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 .
Status of Claims
Claims 1-8 are under examination.
Priority
This application claims the benefit of priority from U.S. Provisional Application No. 63/425,006, filed on 11/14/2022. Accordingly, this is the effective filing date of the instant application.
Information Disclosure Statement
No IDS has been filed in the instant case. Applicant is reminded of the requirements of 37 CFR 1.56. If Applicant is aware of any materially relevant prior art, it should be submitted in an IDS for consideration.
Specification
The specification is objected to as it contains non-standard section headings. See 37 CFR 1.77(b). In particular, the specification (starting on page 44) recites a section entitled “REFERENCES”. Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and MPEP § 609.04(a), subsection I. states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. This objection may be overcome by amending section headings to comply with 37 CFR 1.77(b).
Drawings
The drawings filed 11/14/2023 (black and white) are objected to as failing to comply with 37 CFR 1.84 because several of the Figures are not legible. See at least Figures 1-3, 6-17, and 13. 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.
Applicant' s petition under 37 CFR 1.84(a)(2), filed 11/14/2023, is acknowledged. The petition decision to accept color drawings was rendered and mailed on 03/05/2024. However, the petition was found to be deficient because the statement of color drawings was missing, inaccurate, or misplaced. Accordingly, the petition was dismissed. Accordingly, applicant should refer to the dismissal for corrective action.
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 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and ‘as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355).
Guidance: Step 1. Under the broadest reasonable interpretation, the claimed invention (claims 1 being representative) is directed to a method for performing a process and therefore falls within one of the four statutory categories.
A. Guidance Step 2A, Prong 1
The Revised Guidance instructs us first to determine whether any judicial exception to patent eligibility is recited in the claim. The Revised Guidance identifies three judicially-excepted groupings identified by the courts as abstract ideas: (1) mathematical concepts, (2) certain methods of organizing human behavior such as fundamental economic practices, and (3) mental processes. In this case, the following steps of claim 1 recite an abstract idea:
(c) comparing the gene expression profiles of above-mentioned seven genes in the tissue sample from a high-risk primary tumor from the subject with metastatic or death outcomes with the expression profiles of these genes from a low-risk primary tumor, thereby comprising a seven-gene prognostic signature;
(d) determining the risk of the subject using data-driven grouping (DDg) methods, gene expression data and statistically weighted voting grouping (SVWg) algorithms; and
(e) stratifying the subject in a high, moderate, or low risk group based on the determining step.
Mental Processes
Under MPEP §2111, during patent examination, claims must be interpreted in their broadest reasonable manner consistent with the specification. This means that examiners consider the claim language in light of the specification as understood by a person of ordinary skill in the art, ensuring that the claims are not unduly narrowed by implicit limitations not explicitly recited in the claim (37 CFR 1.75(d)(1)).
In this case, the comparing and determining steps are recited at a high level of generality and are not limited to any particular techniques or operations. Accordingly, under the BRI, these steps set forth or describe observing and/or analyzing data, which scientists can perform using their brains or a pencil and paper. As such, these steps encompass a mental process of observing data and/or manipulating data. MPEP 2106.04(a)(2), section III.
In this case, the stratifying step is recited at a high level of generality and is not limited to any particular techniques or operations. Accordingly, under the BRI, this step sets forth or describes analyzing data and/or making a decision, which scientists can perform using their brains or a pencil and paper. As such, these steps encompass a mental process of observing data and/or manipulating data. MPEP 2106.04(a)(2), section III.
It is important to note that “Claims that recite performing information analysis as well as the collection and manipulation of information related to such analysis, have been determined by our reviewing court to be an abstract concept that is not patent eligible. See SAP, 898 F.3d, 1165, 1167, 1168 (Claims reciting "[a] method for providing statistical analysis" (id. at 1165) were determined to be "directed to an abstract idea" (id. at 1168)); see also Content Extraction & Transmission LLC v. Wells Fargo Bank, Nat'l Ass 'n, 776 F.3d 1343, 1345, 1347 (Fed. Cir. 2014). [Step 2A, Prong 1: YES].
Mathematical Concept
With regards to said determining, this step determines risk (i.e. a numerical value) using data-driven grouping methods and statistically weighted grouping algorithms. Accordingly, under the BRI, this step sets forth or describes using mathematical algorithms for calculating a numerical value. This position is further supported by applicant’s own specification, which teaches specific equations and conditions associated with the above analysis methods [Examples 4 and 5]. As such, this step encompasses a mathematical concept of manipulating information through mathematical correlations or calculations. MPEP 2106.04(a)(2) Section I. It is important to note that a mathematical concept need not be expressed in mathematical symbols, because “[w]ords used in a claim operating on data to solve a problem can serve the same purpose as a formula.” In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). [Step 2A, Prong 1: YES].
Natural Correlation
Under the broadest reasonable interpretation, the above claims also recite a natural correlation. In particular, the instant claims require performing stratifying gene expression data with various levels of breast cancer stratification which amounts to a natural correlation. See MPEP 2106.04(b). It is noted that even if a claim does recite a law of nature or natural phenomenon, it may still be eligible. For example, claims reciting a naturally occurring relationship between a patient’s genotype and the risk of QTc prolongation (a law of nature) were held eligible as not “directed to” that relationship because they also recited a step of treating the patient with an amount of a particular medication that was tailored to the patient’s genotype. Vanda Pharms., 887 F.3d at 1134-36, 126 USPQ2d at 1279-81. This particular treatment step applied the natural relationship in a manner that integrated it into a practical application. The court’s analysis in Vanda is equivalent to a finding of eligibility at Step 2A Prong Two (Pathway B).
B. Guidance Step 2A, Prong 2
Having made that determination, under the 2019 Guidance, the examiner next determines whether there are additional elements beyond the recited abstract idea(s) that integrate them into a practical application.
In this case, the additional steps/elements that are not part of the abstract idea are as follows:
obtaining a tissue sample from the subject;
(b) measuring gene expression profiles of ABIl, BRK1, WASF3, CYFIP1, CYFIP2, RAC1 and NDEL1 genes in the tissue sample;
With regards to said obtaining and measuring, these steps are recited at a high level of generality and require collecting data for use by the abstract idea. Accordingly, these steps both amount to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g). Notably, the claim does not include a computer or any specific machine for practicing the claimed invention. In summary, the claimed invention does not provide any objective evidence of an improvement to the technology, nor does the specification explain the details of an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art. See MPEP 2106.04(d)(1) and MPEP 2106.05(a). Therefore, even when viewed in combination, these additional steps/elements do not integrate the recited judicial exception into a practical application. [Step 2A, Prong 2: NO].
C. Guidance Step 2B:
This part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the recited exception i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP 2106.05.
As discussed above, the non-abstract steps/elements amount to nothing more than insignificant extra-solution activity. Moreover, applicant’s own specification teaches well understood, routine, and conventional methodologies for obtaining samples and measuring gene expression profiles for the set of genes presently claimed [Examples 1 and 8]. In addition, Rana et al. (Biomedicines, 2021, 9(9), 1217, pp. 1-17) teaches expression data for ABI1, BRK1, WASF2, RAC1. Regua et al. (cited in the 35 USC 102 rejection below) teaches obtaining a tissue sample; measuring gene expression profiles of a subset of WAVE complex genes (ABI1, BRK1, WASF3, CYFIP1, CYFIP2, RAC1 and NDEL1). Kwon et al. (Cell Death Discovery (2023) 9:7, pp.1-11) teaches methods for novel cancer marker discovering that include obtaining gene expression data for 24,695 genes using the Affymetrix GeneChip® Human 2.0 ST array, which provides coverage of the entire human genome and includes ABI1, WAVE, and CYFIP1 genes [See entire].
In addition, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. 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);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps or the nature of the data being collected. See MPEP 2106.05(d)(Part II). Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. Therefore, the claim(s) is/are not patent eligible. [Step 2B: NO].
Dependent Claims
Dependent claims 2-8 have also been considered under the two-part analysis but do not include additional steps/elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons. Regarding claim(s) 2 and 8, these claims are directed to limitations that further limit the specificity of the abstract idea set forth above or how the gene expression data is stratified. Accordingly, these steps also recite an abstract idea for reasons discussed above in the Step 2A (prong 1) analysis. Regarding claim(s) 3-7, these claims further limit the type of markers or samples used or the nature of the gene expression. Accordingly, this amounts to insignificant extra-solution activity and/or generally linking the use of a judicial exception to a particular technological environment or field of use as set forth above. MPEP 2106.04(g) and (h). Therefore, the claims as a whole are not patent eligible. For additional guidance, applicant is directed generally to MPEP 2106.
Claim rejections - 35 USC § 112b
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 1-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims that depend directly or indirectly from claim(s) 1 are also rejected due to said dependency.
Claim 1 recites “(d) determining the risk of the subject using data-driven grouping (DDg) methods, gene expression data and statistically weighted voting grouping (SVWg) algorithms”. Firstly, it is unclear as to the metes and bounds of the claimed data-driven grouping (DDg) methods and statistically weighted voting grouping (SVWg) algorithms, which appear to be critical aspects of invention. A review of the specification does not provide any limiting definitions that would serve to clarify the scope of these terms such that the artisan would know how to avoid infringement. The specification does provide a limited example of DDG and SWVg algorithms with specific mathematical equations associated [Examples 4 and 5]. However, examples are not limiting definitions and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Moreover, with regards to using the DDg methods and SVWg algorithm, a claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP § 2173.05(q). As a result, it is unclear what computational techniques are included or excluded by the claimed “determining” step such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claim 1 recites “(e) stratifying the subject in a high, moderate, or low risk group based on the determining step.” Firstly, such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. See MPEP 2173.05(g). A review of the specification does not provide any conditional operations, equations, or prose equivalent that would serve to clarify the claimed function or clarify in what way is the data being stratified into the desired groupings. At best, the specification merely reiterates the claim language without any further details [0039]. Therefore, it is unclear as to the metes and bounds of the claimed “stratifying” such that the artisan would recognize what computational operations are included or excluded. Secondly, the terms high, moderate, and low are relative terms and the specification does not provide any limiting definitions, specific properties, or scoring criteria indicating the scope of these terms. As a result, it is unclear as to the metes and bounds of these terms, as the result is subjective and imperceptible, i.e. what quantitative metrics are indicative high, moderate, and low risk. Clarification is requested via amendment.
Claim 2 recites “The method of claim 1, wherein a computer readable medium having stored thereon a computer program which, when executed by a computer system operably connected to a gene or protein expression assay system configured to measure an expression signal…causes the computer system to perform a method of calculating a cut-off value by a method comprising…”. Firstly, there is lack of antecedent basis for said “computer readable medium”, “computer system” and “assay system” because these features are not previously recited in parent claim 1 nor are they inherent. In addition, the above ‘wherein’ clause suggests performing an additional step (calculating a cut-off value) that is not previously recited in parent claim 1. As a result, it is unclear what limiting effect of the above “wherein” clause it intended (because parent claim 1 does not recite any of these features). See MPEP 2111.04. Clarification is requested via amendment. The examiner suggests amending claim 1 to include a computer processor and any other hardware elements required to practice the claimed invention.
Claim 2 recites “(a) fitting said measured expression signal of ABIl, BRK1, WASF3, CYFIP1, CYFIP2, the WAVE complex members, and also RAC1 and NDEL1 as independent variables, interpreting the expression signals and calculating a p-value using a data-driven grouping (DDg) method; (b) constructing a seven-gene prognostic signature using a statistically weighted voting grouping (SVWg) algorithm and input data provided by the data-driven grouping (DDg) method; and, stratifying the subject in a high, moderate, or low risk group based on the seven-gene prognostic signature.” This limitation is problematic for the following reasons. (1) There is lack of antecedent basis for “said measured expression signal” and “the WAVE complex members”. There is no prior mention of any “signal” or “WAVE complex members” in parent claim 1 and these terms are not inherent. Parent claim 1 does provide support for gene expression profiles. (2) With regards to said “fitting”, it is unclear what the independent variables are being fitted to, e.g. a model, an equation, or otherwise. (3) With regards to said “constructing”, such generic functional claim language amounts to descriptions of problems to be solved and covers all means or methods of performing the claimed function. See MPEP 2173.05(g). A review of the specification does not provide any conditional operations, equations, or prose equivalent that would serve to clarify the claimed function. Therefore, it is unclear as to what computational operations are included or excluded. In each case, clarification is requested via amendment.
Claim 8 recites “The method of claim 1, wherein ABIl gene is highly or abnormally expressed, thereby representing a therapeutic target, as defined in a metastatic ABI1/PyMT mouse model system, wherein ABIl gene downregulation reduces metastatic burden in lungs.” Firstly, there is lack of antecedent basis for “a metastatic…mouse model system” as there is no previous mention of such a system in parent claim 1. Secondly, parent claim 1 merely results in stratifying the subject (as high, moderate, or low risk) and does not explicitly require evaluating ABI1 gene expression with regards to abnormality. As a result, it is also unclear what limiting effect of the above “wherein” clause it intended. See MPEP 2111.04. Clarification is requested via amendment.
Claim rejections - 35 USC § 112d
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following rejection is modified in view of applicant’s amendments.
Claim 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As discussed above, claim 8 recites “The method of claim 1, wherein ABIl gene is highly or abnormally expressed, thereby representing a therapeutic target, as defined in a metastatic ABI1/PyMT mouse model system, wherein ABIl gene downregulation reduces metastatic burden in lungs.” As discussed above, there is no previous mention of a mouse model system in parent claim 1. In addition, the claimed ‘wherein’ limitation is directed to an evaluation with regards to the expression of the ABI1 gene. However, parent claim 1 merely results in stratifying the subject (as high, moderate, or low risk) and does not explicitly require evaluating ABI1 gene expression with regards to abnormality. Therefore, it unclear in what way claim 8 further limits the subject matter of parent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
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 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.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Regua et al. (Molecular Oncology, July 2022, Volume 16, Issue 14, pp.2609-2767; Online Pub. Date: Jan. 2022).
It is noted that the cited prior art reference shares a common inventor but is a different inventive entity. To overcome a proper rejection based on such a reference without amending the claims, the applicant must invoke an exception under §102(b)(1)(A) or 102(b)(1)(B). See MPEP 717.
Regarding claim(s) 1, Regua teaches methods of predicting breast cancer metastasis and survival based on ABI1-based expression signatures. In particular, Regua teaches obtaining a tissue sample; measuring gene expression profiles of a subset of WAVE complex genes (ABI1, BRK1, WASF3, CYFIP1, CYFIP2, RAC1 and NDEL1) [Section 1, Section 2.1, and Section 2.3.4]. Regua teaches comparing said profiles with controls metastatic or death outcomes [Section 2.1, Section 2.8, and Figure 5]. Regua teaches using data-driven grouping (DDg) methods (one-dimensional (univariate), 1D-DDg, two dimensional (bivariate) 2D-DDg), and statistically weighted voting grouping (SVWg) algorithms for determining patient’s risk stratification onto two and three survival groups representing Kaplan–Meier survival functions [Section 2.3, entire].
Regarding claim(s) 2, Regua teaches constructing the multigene prognostic signature using the results data-driven grouping methods, and statistically weighted voting grouping (SWVg); determining cutoff values for the model variables; identifying subdomains that maximize discrimination of all subjects (patients) onto low-and high-risk groups [Section 2.3.1 and Section 2.3.2]. The ability of individual prognostic variables (voting weight) to stratify patients in risk groups is represented by the P-values associated with log-rank statistics [Section 2.3.2]. Regarding claim(s) 3, 4, 5, 6, Regua teaches ABI1 as a marker for investigating human breast cancer [Section 3.1]. Regarding claim(s) 7, Regua teaches samples that include the human mammary tissue [Section 3.4]. Regarding claim(s) 8, Regua teaches that PyMT trans gene induces expression of Abi1 in primary tumors vs. normal mammary gland epithelium of Abi1 floxed mice (i.e. mouse model systems), and conclude that PyMT mouse recapitulates overexpression of ABI1 observed in human tissue, and thus, it is an appropriate model to examine the role of ABI1 in breast cancer tumor progression [Section 3.5, Fig. 3G].
Cited Prior Art
The following prior art made of record and not relied upon is considered pertinent to applicant' s disclosure.
Lance et al. (US2016/0222458), which teaches a method of assigning a grade to a breast tumour by obtaining gene expression data of BRRN1, AURKA, MELK, PRR11, CENPW and E2F1; assigning a grade to the tumour by applying a class prediction algorithms to the gene expression data (including data-driven and weighted voting algorithms); classiyfing tumours as a high aggressiveness or low aggressiveness tumour; and specifically treating the patient accordingly.
Munnes et al. (US2008/0299550), which teaches methods for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasia and breast cancer. The invention further relates to genes that are differentially expressed in breast tissue of breast cancer patients versus those of normal “healthy” tissue.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PABLO S WHALEY whose telephone number is (571)272-4425. The examiner can normally be reached between 1pm-9pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Anita Coope can be reached at 571-270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PABLO S WHALEY/Primary Examiner, Art Unit 3619
