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 .
Claim Status
Original claims 1-12 are pending.
Priority
This application filed 3/2/2023 is a CIP of PCT/KR2021/011804 filed 9/2/2021 and claims benefit to foreign application KR10-2020-0112176 filed 9/3/2020 in Korea.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/2/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 6, 7 and 12 are objected to because of the following informalities:
In claims 1 and 7, it is noted that ‘MSS-type’ is spelled out in the claims, but it is custom to provide this when the term is first presented. In this case, the pre-amble of the claim provides MSS but it is not spelled out until later in the method steps.
In claims 6 and 12, there are two periods and discriminant algorithms that are provided as parentheticals in a separate sentence. The first sentences recite ‘using the following discriminant.’ Which implies the following equation is exemplary, and for examination this will be interpreted as a typographical error in interpreting the claims.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: starting claim 7 as directed to a system the components ‘a selection unit’, ‘a measurement unit’, ‘a classification unit’ and a ‘determination unit’ each providing a specific function. To the extent these are physical requirements of a physical system, an evaluation of the art of record does not provide that these are known ‘units’ and in review of the specification the functions of the units appear be steps of analysis not necessarily tied to any specific type of device. More generally, these limitations appear to be instructions which can be implemented on a general purpose computer given the guidance of the instant specification, and can be interpreted as units of coding that provides instructions for the indicated analysis.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 1-12 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. Specifically, step c) is vague and unclear in the recitation of classification of a ‘high degree’ as this term appears relevant and is not defined in the claims nor the specification. While one may be able to determine if one value is higher than another, there are no steps which provide a comparison, nor one that provides a cut-off when classifying such that the skilled artisan clearly know the metes and bounds of high and low degree of gene mutation when measured. The system of claim 7 provides the same instruction for the unit to provide and creates the same issue of failure to clearly provide what is performed or what the metes and bounds of the outcome are defined for any values measured, and generally appear to be relative terms which can only be assessed by have a low value and a threshold clearly defined between the two. Dependent claims fail to clearly set forth what the metes and bounds are either in analysis or in clear thresholds and they are included because they rely on practicing these steps and embodiments.
Additionally, the claims are generally drawn to ‘predicting the possibility of immunotherapy’ however the analysis does not appear to be consistent with predicting if the subject will receive any therapy, but rather if there is a certain type of therapy that is correlated with the observed number of alterations in the data analyzed. It is unclear what the ‘potential’ is and how this is correlated to immunotherapy as set forth in the claims.
More clearly providing classification steps or a definition of high and/or low which clearly defines the metes and bounds would address the basis of the rejection.
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 1-12 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.
Claim analysis
Claim 1 is generally directed to ‘method for predicting the possibility of immunotherapy for MSS-type colorectal cancer’ as set forth in the preamble. More specifically, the method of claims 1-6 provide for steps of measuring alterations in the genome of an obese subject, classifying what is observed, indicating/specifying that a large amounts of alterations have a ‘high immunotherapy potential’. Dependent claims provide other considerations such as physical characteristics of the obese patient (claim 2), and indication of methods known in the art for ‘clustering’ (claims 3-5) and a specific algorithm labelled ‘Discriminant 1’ which appears to provide a means to evaluate a population group to provide a ‘centroid of observation’ (claim 6). The system claims provide for the same analysis in the form of ‘units’ which are interpreted to be instructional units performed by a computer.
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a method and a product.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of accessing sequence data for altered/mutated sequences and classifying the observations where a high amount of alterations can be correlated to the subject for possible immunotherapy. The step of aligning and comparing sequence to arrive at the identification of alterations, and then classifying the observations into two groups are considered instructional and data analysis. Correlating what is observed appears in part related to describing the natural correlation between observing large amounts of gene mutations and the subject be a possible good candidate for some form of immunotherapy. The claim requires computing similarity scores to identify alterations and to measure and classify what is observed in any give sequence. The judicial exception is a set of instructions for analysis of sequence data for alterations to a reference and grouping what is observed and appears to fall into the group of Mathematical Concepts
mathematical formulas or equations to the extent a specific algorithm is recited and broadly encompassed by the various statistical analysis set forth in dependent claims, and to Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion) whereas here difference in sequences versus a reference can be observed and counted, and put into two groups based on what is observed. The breadth of “measuring”, “classifying”, and “determining” encompasses non-transformative visual assessment of an individual for given genotypes/mutations, coupled with prior knowledge of the correlation of said number observed with possible immunotherapy approaches. This breadth does not impose a meaningful limit on the claim scope, such that all others are not precluded from using the natural principle of observing alterations and suggesting or indicating a standard of care for immunotherapy treatment of a cancer patient. Although the claims provide for a system in which the method is implemented, the courts have also identified limitations that did not integrate a judicial exception into a practical application; for example, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f). The steps of the claims are very generally recited, the combination of which is together reasonably interpreted as mere data gathering and analysis. Computing, constructing datasets and using statistical models was well understood, conventional, and routinely performed in the art at the time the application was filed. See MPEP § 2106.05(g) for a discussion on adding insignificant extra-solution (both pre-solution and post-solution) activity to the judicial exception. See also MPEP § 2106.05(h) for a discussion on generally linking the use of a judicial exception to a particular technological environment or field of use. The claims appear to fall into the category of Mathematical Concepts, as it applies the use of statistics and mathematical relationships in analyzing probabilities, and also into the category of mental processes, as concepts performed in the human mind (including an observation, evaluation, judgment, opinion) because there is no apparent complexity to or amount of data that is collected and analyzed as presently claimed.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element to which the analysis is applied, the claims simply require data analysis. The system can be interpreted as physical, but appears to be simply a system, such as a general purpose computer, on which the method is performed. This judicial exception requires steps recited at high level of generality and are only stored on a non-transitory, and is not found to be a practical application of the judicial exception as broadly set forth.
For step 2B of the 101 analysis, each of the independent claims recites additional elements and are found to be the steps of obtaining sequence data to the extent that the claims require ‘measuring’; however there is no physical step and the system claims imply that the physical step of measurement can be performed outside the scope of the claims and the first step is simply analyzing data. As such, the claims do not provide for any additional element to consider under step 2B. It is noted that in explaining the Alice framework, the Court wrote that "[i]n cases involving software innovations, [the step one] inquiry often turns on whether the claims focus on the specific asserted improvement in computer capabilities or, instead, on a process that qualifies as an abstract idea for which computers are invoked merely as a tool." The Court further noted that "[s]ince Alice, we have found software inventions to be patent-eligible where they have made non-abstract improvements to existing technological processes and computer technology." Moreover, these improvements must be specific -- "[a]n improved result, without more stated in the claim, is not enough to confer eligibility to an otherwise abstract idea . . . [t]o be patent-eligible, the claims must recite a specific means or method that solves a problem in an existing technological process.” As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence data. While the instruction are stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer. Dependent claims set forth additional steps which are more specifically define the considerations and steps of calculating, and comparing, and do not add additional elements which result in significantly more to the claimed method for the analysis. No additional steps are recited in the instantly claimed invention that would amount to significantly more than the judicial exception. Without additional limitations, a process that employs mathematical algorithms (aligning sequences) to manipulate existing information (identify a probe that starts at a deletion or insertion) to generate additional information is not patent eligible. Furthermore, if a claim is directed essentially to a method of calculating, using a mathematical formula, even if the solution is for a specific purpose, the claimed method is non-statutory. In other words, patenting abstract idea (designing probes to a target sequence) cannot be circumvented by attempting to limit the use to a particular technological environment or purpose and desired result.
One way to overcome a rejection for non-patent-eligible subject matter is to persuasively argue that the claimed subject matter is not directed to a judicial exception. Another way for the applicants to overcome the rejection is to persuasively argue that the claims contain elements in addition to the judicial exception that either individually or as an ordered combination are not well understood, routine, or conventional. Another way for the applicants to overcome the rejection is to persuasively argue that the claims as a whole result in an improvement to a technology. Persuasive evidence for an improvement to a technology could be a comparison of results of the claimed subject matter with results of the prior art, or arguments based on scientific reasoning that the claimed subject matter inherently results an improvement over the prior art. The applicants should show why the claims require the improvement in all embodiments.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Mandal et al. (2019).
Claim 1 provides method steps for ‘predicting the possibility of immunotherapy for MSS-type colorectal cancer’ as set forth in the preamble, and the method of claims 1-6 provide for steps of measuring alterations in the genome of an obese subject, classifying what is observed, indicating/specifying that a large amounts of alterations have a ‘high immunotherapy potential’. Dependent claims provide other considerations such as physical characteristics of the obese patient (claim 2), and indication of methods known in the art for ‘clustering’ (claims 3-5) and a specific algorithm labelled ‘Discriminant 1’ which appears to provide a means to evaluate a population group to provide a ‘centroid of observation’ (claim 6). The system claims provide for the same analysis in the form of ‘units’ which are interpreted to be instructional units performed by a computer. At the time, it was known that alterations in the genome that might result in altered proteins might serve as possible targets of altered proteins in immunotherapy protocols. For example, Mandal et al. provide evidence that genetic diversity of tumors with mismatch repair deficiency influences anti–PD-1 immunotherapy response. More specifically, it is summarized and demonstrated that tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations and that this high mutational burden renders tumors immunogenic and sensitive to programmed cell death–1 (PD-1) immune checkpoint inhibitors. However, despite their tumor immunogenicity, patients with MMR-deficient tumors experience highly variable responses, and roughly half are refractory to treatment. With respect to different types of possible alterations, Mandal et al. present experimental and clinical evidence showing that the degree of microsatellite instability (MSI) and resultant mutational load, in part, underlies the variable response to PD-1 blockade immunotherapy in MMR-d human and mouse tumors, and demonstrate that the extent of response is particularly associated with the accumulation of insertion-deletion (indel) mutational load. This study provides a rationale for the genome-wide characterization of MSI intensity and mutational load to better profile responses to anti–PD-1 immunotherapy across MMR-deficient human cancers.
Mandal et al. do not specifically state the patient is obese or high-light any importance to colorectal cancer and it appears to apply to any cancer with MSI, however it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to appreciate that MSI occurs in multiple types of cancers and patients with different physical attributes and appreciate that Mandal et al. could be applied to any cancer such as colorectal cancer which displays MSI. One having ordinary skill in the art would have been motivated to apply the use of PDI inhibitors in immunotherapy as provided in Mandal et al. when MSI is observed to increase the possibility of success of the immunotherapy in any patient. Given that immunotherapy was known and the specific guidance of Mandal et al. for the use of specific types of inhibitors when MSI is observed, there would have been a reasonable expectation of success given the results of Mandal et al in human and mouse tumors.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Joseph T Woitach whose telephone number is (571)272-0739. The examiner can normally be reached Mon-Fri; 8:00-4:00.
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/Joseph Woitach/ Primary Examiner, Art Unit 1687
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