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 .
Election/Restrictions
Applicant’s election without traverse of Group 1 (claims 1-8 and 15); Species 1 Subtype 4 and CDK1 in the reply filed on 05/20/2026 is acknowledged.
Claims 9-14, and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/20/2026.
The restriction requirement for species 2, as set forth in the Office Action mailed on 03/20/2026 has been reconsidered and is hereby withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or non-statutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Status
Claims 1-8 and 15 are examined, as encompassing the elected invention. Claims 9-14 and 16 are withdrawn.
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 1-8 and 15 are rejected under 35 U.S.C. 101 because the claimed invention directed to a judicial exception (abstract idea) without significantly more. The claim(s) recite(s) a method of determining pancreatic ductal adenocarcinoma (PDAC) subtypes.
With regards to Step 1, claim 1 is considered to be in a statutory category of process.
With regards to Step 2A, prong 1, claim(s) 1, 2-8 and 15 recite(s) the abstract idea of determining a subtype of PDAC by comparing expression levels of representative genes of PDAC subtypes. This limitation constitutes evaluations and judgments that can practically be performed in the human mind and therefore falls within the mental process grouping of abstract ideas under the 2019 PEG.
With regards to Step 2A, prong 2, regarding claim(s) 1, 2-8 and 15, the claim(s) recite(s) additional steps which are merely to gather information for use in the abstract comparison(s). They do not improve technical methods, mass spectrometry, gene-expression, sample preparation, which are all conventional to the art. The steps do not provide a meaningful limitation on the judicial exception. The conventional methods are generally used to collect data that is used in the abstract classification process.
With regards to Step 2B: in claim(s) 1, 2-8 and 15, the additional elements beyond the abstract idea (mental processes) of cryogenic grinding of tissues, peptide extraction, cryogenic pressure cycling, transcriptomics, proteomics/phosphoproteomics, and the use of mass spectrometry methods are routine conventional in the prior art, as evidenced by Humphrey et al, Gross et al, Lou et al, and Cappadona et al. Accordingly, the claim as a whole does not recite additional elements that amount to significantly more than the judicial exception itself and does not integrate the exception into a practical application.
Claim 2 recites limitations that merely organize and stratifying genes associated with PDAC subtypes and merely expand the scope of the abstract mental process. The additional elements such as, categorizing genes into PDAC subtypes are conventional in the art as evidenced by Humphrey et al and Lou et al who also cite multiple seminal studies. Accordingly, the claims do not recite additional elements that alone or together amount to significantly more than the judicial exception.
Claims 3 and 4 recite additional steps of obtaining protein/peptides for downstream measurements; to then determine peptide concentrations relative to gene products, these additional steps are simply data-gathering steps that are routine and conventional to the art as evidenced by Humphrey et al and Gross et al.
Claims 5,6,7,8, and 15 further recites at a high level of generality additional steps of data-acquisition, data-analysis, and performing mRNA gene expression analysis and/or proteomic/phosphoproteomic analysis to create data sets with additional analysis to characterize the data, without further integration of the judicial exception. These additional limitations merely recite obtaining additional molecular expression data and analyzing that information for purposes of classifying PDAC subtypes.
Summarily, the claims assemble PDAC subtype(s) and do not further apply the determination to affect a treatment, modify scientific instruments and/or a technological process, or otherwise they do not integrate the judicial exception into a practical application.
For the forgoing reasons, claims 1-8 and 15 are not deemed to encompass patent eligible subject matter under 35 USC § 101.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-7, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Humphrey, E.S. et al., Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling. Molecular & Cellular Proteomics. 2016; (15.8): pp 2671-2685 in view of Gross, V. et al., Tissue Fractionation by Hydrostatic Pressure Cycling Technology: The Unified Sample Preparation Technique for Systems Biology Studies. Journal of Biomolecular Techniques.2008. (9): pp 189–199 and. Luo, G. et al., Characteristics and Outcomes of Pancreatic Cancer by Histological Subtypes.2019. (48): pp 817-822.
Regarding Claim 1, 3 and 4, Humphrey et al., teaches digesting tissues for protein extraction from patient tissues and/or human cell lines and measuring expression of genes of pancreatic ductal adenocarcinoma (PDAC) and identifying four subtypes based on proteomic and/or phosphoproteomic expression, using mass spectrometry methods to compare: gene cohorts, subtypes identified through phosphoproteomic profiling, and/or somatic mutation profiles from PDAC. Humphrey et al., identifies CDK1 as a phosphopeptide that is analyzed for phosphorylation site intensity (page 2675, Figure 1(E)).
Humphrey et al., does not teach cryogenic pulverization (claims 1 and 3) and the use of protein extraction using pressure cycling technology (claim 4).
However, Gross et al., teaches methods of extraction with flash-frozen tissues, for systems biology studies including: conventional cryogenic pulverization (page 198, paragraph 1) and pressure cycling technology used for proteomic analysis using mass spectrometry methods (page 190, figure 1).
Therefore, it would have been obvious to one of ordinary skill in the art at the effective date of filing to combine the teachings of Humphrey et al., with Gross et al to use frozen PDAC samples for downstream extraction methods, as taught by Gross et al., for the purposes of mRNA, and/or protein expression analysis.
One would have been motivated to do so because multiple seminal studies on PDAC subtypes, highlighted by Humphrey et al., demonstrate clinical efficacy based on transcriptomic and proteomic/phosphoproteomic studies which provide diagnostic and/or prognostic insight using the same method(s). Therefore, a skilled artisan would have reasonably expected success in the combination since the prior art produces the same outcome, using the same methods through the combination of Humphrey et al and Gross et al. Accordingly, it would have been prima facie obvious, as the combined prior art teaches the same outcome with the same methods.
Further, while Humphrey et al. teaches PDAC subtypes for cell lines, Humphrey et al. does not expressly disclose 6 subtypes of PDAC for human patient samples.
However, Lou et al., teaches a summation of seminal studies directed to developing PDAC subtypes based on a compilation of PDAC tissues from the Surveillance, Epidemiology, and End Results (SEER) Program sponsored by the U.S. National Cancer Institute (NCI); these subtypes are based on gene expression analyses (mRNA data), tissue pathology, and/or other PDAC associated patient traits and biology (page 817, section titled, “Patients and Data Collection”).
Therefore, it would have been obvious to one of ordinary skill in the art at the effective date of filing to combine the teachings of Humphrey et al., and Lou et al., to develop stratified clinical subtypes of PDAC, based on gene expression and/or proteomic/phosphoproteomic analysis acquired through mass-spectrometry (MS) methods.
The motivation to combine Humphrey et al., with Lou et al., are to create clinically relevant PDAC subtypes to inform diagnostic/ therapeutic decision-making.
An artisan would have expected success, as Humphrey et al., teaches identifying PDAC subtypes based on similar methods: mRNA gene expression analysis and protein/phosphoprotein expression using MS methods. Additionally, Lou et al., demonstrates developing PDAC subtypes using gene expression analysis from the well-known US NIH/NCI SEER database, containing a consortium of patient tissues, that is publicly accessible. Accordingly, it would have been prima facie obvious, as the combined prior art teaches the same outcome with the same methods.
Regarding Claims 2, 6, 7, and 15: Humphrey et al, teaches tyrosine phosphorylation patterns of MYO6, PKP3, and S100A11 (page 2679, Figure 5 (C) in PDAC subtype(s) (claim 2). Further, Humphrey et al., teaches a mixture of label-free and isotope-labelled peptides for specified genes from PDAC human tissues and/or cell lines (page 2673; section titled: “Normalization and Imputation of Label-free Data with “Spike-in” Standard Heavy Peptides”) to detect phosphorylated tyrosine using mass-spectrometry methods (page 2673; section titled: “LC-MS/MS, Identification and Quantification”). Signal intensities are analyzed between label-free and isotope-labeled peptides (page 2673, section titled, “LC-MS/MS, Identification and Quantification”) (claim 6 and 7) providing data towards developing stratified cohorts of PDAC subtypes.
Regarding claim 5, Humphrey et al., teaches mRNA gene expression analyses from a compilation of PDAC subtyping studies in comparison to proteomic/phosphoproteomic data for genes, illustrating a relationship between the two sets of data (page 26, paragraph 2).
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over Humphrey, E.S. et al., Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling. Molecular & Cellular Proteomics. 2016; (15.8): pp 2671-2685 and Gross, V. et al., Tissue Fractionation by Hydrostatic Pressure Cycling Technology: The Unified Sample Preparation Technique for Systems Biology Studies. Journal of Biomolecular Techniques.2008. (9): pp 189–199 and Luo, G. et al., Characteristics and Outcomes of Pancreatic Cancer by Histological Subtypes.2019. (48): pp 817-822. , as applied to claims 1-7 and 15 above and further in view of Cappadona, S. et al., Current challenges in software solutions for mass spectrometry-based quantitative proteomics. Amino Acids. 2012. (43): pp. 1087-1108.
Regarding claim 8, Humphrey et al., teaches signal intensities from peptide analyses (page 2679, Figure 5) using an intensity heat map to illustrate each peptide and intensity of phosphorylation from MS analysis.
Humphrey et al., does not teach a signal-intensity contour map with the ratio of signal intensities depicted on two axes (peptide vs peptide elution time).
However, Cappadona, et al., teaches contour maps for proteomics in which the axes illustrate elution time vs intensity for label-free and isotope-labeled peptides (page 1089, Figure 1)
It would have been obvious to a person of ordinary skill in the art at the time of the effective filing date to have substituted the contour map of Cappadona et al., for the intensity heat map of Humphrey et la., because both are known techniques for visualizing data, and the substitution would have predictably yielded the signal intensity data using alternative graphical representation, as the same essential data, regarding the peptides used in the graphical interpretations, are provided through MS analysis.
Since the same proteomic/phosphoproteomic data and information are collected and used to inform the heat-map, the same data can be used to illustrate a signal-intensity contour map. The motivation to create a signal-intensity contour map are to illustrate each peptide, from a specified gene, relative to elution and with regards to expression in each PDAC subtype; and is merely a relative optimization and/or preference of data illustration. The substitution of a contour map would have predictably yielded intensity data using an alternative graphical presentation; therefore, one would have expected success and the outcome is prima facie obvious.
Conclusion
No claims are deemed patentable.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ENUSHA KARUNASENA whose telephone number is (571)272-3972. The examiner can normally be reached Monday-Friday 7:30am-5pm.
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/ENUSHA KARUNASENA/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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