The present application is being examined under the pre-AIA first to invent provisions.
This office action is in response to Applicants’ amendments/remarks received March 16, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 2, 5, 9, 11, 13, 16-18 are canceled. Claims 20-22 are withdrawn. Claims 1, 3-4, 6-8, 10, 12, 14-15, 19 are under consideration.
Priority: This application is a 371 of PCT/US2021/022926, filed March 18, 2021, which claims benefit of provisional application 62/992379, filed March 20, 2020.
The declaration under 37 CFR 1.130 filed by Alexandra C. Newton is sufficient to overcome the previous rejections based upon Baffi et al.
Objections and Rejections
Claim 15 is objected to because of the following informalities: claim 15, line 1 recites “the each” in the claim. The term “the” should be deleted before “each”. Appropriate correction is required.
Where the description of a patent application discusses a sequence of 4 or more amino
acids or a sequence of 10 or more nucleic acids, reference must be made to the sequence by use
of the sequence identifier preceded by “SEQ ID NO:” in the text of the description even if the
sequence is also embedded in the text of the description of the patent application (see MPEP
2412.03). The sequence identifier may be used in either the drawing or the Brief Description of
Drawings (see MPEP 2412).
Objection to the Drawings:
The drawings are objected to for failure to comply with the sequence rules for the reasons as given above. See at least Fig. 5B (bottom sequence).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The sequence must be in computer readable form (CRF) for search. See also MPEP 2422 for sequence compliance requirements. Appropriate correction is required.
Reply: In their remarks of March 16, 2026, Applicants assert that replacement drawing sheets in compliance with 37 CFR 1.84 and 1.121(d) are submitted to resolve the alleged informalities. However, the replacement drawing sheet for Fig. 5B still does not appear to comply with the sequence rules for the reasons given above. Fig. 5B depicts a top sequence and a bottom sequence. As previously noted, the bottom sequence appears to be missing a sequence identifier. Appropriate correction is required.
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, 3-4, 6-8, 10, 12, 14-15, 19 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 1, 3-4, 6-8, 10, 12, 14-15, 19 do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
Claim 1 is directed to a naturally occurring correlation between a subject having a pancreatic cancer and levels of PKC (protein kinase C) and PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1). The claim recites a series of steps or acts, including determining (or detecting) an amount or level of PKC and PHLPP1 in a sample obtained from a subject. Therefore, the claim is directed to a process, which is one of the statutory categories of invention (step 1: YES). In step e, the claim recites comparing the level of PKC and PHLPP1 in the subject sample to a level of PKC and PHLPP1 in a control sample (to diagnose or prognose a pancreatic cancer in a subject). Claim 1, step e, describes a correlation or relationship between the levels of PKC and PHLPP1 in a subject sample and the presence of a pancreatic cancer in the subject. This limitation sets forth a judicial exception, because this type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo. See Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012). Additionally, claim 1 step e, could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). See University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) and In re Grams, 888 F.2d 835, 840, 12 USPQ2d 1824, 1828 (Fed. Cir. 1989). Therefore, the claim is directed to at least one exception (step 2A: YES), which may be termed a law of nature, an abstract idea, or both.
Next, the claim is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Claim 1 recites the addition steps of obtaining a sample from the subject (step a), contacting the subject sample with a PKC antibody and a PHLPP1 antibody (step b), determining the amount of antibody binding with an antibody quantification technique (step c), and correlating the amount of antibody binding to the level of PKC and PHLPP1 in the subject sample (step d). All of the steps integrate or relate to the correlation.
The combination of steps recited in the claim taken as a whole, including the steps of obtaining a sample from a subject and determining the level of PKC and PHLPP1 in the sample, are well understood steps that are routinely conducted to analyze a sample and make direct use of the correlation. Obtaining a sample in order to perform tests is well-understood, routine and conventional activity for those in the field of diagnostics. The steps are recited at a high level of generality and to not require substantially more than simply obtaining a sample to investigate and determining whether the level of PKC and PHLPP1 is altered in the sample. Determining whether levels of the biomarkers PKC and PHLPP1 are present in the subject merely instructs a scientist to use a general antibody detection technique with any general components and materials. In this instance, the steps of contacting a cell sample with a PKC antibody and PHLPP1 antibody to bind to PKC and PHLPP1 and determining the level of PKC and PHLPP1 based on the antibody binding to PKC and PHLPP1 are routine and conventional (see at least Gao et al. 2008, which disclose PKC and PHLPP1 antibodies for binding PKC and PHLPP1; cited on IDS 12.07.23). Therefore, when the claim is considered as a whole, the steps taken together amount to no more than recognizing the law of nature itself since a subject having a pancreatic cancer would have levels (increased or decreased) of the biomarkers PKC and PHLPP1. Thus, the claim as a whole does not amount of significantly more than the exception itself (step 2B: NO).
Claims 3-4, 6-8, 10, 12, 14-15, 19 are included in this rejection because they are dependent on claim 1, and do not recite additional elements that amount to significantly more to the judicial exception, i.e. the naturally occurring correlation between the at least one biomarker and cancer.
Reply: Applicants’ amendments/remarks have been fully considered but they are not persuasive for the reasons noted above and herein.
Applicants assert that amended independent claim 1 now recites an active administration step of anti-PKC and anti-PHLPP1 antibodies which, upon the determination of binding to the substrates PKC and PHLPP1 by an antibody quantification technique (see instant claim 19), serves as a correlate to the level of PKC and PHLPP1. Applicants assert that this active administration step provides for the determination of PKC and PHLPP1 levels in the subject sample, which was surprisingly discovered in the application to significantly correlate with pancreatic cancer subject survival. Applicants assert that similar to Vanda, where the claims were found to be patent eligible as directed to a method of treatment based on the application of the relationship between iloperidone, CYP2D6 metabolism, and QTc prolongation, the claims of the instant application are directed to an application based on the results of the assay.
Applicants’ remarks are not persuasive. Instant claim 1 is still directed to a naturally occurring correlation between a subject having a pancreatic cancer and levels of PKC and PHLPP1. All of the steps integrate or relate to the correlation.
While instant claim 1 has been amended to recite contacting the subject sample with PKC antibody and PHLPP1 antibody to determine the amount of antibody binding with an antibody detection technique, these limitations are well understood steps that are routinely conducted to analyze a sample and make direct use of the correlation. See the 101 rejection above. The steps are recited at a high level of generality and do not require substantially more than simply obtaining a sample to investigate and determining whether the level of PKC and PHLPP1 is altered in the sample.
The claims of the present application are not like the claims of Vanda. The claims of Vanda recite a specific treatment that practically apply natural relationships. This is not the case here. Instant claim 1 does not recite any specific treatment step.
For at least these reasons, the 101 rejection is maintained.
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.
Claims 1, 3-4, 6-8, 10, 12, 14-15, 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of measuring levels of PKC and PHLPP1 in pancreatic adenocarcinoma samples from subjects (see at least example 8 of instant specification), does not reasonably provide enablement for a method for diagnosing or prognosing a pancreatic cancer in a subject comprising obtaining any sample from the subject, measuring a level of PKC and PHLPP1 in the subject, and comparing the level of PKC and PHLPP1 in the subject to a level of PKC and PHLPP1 in a control sample. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The instant claims are drawn to a method for diagnosing or prognosing a pancreatic cancer in a subject comprising obtaining any sample from the subject, contacting the subject sample with a PKC antibody and a PHLPP1 antibody, determining an amount of binding using an antibody quantification technique, correlating the amount of antibody binding to the level of PKC and PHLPP1, and comparing the level of PKC and PHLPP1 in the subject sample to a level of PKC and PHLPP1 in a control sample from a subject not having a pancreatic cancer. As such, the broadest reasonable interpretation of the claimed method is that it allows diagnosis or prognosis of a pancreatic cancer in all types of subjects by measuring levels of the PKC and PHLPP1 in any type of sample from the subject. The instant specification does not adequately describe a method of diagnosing or prognosing a pancreatic cancer in a subject, comprising measuring levels PKC and PHLPP1 in any sample from a subject, wherein said method has been shown to successfully or can reasonably diagnose or prognose a pancreatic cancer in any type of sample from a subject. Therefore, for the instant claimed invention, it would require an undue burden of experimentation for a skilled artisan to determine exactly which sample types from a subject the levels of PKC and PHLPP1 have diagnostic or prognostic potential.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
In this instance, the quantity of experimentation would be large since statistical measures and clinical value of risk markers have to be assessed and cancer is a diverse disease. The amount of guidance in the specification is minimal with regard to which subject samples are to be obtained for measuring levels of the PKC and PHLPP1 to successfully diagnose or prognose a pancreatic cancer. The specification discloses measuring levels of PKC and PHLPP1 in pancreatic adenocarcinoma samples from subjects (see at least example 8 of instant specification). The present claimed invention is complex in that a pancreatic cancer is being diagnosed or prognosed in any type of subject sample. However, it is known that no biomarker has been established as an “ideal” cancer screening tool that can meet the diagnostic, prognostic, and predictive requirements simultaneously (Wu et al. p. 2964). Further, some biomarkers purport to have a high sensitivity, but actually tend to have a low specificity, which raises a high risk of false-positive signals and may translate into a large number of people subjected to unnecessary and costly diagnostic procedures and psychological stress (Wu et al. p. 2964). Also, being considered as a “liquid biopsy”, the fluid sampling of biomarkers is of great interest, as it is a widely accepted technique, readily repeated, convenient, noninvasive, and low cost; fluid biomarkers include a variety of components in blood, urine, or other fluids that reflect the presence of a tumour in the body; although fluid-based biomarkers seem promising, their reliability has not been determined (Wu et al. p. 2964). Unfortunately, despite the impressive advances in tumor biology research as well as in high-powerful “omics” technologies, the translation of candidate cancer biomarkers from bench to bedside is length and challenging and only a few tumor marker tests have been adopted successfully into routine clinical care of oncologic patients (Mordente et al. p. 9-10). None of the biomarker tests currently used in clinical oncology is suitable for population screening or early diagnosis of cancer, that still remains the biggest clinical challenge of all (Mordente et al. p. 14-15).
The instant specification fails to show actual reduction to practice of a method for diagnosing or prognosing a pancreatic cancer and at any stage in a subject comprising measuring levels of the PKC and PHLPP1 in any type of sample from the subject and fails to provide adequate guidance on how to overcome the art-recognized difficult nature of this goal. Thus one skilled in the art could not make/use the claimed invention for diagnosing or prognosing a pancreatic cancer and at any stage in all subjects by measuring levels of the PKC and PHLPP1 in any type of sample from the subject as claimed.
When the factors are considered in their entirety, the Wands analysis dictates a finding of undue experimentation and thus, the claims are not enabled.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
As previously noted, the instant specification is enabling for a method of measuring levels of PKC and PHLPP1 in pancreatic adenocarcinoma samples from subjects (see at least example 8 of instant specification). However, the instant claims are far broader than the noted enabled embodiment. As noted above, the claimed method allows for diagnosis or prognosis of a pancreatic cancer in all subjects by measuring levels of the PKC and PHLPP1 in any type of sample from the subject. However, for the reasons noted in the 112(a) rejection above, the claims are not enabled as the Wands analysis dictates a finding of undue experimentation.
No claim is allowed.
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 Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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