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 .
Claims 1-9 and 11-15 are pending.
Claim 10 has been cancelled.
Claims 1, 3-6, 9, 11, and 13-15 are amended.
Applicant’s election without traverse of the species of:
Claim 1 and its dependent claims (now claims 2-9 and 11-15 via the 04/28/2026 amendments);
The antibody combination of CD45,HLADR/DP/DQ, CD14, and SMA (of claim 6) as sufficient to identify periductal APCs; and
The combination of periductal APCs and ductal myoepithelial cells (from claim 11),
in the reply filed on 04/28/2026 is acknowledged.
It is noted that the species election of a feature or combination thereof was not substantively moot as Applicant merely imported the features of now canceled claim 10, verbatim, into claim 1. However, the species election of antibodies for periductal antigen presenting cells (noted in point 2 above) is a constructive election of periductal APCs and ductal myoepithelium as the combination of biomarkers/cell types/features to be measured as the elected species were required to be commensurate with one another (directed to the same embodiment) as noted in the text of the restriction requirement. Therefore, any claims measuring anything other than periductal APCs are outside of the elected species/embodiment.
Claims 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species/embodiment, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/28/2026.
Claims 1-9 are under examination on the merits.
Priority
This application is a 371 of PCT/US2021/062909, filed 12/10/2021, which claims benefit of US Provisional Application No. 63/123,905, filed 12/10/2020. Note that the discovery that a thin/discontinuous myoepithelium with low E-CAD expression is associated with a non-progressive DCIS, where the myoepithelial thinness is protective is given a priority date of 12/10/2021 as this was not reasonably disclosed in the provisional application. Similarly, the use of an HLADR/DP/DQ antibody, all mentions of periductal APCs, use or procurement of a composite score, and any mention of survival or status at a 10 year period will also be given a 12/10/2021 priority date as they were not reasonably disclosed in the provisional application.
IDS
The information disclosure statement (IDS) filed 06/06/2023 has been considered.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
While it is noted that the drawings submitted are not in color, the problem is that they clearly are intended to be in color given the descriptions of the figures discussing key features of the figures as represented by color(s) (see for example, the description of figure 2F at page 4 of the instant specification). This creates unnecessary confusion. To fix the problem, Applicant must either submit color drawings with a petition, which must then be formally accepted or Applicant must amend the description of the figures to remove all reference to color(s).
Specification
The disclosure is objected to because of the following informalities: “onnormalized” should read “on normalized” at page 3 of the instant specification in paragraph 0013.
Appropriate correction is required.
Claim Interpretation
All disclosures and mentions of recurrence throughout the instant specification pertain to recurrence as defined by invasion (progression of pure DCIS to invasive breast cancer (IBC) and/or ipsilateral invasion). Further the amendment to claim 1 would suggest that recurrence is recited as synonymous with progression of pure (non-invasive) DCIS into IBC or ipsilateral invasion so as to make the claim preamble sufficiently correlated with the claim body. Therefore, for consistency, clarity, and compact prosecution, the Examiner is interpreting recitations of recurrence to be synonymous with progression of pure (non-invasive) DCIS into IBC or ipsilateral invasion.
Note that no closed and clear definition is provided for ‘tissue imaging’. The closest definition/description appears at paragraph 0007 of the instant specification which notes that “imaging of the myoepithelium and other features may be performed with multiplexed ion beam imaging by time of flight (MIBI-TOF). The classification can be made by targeted inspection of the imaging data. In some embodiments the method comprises analysis of features extracted from MIBI-TOF data, including, for example, phenotypic, functional, spatial, and morphologic features.” Therefore, art teaching the use of MIBI-TOF or any other methods which provide spatial, morphometric, and/or phenotypic data of tissue is deemed to make obvious tissue imaging and analysis of phenotypic, functional, spatial, and morphologic features as recited in throughout the claims. Additionally other art known means of imaging a tissue sample would also read on the recited “tissue imaging.”
“[T]hese cell types” as recited in claim1, line 16 are being interpreted as encompassing all of the recited biomarkers/cell types in the interest of advancing prosecution.
Claim Objections
Claim 1 is objected to because of the following informalities: “nacrophage” should read “macrophage (see line 9). Additionally “myoepithelial E-cadherin” (see line 5), “myoepithelial continuity”(see line 8), and “variation in collagen fiber orientation” are not consistent with “these cell types” as recited in line 17. The claim should be drafted such that it is internally consistent to promote clarity.
35 U.S.C. 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 1-9 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.
Where a claim describes a judicial exception, such a claim “requires closer scrutiny for eligibility because of the risk that it will ‘tie-up’ the excepted subject matter and pre-empt others from using [the judicial exception]" (federal register, p.74622, C1). While all inventions to some degree involve natural laws, products, and other judicial exceptions, the new guidance regarding patent eligibility makes clear that a practical application of these exceptions is necessary, offering “significantly more” than the exception itself. Limitations that were found not to be enough to qualify as “significantly more” include:
Mere instructions to implement an abstract idea on a computer;
Adding generic instructions that the judicial exception should be used ("apply it");
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality;
Adding insignificant extra solution activity to the exception ("mere data gathering"); and
Generally linking the use of the exception to a particular technological environment or field of use.
The MPEP (see § 2103-2106.07) provides a means of determining whether a particular claim is patent eligible under 35 U.S.C. 101. The Guidance requires an analysis of multiple steps, Steps 1, 2A, and 2B:
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A.
Step 2A - A two-prong analysis. For prong one, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong two, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101.
In the instant case, the claims are drawn to a process, so the answer to Step 1 is “Yes.”
With respect to prong one of Step 2A, the answer is “Yes,” because as indicated above, the claims are drawn to mathematical concepts.
Claim 1 is directed to a method of classifying a DCIS lesion as indolent or invasive recurrent, the method comprising obtaining a sample, analyzing the sample for the spatial location, morphology, and phenotype of one or more biomarkers, and classifying the DCIS lesion wherein the spatial location, morphology, and phenotype of the biomarker are used to compute a composite score on a computer system to classify DCIS patients at low or high risk of having a disease recurrence within 10 years of diagnosis.
Step 1: Is the claim drawn to a process, machine, manufacture, or composition of matter?
YES-Claim 1 is directed to a method which is a process.
Step 2A – Prong I: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES- Claim 1 includes correlating a measured biomarker/cell type with a recurrence/invasion risk (a natural phenomenon) and use of said measured biomarker/cell type and a computer system (an abstract idea) to compute a composite score (mathematics). The claim language reciting the judicial exception is found starting at line 3 of the claim 1 through the end of claim 1.
Step 2A – Prong II: Does the claim integrate the judicial exception into a practical application?
NO- Here, the instant claim 1 fails to recite any claim limitations which would integrate the recited judicial exception, for example, by applying or using said judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition.
Step 2B- Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO-The additional claim elements are insufficient to amount to significantly more than the judicial exception for the following reasons.
The generic recitation of obtaining a sample and measuring one or more of the recited biomarkers/cells types (spatial location, morphology, and phenotype) from a sample amounts to no more than mere data gathering steps and does not add ‘significantly more,’ (see Mayo v. Prometheus, 566 U.S.66, 132 SA. Ct. 1289). The claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s) recited in the claim starting at line 3 of claim 1.
Claims 2-9 incorporate, via dependency, the judicial exceptions recited in claim 1 and are therefore included in this rejection.
Claim 2 recites the method of claim 1 further comprising treating the DCIS in accordance with the classification. Treatment is recited at a high level of generality in this claim. This amounts to no more than a suggestion to apply the judicial exceptions of claim 1 (see MPEP §2106.05(f)). No further active steps are added by claim 2 so as to add significantly more.
Claim 3 recites wherein the analyzing of claim 1 involves contacting the sample with one or a panel of antibodies. There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. Contacting the sample with 1 or a panel of antibodies is recited at a high level of generality and amounts to no more than mere data gathering and does not add significantly more.
Claim 4 recites that analyzing comprises performing tissue imaging. There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. Noting the very open claim interpretation in the absence of a clear and closed definition provided by Applicant, any imaging of a tissue sample is encompassed by the claim as drafted, which amounts to no more than mere data gathering and does not add significantly more.
Claim 5 recites the method of claim 4 wherein analyzing comprises analysis of features extracted from tissue imagine data, including one or more of phenotypic, functional, spatial, or morphologic features. There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. The narrowed analysis amounts to no more than mere data gathering and does not add significantly more.
Claim 6 recites the method of claim 3 wherein the one antibody or panel of antibodies includes antibodies specific for one or more of alternatively recited biomarkers. There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. The measurement of one or more further biomarker(s), and the antibody(ies) for said measurement as generically recited amounts to no more than mere data gathering.
Claim 7 further recites the method of claim 6 further comprising treating the DCIS in accordance with the classification. Treatment is recited at a high level of generality in this claim. This amounts to no more than a suggestion to apply the judicial exceptions of claim 1 (see MPEP §2106.05(f)). No further active steps are added by claim 7 so as to add significantly more.
Claim 8 recites the method of claim 6, wherein the panel comprises at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, or all of the biomarkers. This is arguable a further judicial exception of measuring one or more biomarkers as correlated with recurrence/invasion risk of DCIS (natural correlation). There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. The measurement of one or more further biomarker(s), and the antibody(ies) for said measurement as generically recited amounts to no more than mere data gathering.
Claim 9 recites the method of claim 6, comprising analysis of the lesion following contact with the panel of antibodies to extract a plurality of features. This is a further judicial exception (analysis is merely either or a mental step or an abstract idea). There is no step that would integrate the claim, such as a particular treatment/prophylaxis step. The analysis of the lesion as generically recited amounts to no more than mere data gathering, if even that, as no active step beyond analyzing (a judicial exception) is explicitly required by the claim as presently drafted.
Therefore, claims 1-9 are rejected under 35 USC §101 as being directed towards patent ineligible natural phenomena and abstract ideas, failing to integrate or add substantially more so as to transform the metes and bounds of the claims into subject matter eligible for patentability.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
MPEP 2164.01(a) states that in order to determine compliance with the enablement requirement, the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.”
These factors include but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
Claims 1-9 are broadly directed to a method of classifying a DCIS or any disease (see the rejection under 35 USC§ 112(b) below) as indolent or invasive recurrent, by measuring certain recited aspects, using said aspects to calculate a composite score on a computer system to classify DCIS patients as having a low or high risk of having a disease (which could be a common cold or a psoriasis) recurrence within 10 years of diagnosis. This encompasses a broad range of potential diseases for which recurrence risk is predicted, a broad array of data input combinations for arriving at the composite score, a wide array of potential equations/algorithms/formulas (encompassing a broad number of coefficients or weighting measures) to arrive at the composite score, interpretations (such as cutoffs) of the composite score as indicating high or low recurrence risk, and training means/methodologies/computer system/software for the computer system (understood to be a random forest classifier as this is the only described means, but noting that other machine learning tools/algorithms are currently encompassed by the claims as drafted, said tools/algorithms having different weaknesses, blind spots, and limitations and requiring different training means/measures (such as a Monte Carlo Cross-Validation Model)).
The nature of the invention
Claims 1-9 are broadly directed to a method of classifying a DCIS or any disease (see the rejection under 35 USC§ 112(b) below) as indolent or invasive recurrent, by measuring certain recited aspects, using said aspects to calculate a composite score on a computer system to classify DCIS patients as having a low or high risk of having a disease recurrence within 10 years of diagnosis. The claims are directed to biological subject matter which is understood to be complex and often unpredictable.
The state of the prior art
The art teaches the heterogeneity of cancers (see Allison et al (Heterogeneity and Cancer, retrieved from: https://www.cancernetwork.com/view/heterogeneity-and-cancer (2014) at exemplary paragraph 1 of the Introduction) supporting that a system for classifying an leukemia would not necessarily be enabled for classification of a lymphoma. Bremer (US 20220187301 A1) teaches that normal breast ducts and lobules as well as intraductal epithelial proliferations are composed of two epithelial layers. Loss of the outer myoepithelial layer is the hallmark of infiltrating carcinoma of the breast. The outer myoepithelial layer is retained in all benign proliferative processes as well as ductal carcinoma in situ. Consequently identification of the presence or loss of myoepithelium using antibodies to the myoepithelial-specific proteins can be helpful in distinguishing in situ from infiltrating carcinoma in circumstances where morphology may be equivocal (see for example, paragraph 0182). Bai et al analyzed the expression of MMP-9, E-cadherin, and vimentin, in ESCC cells (EC-1), before and after the treatment with exogenous TGF-β1 or a broad spectrum MMP inhibitor, GM6001. Additionally, Bai et al (analyzed the activity of MMP-9 in these cells and performed MMP-9 knockdown experiments. The results obtained by Bai et al demonstrated that the treatment of EC-1 cells with TGF-β1 can induce EMT, together with the upregulation of vimentin and downregulation of E-cadherin expression in a time-dependent manner. Bai et al (Onco Targets Ther. 2017 Jun 2;10:2837-2847. doi: 10.2147/OTT.S134813) further teach that treatment with GM6001 was shown to attenuate TGF-β1-induced EMT. The art teaches that cancer is highly heterogenous and that, at most, a thick/continuous myoepithelium with higher E-Cad would be associated with non-invasive, lower grade DCIS.
The level of one of ordinary skill
As the claims are directed to classifying a DCIS or any disease (see the rejection under 35 USC§ 112(b) below) as indolent or invasive recurrent, by measuring certain recited aspects, using said aspects to calculate a composite score on a computer system to classify DCIS patients as having a low or high risk of having a disease recurrence within 10 years of diagnosis, the artisan is presumed to be highly skilled, tending to have an advanced degree (such as a Ph.D. or an M.D.).
The level of predictability in the art
Naveed et al (Sci Rep 14, 26405 (2024); https://doi.org/10.1038/s41598-024-77664-4) teach that the biological complexity of tumor environments, including immune interactions, is not fully captured in in-silico models (see reference, generally).
In the instant case, those of skill in the art recognize that the in vivo tumor microenvironment (TME) involves a complex and dynamic interaction between a variety of factors influencing different aspects of cancer (such as metastasis or immune evasion) and in general is at most unpredictable, as underscored by Gura (Science, 1997, 278(5340) who discusses the potential shortcomings of potential anti-cancer agents including extrapolating from in vitro to in vivo protocols, the problems of drug testing in knockout mice, and problems associated with clonogenic assays. Indeed, from the time formal screening began in 1955 to the date of the reference, thousands of drugs have shown activity in either cell or animal models, but only 39 that were used exclusively for chemotherapy, as opposed to supportive care, had won approval from the FDA (page 1041, 1st column) wherein the fundamental problem in drug discovery for cancer is that the model systems are not predictive. Moreover, those of skill in the art recognize that in vitro assays are generally useful to observe basic phenomenon such as preliminary screening of potential drugs. However, clinical correlations are generally lacking. The greatly increased complexity of the in vivo environment as compared to the very narrowly defined and controlled conditions of an in vitro assay does not permit a single extrapolation of in vitro assays to human therapeutic efficacy with any reasonable degree of predictability. In vitro assays cannot easily assess cell-cell interactions that may be important in a particular pathological state. Furthermore it is well known in the art that cultured cells, over a period time, lose phenotypic characteristics associated with their normal counterpart cell type. Freshney (Culture of Animal Cells, A Manual of Basic Technique, Alan R. Liss, Inc., 1983, New York, p4) teach that it is recognized in the art that there are many differences between cultured cells and their counterparts in vivo. These differences stem from the dissociation of cells from a three-dimensional geometry and their propagation on a two-dimensional substrate. Specific cell interactions characteristic of histology of the tissue are lost. The culture environment lacks the input of the nervous and endocrine systems involved in homeostatic regulation in vivo. Without this control, cellular metabolism may be more constant in vitro but may not be truly representative of the tissue from which the cells were derived. This has often led to tissue culture being regarded in a rather skeptical light (p. 4, see Major Differences In Vitro). Further, Dermer (Bio/Technology, 1994, 12:320) teaches that, "petri dish cancer" is a poor representation of malignancy, with characteristics profoundly different from the human disease. In addition, Dermer teaches that when a normal or malignant body cell adapts to immortal life in culture, it takes an evolutionary type step that enables the new line to thrive in its artificial environment. This step transforms a cell from one that is stable and differentiated to one that is not. Yet normal or malignant cells in vivo are not like that. The reference states that evidence of the contradictions between life on the bottom of a lab dish and in the body has been in the scientific literature for more than 30 years. Zips et al. (2005, In Vivo 19:1-8) indicate that while in vitro assays are useful as a first step, a cancer therapeutic must be evaluated in vivo for therapeutic benefit (abstract, top of p. 3, p. 6 conclusion). An editorial in Nature Biotechnology in 2013 reviews similar studies and arrives at the same conclusions (2013, Nature Biotechnology 31:85). Clearly it is well known in the art that cells in culture exhibit characteristics different from those in vivo and cannot duplicate the complex conditions of the in vivo environment involved in host-tumor and cell-cell interactions. Likewise, an in silico model such as a machine learning model is unlikely to reliably capture the complexity of the tumor microenvironment in a way that bears predictable success in vivo.
Regarding the breadth of diseases for which the method claims to classify a subject as high or low risk of recurrence within 10 years, the breadth of diseases encompassed is significant encompassing diseases with fungal, viral, proliferative, or autoimmune origins across a variety of tissues. For simplicity, the genus of cancers will be discussed as exemplary of the genus of diseases. The art teaches the heterogeneity of cancers (see Allison et al (Heterogeneity and Cancer, retrieved from: https://www.cancernetwork.com/view/heterogeneity-and-cancer (2014) at exemplary paragraph 1 of the Introduction) supporting that a system for classifying an leukemia would not necessarily be enabled for classification of a lymphoma.
Moreover, Melvus (What trade-offs exist between model complexity and interpretability?, obtained from: https://milvus.io/ai-quick-reference/what-tradeoffs-exist-between-model-complexity-and-interpretability; accessed 06/18/2026) teaches that complex models, like deep neural networks or ensemble methods, excel at handling nonlinear relationships and high-dimensional data but often act as “black boxes,” making it hard to trace how inputs lead to outputs (see for example, paragraph 1 of Melvus). Complex models often achieve higher accuracy on tasks like image recognition or natural language processing by leveraging many parameters, but this comes at the cost of interpretability. For instance, a deep learning model might outperform a logistic regression classifier in detecting tumors from medical images, but doctors cannot easily verify why a specific diagnosis was made. This creates dilemmas in domains like healthcare or finance, where accuracy is critical, but stakeholders also need to trust and validate the model’s logic. Debugging complex models is also harder: if a neural network makes unexpected errors, developers face challenges isolating the cause compared to adjusting a decision tree’s split points (see for example, paragraph 2 of Melvus).
Similarly, Brownlee (Why Do I Get Different Results Each Time in Machine Learning?, Machine Learning Mastery, obtained from: https://machinelearningmastery.com/different-results-each-time-in-machine-learning/ (pub. 08/27/2020)) teaches that machine learning can often provide different results, giving different predictions each time it is trained, even when trained on the same data set each time and will train different models if the training dataset is changed. Further, Brownlee teaches that differences in the development environment, such as software versions and CPU type, can cause rounding error differences in predictions and model evaluations. Note that the data structure, coefficients, procedure to run the data resulting in the model (training), underlying algorithm, evaluation procedures, and software and CPU type are not clearly disclosed and/or required by the claims (all of which are factors which can alter the output/predictions of the machine learning model).
Therefore, the state of the art is highly unpredictable regarding the heterogeneity of cancer, unpredictability of translating in vitro and/or in silico results to in vivo cancer environments (TME)/applications, and the unpredictability of training and developing a model/computing a composite score with accurate, repeatable, and predictable classification of high or low disease recurrence risk within 10 years as claimed.
(F) The amount of direction provided by the inventor
Applicant minimally discloses basic information about the random forest model at paragraph 00129 at pages 36-37 of the instant specification. This disclosure does not appear to sufficiently enable the artisan to train the model using the same data, the same way that Applicant did (as discussed in subsection (E) above). This is important because models trained on different data or differently trained give different outputs. This is not deemed sufficient to enable training of a random forest classifier, let alone other encompassed models/machine learning tools/AI tools (such as a large-language model or a Monte-Carlo Cross Validation model) for any single or combination of the claimed data inputs (i.e.: periductal APCs and/or ductal myoepithelium). The disclosure suggests to the artisan to gather the recited data inputs and somehow use a computer system (such as a random forest classifier) to compute a composite score and classify recurrence of any disease within 10 years of a DCIS diagnosis. There is no showing of how the composite score is obtained (no coefficients, weightings, formula/algorithm/equation used) and no teachings of interpreting the composite score (such as provision of a cutoff for a high versus a low recurrence risk). Further, it is unclear how this cutoff/classification may change as the variety of data inputs (one or all of the recited inputs, for example) are included in the model for composite score calculation. Therefore, the artisan is not enabled to arrive at any of the disclosed conclusions and is not enabled to use the invention as claimed. Additionally, there is nothing to show which combinations of spatial, morphologic, and phenotypic inputs, alone or in what combination(s) would reliably be predicative of a high or low recurrence/invasion risk of any disease as claimed. The artisan is invited to experiment to determine how any or all of the recited data inputs would be combined for reliable risk classification of disease recurrence within 10 years. Classification is not clearly disclosed. Without a clear teaching of training of the algorithm/model/computer system for the recited data inputs and disclosure of classification using the recited combinations of data inputs for all of the diseases encompassed, the artisan is merely invited to invent what Applicant has not enabled, but attempts to claim. The degree of experimentation required to enable use of the invention as claimed is significant and undue.
The existence of working examples
There are no working examples because the training, computation of a composite score, and classification as high or low risk of disease recurrence within 10 years based upon the composite score is not clearly disclosed at Example 1 (see pages 21-57 of the instant specification).
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
The case is directed to biological subject matter, which is by nature complex. There are no working examples provided and the state of the art fails to step in to provide enablement where the instant disclosure is lacking. The artisan would be forced into burdensome experimentation so as to effectively invent what applicant only suggests may be possible.
Thus, in light of the contradictory findings in the prior art, the artisan would not have been enabled to use the invention as claimed as of the effective filing date.
35 USC § 112(b)
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 1-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, “myoepithelial E-cadherin” (see line 5), “myoepithelial continuity”(see line 8), and “variation in collagen fiber orientation” are not consistent with “these cell types” as recited in line 17. Because of this inconsistency, it is unclear whether all or only certain options recited alternatively in lines 5-11 of claim 1 are intended to be used to compute a composite score. Artisans are left to dispute which features/biomarkers/cell types are used to compute a composite score as encompassed by, therefore infringing, the claim as presently drafted.
Claims 2-9 incorporate, via dependency, and fail to remedy the above noted ambiguity and are therefore included in this rejection.
Claim 1 provides for the use of “…these cell types…to compute a composite score…”, but, since the claims do not set forth any steps involved in the method/process for how the features/biomarkers/cell types are used to compute a composite score, it is unclear what method/process applicant is intending to encompass. 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).
Claims 2-9 incorporate, via dependency, and fail to remedy the above noted ambiguity and are therefore included in this rejection.
Claim 1 is rejected because the preamble recites a “…method of classifying a ductal carcinoma in situ (DCIS) lesion as indolent, or invasive recurrent…” but the claim body concludes with the recitation that “ the spatial location, morphology, and phenotype of these cell types are used to compute a composite score on a computer system to classify DCIS patients at low or high risk of having a disease recurrence within 10 years of diagnosis.” The artisan is left to dispute the scope of the claim as the preamble and the claim body do not clearly correlate where “a disease” is not drafted to derive antecedent basis from previous recitations of DCIS and there is no further definition of a disease provided. Some artisans may determine that “a disease” refers back to DCIS or an invasive form of DCIS (such as IBC) whereas others may consider that something like a recurrent common cold may be intentionally encompassed so as to infringe the claim. Further, there is a question of whether the recurrence risk of a disease is within 10 years of diagnosis of said disease or within 10 years of diagnosis of DCIS. Additionally, some artisans may dispute whether or not the subject must have had or currently have DCIS or whether practicing the method for any disease, even in a person with no DCIS diagnosis, would infringe the claim given the significant difference in the scope of the claim preamble and the claim body. Because the metes and bounds of the claim are indefinite, the claims are rejected.
Claims 2-9 incorporate, via dependency, and fail to remedy the above noted ambiguity and are therefore included in this rejection.
Regarding claim 8, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 8 recites the narrow recitation “…at least 5…”, and the claim also recites “…at least 10…15…20…25…30…35…or all…” which is the broader statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on M-F 9:00 am - 6:00 pm EST.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights