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 Invention II (claims 7-11) and species a) mRNA, b) ACTA2, c) TP63, d) PCNA, e) immunotherapy resistance, f) stomach cancer in the reply filed on 2/05/26 is acknowledged. After further consideration, the Examiner has decided to withdraw the election of species requirements between the types of prognosis and the cancer types.
Claims 1-18 are currently pending.
Claims 1-6 and 12-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected invention(s), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/05/26.
Claims 7-11 have been examined to the extent that they read the elected gene (ACTA2) and mRNA analysis. The additionally recited genes and protein analysis have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Claim 10 has been examined to the extent that it reads the elected gene (TP632) and Claim 11 has been examined to the extent that it reads the elected gene (PCNA). The additionally recited genes have been withdrawn from consideration as being directed to non-elected subject matter. Prior to allowance of the claim, any non-elected subject matter that is not rejoined with any allowed elected subject matter will be required to be removed from the claims.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Priority
It is acknowledged that the instant application is a 371 of international PCT Application No. PCT/KR2021/018966, filed 12/14/21, and that it claims benefit of provisional 63/155,865, filed 3/3/21. The effective filing date is considered to be 3/3/21.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show the following as described in the specification:
Relatively high and low expression levels in Fig. 1: the lack of color in this figure does not allow for interpretation of over- and under-expression via z-score
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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.
Claim Objections
Claim 7 is objected to because of the following informalities: Claim 7 depends on the composition of claim 1, however it is improper for a claim to refer to a withdrawn claim. Appropriate correction is required.
Claim 11 is objected to because of the following informalities: Claim 11 depends on the composition of claim 5, however it is improper for a claim to refer to a withdrawn claim. Appropriate correction is required.
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 7-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4, Monday, January 7, 2019).
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite a law of nature. The claims recite a correlation between the expression level of genes/biomarkers and cancer prognosis. 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.
The instant claims recite abstract ideas. The claims recite a step of “comparing” the expression level of genes, with no recited reference level for comparison. Although the specification provides some examples of methods used for comparison (par. 47, 53), neither the specification nor the claims set forth a limiting definition for “comparing” and the claims do not set forth how this step is accomplished. The “comparing” step broadly encompasses mental processes. For example, one may “compare” the expression levels by looking at data and thinking about whether the expression level is high or low. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgement, and opinions) are considered to be abstract ideas.
The claims recite a step of “predicting” or ”determining” prognosis to cancer treatment if the levels of biomarker mRNA correspond to an expression signature (“relatively high”) that is indicative of good or poor response to immunotherapy or chemotherapy. Neither the specification nor the claims set forth a limiting definition for “predicting”/”determining” and the claims do not set forth how this step is accomplished. The broadest reasonable interpretation of the “predicting”/”determining” step is that it may be accomplished by a mental process. For example, one may “predict”/”determine” that prognosis is good or poor by thinking about the subject’s expression levels and expression signature. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgement, and opinions) are considered to be abstract ideas.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exception(s) into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or a technological field;
An additional element that applies or used a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing;
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions, the claims recite a step of “measuring” the expression levels of mRNA(s) in a sample. This step is not considered to integrate the judicial exceptions into a practical application because it merely adds insignificant extra-solution activity (data gathering) to the judicial exceptions.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exceptions, the claims recite a step of “measuring” the expression levels of mRNA(s) in a sample. This step does not amount to significantly more because it simply appends well-understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
The step is recited a high level of generality. Measuring the expression levels of mRNA or a plurality of mRNAs merely instructs a scientist to use any known technique for measuring expression levels. The claim does not require the use of any particular non-conventional reagents or equipment or methodology. 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, and conventional nature of additional elements because it teaches that the additional elements are well-known or commercially available. For example, the specification teaches the following:
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Further, it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, and 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.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
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 the reasons set forth above the claims are not directed to patent eligible subject matter.
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 7-11 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding Claims 7-11, it is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of the claim recites a method of predicting cancer prognosis, yet the method only requires measuring expression levels and comparing expression levels. Thus, it is not clear if applicant intends to cover only a method of measuring expression levels and comparing expression levels OR if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal set forth by the preamble of the claims.
Claims 9-11 are rejected for recitation of “relatively high,” which is a relative term that renders the claims indefinite. The specification recites examples of classifying expression levels (e.g. in par. 53, ACTA2 expression in Fig. 9 is considered to be high or low based on a Log2(FPKM+1) value above or below 5), but a limiting definition is not provided, and it is unclear whether 5 is a definitive cutoff-value for determining ‘high’ expression. Therefore, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim 9 is rejected for recitation of “poor,” which is a relative term that renders the claim indefinite. “Poor” is not defined by the claim, and no clear definition is provided in the specification, making the limitation unclear. For example, is a pre-established cutoff value used to determine that prognosis is poor, or is poor defined as any response worse than the average, or is some other criteria used to identify a “poor prognosis?” Thus, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claims 10 and 11 are rejected for recitation of “good,” which is a relative term that renders the claim indefinite. “Good” is not defined by the claim, and no clear definition is provided in the specification. For example, is a pre-established cutoff value used to determine that prognosis is good, or is good defined as any response better than average, or is some other criteria used to identify a “good prognosis?” Thus, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim 11 is rejected for recitation of ‘using the marker composition of claim 5.’ Claim 11 does not require measuring any markers and can be accomplished by only thinking about prognosis based on the marker(s). Therefore, it is unclear how the ‘agent for measuring’ is being used in claim 11, and one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim Rejections - 35 USC § 112
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 7-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (preAIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Scope of the Claims/Nature of the Invention
The claims are drawn to methods for predicting cancer prognosis. In view of the recitation of "cancer", the claims broadly encompass ANY type of cancer. It is noted that there are more than 200 different types of cancer. In view of the recitation of “prognosis,” the claims broadly encompass ANY type of prognostic factor (i.e., overall survival rates, disease free survival, metastasis free survival, lymph node involvement, response to treatment, time to metastasis, etc.). Only claims 8-11 are limited to specific prognostic factors. The claims further encompass both human and no-human subjects.
The claims recite a first step of measuring the expression levels of ACTA2 mRNA. In view of the non-limiting claim language, the claims broadly encompass measurement using ANY type of biological sample (i.e., blood, urine, stomach tissue, etc.).
The claims recite a second step of comparing the expression level of ACTA2 mRNA. Here the claims do not recite what the expression level is being compared to. The claims broadly encompass comparing the expression level of ACTA2 to anything. This could be level of any gene in any sample type obtained from any organism or set of organisms, with or without any cancer type or prognosis.
Claims 9-11 recite determining that the prognosis of chemotherapy and immunotherapy/immunochemotherapy based on the expression levels of additional genes. Here the claims broadly encompass ANY type of chemotherapy and ANY type of immunotherapy or immunochemotherapy.
The nature of the invention requires a reliable correlation between the expression level of ACTA2 mRNA (and TP63 or PCNA) and ANY type of cancer prognosis.
Teachings in the Specification and Examples
Example 5 describes the use of ACTA2 mRNA expression levels to predict survival rates in the Yonsei cohort (par. 98). Patients were stratified by average value of ACTA2 mRNA expression into ‘High’ and ‘Low’ subgroups, and patients with higher ACTA2 mRNA expression showed a poor overall survival rate compared to patients with lower ACTA2 mRNA expression (par. 99, Fig. 6a). Then multivariate Cox proportional analysis was used to show association between ACTA2 mRNA subgroups and survival rate in other cohorts (par. 100), namely groups of patients from the Asian Cancer Research Group (ACRG; n=300 gastric cancer patients; par. 80) and Sohn et al. (n=267 gastric cancer patients; par. 80). In these analyses, a 1-unit increase in ACTA mRNA expression was associated with survival rate (par. 100). Patients in the TCGA cohort showed statistically different survival outcomes when stratified into high and low levels of ACTA2 (par. 100).
Further analysis in a Samsung cohort (n=45 patients who received ‘immuno-anticancer treatment’) showed that higher levels of ACTA2 mRNA level were associated with resistance to an ‘immunotherapeutic agent’ (par. 103, Fig. 8). The specification cites Kim et al. for the Samsung cohort (Kim et al. Nat Med. 2018 Sep;24(9):1449-1458), which describes the use of pembrolizumab (an anti-PD-1 monoclonal antibody) in its patient population.
State of the Art and the Unpredictability of the Art
While methods of measuring expression levels are known in the art, methods of correlating expression levels with a phenotype such as cancer prognosis are highly unpredictable. The unpredictability will be discussed below.
The claims are drawn to methods of predicting cancer prognosis based on the expression of ACTA2 (and TP63 or PCNA) mRNA levels. The specification discloses expression level data of 32-gene panel of mRNAs, which are clustered into 4 molecular subtypes, and demonstrates the ability of the 4 subtypes, as well as ACTA2 itself, to predict survival rates and immunotherapy resistance in several cohorts of gastric cancer patients. However, it is highly unpredictable if the claimed methods would work using any combination of ACTA2 and TP63 or PCNA. While there is evidence in the specification that high ACTA2 expression levels can be indicative of poor prognosis in terms of survival rate or treatment resistance in gastric cancers (Example 5), there is no evidence that the combinations of ACTA2 + TP63 and ACTA2 + PCNA, nor any other individual genes or subsets of the genes beyond the 4 molecular subtypes recited in the specification, would be able to predict prognosis of gastric cancer immunotherapy. The specification only provides evidence that increased expression levels of ACTA2 are correlated with (i) poor overall survival and (ii) resistance to treatment with pembrolizumab in patients with gastric cancer.
As discussed above the claims broadly encompass a method of determining the prognosis of ANY cancer type. Xu et al. (PLoS One. 2010 Oct 27;5(10):e13696. doi: 10.1371/journal.pone.0013696) teaches an attempt to identify genes that could be used as indicators for cancer generally, or for groups of cancers. Xu examined genes with at least 2-fold expression change between cancerous and corresponding control tissues, across seven different cancer types (breast, colon, kidney, lung, pancreas, prostate, stomach). Only 85 genes were differentially expressed across 3 cancer types, 19 genes were differentially expressed across four cancer types, and 5 genes were differentially expressed across five cancer types (pg. 5, col. 2: Markers for multiple cancer types). Thus, it is highly unpredictable as to whether the findings in the specification regarding ACTA2 and gastric cancer could be extrapolated to any of the more than 200 known cancers.
The instant claims encompass a method of predicting cancer prognosis and encompass the analysis of both human and non-human subjects. However, the data presented in the specification is based on the analysis of samples from human subjects. The prior art teaches that there is a large amount of unpredictability with regard to comparing results from gene expression analysis in humans to even closely related animals. For example, Coleman (Drug Discov Today. 2003 Mar 15;8(6):233-5) found that gene expression patterns between mice and humans shared some degree of similarity, but that the basic patterns of gene expression differed and that there was no general rule for predicting gene expression (page 234). Coleman concluded that “…the validity of mouse or other animal species as a human surrogate should not be assumed." These teachings support the finding that there is no predictable means for determining whether the gene expression profile that is predictive of cancer in a human subject will also be predictive of cancer in a representative number of non-human subjects. The specification only provides support for human subjects.
The claims broadly claim predicting immunotherapy prognosis based on the mRNA expression level of ACTA2 (and TP63 or PCNA) mRNA in ANY type of sample (i.e. blood, urine, CSF, hair, skin cells, breast tissue, stomach tissue, etc.). However, the specification only provides examples of mRNA expression levels measured from tumor samples (par. 21, 72). Therefore, it is highly unpredictable if the expression levels observed in tumor tissue samples could be extrapolated to other sample types such as blood or plasma, as encompassed by the claims. Whitehead (Genome Biol. 2005;6(2):R13) teaches that variation in gene expression is extensive among tissues (abstract). Whitehead further teaches that many different cancers have unique tissue specific patterns of gene expression (page 1, col 2). The specification teaches that the 32-gene panel was generated from genes with mutation profiles specifically altered in gastric cancer vs other cancers, and later validated for mRNA expression levels in ‘pre-treated tumor samples.’ There is no analysis in the specification on the level of these mRNAs in other sample types (blood, stool, stomach tissue, saliva etc.) obtained from subjects with gastric cancer. Thus, in the absence of evidence to the contrary it is highly unpredictable if any of the 32 genes (including ACTA2, TP63, and PCNA) are differentially expressed in other samples types obtained from patients with gastric cancer. The specification only provides support for the analysis of tumor tissue.
Further, it is highly unpredictable if the claimed method can be practiced using any reference level. As discussed above, the claims do not set forth what the reference level is and it could be the level of any mRNA, in any sample type, obtained from any organism, with or without any cancer type. However, the teachings in the specification are limited to the analysis of ACTA2-specific mRNA levels in human tumor tissue samples obtained from patients with gastric cancer. Specifically, comparisons between groups of ‘high’ ACTA2 mRNA expression are compared to groups of ‘low’ ACTA2 mRNA expression. It is highly unpredictable if ACTA2 (and TP63 or PCNA) mRNA, which may be differentially expressed among gastric cancer patients, will also be differentially expressed between gastric cancer groups and ANY other type of reference level that is encompassed by the claims.
Further, it is highly unpredictable if the claimed methods can be practiced using any immunotherapy. The claims broadly encompass ANY immunotherapy (i.e. immune checkpoint inhibitors, CAR T-cell therapy, monoclonal antibodies, cancer vaccines, etc.). However, the teachings of ACTA2 as a biomarker for immunotherapy resistance in the specification are based on a cohort which was treated with an anti-PD-1 immune checkpoint inhibitor (as described in Kim et al. Nat Med. 2018 Sep;24(9):1449-1458). In the absence of evidence to the contrary, these correlations would be highly unpredictable.
Further, it is highly unpredictable if the claimed methods can be practiced using any form of anti-cancer therapy. The claims broadly encompass ANY chemotherapy and/or immunotherapy. However, the teachings in the specification are limited to a correlation between mRNA expression of ACTA2 and resistance to immunotherapy (specifically, the anti-PD-1 monoclonal antibody pembrolizumab). Although the specification states that ‘it could be confirmed that ACTA2 was overexpressed in a high-risk subgroup showing resistance to chemotherapy and immunotherapy’ (par. 104), there is no evidence in the specification showing that the specific mRNA expression of ACTA2 (and TP63 or PCNA) is correlated with response to any anti-cancer treatments (including chemotherapies) other than the pembrolizumab immunotherapy analyzed in a Samsung cohort (par. 103).
Finally, it is highly unpredictable if mRNA expression of the 32-gene panel generally or ACTA2 (and TP63 or PCNA) is predictive of ANY clinical parameter relevant to immunotherapy resistance. The claims broadly encompass ANY clinical parameter which can be used to measure resistance to immunotherapy (i.e., survival rates, clinical evaluations, blood biomarkers, tumor measurements etc.). However, the teachings in the specification are limited to a correlation between mRNA expression of ACTA2 and overall response rate (ORR), which involves assessment into response categories based on tumor imaging/measurement. There is no data in the specification showing that ACTA2 (and TP63 or PCNA) is correlated with any other clinical parameters in patients with gastric cancer or any other type of cancer.
Quantity of Experimentation:
To enable to full scope of the claims, the quantity of experimentation necessary is great, on the order of many man-years, and there is little, if any, reasonable expectation of success. In support of this position, it is noted that the claimed methods encompass being able to prognose resistance of ANY cancer to ANY type of immunotherapy based on the mRNA expression of ACTA2 (and TP63 or PCNA), measured from ANY type of biological sample obtained from ANY organism, compared to ANY reference level, and assessed using any clinical parameter.
In order to practice the breadth of the claimed invention one of skill in the art would first have to gather samples from human and non-human subjects having a representative number of greater than 200 different cancers, treated with a representative number of immunotherapies. The samples would need to include tumor tissue and a representative number of other samples types. Then the mRNA expression level of ACTA2 and TP63 and PCNA would have to be measured, and patient outcomes determined using a representative number of clinical parameters. Then sophisticated data analysis would have to be conducted to determine whether ACTA2 (and ACTA2 + TP63 and ACTA2 + PCNA) mRNA expression, compared to any type of reference level, could be used to predict immunotherapy resistance to any immunotherapeutic agent. The specification has merely provided an invitation for further experimentation. The results of such experimentation are highly unpredictable.
The amount of experimentation that would be required to practice the full scope of the claimed invention and the amount of time and cost this experimentation would take supports the position that such experimentation is undue. Attention is directed to Wyeth v. Abbott Laboratories 107 USPQ2d 1273, 1275, 1276 (Fed. Cir. June 2013):
Claims are not enabled when, at the effective filing date of the patent, one of ordinary skill in the art could not practice their full scope without undue experimentation. MagSil Corp. v. Hitachi Global Storage Techs., Inc., 687 F.3d 1377, 1380-81 [103 USPQ2d 1769] (Fed. Cir. 2012).
The remaining question is whether having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation. We hold that it does. Undue experimentation is a matter of degree. Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 [70 USPQ2d 1321] (Fed. Cir. 2004) (internal quotation omitted). Even "a considerable amount of experimentation is permissible," as long as it is "merely routine" or the specification "provides a reasonable amount of guidance" regarding the direction of experimentation. Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342, 1360- 61 [47 USPQ2d 1705] (Fed. Cir. 1998) (internal quotation omitted). Yet, routine experimentation is "not without bounds." Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013). (Emphasis added)
In Cephalon, although we ultimately reversed a finding of nonenablement, we noted that the defendant had not established that required experimentation "would be excessive, e.g., that it would involve testing for an unreasonable length of time." 707 F .3d at 1339 (citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] (Fed. Cir. 1983)). Finally, in In re Vaeck, we affirmed the PTO's nonenablement rejection of claims reciting heterologous gene expression in as many as 150 genera of cyanobacteria. 947 F.2d 488, 495-96 [20 USPQ2d 1438] (Fed. Cir. 1991). The specification disclosed only nine genera, despite cyanobacteria being a "diverse and relatively poorly understood group of microorganisms," with unpredictable heterologous gene expression. Id. at 496. (Emphasis added)
Additionally, attention is directed to Cephalon at 1823, citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 218 USPQ 961, that work that would require 18 months to 2 years so to enable the full scope of an invention, even if routine, would constitute undue experimentation. As stated therein:
Permissible experimentation is, nevertheless, not without bounds. This court has held that experimentation was unreasonable, for example, where it was found that eighteen months to two years' work was required to practice the patented invention. See, e.g., White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] Fed. Cir.1983). (Emphasis added)
Attention is also directed to MPEP 2164.06(b) and In re Vaeck, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991):
Where, as here, a claimed genus represents a diverse and relatively poorly understood group of microorganisms, the required level of disclosure will be greater than, for example, the disclosure of an invention involving a "predictable" factor such as a mechanical or electrical element. See Fisher, 427 F.2d at 839, 166 USPQ at 24.
In view of such legal precedence, the aspect of having to work for so many years just to provide the starting materials for minute fraction of the scope of the claimed invention is deemed to constitute both an unreasonable length of time and undue experimentation.
Conclusions:
Herein, although the level of skill in the art is high, given the lack of disclosure in the specification and in the prior art and the unpredictability of the art, it would require undue experimentation for one of skill in the art to make and use the invention as broadly claimed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 7 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luca et al. (published April 12, 2018; International Publication No. WO 2018/065525).
Luca et al. recites methods for prognosis (Abstract) of many aggressive cancers (pg. 23, ln. 20-28: Luca calls them DESNT cancers), including stomach cancer (pg. 24, ln. 1-2).
Regarding claim 7, Luca teaches predicting cancer prognosis (pg. 31, lines 31-34) by measuring an expression level of mRNA (pg. 16, ln. 12-24) for ACTA2 gene expression (pg. 40, ln. 26-30; pg. 54, Table 2), and comparing the expression level (pg. 32, ln. 16-21).
Claim 8 states that the prognosis is a survival rate, chemo-sensitivity, chemo-resistance, immunotherapy sensitivity, immunotherapy resistance, or any combination thereof. This recitation further limits (i) the preamble, which recites a method of predicting cancer, and (ii) the intended use of the marker composition of claim 1. MPEP 2111.02 states the following:
“If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
In the present situation, the process steps are able to stand alone and therefore the preamble and the limitations that modify the preamble (such as in claim 8) are not accorded patentable weight because they merely set forth the purpose of the process, but do not limit the scope of the claims. Further, the recited intended use of the marker of claim 1 does not limit the scope of the claims when there are no active process steps of predicting cancer prognosis.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine M Jones whose telephone number is (571)272-2585. The examiner can normally be reached Monday - Friday, 8AM - 4PM.
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/C.M.J./Examiner, Art Unit 1682
/AMANDA HANEY/Primary Examiner, Art Unit 1682