BitLaw

Example 49. Fibrosis Treatment

This example illustrates the analysis of method claims reciting an artificial intelligence model that is designed to assist in personalizing medical treatment to the individual characteristics of a particular patient. The recited condition (post-implantation inflammation) is hypothetical, but open angle glaucoma and fibrosis are known medical conditions. The recited anti-fibrotic drugs (drug A and Compound X) are hypothetical fibrosis treatments. Lifestyle adjustments, pharmaceutical eye drops, laser eye surgery, and eye drainage device implants (including microstents) are known glaucoma treatments. The recited computer-implemented machine learning model (ezAI model) is hypothetical; however, genome-wide association studies, polygenic risk scores, and single-nucleotide polymorphisms (SNPs) are known in the genomics field. Claim 1 is ineligible because it recites a judicial exception (an abstract idea) and the claim as a whole does not integrate the exception into a practical application (and is thus directed to an abstract idea) and the claim does not provide significantly more than the exception (does not provide an inventive concept). Even though claim 2 recites the same judicial exception, claim 2 is eligible because the claim as a whole integrates the exception into a practical application and is therefore not "directed to" the judicial exception.

BACKGROUND

Glaucoma is a leading cause of blindness globally. The most common form is open angle glaucoma, in which irreversible vision loss results from cell and optic nerve damage caused largely by poor drainage of aqueous humor from the eye. Depending on condition severity and the timing of the diagnosis, treatment can include lifestyle adjustments, pharmaceutical eye drops, laser eye surgery, or drainage device implants to facilitate healthy drainage. While newer drainage devices, such as microstents, are more comfortable than earlier drainage devices, post- surgery scarring and inflammation due to fibrosis remain issues. Commonly prescribed anti- fibrotic drugs, such as drug A, can reduce scarring but do so non-specifically while causing more inflammation ("post-implantation inflammation" or "PI") that further damages the eye.

Applicant developed a new anti-fibrotic drug, Compound X, that effectively reduces scarring around a microstent implantation site in glaucoma patients at high risk of PI after microstent implant surgery without the undesirable side effects of drug A. In connection with this invention, the applicant filed a patent application disclosing Compound X and describing how it may be topically administered in eye drop form after microstent implant surgery.

The applicant also discovered that PI is a polygenic condition, meaning that it results from the interaction of multiple genes rather than any single gene. Using standard methodologies, the applicant conducted a large-scale genome wide association (GWA) study on PI in glaucoma patients and identified 37 informative single-nucleotide polymorphisms (SNPs) that have a statistically significant association with PI. The application defines "informative SNPs" as the 37 SNPs identified in the GWA study. These informative SNPs serve as genetic markers for the genes that give rise to PI.

From the GWA study data, the applicant developed a polygenic risk score (PRS) model by classic clumping and thresholding methods to provide a weighted PRS. As is known in the art, a PRS is a single value estimate of an individual's relative risk for a given phenotype or condition based on the individual's genotype. In brief, after collecting a sample from a patient, the sample is sequenced and genotyped to provide a genotype dataset. Alleles in the genotype dataset corresponding to informative SNPs selected from the GWA study are identified, tallied, and weighted (using effect sizes derived from GWA study summary statistics as weights). A PRS is then generated as a sum of the weighted values. Sample collection, sequencing, and genotyping for the purposes of providing a genotype dataset may be carried out by conventional methods known in the art.

The specification discloses a method of identifying glaucoma patients at high risk of PI using this PRS model. An identification of a patient as being at high risk of PI is made by ranking a weighted PRS once the score has been generated. The application defines a "glaucoma patient at high risk of PI" as a glaucoma patient having a weighted PRS in the top quartile of PRS values when ranked against reference PRS values established during PRS model development. The disclosure teaches that determining patient risk using a weighted PRS as disclosed and accordingly customizing treatment lends to better prognosis after implant surgery.

The applicant also discloses a computer-implemented machine learning model (referred to as "the ezAI model" for the purposes of this disclosure) and its clinical applications. Given an input of a patient's genotype dataset, the ezAI model calculates a weighted PRS from informative SNPs in the dataset—using multiplication to weight corresponding alleles in the dataset by their effect sizes and addition to sum the weighted values. Using the same weights and informative SNPs, the ezAI model improves upon the base PRS model by determining a risk score and providing a classification in less time.

CLAIMS

[Claim 1] A post-surgical fibrosis treatment method comprising:

(a) collecting and genotyping a sample from a glaucoma patient to a provide a genotype dataset;

(b) identifying the glaucoma patient as at high risk of post-implantation inflammation (PI) based on a weighted polygenic risk score that is generated from informative single-nucleotide polymorphisms (SNPs) in the genotype dataset by an ezAI model that uses multiplication to weight corresponding alleles in the dataset by their effect sizes and addition to sum the weighted values to provide the score; and

(c) administering an appropriate treatment to the glaucoma patient at high risk of PI after microstent implant surgery.

[Claim 2] The method of claim 1, wherein the appropriate treatment is Compound X eye drops.

ANALYSIS

Claim 1 is ineligible.

Claim Interpretation: Under the broadest reasonable interpretation, the terms of the claim are presumed to have their plain meaning consistent with the specification as it would be interpreted by one of ordinary skill in the art. See Manual of Patent Examining Procedure (MPEP) 2111.

Claim 1 does not restrict how the sample is collected or genotyped in step (a). The specification explains that these steps may be carried out by any conventional method known in the art.

In step (b), the terms "glaucoma patient . . . at high risk of PI" and "informative SNPs" are given special definitions in the specification. Based on these special definitions, step (b) requires identifying the glaucoma patient as at high risk of PI where the patient's weighted PRS is in the top quartile of PRSs when ranked against reference PRS values established during PRS model development. Step (b) also requires that the weighted PRS is generated using an ezAI model from the 37 SNPs identified in the GWA study that are present in the patient's genotype dataset.

Step (b) indicates that the PRS is generated from informative SNPs in the genotype dataset by "an ezAI model." As explained in the specification, an ezAI model can be a computer- implemented machine learning model that calculates a weighted PRS from alleles corresponding to informative SNPs present in a given input of a patient's genotype dataset. See MPEP 2111.01, subsection V. The score is calculated using multiplication to weight the alleles in the dataset by their effect sizes and addition to sum the weighted values according to the plain language of the claim.

Step (c) does not require any specific treatment or prophylaxis because the claim merely recites "administering an appropriate treatment." For instance, treatment can involve administering Compound X or any common anti-fibrotic treatment, such as drug A, after microstent implant surgery.

Based on the plain meaning of the words in the claim, the broadest reasonable interpretation of claim 1 is: a method of collecting and genotyping a sample to provide a genotype dataset, identifying the glaucoma patient by phenotype (at high risk of PI) based on a weighted PRS generated from informative SNPs in the genotype dataset using an ezAI model that calculates the score using multiplication to weight alleles corresponding to the informative SNPs by their effect sizes and addition to sum the weighted values, and administering a treatment to the patient at high risk of PI after microstent implant surgery.

Step 1:This part of the eligibility analysis evaluates whether the claim falls within any statutory category. MPEP 2106.03. The claim recites at least one step or act of determining the patient's risk for a condition. Thus, the claim is a process, which is a statutory category of invention. (Step 1: YES).

Step 2A, Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP 2106.04, subsection II, a claim "recites" a judicial exception when the judicial exception is "set forth" or "described" in the claim.

Limitation (b) in the claim recites "identifying the glaucoma patient as at high risk of PI based on a weighted PRS." Under its broadest reasonable interpretation consistent with the specification, the plain and ordinary meaning of this limitation requires an evaluation of patient risk by determining whether a patient's weighted PRS falls within the top quartile of scores when ranked against reference PRS values established during PRS model development. As this step requires comparing a patient's score against known top-quartile scores, the limitation falls into the "mental process" grouping of abstract ideas because the evaluation can be practically performed in the human mind. This limitation further recites a law of nature because it describes the naturally occurring relationship between a patient's genotype (a particular combination of genes giving rise to PI) and phenotype (risk for PI).

Limitation (b) also recites "a weighted PRS that is generated from informative SNPs in the genotype dataset by an ezAI model that uses multiplication to weight corresponding alleles in the dataset by their effect sizes and addition to sum the weighted values to provide the score." As discussed above, the broadest reasonable interpretation of this limitation requires a mathematical calculation. Namely, an arithmetic calculation (multiplication to weight alleles by their effect sizes and addition to sum the weighted values) is required to generate a weighted risk score. Limitation (b) hence recites a "mathematical calculation" and so falls into the "mathematical concepts" grouping of abstract ideas. For instance, given a genotype dataset, a physician would identify, tally, and weight alleles corresponding to informative SNPs present in the dataset by their effect sizes, then sum the resulting values to generate a risk score. See MPEP 2106.04(a)(2), subsection I.C. This limitation also falls into the "mental process" grouping because it requires an assessment of the genotype dataset in order to identify informative SNPs in evaluating patient risk. Moreover, the recited mathematical calculation is simple enough that it can be practically performed in the human mind. Even if most humans would use a physical aid, like a pen and paper or a calculator, to make such calculations, the use of a physical aid would not negate the mental nature of this limitation. See MPEP 2106.04(a)(2), subsection III.B.

As there are no bright lines between the types of judicial exceptions, and many of the concepts identified by the courts as exceptions can fall under several exceptions, MPEP 2106.04, subsection I instructs examiners to "identify . . . the claimed concept (the specific claim limitation(s) that the examiner believes may recite an exception) [that] aligns with at least one judicial exception." While limitation (b) can be categorized under several exceptions (a mathematical concept-type abstract idea, a mental process-type abstract idea, and a law of nature), it is adequate for an examiner to identify the limitation as falling under at least one judicial exception and to base further analysis on that identification. The remainder of this discussion is premised on the recited exception as an abstract idea. See MPEP 2106.04, subsection II.B. (Step 2A, Prong One: YES).

Step 2A, Prong Two: 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. This evaluation is performed by (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (2) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. MPEP 2106.04(d).

The claim recites the additional elements of "collecting" and of "genotyping a sample from a glaucoma patient to provide a genotype dataset" in limitation (a). The additional element of "collecting" a sample is an insignificant extra-solution activity that amounts to mere data gathering incidental to limitation (b). The additional element of "genotyping" also represents mere data gathering (a set of genotypes from the collected sample) because all uses of the judicial exception require genotyping the collected sample (the mental process in limitation (b) uses the genotype dataset to determine a patient's risk). See MPEP 2106.05(g). As such, genotyping the sample is also an insignificant extra-solution activity.

The claim also recites the additional element of "administering an appropriate treatment to the glaucoma patient at high risk of PI" in limitation (c). Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated or what the treatment is, but instead covers any possible treatment that a medical professional decides to administer to the patient. As such, there are no meaningful constraints on the administering step such that the particular treatment or prophylaxis consideration would apply because it is not limited to any particular manner or type of treatment. See MPEP 2106.04(d)(2). Moreover, like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012), the claim merely provides the identification made in limitation (b) to the relevant audience (such as a physician or another medical professional) and at most adds a suggestion to take that identification into account when treating patients. Limitation (c) may thus be understood as no more than an attempt to generally link the judicial exception to a field of use. See MPEP 2106.05(h). Therefore, limitation (c) fails to meaningfully limit the claim because it does not require any particular application of the abstract idea and therefore amounts only to a generic instruction to "apply" the exception or to a mere indication of the field of use or technological environment in which the abstract idea is performed.

While the disclosure states that "the ezAI model improves upon the base PRS model by determining a risk score and providing a classification in less time," there is no improvement to the functioning of a computer nor to any other technology. At best, the claimed combination amounts to an improvement to the abstract idea of determining patient risk rather than to any technology. See MPEP 2106.05(a). Thus, even when considering the elements in combination, the claim as a whole does not integrate the recited exception into a practical application. (Step 2A, Prong Two: NO). Thus, claim 1 is directed to a judicial exception. (Step 2A: YES).

Step 2B:This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. Additional elements in limitation (a) were considered insignificant extra-solution activities (mere data gathering) in Step 2A, Prong Two. The additional element of "an appropriate treatment" in limitation (c) does not require any particular application of the patient risk determination and is at most an instruction to "apply" the abstract idea.

These additional elements should be re-evaluated in Step 2B, in which the extra-solution activity consideration takes into account whether or not an extra-solution activity is well-known. The data gathering activities in limitation (a) are recited at a high level of generality and have been recognized by the courts as being routine laboratory techniques. See Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1377 (Fed. Cir. 2016) (analyzing DNA to provide sequence information or to detect allelic variants is conventional in the art); MPEP 2106.05(d), subsection II. The specification otherwise only describes carrying out sample collection and genotyping by conventional methods. See paragraph 4 of the Background.

Consequently, for the reasons discussed above, the additional elements individually or in combination with the judicial exception do not provide an inventive concept; so, the claim as a whole does not amount to significantly more than a generic instruction to "apply" the judicial exception. (Step 2B: NO). The claim is not eligible.

Claim 2 is eligible.

Claim Interpretation: Under the broadest reasonable interpretation, the terms of the claim are presumed to have their plain meaning consistent with the specification as it would be interpreted by one of ordinary skill in the art. See MPEP 2111. Claim 2 depends from claim 1 and adds a "wherein" clause specifying that the appropriate treatment is Compound X eye drops. As a dependent claim, claim 2 is construed as incorporating by reference all the limitations of the claim (claim 1) that it refers back to and further limits. See MPEP 608.01(n), subsection III. It is important to remember during claim interpretation that no limitations can be disregarded and the mere fact that a limitation appears in a wherein clause does not automatically mean that it is not given weight. Here, when the clause in limitation (c) is considered in view of the specification, it is clear that the wherein clause has patentable weight. Namely, the claim requires that the appropriate treatment be Compound X eye drops, and does not make the appropriate treatment optional or simply express the result of a process step. The claim does not require any particular dosage or frequency of administration.

Step 1:This part of the eligibility analysis evaluates whether the claim falls within any statutory category. MPEP 2106.03. The claim recites at least one step or act of determining the patient's disease risk. Thus, the claim is a process, which is a statutory category of invention. (Step 1: YES).

Step 2A, Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP 2106.04, subsection II, a claim "recites" a judicial exception when the judicial exception is "set forth" or "described" in the claim. Because claim 2 depends from claim 1, thereby incorporating by reference all the limitations of claim 1, it recites an abstract idea in limitation (b) for the reasons discussed above. As a result, it is necessary to continue to analysis under Step 2A, Prong Two. (Step 2A, Prong One: YES).

Step 2A, Prong Two: 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. This evaluation is performed by (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (2) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. MPEP 2106.04(d).

In addition to the abstract idea in claim 1, from which claim 2 depends, claim 2 recites the additional element of "the appropriate treatment is Compound X eye drops." Step 2A specifically excludes consideration of whether the additional elements represent well-understood, routine, conventional activity. Instead, analysis of well-understood, routine, conventional activity is done in Step 2B. Therefore, the assessment below does not evaluate the conventionality of additional elements.

Under the broadest reasonable interpretation of the claim, additional element (c) and the wherein clause encompass the administration of a "particular treatment" when considered in the context of the claim as a whole. Specifically, the additional elements have more than a nominal relationship to the judicial exception because they use the abstract idea of determining patient risk of PI in a manner that meaningfully limits it. That is, the abstract idea is used to identify the patient as belonging to a specific patient population (glaucoma patients at high risk of PI), and the patient is then administered a treatment (Compound X eye drops instead of any common anti-fibrotic treatment, such as drug A, after microstent implant surgery) that is particular to that specific patient population (glaucoma patients at high risk of PI). Relying on the determination of patient risk to administer Compound X eye drops to glaucoma patients at high risk of PI after microstent implant surgery is therefore a particular treatment for a medical condition such that the claim as a whole integrates the judicial exception into a practical application. See MPEP 2106.04(d)(2). (Step 2A, Prong Two: YES). Therefore, the claim is not directed to a judicial exception. (Step 2A: NO). The claim is eligible.