns of individuals belonging to the group of normal people is calculated. A distribution of a similarity of each of the estimated gene expression patterns of the individuals and the subject is analyzed with respect to the representative expression pattern.)
US20110125683A1 (involved in selecting clustering algorithm based on dissimilarity measure between gene expression levels and defining clusters of gene expression levels within labeled class.)
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 JEAN M CORRIELUS whose telephone number is (571)272-4032. The examiner can normally be reached Monday-Friday 6:30a-10p(Midflex).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ann J Lo can be reached at (571)272-9767. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEAN M CORRIELUS/Primary Examiner, Art Unit 2159 June 22, 2026
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