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 .
Applicant's amendments and remarks, filed 01/29/2026, are acknowledged. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Priority
The present application claims priority to and the benefit of U.S. Provisional Patent Application Serial No. 63/107,906, filed on October 30, 2020.
Status of Claims
Claims 1-4, 6-17, 19-22 are under examination.
Claims 5 and 18 are cancelled. Claims 21 and 22 are newly added.
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.
The following rejection is modified in view of applicant’s amendments.
Claims 1-4, 6-17, 19-22 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 United States Patent and Trademark Office published revised guidance on the application of 35 U.S.C. § 101. USPTO’s 2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”). Under the Guidance, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes) (Guidance Step 2A, Prong 1); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)) (Guidance Step 2A, Prong 2).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that are not “well-understood, routine and conventional in the field” (see MPEP § 2106.05(d)); or 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-57 (January 7, 2019).
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.(Guidance Step 2B). See Guidance, 84 Fed. Reg. at 54-56.
Guidance Step 1:
The instant invention (claims 1 and 13 being representative) is directed to a method for characterizing response of a tumor to immunotherapy. Thus, the claims are directed to one of the statutory categories of invention. MPEP 2106.03.
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. Regarding claim(s) 1 and 13, the claimed steps that are part of the abstract idea are as follows:
Claim 1
calculating, from the immune gene expression dataset, an immunogenic signature score, wherein the immunogenic signature score comprises a mean expression rank for the gene expression data for the plurality of immune genes; (mental process; mathematical concept)
identifying, based on the calculated immunogenic signature score, the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic; (mental process)
predicting, based on the identification of the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic, the response of the tumor to immunotherapy, wherein: the tumor is identified as strongly immunogenic and the tumor is predicted to respond more favorably to immunotherapy…; (mental process)
Claim 13
calculating, from the immune gene expression dataset, an immunogenic signature score, wherein the immunogenic signature score comprises a mean expression rank for the gene expression data for the plurality of immune genes; (mental process; mathematical concept)
identifying, based on the calculated immunogenic signature score, the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic; (mental process)
predicting, based on: (1) the identification of the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic; (2) the generated PD-L1 expression profile; and (3) the generated TMB profile, the response of the tumor to immunotherapy, wherein: the tumor is identified as strongly immunogenic and the tumor is predicted to respond more favorably to immunotherapy…;(mental process)
Mental Processes
With regards to calculating a score, this step is recited at a high level of generality (without any technological details directed to how it is performed) and is not computer-implemented. As such, this step encompasses a mental process of observing and analyzing data. MPEP 2106.04(a)(2), section III.
With regards to identifying, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed) and is not computer-implemented. As such, this step encompasses a mental process of analyzing the data and making a judgement. MPEP 2106.04(a)(2), section III.
With regards to predicting, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed, the particular variants or diseases, or the nature of the associations) and is not computer-implemented. As such, this step encompasses a mental process of analyzing the data and making a judgement. MPEP 2106.04(a)(2), section III.
Mathematical Concept
With regards to said calculating, this step is recited at a high level of generality (without any technological details or rules directed to how it is performed) and is not computer-implemented. 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). See, e.g., SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161, 1163, 127 USPQ2d 1597, 1599 (Fed. Cir. 2018) (holding that claims to a ‘‘series of mathematical calculations based on selected information’’ are directed to abstract ideas). See also Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). Therefore, when read in light of applicant’s own specification, this limitation is directed to mathematical concept. See MPEP 2106.04 and 2106.05(II). [Step 2A, Prong 1: YES].
Natural Correlation
Under the broadest reasonable interpretation, the instant claims require correlating gene expression data with a particular tumor classification. Therefore, the claimed invention amounts to identifying a naturally occurring relationship between genes and disease. 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 tissue from the tumor;
generating, from the obtained tissue, an immune gene expression dataset comprising gene expression data for a plurality of immune genes;
generating, from the obtained tissue: (1) an immune gene expression dataset comprising gene expression data for a plurality of immune genes; (2) a PD-L1 expression profile; and (3) a tumor mutational burden (TMB) profile, wherein the TMB profile comprises mutational burden information about a plurality of genes generated from DNA sequencing data, and wherein the TMB profile is based on a number of non-synonymous mutations per megabase (Mut/Mb) of sequenced DNA;
With regards to obtaining, this step is recited at a high level of generality and results in gathering data for use by the abstract idea. Accordingly, this step amounts to insignificant extra-solution activity and is not indicative of an integration into a practical application. See MPEP 2106.05(g).
With regards to said generating, these steps are recited at a high level of generality (without any technological details directed to how they are performed) and result in gathering data for use by the abstract idea. Accordingly, these steps amount to insignificant extra-solution activity and are not indicative of an integration into a practical application. See MPEP 2106.05(g).
Even when viewed in combination, these additional elements do not integrate the recited judicial exception into a practical application. It is noted with particularity that the claimed methods do not require the use of any computer processor for performing the claimed analysis steps. [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, a review of the specification teaches a plurality of routine and conventional technologies for obtaining and processing tissue samples to obtain gene expression data [0066]. In addition, Davison et al. (WO/2017/013436; Pub. Date: 01/26/2017) teaches a method for predicting responsiveness to an inhibitory immune checkpoint therapy, including obtaining a gene expression profile for set of biomarkers from a patient tissue sample [pages 71-72, 76, 95-96, Table 2A, Table 2B and ref. claims 1-5]. Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps. 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].
D. Dependent Claims
Dependent claims 2-4, 6-12 and 14-17, 19-22 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 dependent claims 2-4, 6-8, 15-17 are directed to limitations that further limit the specificity of the data being used by the abstract idea. Accordingly, these steps amount to insignificant extra-solution activity and are not indicative of an integration into a practical application (Step 2A, prong 2 and Step 2B analysis). Regarding dependent claim 9, this claim recites administering a generically recited “immunotherapy”. According, this claim does not recite a particular treatment. See MPEP 2106.04(d)(2). For example, consider a claim that recites “administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype.” This administration step recites a particular dosage and type of medication and it integrates the mental analysis step into a practical application. Therefore, the claimed invention does not integrate the abstract idea into a “practical application. Dependent claims 6, 10, 11, 12, 14, 18, 19, 20, 21, 22 are all directed to limitations that further limit the specificity of the abstract idea. Accordingly, these claims are also directed to an abstract idea for the reasons set forth above (Step 2A, prong 1 analysis). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more.
Response to Arguments
Applicant’s arguments, filed 01/29/2026, have been fully considered but are not persuasive for the following reasons.
Applicant argues that the amended claims are patent eligible because they cannot be practically performing by the human mind (because gene expression data is generated by performing RNA-sequencing which generates vast quantities of data). In response, contrary to applicant’s assertions, the claims are not limited to any particular methods or modalities for collecting data (e.g. RNA-sequencing), type of analysis (or statistical calculations), or particular sizes or dimensionality of datasets. Moreover, Applicant is reminded that the Office's eligibility guidance does not set limit on the number of calculations that can or cannot be performed mentally. MPEP § 2106.04(a)(2)III. Therefore, absent any evidence to the contrary, the examiner maintains that the claimed steps clearly encompass an abstract idea in the form of a mental process. [Step 2A, Prong 1: YES].
Applicant additionally argues that the examiner failed to explain why correlating gene expression data with a particular tumor classification is considered to be a law of nature. In response, as set forth above, the examiner clearly explained that instant claims require correlating gene expression data with a particular tumor classification. In particular, this correlation is represented through the use of scores which are calculated from the gene expression data and then related (i.e. correlated) to various types of tumor (i.e. cancer) classifications. In response to applicant’s assertion that the claims do not recite a natural correlation in light of Vanda Pharms, those claims 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. The instant claims clearly do not recite any such limitation. Therefore, absent any evidence to the contrary, the examiner maintains that the claimed invention amounts to identifying a naturally occurring relationship between genes and disease. See MPEP 2106.04(b).
Applicant additionally argues that the claimed invention recites additional elements (namely steps a, b, d, and e) that integrate the JE into a practical application. In response, steps d and e are not “additional elements”, as asserted by applicant, but are abstract ideas for reasons set forth above (Step 2A, prong 1 analysis). The additional steps/elements of steps and b are “additional steps”, however, they do not integrate the JE into a practical application for reasons set forth above (Step 2A, prong 2 analysis). In addition, they also do not qualify as ”significantly more” because they simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception for reasons set forth above and supported by prior art reference (Step 2B analysis). See also MPEP 2106.05 (II). Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps alone or in combination. See MPEP 2106.05(d)(Part II).
Applicant additionally argues that the integration of molecular data, statistical computations, and clinical predictions amount to an improvement to the technology. In response, the MPEP is clear that the word "improvements" in the context of this consideration is limited to improvements to the functioning of a computer or any other technology/technical field, whether in Step 2A Prong Two or in Step 2B. MPEP 2106.04(d)(1). In this case, applicant has not provided any objective evidence to support the case that the claims result in an improvement to the functioning of a computer and no such evidence is provided in the specification. The claims fail to identify any elements that provides for a new clinical technology. To the extent that applicant is arguing that the “identifying” and “predicting” steps (i.e. the abstract idea) are providing the improvement, Applicant is reminded that the claimed invention’s use of the ineligible concept to which it is directed (i.e. the abstract idea) cannot supply the inventive concept that renders the invention ‘significantly more’ than that ineligible concept.” BSG Tech LLC v. BuySeasons, Inc., 899 F.3d 1281, 1290 (Fed. Cir. 2018). As such, the examiner maintains that the claims do not recite an improvement to the technology.
Applicant additionally argues that the combination of steps (a), (b), (d) and (e) are unconventional. In response, applicant has not provided any evidence to support this assertion and no such evidence is apparent in the specification. It is additionally noted that the search for an inventive concept should not be confused with a novelty or non-obviousness determination. See MPEP 2106.05. In other words, it is true that claims can be free of the prior art and yet still rejected under 35 USC 101. That being said, the examiner maintains that steps d and e are abstract for reasons set forth above (Step 2A analysis) and that the additional steps/elements of steps a and b do not qualify a ”significantly more” because the simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception for reasons set forth above and supported by prior art reference (Step 2B analysis). See also MPEP 2106.05 (II). Therefore, even upon reconsideration, there is nothing unconventional with regards to the above non-abstract elements/steps alone or in combination. See MPEP 2106.05(d)(Part II). For these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 112(a)
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
The following rejection is modified in view of applicant’s amendments.
Claims 1-4, 6-17, 19-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”). Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include: A) Partial structure; B) Physical and/or chemical properties; C) Functional characteristics; D) Known or disclosed correlation between structure and function; E) Method of making; and F) Combinations of A-E. See also MPEP 2163 and the 2011 Supplementary Guidelines to analysis under 35 USC 112 (Computer-Implemented Functional Claim Limitations).
Based on a consideration of the above factors, the level of skill and knowledge in the art, and the specification, the instant claims fail to meet the written description requirement for the following reasons:
Regarding claim(s) 1 and 13, under the broadest reasonable interpretation, the claimed subject matter is directed to a method for characterizing response of a tumor to immunotherapy by obtaining tissue from the tumor; generating…an immune gene expression dataset comprising gene expression data for a plurality of immune genes; calculating, from the immune gene expression dataset, an immunogenic signature score; identifying, based on the calculated immunogenic signature score, the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic; and predicting, based on the identification of the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic, the response of the tumor to immunotherapy, wherein: the tumor is identified as strongly immunogenic and the tumor is predicted to respond more favorably to immunotherapy…;
With regards to said identifying and predicting, the claims lack any specificity with regards to (1) how these steps are being achieving and (2) the genes being used (i.e. specific genetic markers) to predict tumor immunogenicity. In addition, with regards to said predicting, absent any type of statistical analysis or clearly defined ranges, it is unclear how the artisan would know what numerical scores correlate with the various “strengths” of immunogenicity. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed functions. The specification does teach examples of standard deviation calculations [0014-0016] and specific scores and equations for determining the strength of immunogenicity [0039, 0040]. However, such disclosures are not limiting definitions and are, in fact, much narrower in scope than what is being claimed---and it is improper to import narrowing limitations into the claims. MPEP 2111.04. However, the specification does not indicate which “signature scores” correlate with treatment response for the full scope genes and therapies embraced by the claims.
Moreover, methods for predicting treatment effectiveness are not trivial and are highly variable based on the nature of the disease and treatment agent. This position is supported by the prior art of Geeleher et al. (Genome Biology 2014, 15:R47, pp. 1-12), which teaches that methods for identifying and applying molecular biomarkers to predict response to therapeutic agents are highly variable and only a handful of markers can reproducibly predict therapeutic response in the clinic [Background]. Similarly, Webb et al. (The Journal of Biomedical Research, 2018 32(5): 317–326) teaches that while immune checkpoint inhibitors have shown great promise in treating various cancer types, it is unlikely that any single biomarker will be able to predict clinical outcomes across the gamut of immunotherapeutics. The specification does provide working examples and sets of genes [0055-0082 and Table 4]. However, such disclosures are not limiting definitions and are, in fact, much narrower in scope than what is being claimed---and it is improper to import narrowing limitations into the claims. MPEP 2111.04. Moreover, applicant is well aware that different methods of statistical analysis produce different numerical results that convey different biological interpretations [Remarks, page 22]. Thus, one of ordinary skill in the art would not have recognized that the inventor possessed a method/system capable of predicting the response of a generically recited tumor based on “signature scores” for the full scope of what is presently embraced by the claims.
For the reasons discussed above, the specification does not satisfy the written description requirement with respect to the full scope of what is being claimed. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Response to Arguments
Applicant’s arguments, filed 01/29/2026, have been fully considered but are not persuasive in view of the modified rejection, as set forth above. In response to applicant’s arguments regarding the calculating step, applicant’s arguments are persuasive on this point and the rejection has been modified accordingly. In response to applicant’s additional arguments regarding working examples and sets of genes [0055-0082 and Table 4], such disclosures are not limiting definitions and are, in fact, much narrower in scope than what is being claimed---and it is improper to import narrowing limitations into the claims. MPEP 2111.04.
Claim rejections - 35 USC § 112, 2nd Paragraph
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.
The following rejection is modified in view of applicant’s amendments.
Claims 1-4, 6-17, 19-22 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 and 13 is/are also rejected due to said dependency.
Claims 1 and 13 recite “identifying, based on the calculated immunogenic signature score, the tumor as strongly immunogenic, moderately immunogenic, or weakly immunogenic”. However, the claims are not limited to any particular acts or operations for identifying tumors as claimed. The specification does teach statistical scores associated with the claimed function [0039-40]. However, these do not clarify the scope of said identifying, as examples are not limiting definitions, and it is improper to import narrowing limitations into the claims. MPEP 2111.01. Moreover, the terms “strongly”, “moderately”, and “weakly” are relative terms and the specification does not provide any limiting definitions, specific properties, or scoring criteria indicating the scope of this term, i.e. the result is subjective and imperceptible. Accordingly, clarification is requested via amendment. Applicant has not provided any illuminating arguments or clarifying amendments to correct this issue.
Claims 2-4 and 15-17 recite the term “Table 4”. The claims are indefinite because they refer to tables and/or figures in the specification. In this case, the genes associated with the recited tables can be readily incorporated into the claim, therefore reference to the specification is improper. See MPEP 2173.05(s), which states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).” Accordingly, correction is again requested via amendment. Applicant has not provided any illuminating arguments or clarifying amendments to correct this issue.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The following rejection is modified in view of applicant’s amendments.
Claims 1-4, 7, 9, 13, 15, 16, 17 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Davison et al. (WO/2017/013436; Pub. Date: 01/26/2017).
Davison teaches a method for predicting responsiveness to an inhibitory immune checkpoint therapy [Abstract]. Regarding claim(s) 1 and 13, Davison teaches obtaining tissues samples and generating gene expression profile for set of biomarkers from said samples [pages 71-72, 76, 95-96, Table 2A, Table 2B and ref. claims 1-5], which reads on the claimed obtaining and generating steps.
Davison teaches calculating a compound decision scores based on the gene expression data using a linear classifier [pages 17 and 72, and ref. claims 1-5]. Davison does not specifically teach calculating immunogenic scores, wherein the scores comprise a mean expression rank for the gene expression data, as claimed. However, Davison reasonably suggests this limitation because the weights used in the combined decision scores are determined using algebraic means that explicitly include average weights (i.e. mean rank) [page 27, entire] and used as means for ranking the individual genes [Example 5 and Table 2A and 2B], e.g. the gene with the lowest absolute weight was removed from the signature. Furthermore, the choice of scoring metric is nothing more than a design choice and Applicant has not disclosed that this particular feature provides an advantage, is used for a particular purpose, or solves a stated problem.
Davison additionally teaches using the combined decision scores to identify gene responsiveness to a therapeutic agent for treating cancer including inhibitory immune checkpoints and/or an agonist of a stimulatory immune checkpoints (i.e. immunotherapy) [page 17, entire, pages 107-110, Example 2, and Table 46, and ref. claims 1-5], and that responsiveness is predicted when the combined test score exceeds the threshold score [ref. claims 1-8 and Figure 21].
Davison does not specifically teach identifying a tumor as having strong, moderate, or weak immunogenicity, and predicting the response of the tumor based on having strong, moderate, or weak immunogenicity, as claimed. However, Davison reasonably suggests these limitations by teaching predictions based on different classifications of response to therapy, e.g. overall survival, progression free survival, complete response, partial response, stable disease (i.e. strong, moderate, and weak immunogenicity) [page 3, last ¶] and by teaching the use of scoring ranges associated with strong, moderate, and weak expressions [page 115, Example 4]. Therefore, as the claim does not impose any specificity with regards to how the claimed predicting is being achieved, Davison reasonably suggests the claimed identifying steps wherein tumor immunogenicity is broadly interpreted as the ability of a tumor to stimulate an immune response.].
Regarding claim(s) 2, 15, Davison teaches hundreds of genes being analyzed by the above process, e.g. CCL, CXCL, CD8, etc [Tables 1-43, pp.81-85, ref. claims 5-12]. Davison does not specifically teach all of the claimed 161 genes set forth in Table 4. However, Davison teaches gene expression profiling using the Affymetrix GeneChip Scanner and U133A arrays [Example 1]. Therefore, Davison reasonably suggests the claimed genes since the artisan would recognize that such gene chips were readily used in disease association analysis and provide coverage of the entire human genome. The rationale would have been to improve diagnostic sensitivity using more robust gene chips.
Regarding claim(s) 3, 16, Davison teaches gene expression data generated using methods known in the art such as microarray, Q-PCR, sequencing (e.g. RNA seq), immunohistochemistry, ELISA or other technologies that can quantify mRNA or protein expression [page 22].
Regarding claim(s) 4, 17, Davison teaches not teach tissue comprising great than or equal to 5% tumor tissue, as claimed. However, the choice of a percentage of tumor tissue is nothing more than a design choice that does not change the function of the claimed process steps, as claimed, and Applicant has not disclosed that this particular feature provides an advantage, is used for a particular purpose, or solves a stated problem. Moreover, Davison suggests this limitation by teaching methods for quantifying the amount of tumoral infiltrate [Figure 9], which is expressed in percentages.
Regarding claim(s) 7, Davison teaches predicting response to a plurality of therapies including PD-L1 [ref. claims 1-5, 102, page 74]. Regarding claim(s) 9, Davison teaches selecting and administering treatment for a cancer based on the expression level of genes in samples from the subject, wherein the determined expression level is used to select an antagonist of an inhibitory immune checkpoint and/or an agonist of a stimulatory immune checkpoint for use in treatment of the cancer [page 3, pages 17-18, ref. claims 53-59, 67-70].
Response to Arguments
Applicant’s arguments, filed 01/29/2026, have been fully considered but are moot in view of the modified rejection applied above. In particular, applicant argues that Davison does not teach the calculation of scores comprising mean expression rank. In response, as discussed above, Davison does not specifically teach calculating immunogenic scores, wherein the scores comprise a mean expression rank for the gene expression data, as claimed. However, Davison reasonably suggests this limitation because the weights used in the combined decision scores are determined using algebraic means that explicitly include average weights (i.e. mean rank) [page 27, entire] and used as means for ranking the individual genes [Example 5 and Table 2A and 2B], e.g. the gene with the lowest absolute weight was removed from the signature. Furthermore, the choice of scoring metric is nothing more than a design choice and Applicant has not disclosed that this particular feature provides an advantage, is used for a particular purpose, or solves a stated problem. For at least these reasons, the rejection is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 date of this final action.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
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