Notice of 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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Withdrawal of Objections and Rejections
Applicant's response, filed 07/14/2026, has been fully considered.
In view of the amendment and remarks, the objection to the drawings and objection to the claims are withdrawn
The following rejections and/or objections are either maintained or newly applied for claims 34-36, 59-61, 63-66 and 68-73. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 04/16/2026.
Status of the Claims
Claims 1-33, 37-58, 62 and 67 are canceled.
Claims 34-36, 59-61, 63-66 and 68-73 are pending.
Claim 73 is objected to.
Claims 34-36, 59-61, 63-66 and 68-73 are rejected.
Priority
This US Application No. 17/512,812 is a DIV of US Application No. 14/653,831 (06/18/2015), which claims priority from a 371 of PCT/EP2013/077295 (12/19/2013), which claims priority from US Application No. 61/747,148 (12/28/2012) as reflected in the filing receipt mailed on 11/10/2021. The claims to the benefit of priority are acknowledged and the effective filing date of claims 34-36, 59-61, 63-66 and 68-73 is 12/28/2012.
Claim objections
Claim 73 is objected to because of the following informality: the indentation format in claim 73 is not in agreement with the remaining claims i.e. claim 34. Appropriate correction is required.
Response to applicant's remarks in regard to Claim Objections
The Remarks of 07/14/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 10 para. 3:
The Initially, Applicant would like to thank the Examiner for the indication that claim 66 would be allowable if rewritten in independent form including the limitations of the base claim and any intervening claims. (Id. at 4). In view of that indication, Applicant has prepared new claim 73, which combines the limitations of previously presented claim 34 with the administration limitation of claim 66, as well as the recitations of claims 63 and 61 from which claim 66 depended. Applicant respectfully submits that new claim 73 addresses the dependency objection and presents the allowable subject matter in independent form. Therefore, Applicant respectfully requests that claim 73 be placed in an immediate condition for allowance.
It is respectfully submitted that this is not persuasive because, despite the fact that the objection issue has not been addressed, claim 66 has been further considered and is no longer free of 101 issues (i.e. reason for the claim objection originally) , and therefore not in condition for allowance. Therefore, the objection to claim 66 is withdrawn but 101 issues remain. This second Non-Final rejection explains in details claim 66 issues at Step 2A Prong 2. Claims directed to "administering to the human subject a breast cancer treatment regimen comprising one or more of radiotherapy, a chemotherapeutic agent, additional surgery, or more frequent monitoring when the breast cancer recurrence prognosis score is greater than the predetermined threshold value” (claims 66 and 73) are not sufficient to provide a particular treatment yet because said administering step includes embodiments where "more frequent monitoring" are administered, and "more frequent monitoring" does not constitute a particular treatment.
Claim Rejections - 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.
Claims 66 and 73 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter the invention. Dependent claims are rejected similarly, unless otherwise noted below. The instant rejection is newly stated and is necessitated by further consideration of the claims.The following issues cause the respective claims to be rejected under 112(b) as indefinite:
Claims 66 and 73 recite an “administering to the human subject a breast cancer treatment regimen comprising” as part of a computer-implemented method which is indefinite. It is unclear whether the entire claim is intended to computer implemented or not, i.e. administering step. For compact prosecution, said administering step is not required to be computer implemented.
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 34-36, 59-61, 63-66 and 68-73 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). Any newly recited portions are necessitated by claim amendment. The instant rejection is newly stated for claims 66 and 72-73 and is necessitated by further consideration of the claims.
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 34-36, 59-61, 63-66 and 68-73) which falls within one of the categories of statutory subject matter.
[Step 1: claims 34-36, 59-61, 63-66 and 68-73:Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims found to recite abstract ideas that can fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (in particular procedures for observing, analyzing and organizing information) as well as a law of nature or a natural phenomenon. The identified grouping(s) for this instant claims are as follows:
Mathematical concepts (in particular mathematical relationships and formulas) include:
• "based on the received first plurality of digital fields of view for ER, calculating an H-score for ER, wherein the calculating of the H-score comprises assigning identified nuclei to intensity bins and computing the H-score from bin counts" (independent claims 34 and 73);
• "based on the received second plurality of digital fields of view for PR, calculating a percent positivity for PR, based on counts of positively stained nuclei and negatively stained nuclei" (independent claims 34 and 73);
• "based on the received third plurality of digital fields of view for Ki-67, calculating a percent positivity for Ki-67 based on counts of positively stained nuclei and negatively stained nuclei; based on the received fourth plurality of digital fields of view for HER2, calculating a binned score for HER2" (independent claims 34 and 73);
• "computing an immunohistochemistry combination score from the H-score for ER, the percent positivity for PR, the percent positivity for Ki- 67, and the binned score for HER2; further comprising computing one or more heterogeneity scores, wherein a first heterogeneity score is computed for ER protein expression; and wherein a second heterogeneity score is computed for PR protein expression, wherein computing the first and second heterogeneity scores comprises computing percent positivity measurements for respective fields of view and determining a variability metric based on a standard deviation of the percent positivity measurements across fields of view" (independent claims 34 and 73);
• "computing a heterogeneity combination score derived from the first and second computed heterogeneity scores; and computing a breast cancer recurrence prognosis score by combining the computed immunohistochemistry combination score and the computed heterogeneity combination score" (independent claims 34 and 73);
• "converting the binned score for HER2 into a binary score for HER2" (claim 35);
• "calculating a weighted sum of percentages of nuclei in intensity bins to produce an H-score in a range of 0 – 300” (claim 69).
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation. Thus, without further detail as to the methodology involved in "calculating scores" based on data from image analysis, under the BRI, one may simply, for example, use pen and paper to perform mathematical steps to arrive at a classification for a prognosis. Further support for the mathematical techniques used in the claims is provided in the specification at pg. 7 line 1, which describes the calculation method used. Thus, the recited terms correspond to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words 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). MPEP 2106.04(a)(2) pertains. The human mind is also sufficiently capable of determine staining completeness, assign intensity values and compare intensity colors.
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• "performing … image analysis on the received first, second, third, and fourth pluralities of digital fields of view, wherein the … image analysis is performed on pixel data of the received first, second, third, and fourth pluralities of digital fields of view and comprises segmentation and nuclei detection to identify nuclei in the respective first, second, third, and fourth pluralities of digital fields of view" (independent claims 34 and 73);
• "(i) determining membrane staining completeness" (independent claims 34 and 73);
• " (ii) determining membrane staining and intensity, and (iii) generating the binned score for HER2 based on the determined membrane staining completeness and determined membrane staining intensity, wherein determining the membrane staining intensity for HER2 comprises assigning a staining intensity value based on pixel intensity of a stain color component for stained membrane" (independent claims 34 and 73);
• "performing analysis on the digital fields of view for HER2 collectively" (claim 36)
• "for a plurality of nuclei appearing in the digital fields of view for HER2, determining whether cell membrane surrounding the nuclei are completely stained" (claim 37);
• "determining intensity of staining of cell membrane surrounding respective nuclei" (claim 38);
• "determining whether the human subject diagnosed with breast cancer is at a risk of breast cancer recurrence based on the immunohistochemistry combination score" (claim 60);
• "determining whether the human subject diagnosed with breast cancer is at a risk of breast cancer recurrence based on the breast cancer recurrence prognosis score" (claims 61 and 73);
• "determining that the breast cancer recurrence prognosis score is greater than the predetermined threshold" (claim 63 and 73);
• "comparing a first color component of stained nuclei against one or more thresholds to assign bin values corresponding to weak, moderate, or strong staining” (claim 68).
The instant specification in pg. 15 line 18 discloses that image analysis can be done "manually (e.g., without the use of a digital image) – claims 34 and 36." The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind (i.e. concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) or because the method only requires a user to manually determine action based on an added number. Under the BRI, the recited limitations are mental processes because a human mind is also sufficiently capable of evaluating data to perform image analysis, to determine the level of staining obtained and compare said level of staining, to determine if a score is greater than a threshold or not and to determine the risk based on a score.
Dependent claims 64-65 recite further steps that limit the judicial exceptions in independent claim 34 by limiting the scores obtained and, as such, also are directed to those abstract ideas.
Furthermore, the instant claims recite a natural correlation by correlating the measurement of biomarker in a cancer sample with its score classification. (see MPEP 2106.04(b).I).
[Step 2A Prong One: claims 34-36, 59-61, 63-66 and 68-73: Yes ]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claims 34, 66, 70 and 73 recite additional elements that are not abstract ideas:
• "computer-implemented" (independent claims 34 and 73);
• "receiving a first plurality of digital fields of view of a first image depicting a breast cancer sample detectably labeled with an antibody for an estrogen receptor (ER) biomarker" (independent claims 34 and 73);
• "receiving a second plurality of digital fields of view of a second image depicting a breast cancer sample detectably labeled with an antibody for a progesterone receptor (PR) biomarker" (independent claims 34 and 73);
• "receiving a third plurality of digital fields of view of a third image depicting a breast cancer sample detectably labeled with an antibody for a Ki-67 biomarker" (independent claims 34 and 73);
• "receiving a fourth plurality of digital fields of view of a fourth image depicting a breast cancer sample detectably labeled with an antibody for a human epidermal growth factor receptor 2 (HER2) biomarker" (independent claims 34 and 73);
• "automatically generating a communication comprising the breast cancer recurrence prognosis score and delivering the communication electronically to one or more of a physician or a patient" (claim 70);
• "administering to the human subject a breast cancer treatment regimen comprising one or more of radiotherapy, a chemotherapeutic agent, additional surgery, or more frequent monitoring when the breast cancer recurrence prognosis score is greater than the predetermined threshold value” (claims 66 and 73);
Dependent claims 59 and 61 recite further details about the breast cancer sample and dependent claim 72 recites further details about the pixel data.
Considerations under Step 2A, Prong Two
The recited limitations in claims 34, 70 and 73 are interpreted as requiring the use of a computer. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer. Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. The instant claims state nothing more than that a generic computer performs the functions that constitute the abstract idea (MPEP 2106.05(f)).
Limitations of claims 34 and 73 are considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C.
Claims directed to "receiving" read on receiving or transmitting data over a network -Symantec, 838 F.3d at 1321 - MPEP 2106.05(a) pertains; which constitutes just necessary data gathering and therefore correspond to insignificant extra-solution activity.
Claims directed to " generating a communication comprising the breast cancer recurrence prognosis score" are interpreted as data outputting (i.e. the output from mathematical calculations in the judicial exception) and as such insignificant extra-solution activity.
Claims directed to "administering to the human subject a breast cancer treatment regimen comprising one or more of radiotherapy, a chemotherapeutic agent, additional surgery, or more frequent monitoring when the breast cancer recurrence prognosis score is greater than the predetermined threshold value” (claims 66 and 73) are not sufficient to provide a particular treatment yet because said administering step includes embodiments where "more frequent monitoring" are administered, and "more frequent monitoring" does not constitute a particular treatment.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information.
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 34-36, 59-61, 63-66 and 68-73: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claims 34 and 70 recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Further, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versa ta Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(Il)(i)).
With respect to the instant claims, the prior art review to Ludwig (Biomarkers in cancer staging, prognosis and treatment selection." Nature Reviews Cancer 5.11:845-856 (2005); newly cited) discloses that selection of therapy (i.e. administering step) based on biomarkers analysis (pg. 848 Table 1) for cancer diagnosis, risk assessment and screening (pg. 850 Box. 1) is routine, well-understood and conventional in the art.
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 34-36, 59-61, 63-66 and 68-73: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 07/14/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 10 para. 3:
The Applicant respectfully submits that the Patent Office's Step 2A, Prong One analysis improperly characterizes multiple limitations of claim 34 as mental processes merely because the claim includes "calculating," "determining," and "computing" steps. (Id. at 6-11). That characterization does not account for the actual language of claim 34.. Claim 34 as amended requires "performing automated image analysis" that is expressly "performed on pixel data" of the received pluralities of digital fields of view and includes segmentation and nuclei detection to identify nuclei. Under MPEP 2106.04(a)(2)(111), a "mental process" is a concept "practically performed in the human mind." Claim 34 does not merely recite observations, evaluations, judgments, or opinions that can practically be performed in the human mind. Rather, claim 34 requires computer-implemented image analysis operations performed on digital image information, including segmentation and nuclei detection across plural digital fields of view. Accordingly, the claimed automated segmentation and nuclei detection steps cannot fall within the "mental process" grouping, and the rejection should not treat claim 34 as merely reciting a mental process.
It is respectfully submitted that this is not persuasive because this examination does account for the exact language in the claims as "calculating," "determining," and "computing" steps are indeed recited in the claims. To further clarify how each abstract idea has been identified, this instant examination has separated the recited abstract ideas in groupings such as mathematical concepts, mental processes and laws of nature. The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation and determined to each cover performance either in the mind (i.e. concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) or because the method only requires a user to manually determine action based on an added number.
Regarding the argued automated image analysis step, the instant specification in pg. 15 line 18 discloses that image analysis can be done "manually (e.g., without the use of a digital image) – claims 34 and 36. The use of a physical aid, such as a computer, does not negate the mental nature of said limitations. The computer as claimed herein is not specifically implemented and changed by operation of said steps. Rather, the computer functions as a tool to perform said steps and any computer is capable of performing said tasks. The MPEP at 2106.05(f) states that claims which merely include instructions to implement an abstract idea on a computer, or merely use a computer as a tool to perform an abstract idea, effectively add words that "apply" the judicial exception in a computer. Furthermore, limitations considered as using a computer to perform a judicial exception are not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and performing the mental process in a computer environment, in an automatic manner, do not negate the fact that something that can be carried out in the human mind, and are merely instructions to apply the judicial exceptions to a computer. See MPEP 2106.04(a)(2).III.C.
Applicant asserts starting in pg. 11 para. 4:
The Patent Office's analysis also characterizes "determining membrane staining completeness" and "determining membrane staining intensity" as mental steps. (Id. at 8). That characterization is inconsistent with the claim language. Claim 34 as amended requires that HER2 membrane staining intensity is determined by "assigning a staining intensity value based on pixel intensity of a stain color component for stained membrane." A step that requires deriving an intensity value from pixel intensity of a stain color component in digital image data cannot be "practically performed in the human mind," and therefore does not reasonably fall within the "mental process" grouping. … Applicant does not dispute that certain intermediate values may be expressed mathematically. The relevant inquiry, however, is not. whether the claim includes calculations but whether the claim is directed to a mathematical concept as such. See MPEP § 2106.04(a)(2)(1). As the Federal Circuit explained in Thales Visionix Inc. v. United States, 850 F.3d 1343, 1349 (Fed. Cir. 2017), "That a mathematical equation is required to complete the claimed method and system does not doom the claims to abstraction." Claim 34 is directed to a specific multi-biomarker digital pathology image-processing workflow in which the recited computations are grounded in image-derived features extracted through automated processing of digital fields of view. Properly construed, claim 34 does not preempt mathematical calculations in the abstract; it confines any computations to a particular computerized image-analysis workflow for digital pathology images. Accordingly, claim 34 is not directed to mathematical concepts or mental processes in the abstract, but instead recites a specific computer-implemented digital pathology image-analysis workflow that uses automated image-derived feature extraction as part of the claimed scoring process
It is respectfully submitted that this is not persuasive because the claims do not recite “deriving an intensity value from pixel intensity of a stain color component in digital image data”, the claims recite "determining membrane staining completeness" and "determining membrane staining intensity" which have been correctly identified as mental processed based on data evaluation. The claims are evaluated under the Broadest Reasonable Interpretation and there has been no inconsistent characterization of the recited claim language.
Regarding the argued “dooming the claims to abstraction”, said claims have not been identified as abstract in its entirety. The Applicant is reminded that at Step 2A, Prong 1, the claims are examined limitation by limitation to identify whether the claimed concept in the recited claim element aligns with at least one judicial exception (see MPEP 2106.04(I)). The fact that some claims recite limitations not considered to align with a judicial exception does not negate that the claims also recites other limitations which do align.
Regarding the argued “automated processing of digital fields of view”, the use of a physical aid, such as a computer, does not negate the mental nature of said limitations. The computer as claimed herein is not specifically implemented and changed by operation of said steps. Rather, the computer functions as a tool to perform said steps and any computer is capable of performing said tasks. The MPEP at 2106.05(f) states that claims which merely include instructions to implement an abstract idea on a computer, or merely use a computer as a tool to perform an abstract idea, effectively add words that "apply" the judicial exception in a computer. Furthermore, limitations considered as using a computer to perform a judicial exception are not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and performing the mental process in a computer environment, in an automatic manner, do not negate the fact that something that can be carried out in the human mind, and are merely instructions to apply the judicial exceptions to a computer. See MPEP 2106.04(a)(2).III.C
Applicant asserts starting in pg. 12 para. 2:
Contrary to the Patent Office's assertion, the Specification's manual-analysis disclosure does not broaden amended claim 34 to a mental process The Patent Office asserts that, because the Specification indicates image analysis may be performed "manually (e.g., without the use of a digital image)," claim 34 is broad enough that one could "use pen and paper to perform mathematical steps" to reach a prognosis classification. (Id. At 10, 18). Applicant respectfully submits that this rationale is inconsistent with the amended claim language. As noted above, claim 34 as amended affirmatively requires receiving pluralities of "digital fields of view" from four "image[s]" and performing "automated image analysis" that is performed on pixel data and includes segmentation and nuclei detection. Under any reasonable interpretation, those limitations require computer-implemented processing of digital image data and do not read on manual review without a digital image. Even assuming that the downstream scoring computations could be performed on paper after the relevant image-derived values are known, claim 34 first requires automated segmentation and nuclei detection on pixel data across plural digital fields of view for multiple biomarker-labeled images. Those prerequisite image-processing operations cannot reasonably be characterized as "manual analysis" or "pen and paper" activity. Accordingly, the asserted mental-process rationale is inconsistent with amended claim 34 and should be withdrawn.
It is respectfully submitted that this is not persuasive because the asserted mental-process rationale is not inconsistent. 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 having ordinary skill in the art. The instant specification in pg. 15 line 18 discloses that image analysis can be done "manually (e.g., without the use of a digital image) which supports this instant examination. Furthermore, the use of a physical aid, such as a computer, does not negate the mental nature of said limitations. The computer as claimed herein is not specifically implemented and changed by operation of said steps. Rather, the computer functions as a tool to perform said steps and any computer is capable of performing said tasks. The MPEP at 2106.05(f) states that claims which merely include instructions to implement an abstract idea on a computer, or merely use a computer as a tool to perform an abstract idea, effectively add words that "apply" the judicial exception in a computer. Furthermore, limitations considered as using a computer to perform a judicial exception are not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and performing the mental process in a computer environment, in an automatic manner, do not negate the fact that something that can be carried out in the human mind, and are merely instructions to apply the judicial exceptions to a computer. See MPEP 2106.04(a)(2).III.C
Additionally, the instant claims do not recite “automated segmentation and nuclei detection on pixel data across plural digital fields of view for multiple biomarker-labeled image,” the claims actually recite “wherein the automated image analysis … comprises segmentation and nuclei detection to identify nuclei in the respective first, second, third, and fourth pluralities of digital fields of view.” Regarding said recitation, the human mind is capable of evaluating imaging data “manually” by segments to identify information about nuclei and the use of a physical aid, such as a computer, does not negate the mental nature of said limitations. See MPEP 2106.04(a)(2).III.C
Applicant asserts starting in pg. 13 para. 2:
The Patent Office asserts that the pending claims recite a "natural correlation" by correlating biomarker measurement with score classification. (Id. at 11 ). Applicant respectfully submits that this characterization does not match the language of claim 34. Claim 34 does not claim a biological fact, natural relationship, or correlation in isolation. Instead, claim 34 recites a computer implemented digital pathology workflow that receives digital fields of view from multiple biomarker-labeled images, performs automated image analysis on those digital fields of view, extracts image-derived features, and computes integrated scores from those image-derived features. Thus, even if the resulting prognosis score may be clinically useful, the claim is directed to a specific digital image-analysis workflow and its associated image-derived feature extraction, not to a natural law itself Accordingly, the Patent Office's "natural correlation" characterization should not be sustained.
It is respectfully submitted that this is not persuasive because the identified natural correlation does match the recited language in claims 34 and 73. Said characterization originated from the fact that the claims recite “receiving” image depicting the breast cancer sample and then correlates the analysis of said image to a score that can be assessed to determine the risk of cancer. Thus, the instant claims recite a natural correlation by correlating the measurement of biomarker in a cancer sample with its score classification. (see MPEP 2106.04(b).I).
Applicant asserts starting in pg. 13 para. 4:
The Claim 34 as amended is not limited to generic computer implementation or passive receipt of information. Rather, claim 34 recites a particular digital pathology image-analysis workflow that uses automated image processing to extract image-derived features from digital fields of view and then uses those extracted features in the claimed scoring process. In particular, claim 34 as amended requires automated image analysis performed on pixel data, including segmentation and nuclei detection, across plural digital fields of view for multiple biomarker images. That is not generic data gathering but is instead the required technical means by which the method identifies biomarker features from digital pathology image data as a prerequisite to the downstream biomarker-specific quantification. Claim 34 is not directed to generic data intake and reporting. Rather, claim 34 recites a specific ordered combination that includes: (i) receiving plural digital fields of view from four biomarker-labeled images; (ii) performing automated image analysis on pixel data, including segmentation and nuclei detection; (iii) computing biomarker-specific scores from image-derived features; (iv) quantifying heterogeneity across fields of view using a standard-deviation-based variability metric; and (v) combining the IHC combination score and heterogeneity combination. score to compute a breast cancer recurrence prognosis score. Viewed as an ordered combination, these limitations define a particular digital pathology image-processing workflow that operates on pixel-level digital image information and produces image-derived measures for use in a defined recurrence-prognosis scoring process. The claim is therefore materially different from a generic "receive information and output a result" pattern. Accordingly, Applicant respectfully submits that claim 34 recites significantly more than routine receiving and outputting on a generic computer, and the Step 2B rejection should be withdrawn.
It is respectfully submitted that this is not persuasive because the identified receiving and outputting steps have been correctly examined at Steps 2A Prong 2 and Step 2B. The type of data or “specific ordered combination” being received and outputted does not change that data is being received and outputted by conventional computer means, which constitutes just necessary data gathering and, therefore, correspond to insignificant extra-solution activity at Step 2A Prong 2 and correspond to well-understood, routine, and conventional functions of a computer when claimed in a generic manner or as insignificant extra-solution activity at Step 2B.
Applicant asserts starting in pg. 15 para. 2:
The Patent Office asserts Applicant's prior arguments were unpersuasive because the Specification discloses "manual" image analysis, and thus "one may simply ... use pen and paper" under BRI. (Id. at 17-18). Applicant respectfully submits that this response does not address claim 34 as amended. Claim 34 as amended requires that automated image analysis be performed on pixel data of the received pluralities of digital fields of view and includes segmentation and nuclei detection. The Patent Office's response does not explain how these requirements could be satisfied "in the human mind" or by "pen and paper." A permissive disclosure that some embodiments may involve manual analysis does not broaden claim 34 as amended beyond its requirements for digital fields of view, pixel-data based automated image processing, segmentation, and nuclei detection. Accordingly, the "human mind/ pen and paper" rationale does not rebut the language of claim 34 as amended. …. Applicant respectfully submits that machine learning is not the dividing line for section 101 eligibility. Instead, the relevant inquiry under MPEP 2106.04(a)(2)(111) is whether the limitation is "practically performed in the human mind." Claim 34 as amended requires automated segmentation and nuclei detection performed on pixel data and further requires pixel-intensity-based stain color component intensity assignment for HER2. Those limitations are not practically performed in the human mind. …Id. at 18). Applicant respectfully submits that claim 34 is not premised on an improvement to computer hardware architecture. Rather, claim 34 recites a specific computer-implemented digital pathology image-analysis workflow applied to digital pathology images. For instance, claim 34 requires automated image analysis performed on pixel data across plural fields of view for multiple biomarker images, coupled with biomarker-specific quantification tied to image-derived features and heterogeneity computation across … Accordingly, the asserted improvement is the claimed computer implemented image-analysis workflow for extracting and integrating image-derived pathology features, not a change to the physical architecture of the computer itself The Patent Office additionally contends that Applicant's unconventional-combination arguments are unpersuasive because unconventionality is examined only for "additional elements," and suggests the claims are not examined as a whole under Step 2B. (Id. at 20-21 ). Applicant respectfully submits that this Step 2B argument is too restrictive as applied to claim 34 as amended. Step 2B requires evaluating whether the claim includes an inventive concept, considering the elements "both individually and as an ordered combination." Claim 34 as amended recites an ordered combination that extends well beyond generic "receiving" and "outputting." In particular, claim 34 as amended requires automated image analysis performed on pixel data, including segmentation and nuclei detection, and further requires biomarker-specific quantification tied to image-derived features (including intensity-bin assignment and bin counts, positive/negative nuclei counts, and pixel-intensity-based membrane staining intensity), as well as heterogeneity quantified across fields of view via a standard-deviation-based variability metric. … The Patent Office's argument effectively treats these pixel-data-based image-processing limitations as part of the alleged judicial exception and then reduces the "additional elements" to generic computer implementation and generic receiving/outputting. That approach does not meaningfully evaluate the ordered combination recited in claim 34, and it is not a proper Step 2B analysis of whether the claim, as a whole, amounts to significantly more than any alleged exception. When claim 34 as amended is considered as a whole, the amended limitations tie the recited computations to a particular technical process performed on digital pathology images and meaningfully limit any alleged exception.
It is respectfully submitted that this is not persuasive because the argued “automated image analysis be performed on pixel data” still recites the analysis of image data – which is comprised by pixels – and that does not change the fact that analysis of image data can be performed mentally as supported by this instant specification in pg. 15 line 18. The disclosed manual analysis is not being used to “broaden claim 34 as amended beyond its requirements for digital fields of view” because all limitations 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 having ordinary skill in the art.
Regarding the argued “explaining how these requirements could be satisfied "in the human mind" or by "pen and paper,” the human mind is capable of evaluating imaging data “manually” by segments to identify information about nuclei and the use of a physical aid, such as a computer, does not negate the mental nature of said limitations. See MPEP 2106.04(a)(2).III.C.
Regarding the argument “that machine learning is not the dividing line for section 101 eligibility”, the Examiner agrees, however the exemplified process as argued in the last previous action are non-analogous to that recited by the instant claims.
Regarding the argued “automated segmentation and nuclei detection performed on pixel data”, the human mind is capable of evaluating imaging data “manually” by segments to identify information about nuclei and limitations considered as using a computer to perform a judicial exception are not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and performing the mental process in a computer environment, in an automatic manner, do not negate the fact that something that can be carried out in the human mind, and are merely instructions to apply the judicial exceptions to a computer. See MPEP 2106.04(a)(2).III.C
Regarding the analysis under Step 2B, MPEP 2106.05(d) sets forth that, at Step 2B, it is the additional elements which are examined to determine whether they are well-understood, routine, conventional activities previously known to the industry. The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B instructs that an inventive concept cannot be provided the by judicial exception. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). The limitations directed to the argued “biomarker-specific quantification” pointed by the Applicant are considered to recite a judicial exception as described above and are therefore not considered at Step 2B. Therefor the analysis under Step 2B has correctly included additional elements that involve generic computer implementation and generic receiving/outputting.
Regarding the argued “specific computer-implemented digital pathology image-analysis workflow”, “asserted improvement is the claimed computer implemented image-analysis workflow” and “computations to a particular technical process performed on digital pathology images and meaningfully limit any alleged exception”, the Examiner understands that Applicant does not claim improvements to computer hardware architecture, however the use of a general purpose computer to perform judicial exceptions still applies here. Even if the Applicant is aiming for a "other meaningful limits" consideration under Step 2A Prong 2, the Examiner still have to look at "do the additional elements, not the judicial exceptions, provide that meaningful limitation. In this case, for a computer to be considered as proving such meaningful limitation, the claims that purport to improve computer capabilities or to improve an existing technology may integrate a judicial exception into a practical application or provide significantly more, which does not happen here. Even if the recited “performing automated image analysis” had been identified as being performed by algorithmic operations done by a computer, such identification would still fall under abstract ideas performed by a computer (i.e. math). It is submitted here that the instant claims do not include any additional elements that provide for a practical application.
Regarding particular treatment considerations at Step 2A Prong 2, claims directed to "administering to the human subject a breast cancer treatment regimen comprising one or more of radiotherapy, a chemotherapeutic agent, additional surgery, or more frequent monitoring when the breast cancer recurrence prognosis score is greater than the predetermined threshold value” (claims 66 and 73) are not sufficient to provide a particular treatment yet because said administering step includes embodiments where "more frequent monitoring" are administered, and "more frequent monitoring" does not constitute a particular treatment.
No prior art has been applied to the following claims
Claims 34-36, 59-61, 63-66 and 68-73 are free of the analogous art at least because close art, e.g. Loyd, Cuzick, Potts and Cordon-Cardo as cited in 06/03/2025 Form PTO-892, either individually or in obvious combination, does not teach the recited combination of “computing an immunohistochemistry combination score … computing one or more heterogeneity scores, … computing a heterogeneity combination score derived from the first and second computed heterogeneity scores; and computing a breast cancer recurrence prognosis score by combining the computed immunohistochemistry combination score and the computed heterogeneity score.”
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
