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 1-27 are under examination.
Priority
This U.S. patent application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application 63/329,352, filed on April 8, 2022, and U.S. Provisional Application 63/422,763, filed on November 4, 2022. Accordingly, the effective filing date of the instant application is April 8, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) document(s) submitted are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
Drawings
The drawings filed 04/07/2023 are acknowledged and acceptable.
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 1-27 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 is directed to a method and system for performing a process and therefore fall 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:
processing, using a cell classification model, the input histology image to generate one or more lymphocyte density maps within the input histology image;
performing morphological image processing on the one or more lymphocyte density maps to identify one or more TLS regions within the input histology image, each TLS region represented by a respective cluster of lymphocyte cells;
extracting, from the respective cluster of lymphocyte cells representing the corresponding TLS region, a respective set of TLS features;
processing, using a TLS classification model, the respective set of TLS features to classify the corresponding TLS region as one of a first TLS maturation state, a second TLS maturation state, or a third TLS maturation state.
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)).
Under the BRI, the recited acts of processing, performing, and extracting set forth or describe manipulating and/or analyzing data (which scientists can performing 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
Under the BRI, the recited acts of processing require using a “classification model”, which sets forth or describes a mathematical calculation and/or mathematical relationship (since the artisan would recognize that such models necessarily require mathematically relating data). While no specific equation is being claimed, Applicant is reminded that there is no particular word or set of words that indicates a claim recites a mathematical calculation. See MPEP 2106.04(a)(2). Similar to the ineligible claims at issue for In re: Board of Trustees of the Leland Stanford Junior University, 991 F.3d 1245 (Fed. Cir. 2021), the instant claims are written effectively as a method for mathematically manipulating or relating data to ascertain additional data. As such, this step recites a mathematical concept. MPEP 2106.04(a)(2) Section I. [Step 2A, Prong 1: YES].
B. Guidance Step 2A, Prong 2
This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception or whether the claim is “directed to” the judicial exception. This evaluation is performed by (1) identifying whether there are any additional steps/elements recited in the claim beyond the judicial exception, and (2) evaluating those additional steps/elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. See MPEP 2106.04(d). In this case, the additional steps/elements recited in the claim beyond the judicial exception are as follows:
receiving an input histology image for a patient diagnosed with cancer, the input histology image comprising a plurality of image pixels;
data processing hardware; memory hardware
In this case, the claimed obtaining and enriching steps are both recited at a high level of generality and amount to necessary gathering of data for use by the abstract idea. Therefore, these steps amount to “insignificant extra-solution activity” and do not integrate the judicial exception into a practical application. See MPEP 2106.05(g).
With regards to the recited hardware elements, these are recited at a high level of generality and thus can be viewed as nothing more than an attempt to generally link the use of the judicial exception to the technological environment of a computer. In addition, “generic computer components such as a computer and database do not satisfy the inventive concept requirement.” See MPEP 2106.05(h).
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:
Under the 2019 PEG, a conclusion that an additional element is insignificant extra-solution activity in Step 2A should be re-evaluated in Step 2B. In this case, the claims do not include additional steps and/or elements appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception(s) for the following reasons:
As discussed above, the above non-abstract steps (including the full limitations and not just the verbs) amount to nothing more than insignificant extra-solution activity and/or instructions to “apply” the exception in a generic way. In this case, the specification teaches routine and conventional computer hardware for carrying out the claimed invention [0011, 0134, and Figure 1]. Moreover, a review of the prior art teaches that the above non-abstract limitations were routine and conventional in the art.
Therefore, even when viewed as a combination, there is nothing unconventional with regards to the non-abstract steps and/or elements as claimed. Thus, the independent claim(s) as a whole do not amount to significantly more than the exception itself. For these reasons, the claim(s) is/are not patent eligible. [Step 2B: NO].
Dependent Claims
Dependent claims 2-14 and 16-27 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) 2-14, 16-27, these are all directed to limitations that further limit the specificity of the abstract idea set forth above or the nature of the data being used by the abstract, and therefore are also recite mathematical concepts for reasons discussed above in the Step 2A (prong 1) analysis. Regarding claim(s) 8, this claim further recites a displaying step that amounts to insignificant extra-solution activity and therefore are is not patent eligible for all the reasons discussed above in the Step 2A (prong 2) and Step 2B analysis. Therefore, the claims as a whole are not patent eligible.
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 1-27 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 15 are also rejected due to said dependency.
Claims 1 and 15 recite “processing, using a cell classification model, the input histology image to generate one or more lymphocyte density maps within the input histology image.” In this case, 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). In particular, the instant claims do not define the model in terms of parameters nor do they set forth any steps involved in the method/process use. As such, it is unclear as to the metes and bounds of the claimed “cell classification model” such that the artisan would recognize what internal structure of the claimed model is intended and in what way it is being “used” to generate density maps. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function and Figure 3 merely provides a generic box of said model, which is not informative. Moreover, 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 claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 1 and 15 recite “processing, using a TLS classification model, the respective set of TLS features to classify the corresponding TLS region as one of a first TLS maturation state, a second TLS maturation state, or a third TLS maturation state.” In this case, 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). In particular, the instant claims do not define the model in terms of parameters nor do they set forth any steps involved in the method/process use. As such, it is unclear as to the metes and bounds of the claimed “TLS classification model” such that the artisan would recognize what internal structure of the claimed model is intended and in what way it is being “used” to achieve the claimed classification function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function and Figure 4 merely provides a generic box of said model, which is not informative. Moreover, 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 claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 1 and 15 recite “extracting….a respective set of TLS features”. In this case, such generic functional claim language amounts to descriptions of problems to be solved and covers conflicting embodiments of extraction, i.e. physical removal, digital filtering, algorithmic subtraction, etc. See MPEP 2173.05(g). A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. In addition, it is unclear as to the metes and bounds of the claimed “TLS features”. A review of the specification does not provide any limiting definition that would serve to clarify the scope. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 2 and 16 recite “processing, using a tumor detection model…”. In this case, 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). In particular, the instant claims do not define the model in terms of parameters nor do they set forth any steps involved in the method/process use. As such, it is unclear it is unclear as to the metes and bounds of the claimed “model” such that the artisan would recognize what internal structure of the claimed model is intended and in what way it is being “used” to achieve the claimed classification function. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. Moreover, 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 claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 3, 4, 17, 18 recite “training, using a neural network, the…model….”. It is unclear as to the metes and bounds of the claimed “training” such that the artisan would recognize what processing steps are minimally encompassed. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. Moreover, the artisan would recognize that “training” a model can include a plurality of distinct processes including feature selection, adjusting model parameters, optimizing loss functions, etc. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 5 and 19 recite “a ground-truth TLS maturation state indicating that the corresponding TLS region comprises a first TLS maturation state, a second TLS maturation state, or a third TLS maturation state.” The term “ground-truth” is a relative term and the specification does not provide any limiting definitions, specific properties, or scoring criteria indicating the scope of this term. As a result, it is unclear as to the metes and bounds of the term “ground-truth TLS maturation state”, as the result is subjective and imperceptible. Clarification is requested via amendment.
Claims 5 and 19 recite “training the TLS classification model on the respective set of training TLS features extracted for each TLS region to teach the TLS classification model to learn how to predict the ground-truth TLS grade for each corresponding TLS region.” It is unclear as to the metes and bounds of the claimed “training” such that the artisan would recognize what processing steps are minimally encompassed. A review of the specification does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. Moreover, the artisan would recognize that “training” a model can include a plurality of distinct processes including feature selection, adjusting model parameters, optimizing loss functions, etc. As a result, it is unclear what computational techniques are included or excluded by the claim language such that one of ordinary skill in the art would know how to avoid infringement. Clarification is requested via amendment.
Claims 12 and 26 recite “…determining a treatment recommendation to treat the patient using immunotherapy based on the overall TLS score.” In this case, 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). In particular, it is unclear as to the metes and bounds of the claimed “treatment recommendation” and in what way the immunotherapy is “based on the overall TLS score”. A review of the specification does not provide any limiting definition for this term (e.g. particular drugs) and does not describe, to any appreciable extent, any algorithms, equations, or prose equivalent that correspond to the claimed function. Clarification is requested via amendment.
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, 2, 3, 4, 8-11, 15-18, 22, 23, 24, 25 are rejected under 35 U.S.C. 103 as being unpatentable over Barmpoutis et al. (PLoS ONE, 2021, 16(9): e0256907, pp.1-19).
Barmpoutis teaches methods for identifying Tertiary lymphoid structures (TLS) and performing density assessment on H&E-stained digital slides of lung cancer data [Abstract].
Regarding claim(s) 1, Barmpoutis teaches receiving histology images of cancer patients and feeding these images into a Deeplab model to generate density maps [Figure 1]. Barmpoutis teaches identifying TLS regions within histology images [page 3 and Figure 1]. Barmpoutis teaches performing segmentation of TLS features [page 5 and Figures 1 and 2], which at a minimum suggests extracting TLS features as claimed absent any limiting definition to the contrary, as well as extracting the size and number of lymphocytes per unit area of each candidate TLS region [page 7]. Barmpoutis teaches final classification and detection of TLS regions using said model [page 7 and Figures 1 and 4].
Barmpoutis does not specifically teach classifying the TLS regions based on maturation state, as claimed. However, Barmpoutis makes obvious this limitation by teaching a well known quantitative pathology approach for the identification and quantification of different TLS maturation stages using seven-color immunofluorescent staining and segmentation algorithms of Inform software [page 2, ¶3]. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Barmpoutis by additionally classifying the TLS regions based on maturation state, as claimed since software for performing this function was routine and convention and available, as set forth above. The rationale would have been the predictable use of prior art elements according to their established functions. KSR, 550, U.S. at 417.
Regarding claim(s) dependent claims 2, 3, 4, 8, 9, 10, 11, 16, 17, 18, 22, 23, 24, 25, all aspects of these claims were taught or suggested by Barmpoutis for the following reasons. Regarding claim(s) 2 and 16, Barmpoutis teaches processing image data to identify a tumor region within the image using a trained model [Figures 1-4]. Regarding claims 3, 4, 17, 18, Barmpoutis teaches annotating slides with normal and tumor tissue, incorporating augmented data into training images, and training their neural network model using a loss function to identify TLS regions, and performing boundary refinement such that their model can differential between tumors and lymphocytes [pages 7-8, “Dataset Description”; pages 3-5, and Figures 1-2; and page 8].
Regarding claim(s) 8, 9, 22, 23, Barmpoutis teaches generating pixel boundary regions (i.e. masks) that highlight a perimeter of the TLS region and generating an augmented output image [Figures 1, 2, 4]. Barmpoutis does not specifically teach first and second maturation states associated with pixel masks, as in claims 9, 23. However, as discussed above, Barmpoutis makes obvious this limitation by teaching a well known quantitative pathology approach for the identification and quantification of different TLS maturation stages using seven-color immunofluorescent staining and segmentation algorithms of Inform software [page 2, ¶3]. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Barmpoutis by additionally classifying the TLS regions based on maturation state, as claimed since software for performing this function was routine and convention and available, as set forth above. The rationale would have been the predictable use of prior art elements according to their established functions. KSR, 550, U.S. at 417. Regarding claim(s) 10, 24, Barmpoutis teaches the use of k-neareset neighbor classification and calculating ellipses and areas of boundary regions in the images [pages 6-7]. Regarding claim(s) 11, 25, Barmpoutis teaches scoring methods that include ROC [page 8-9 and Figure 3].
Cited Prior Art
In the interest of advancing prosecution, the following prior art made of record and not presently relied upon is considered pertinent to applicant' s disclosure.
Rijthoven et al. (Medical Image Analysis, February 2021, Article: 101890, Volume 68, pp.1-16) teaches a computational method (HookNet) comprising multi-resolution convolutional neural networks for semantic segmentation in histopathology whole-slide images. They describe a framework to design and train HookNet for achieving high-resolution semantic segmentation and introduce constraints to guarantee pixel-wise alignment in feature maps during hooking, and show the advantages of using HookNet in histopathology image segmentation.
Rakaee et al. (British Journal of Cancer (2021) 124:1680–1689) teaches a method for classifying and scoring tertiary lymphoid structures (TLS) to refine the TNM staging system. Subgroup analyses revealed a significant prognostic impact of TLS score within each pathological stage, patient cohort and main histological subtype.
Charles et al. (WO/2019012147) teaches a radiomics-based imaging tool to monitor tumor-lymphocyte infiltration and for detecting the presence and the density of tumor infiltrating CD8 T-cells in a solid tumor without having to use any biopsy of said tumor.
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.
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/PABLO S WHALEY/Primary Examiner, Art Unit 3619
Prosecution Insights