DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claim 1 has been amended.
Claims 1-5 and 9-20 as presented October 14, 2025 are currently pending and considered below.
Claim Objections
Claim 9 is objected to because of the following informalities: Claim 9 depends on a cancelled claim (claim 8). Claim 8 was cancelled and the subject matter of claim 8 was amended into independent claim 1 in the most recent response/amendment by the Applicant. Appropriate correction is required. For the purposes of compact prosecution, claim 9 will be interpreted as depending on claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 and 9-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., an abstract idea) without significantly more.
Claims 1-5 and 9-20 recite a method of predicting bone fracture risk in a type 2 diabetes ("T2D") patient, which is within the statutory category of a process.
Step 2A - Prong One:
Regarding Prong One of Step 2A , the claim limitations are to be analyzed to determine whether, under their broadest reasonable interpretation, they "recite" a judicial exception or in other words whether a judicial exception is "set forth" or "described" in the claims. An "abstract idea" judicial exception is subject matter that falls within at least one of the following groupings: a) mathematical concepts, b) certain methods of organizing human activity, and/or c) mental processes. Representative independent claim 1 includes limitations that recite at least one abstract idea.
Specifically, independent claim 1 recites: A method of predicting bone fracture risk in a type 2 diabetes ("T2D") patient, comprising:
obtaining a measurement of a glycated hemoglobin ("HbA1c") value of a T2D patient; and
analyzing the HbA1c value of the T2D patient with a bone fracture rate prediction model to determine the T2D patient's risk of bone fracture for a future period;
wherein the bone fracture rate prediction model is created by:
obtaining a plurality of averaged HbA1c values for a plurality of T2D subjects over an observational period;
binning the plurality of averaged HbA1c values into two predetermined categories;
obtaining a plurality of total fracture incidences for the plurality of T2D subjects over a follow-up period;
performing linear regression model correlations between the binned HbA1c values and the plurality of total fracture incidences by first using a univariate Kaplan-Meier survival estimation model and then using a multivariate Cox proportional hazards model to determine the bone fracture rate prediction model.
The following limitations constitute concepts performed in the human mind and mathematical concepts. That is, other than reciting steps as performed by the generic computer components, nothing in the claim elements precludes the steps from practically being performed in the mind. The claim encompasses a mental process of obtaining a measurement of an HbA1c value, obtaining a plurality of averaged HbA1c values and obtaining a plurality of total fracture incidences. The identified abstract idea, as drafted, is a process that, under its broadest reasonable interpretation, covers performance of the limitation in the mind except for the recitation of generic computer components. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind except for the recitation of generic computer components, then it falls within the “Mental Processes” grouping of abstract ideas.
Additionally, the claim encompasses an abstract idea that falls under the mathematical concepts grouping because analyzing the HbA1c value of the T2D patient with a bone fracture rate prediction model, binning the plurality of averaged HbA1c values and performing linear regression model correlations by first using a univariate Kaplan-Meier survival estimation model and then using a multivariate Cox proportional hazards model, under its broadest reasonable interpretation, represents mathematical calculations, formulas or equations and relationships (see MPEP 2106.04(a)(2)). Any limitations not identified above as part of the limitation in the mind or mathematical concepts, are deemed “additional elements” and will be discussed further in detail below.
Additionally, dependent claims 2-5 and 9-20 further narrow the abstract idea described in the independent claims. Claims 2-5 describe the predetermined categories of HbA1c values. Claim 9 describes the multivariate model. Claims 10-13 describe the durations for the observational or future periods. Claims 14-20 describe modification of the predicted risk based on the patient’s medications. These limitations only serve to further limit the abstract idea and hence, are directed toward fundamentally the same abstract ideas as independent claims 1.
Step 2A - Prong Two:
Regarding Prong Two of Step 2A, it must be determined whether the claim as a whole integrates the abstract idea into a practical application. As such, it must be determined whether any additional elements in the claim beyond the abstract idea integrate the exception into a practical application in a manner that imposes a meaningful limit on the judicial exception. The courts have indicated that additional elements merely using a computer to implement an abstract idea, adding insignificant extra solution activity, or generally linking use of a judicial exception to a particular technological environment or field of use do not integrate a judicial exception into a "practical application."
In the present case, claims 1-5 and 9-20 as a whole do not integrate the abstract idea into a practical application because they do not impose meaningful limits on practicing the abstract idea. Claims 1-5 and 9-20 do not recite any additional elements.
Step 2B
Regarding Step 2B, representative independent claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception for the same reasons to those discussed above with respect to determining that the claim does not integrate the abstract idea into a practical application.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, claims 1-5 and 9-20 do not recite any additional elements
Therefore, claims 1-5 and 9-20 are rejected under 35 USC §101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-5 and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Conway ("Glycemic control and fracture risk in elderly patients with diabetes", Diabetes Research and Clinical Practice, 2016.) in further view of Martinez-Laguna ("Fracture Risk In Type 2 Diabetic Patients: A Clinical Prediction Tool Based On A Large Population-Based Cohort", PLoS One, 2018).
Regarding claim 1, Conway teaches: A method of predicting bone fracture risk in a type 2 diabetes ("T2D") patient, comprising:
obtaining a measurement of a glycated hemoglobin ("HbA1c") value […]; and (“Baseline was defined as age at first HbA1c”, e.g. see abstract; “The study population was in good glycemic control, with a mean baseline HbA1c of 7.3%”, e.g. see pg. 49 para. 4)
analyzing the HbA1c value of the […] patient with a bone fracture rate prediction model to determine the […] patient's risk of bone fracture for a future period; (“We tested the association of baseline…with fracture risk.”, e.g. see pg. 49 para. 2; “Compared to those with a baseline HbA1c between 7 and 7.9%, those with a higher HbA1c were at an increased fracture risk (HbA1c 8–8.9% HR = 1.35…)” (calculating the risk (HR) for the follow-up period), e.g. see pg. 49 para. 6)
wherein the bone fracture rate prediction model is created by: obtaining a plurality of averaged HbA1c values for a plurality of […] subjects over an observational period; (“This study prospectively followed a cohort of 10,572 patients” (creating the model using retrospective/observational data), e.g. see pg. 48 para. 5; “Updated mean HbA1c values was defined as the average of all HbA1c values from baseline until the first fracture or censoring”; 10,572 patients with diabetes with at least two HbA1c values during the study time period, e.g. see pg. 48 paras. 1-2)
binning the plurality of averaged HbA1c values into two predetermined categories; (HbA1c was modeled in groups defined by HbA1c levels: < 6.5%, 6.5–6.9%, 7–7.9%, 8–8.9%, ≥ 9%, e.g. see pg. 49 para. 2)
obtaining a plurality of total fracture incidences for the plurality of […] subjects over a follow-up period; (during an average of 3.3 years follow-up, there were 949 first fracture events, e.g. see pg. 49 para. 6)
performing linear regression model correlations between the binned HbA1c values and the plurality of total fracture incidences by first using a univariate Kaplan-Meier survival estimation model and then using a multivariate Cox proportional hazards model to determine the bone fracture rate prediction model. (“Kaplan–Meier curves depicting risk of fracture by updated mean HbA1c category…are depicted in Fig. 2.” (i.e. first using a univariate Kaplan-Meier survival estimation model), e.g. see pg. 49 para. 7, Fig. 2; Cox proportional hazards modeling was used to determine hazards ratios (HRs) to find correlations between HbA1c data and fracture outcomes, e.g. see pg. 49 para. 2; “Table 2 shows the multivariable adjusted association between updated mean HbA1c and fracture risk. Model 1 shows analyses accounting for age, sex, and race.” (i.e. then using a multivariate Cox proportional hazards model), e.g. see pg. 49 para. 8, Table 2)
Although Conway does not distinguish between type 1 and type 2 diabetes in their study, Conway acknowledges “the percentage of this diabetic population with type 1 diabetes would likely have been minuscule and thus with minimal effect on our results” (pg. 51, para. 4). However, another prior art reference has been cited for purposes of compact prosecution.
Conway does not teach:
a measurement of a glycated hemoglobin ("HbA1c") value of a T2D patient;
analyzing the HbA1c value of the T2D patient to determine the T2D patient's risk of bone fracture for a future period;
a plurality of T2D subjects
However, Martinez-Laguna in the analogous art teaches:
a measurement of a glycated hemoglobin ("HbA1c") value of a T2D patient; (potential predictors included in the model include HbA1c, e.g. see pg. 3 para. 7)
analyzing the HbA1c value of the T2D patient to determine the T2D patient's risk of bone fracture for a future period; (“This model could be useful to clinicians as well as researchers to estimate an individual's profile for 5-year risk of developing a hip or major fracture. The web-based calculator would make it easy for physicians to apply our predictive model. The prediction could then be used to identify subjects at high or low risk of fracture so they can be assessed to manage and reduce their risk.”, e.g. see pg. 5 para. 6)
a plurality of T2D subjects (a cohort of newly diagnosed T2DM patients, e.g. see pg. 1, abstract)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include a measurement of a glycated hemoglobin ("HbA1c") value of a T2D patient, analyzing the HbA1c value of the T2D patient to determine the T2D patient's risk of bone fracture for a future period and a plurality of T2D subjects as taught by Martinez-Laguna, for the purposes of developing a predictive tool for clinical use on individual patients (Martinez-Laguna, pg. 5 para. 6).
Regarding claim 2, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway further teaches:
wherein the two predetermined categories comprise a by every 1% change in HbA1c value category and a by binary change in HbA1c value category (HbA1c was modeled in groups defined by HbA1c levels: < 6.5%, 6.5–6.9%, 7–7.9%, 8–8.9%, ≥ 9%, e.g. see pg. 49 para. 2; pg. 48 paras. 3-4 discuss tight and poor glycemic control and various thresholds for target Hb1Ac (Conway teaches binning Hb1ac data into clinically relevant categories. The selection of specific binning strategies, e.g. using 1% increments or a binary change, is a matter of design choice. A person of ordinary skill in the art would find it obvious to test various standard clinical thresholds to determine the most effective way to categorize the data. See MPEP 21044.05.))
Regarding claim 3, Conway and Martinez-Laguna teach the method of claim 2 as described above.
Conway further teaches:
wherein the by every 1% change in HbA1c value category comprises a 6% to 7% change bin, a 7% to 8% change bin, an 8% to 9% change bin, a 9% to 10% change bin, a 10% to 11% change bin, an 11% to 12% change bin, and a greater than or equal to 12% change bin (HbA1c was modeled in groups defined by HbA1c levels: < 6.5%, 6.5–6.9%, 7–7.9%, 8–8.9%, ≥ 9%, e.g. see pg. 49 para. 2 (Conway teaches binning Hb1ac data into clinically relevant categories. The selection of specific binning strategies, e.g. using 1% increments, is a matter of design choice. A person of ordinary skill in the art would find it obvious to test various standard clinical thresholds to determine the most effective way to categorize the data. See MPEP 21044.05.))
Regarding claim 4, Conway and Martinez-Laguna teach the method of claim 2 as described above.
Conway further teaches:
wherein the by binary change in HbA1c value category comprises an adequate glycemic control bin and a poor glycemic control bin (HbA1c was modeled in groups defined by HbA1c levels, e.g. see pg. 49 para. 2; pg. 48 paras. 3-4 discuss tight and poor glycemic control and various thresholds for target Hb1Ac; (Conway teaches binning Hb1ac data into clinically relevant categories. The selection of specific binning strategies, e.g. a binary change, is a matter of design choice. A person of ordinary skill in the art would find it obvious to test various standard clinical thresholds to determine the most effective way to categorize the data. See MPEP 21044.05.))
Regarding claim 5, Conway and Martinez-Laguna teach the method of claim 4 as described above.
Conway further teaches:
wherein the adequate glycemic control bin comprises an HbA1c value in the range of 6% to 9% and the poor glycemic control bin comprises an HbA1c value greater than or equal to 9% (HbA1c was modeled in groups defined by HbA1c levels including a top bin of ≥ 9% (It would be obvious to label this category as “poor glycemic control” and the combined lower categories as “adequate glycemic control”.), e.g. see pg. 49 para. 2; (Conway teaches binning Hb1ac data into clinically relevant categories. The selection of specific binning strategies, e.g. a binary change, is a matter of design choice. A person of ordinary skill in the art would find it obvious to test various standard clinical thresholds to determine the most effective way to categorize the data. See MPEP 21044.05.))
Regarding claim 10, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway further teaches:
wherein […] the follow-up period is in the range of one year to three years (an average of 3.3 years follow-up, e.g. see pg. 49 para. 6 (Conway teaches a follow-up period. The specific duration of a follow-up period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
Conway does not teach:
the observational period is in the range of one year to three years
However, Martinez-Laguna in the analogous art teaches:
the observational period is in the range of one year to three years (for variables like HbA1c, only results codes within 5 years before the index date were used (i.e. observational period), e.g. see pg. 3 para. 7, pg. 4 para. 2; Included participants were followed up from the time of T2DM diagnosis until the earliest of transfer out/migration, fracture, death, or end of study (i.e. follow-up period), with a median follow-up of 3.2 years for major fracture, e.g. see pg. 3 para. 4, pg. 5 para. 5; (Martinez-Laguna teaches an observational period. The specific duration of an observational period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include the observational period as taught by Martinez-Laguna, for the purposes of identifying relationships between the patient’s baseline characteristics and a future outcome (Martinez-Laguna, pg. 5 para. 4).
Regarding claim 11, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway further teaches:
wherein […] the follow-up period is two years (an average of 3.3 years follow-up, e.g. see pg. 49 para. 6 (Conway teaches a follow-up period. The specific duration of a follow-up period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
Conway does not teach:
the observational period is two years
However, Martinez-Laguna in the analogous art teaches:
the observational period is two years (for variables like HbA1c, only results codes within 5 years before the index date were used (i.e. observational period), e.g. see pg. 3 para. 7, pg. 4 para. 2; Included participants were followed up from the time of T2DM diagnosis until the earliest of transfer out/migration, fracture, death, or end of study (i.e. follow-up period), with a median follow-up of 3.2 years for major fracture, e.g. see pg. 3 para. 4, pg. 5 para. 5; (Martinez-Laguna teaches an observational period. The specific duration of an observational period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include the observational period as taught by Martinez-Laguna, for the purposes of identifying relationships between the patient’s baseline characteristics and a future outcome (Martinez-Laguna, pg. 5 para. 4).
Regarding claim 12, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway does not teach:
wherein the future period is in the range of one year to three years
However, Martinez-Laguna in the analogous art teaches:
wherein the future period is in the range of one year to three years (a clinical prediction tool for the estimation of 5-year hip and major fracture risk in T2DM patients, e.g. see pg. 1, abstract); (Martinez-Laguna teaches a future period. The specific duration of a future period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include the future period as taught by Martinez-Laguna, for the purposes of creating a useful predictive tool (Martinez-Laguna, pg. 5 para. 6).
Regarding claim 13, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway does not teach:
wherein the future period is two years
However, Martinez-Laguna in the analogous art teaches:
wherein the future period is two years (a clinical prediction tool for the estimation of 5-year hip and major fracture risk in T2DM patients, e.g. see pg. 1, abstract); (Martinez-Laguna teaches a future period. The specific duration of a future period is a matter of design choice, and a person of ordinary skill in the art would find it obvious to select an optimum timeframe. See MPEP 21044.05.))
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include the future period as taught by Martinez-Laguna, for the purposes of creating a useful predictive tool (Martinez-Laguna, pg. 5 para. 6).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Conway and Martinez-Laguna in further view of Dufour ("Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study", Diabetes Care, 2021).
Regarding claim 9, Conway and Martinez-Laguna teach the method of claim 8 as described above.
Conway further teaches:
wherein the multivariate model comprises the variables of age, gender (multivariable models included age, sex and race, e.g. see pg. 49 paras. 2-3, pg. 47 abstract)
Conway does not teach:
the multivariate model comprises the variables of comorbidities, glucocorticoids use, previous fragility fractures during the observational period
However, Martinez-Laguna in the analogous art teaches:
the multivariate model comprises the variables of comorbidities, glucocorticoids use, previous fragility fractures during the observational period (potential predictors included in the model include age, sex, use of oral corticosteroids, comorbidities, previous major fractures, e.g. see pg. 3 para. 7; pg. 14 para. 1)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway to include the multivariate model comprises the variables of comorbidities, glucocorticoids use, previous fragility fractures during the observational period as taught by Martinez-Laguna, for the purposes of more accurately identifying T2DM patients at high risk of fracture (Martinez-Laguna, pg. 7 para. 1).
Conway and Martinez-Laguna do not teach:
the multivariate model comprises the variable of prevalent T2D
However, Dufour in the analogous art teaches:
the multivariate model comprises the variable of prevalent T2D (Type 2 diabetes duration in years as a variable in multivariable Cox regression models, e.g. see Table 3, pg. 1549 cols. 2-3)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway and Martinez-Laguna to include the multivariate model comprises the variable of prevalent T2D as taught by Dufour, for the purposes of identifying characteristics contributing to fractures in T2D (Dufour, pg. 1548 col. 1).
Claims 14, 15, 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Conway and Martinez-Laguna in further view of Lee ("Glycemic Control and Insulin Treatment Alter Fracture Risk in Older Men With Type 2 Diabetes Mellitus", J Bone Miner Res., 2019).
Regarding claim 14, Conway and Martinez-Laguna teach the method of claim 1 as described above.
Conway and Martinez-Laguna teach obtaining variables of the T2D patient and analyzing the variables using the prediction model to determine the risk of bone fracture for the T2D patient as described above.
Conway and Martinez-Laguna do not teach:
obtaining diabetic treatment medication information; and adjusting the risk of bone fracture based on the diabetic treatment medication information
However, Lee in the analogous art teaches:
obtaining diabetic treatment medication information; and adjusting the risk of bone fracture based on the diabetic treatment medication information (determine the relative association and possible interactions between HbA1c and diabetes treatment regimen on fracture risk, e.g. see pg. 3 para. 2)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway and Martinez-Laguna to include obtaining diabetic treatment medication information and adjusting the risk of bone fracture based on the diabetic treatment medication information as taught by Lee, for the purposes of identifying the effects of medication on fracture risk (Lee, pg. 2 para. 2).
Regarding claim 15, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway and Martinez-Laguna do not teach:
wherein the diabetic treatment medication information comprises metformin and the T2D patient's risk of bone fracture is decreased by about 12% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is decreased by about 12% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Lee has been cited to teach this limitation.
However, Lee in the analogous art teaches:
wherein the diabetic treatment medication information comprises metformin and the T2D patient's risk of bone fracture is decreased by about 12% from an initial value (Metformin use was associated with decreased fracture risk (HR 0.88, 95% CI: 0.87–0.90) (a Hazards Ratio of 0.88 corresponds to 12% risk reduction), e.g. see pg. 2 abstract)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway and Martinez-Laguna to include the diabetic treatment medication information comprises metformin and the T2D patient's risk of bone fracture is decreased by about 12% from an initial value as taught by Lee, for the purposes of identifying the true effect of Metformin on fracture risk (Lee, pg. 6 para. 2).
Regarding claim 18, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway and Martinez-Laguna do not teach:
wherein the diabetic treatment medication information comprises thiazolidinediones ("TZDs") and the T2D patient's risk of bone fracture is increased by about 20% to about 23% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is increased by about 20% to about 23% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Lee has been cited to teach this limitation.
However, Lee in the analogous art teaches:
wherein the diabetic treatment medication information comprises thiazolidinediones ("TZDs") and the T2D patient's risk of bone fracture is increased by about 20% to about 23% from an initial value (use of thiazolidinediones was significantly associated with any clinical fracture (HR 1.16; 95% CI: 1.13 – 1.19) (a Hazards Ratio of 1.16 corresponds to 16% increase in fracture risk, which is similar to 20-23%), e.g. see pg. 5 para. 3)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway and Martinez-Laguna to include the diabetic treatment medication information comprises thiazolidinediones and the T2D patient's risk of bone fracture is increased by about 20% to about 23% from an initial value as taught by Lee, for the purposes of identifying the effects of thiazolidinediones use on fracture risk (Lee, pg. 2 para. 2).
Regarding claim 19, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway and Martinez-Laguna do not teach:
wherein the diabetic treatment medication information comprises insulin and the T2D patient's risk of bone fracture is increased by about 24% to about 26% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is increased by about 24% to about 26% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Lee has been cited to teach this limitation.
However, Lee in the analogous art teaches:
wherein the diabetic treatment medication information comprises insulin and the T2D patient's risk of bone fracture is increased by about 24% to about 26% from an initial value (use of insulin was associated with increased risk of any clinical fracture (HR 1.10, 95% CI: 1.07–1.12), (a Hazards Ratio of 1.10 corresponds to 10% increase in fracture risk and while the claimed magnitude is different, the underlying principle is taught by Lee), e.g. see pg. 5 para. 3)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway and Martinez-Laguna to include the diabetic treatment medication information comprises insulin and the T2D patient's risk of bone fracture is increased by about 24% to about 26% from an initial value as taught by Lee, for the purposes of isolating the effect of insulin from other compounding factors (Lee, pg. 2 para. 2 – pg. 3 para. 1).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Conway, Martinez-Laguna and Lee in further view of Hou ("Dipeptidyl Peptidase-4 Inhibitor Use Is Associated With Decreased Risk Of Fracture In Patients With Type 2 Diabetes: A Population-Based Cohort Study", Br J Clin Pharmacol, 2018).
Regarding claim 16, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway, Martinez-Laguna and Lee do not teach:
wherein the diabetic treatment medication information comprises dipeptidyl peptidase-4 ("DDP4") inhibitors and the T2D patient's risk of bone fracture is decreased by about 7% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is decreased by about 7% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Hou has been cited to teach this limitation.
However, Hou in the analogous art teaches:
wherein the diabetic treatment medication information comprises dipeptidyl peptidase-4 ("DDP4") inhibitors and the T2D patient's risk of bone fracture is decreased by about 7% from an initial value (The Cox proportional hazard model revealed that DPP-4i use significantly reduced the risk of all-cause fractures with adjusted HRs of 0.86 (95% CI: 0.74–0.99) (a Hazards Ratio of 0.86 corresponds to 14% risk reduction, which is similar to 7%), e.g. see pg. 2029 results)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway, Martinez-Laguna and Lee to include the diabetic treatment medication information comprises dipeptidyl peptidase-4 ("DDP4") inhibitors and the T2D patient's risk of bone fracture is decreased by about 7% from an initial value as taught by Hou, for the purposes of resolving the contradictory evidence and a lack of information concerning the incidence rates of fractures after long-term DPP-4i use (Hou, pg. 2030 para. 4).
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Conway, Martinez-Laguna and Lee in further view of Zhang ("Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis", Front Endocrinol, 2021).
Regarding claim 17, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway, Martinez-Laguna and Lee do not teach:
wherein the diabetic treatment medication information comprises meglitinides and the T2D patient's risk of bone fracture is increased by about 12% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is increased by about 12% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Zhang has been cited to teach this limitation.
However, Zhang in the analogous art teaches:
wherein the diabetic treatment medication information comprises meglitinides and the T2D patient's risk of bone fracture is increased by about 12% from an initial value (analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus patients, e.g. see pg. 1 purpose; nateglinide (i.e. a meglitinide) (RR 1.35; 0.24–7.55) raised the risk of fracture (a Risk Ratio of 1.35 corresponds to 35% increase in fracture risk, and while the claimed magnitude is different, the underlying principle is taught by Zhang), e.g. see pg. 5 para. 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway, Martinez-Laguna and Lee to include the diabetic treatment medication information comprises meglitinides and the T2D patient's risk of bone fracture is increased by about 12% from an initial value as taught by Zhang, for the purposes of resolving contradictory data on the effects of anti-diabetic drugs on fracture risk (Zhang, pg. 1 purpose).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Conway, Martinez-Laguna and Lee in further view of Fraser ("Fractures are increased and bisphosphonate use decreased in individuals with insulin-dependent diabetes: a 10 year cohort study", BMC Musculoskelet Disord, 2014).
Regarding claim 20, Conway, Martinez-Laguna and Lee teach the method of claim 14 as described above.
Conway, Martinez-Laguna and Lee do not teach:
wherein the diabetic treatment medication information comprises bisphosphonates and the T2D patient's risk of bone fracture is increased by about 15% from an initial value
The claim limitation of “the T2D patient's risk of bone fracture is increased by about 15% from an initial value” is interpreted as being an intended result. Applicant is remined that, typically, no patentable distinction is made by an intended result unless some structural difference is imposed by the use or result on the structure or material recited in the claim, or some manipulative difference is imposed by the use or result on the action recited in the claim. An intended result is a description of what necessarily happens as a result of the structure or actions recited in the claims (See MPEP 2111.05). For the purposes of compact prosecution, reference Fraser has been cited to teach this limitation.
However, Fraser in the analogous art teaches:
wherein the diabetic treatment medication information comprises bisphosphonates and the T2D patient's risk of bone fracture is increased by about 15% from an initial value (assessed the association between diabetes status and incident non-traumatic fracture and identified factors associated with bisphosphonate use, e.g. see pg. 1 abstract; variables associated with an increased fracture include bisphosphonate use, with a Hazard Ratio of 1.56 (a Hazards Ratio of 1.56 corresponds to a 56% increase in fracture risk and while the claimed magnitude is different, the underlying principle is taught by Fraser), e.g. see pg. 3 para. 3, Table 3)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Conway, Martinez-Laguna and Lee to include the diabetic treatment medication information comprises bisphosphonates and the T2D patient's risk of bone fracture is increased by about 15% from an initial value as taught by Fraser, for the purposes of controlling for the known confounding variable of bisphosphonate use (Fraser, pg. 3 para. 1).
Response to Arguments
Regarding the rejection under 35 U.S.C. § 101 of Claims 1-5 and 9-20, the Examiner has considered the Applicant’s arguments; however the arguments are not persuasive.
Applicant argues the claims integrate the judicial exception into a practical application and provide an inventive concept.
The Examiner respectfully disagrees. The specific manner of creating the model using Kaplan Meir and Cox regression does not impose meaningful limits because reciting mathematical steps to derive a mathematical result does not transform the claim into eligible subject matter. It merely provides a more detailed description of the abstract idea itself. In addition, Applicant conflates subject matter eligibility with novelty with the assertion that the prediction model represents an inventive concept. “As made clear by the courts, the ‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1315, 120 USPQ2d 1353, 1358 (Fed. Cir. 2016) (quoting Diamond v. Diehr, 450 U.S. at 188–89, 209 USPQ at 9)” (MPEP 2106.05).
Regarding the rejection under 35 U.S.C. § 103 of Claims 1-5 and 9-20, the Examiner has considered the Applicant’s arguments; however the arguments are not persuasive.
Applicant argues the cited references do not disclose or suggest “first using a univariate Kaplan-Meier survival estimation model and then using a multivariate Cox proportional hazards model”.
The Examiner respectfully disagrees. Conway first presents the univariate Kaplan-Meier survival estimation to establish the unadjusted fracture risk probability for each HbA1c bin (Fig. 2, pg. 49 para. 7). Conway then presents the multivariate Cox proportional hazards analysis to determine the adjusted hazards ratios (pg. 49 para. 8, Table 2). Therefore, Conway teaches the sequential step of “first using a univariate Kaplan-Meier survival estimation model and then using a multivariate Cox proportional hazards model to determine the bone fracture rate prediction model” as claimed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aaisha Abdullah whose telephone number is (571)272-5668. The examiner can normally be reached on Monday through Friday 8:00 am - 5:00 pm.
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, Peter H Choi can be reached on (469) 295-9171. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.A./Examiner, Art Unit 3686
/PETER H CHOI/Supervisory Patent Examiner, Art Unit 3681