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 .
Claim Status
Claims 1-8, 10-20, and 22-26 are pending and under examination.
Claims 1-8, 10-20, and 22-26 are rejected.
Claims 19 is objected to.
Claims 1, 13-15, and 25-26 are independent.
No claims are allowed, new, or withdrawn.
Office Action Outline
Rejections applied
Abbreviations
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
x
102, 103
JE
Judicial Exception
x
101 JE(s)
112/a
35 USC 112(a) and similarly for 112/b, etc.
101 Other
N:N
page:line
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed in the 06/08/2022 filing receipt, this application is a 371 of PCT/US2020/047173 filed 08/20/2020, which claims benefit of Provisional Application 62/889,116 filed 08/20/2019. At this point in examination, all claims have been interpreted as being accorded the priority date of 08/20/2019.
Overview of Withdrawal/Revision of Objections/Rejections
In view of the amendment and remarks received 06/01/2026:
• The objection to the Specification is withdrawn.
• The 112(b) rejections are withdrawn.
• The 101 rejection is maintained with revision to reflect the 06/01/2026 amendment.
• The 103 rejection in the 12/04/2025 Office action is withdrawn. A new 103 rejection, necessitated by amendment, is applied below.
Claim Objections
Claim 19 is objected to because of the following informalities: Claim 19 appears to be missing a digit when reciting "The method of claim 1," which, if it is Applicant’s intention, should be corrected to "The method of claim 15." Appropriate correction is required.
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 1-8, 10-20, and 22-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 details the following framework to analyze Subject Matter Eligibility:
• Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? (see MPEP § 2106.03)
• Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. an abstract idea, a law of nature, or a natural phenomenon? (see MPEP §§ 2106.04(a), 2106.04(a)(2), and 2106.04(b))
• Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application? (see MPEP § 2106.04(d))
• Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? (see MPEP § 2106.05)
Step 1:
Claims 1-8, 10-12, 15-20, and 22-24 are directed to 101 processes, here methods. Claims 13 and 25 are directed to 101 machines, here systems. Claims 14 and 26 are directed to 101 machines, here non-transitory computer-readable media (CRM). As such, claims 1-8, 10-20, and 22-26 are directed to related method , system , and CRM, which fall under categories of statutory subject matter. (See MPEP § 2106.03). (Step 1: Yes.)
Step 2A, Prong One:
The claims recite judicial exceptions of abstract ideas of mathematical concepts and mental processes as follows:
• Calculating parameter(s) (recited in claims 1, 13, -15, 25, and 26).
• Determining an RBC age distribution and a mean RBC age (recited in claim 1,13-14, and 25-26).
• Determining an RBC age distribution (recited in claim 15).
• Determining a pathophysiological state based on the RBC age distribution (recited in claims 1 and 13-14).
• Determining an RBC clearance rate or production rate (recited in claim 2).
• Determining a rate of change in white blood cell count, a rate of change in platelet count, a rate of blood loss, or a rate of bone marrow cellular output (recited in claim 3).
• Determining information indicative of a degree of morbidity (recited in claim 4).
• Claims 5, 6, 17, and 18 further limit the parameters of claims 1 or 15.
• Calculating a probability density (recited in claims 7 and 19).
• The expression for the probability density as a function of time in claims 8 and 20.
• Determining a HbA1c level indicative of diabetes or prediabetes by adjusting a nominal HbA1c level based on the RBC age distribution (recited in claim 10, 11, 22, and 23).
To summarize, the claims recite judicial exceptions in abstract ideas, characterized as mathematical concepts and mental processes. Considering the broadest reasonable interpretation (BRI) of the claims, the mental processes recited in independent claim 1 (e.g., calculating parameters, determining a pathophysiological state, determining rates of change, calculating probability densities, etc.) are directed to processes that may be performed in the human mind, or with pen and paper, because there are no particular limitations recited in the claims which would prevent performance in the human mind or with pen and paper. Additionally, the claims recite mathematical concepts; explicitly in the calculating recitations, as well as implicitly in the determining of states, rates, or levels; the mathematical concepts are disclosed in the Specification [3:10-19], [13:22-15:7], [17:3-19:16], etc. Such analysis performed mentally, or with paper and pencil, may take considerable time and effort, and although a general-purpose computer can perform these calculations at a rate and accuracy that can far exceed the mental performance of a skilled artisan, the nature of the activity is essentially the same, and therefore constitutes an abstract idea.
Therefore, claims 1-26 recite elements that constitute a judicial exception in the form of abstract ideas. (Step 2A, Prong One: Yes.)'
Step 2A, Prong Two:
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). Here at Step 2A, Prong Two, any remaining steps and/or elements not identified as JEs are therefore in addition to the identified JE(s) and are considered additional elements. Because the claims have been interpreted as being directed to judicial exceptions (abstract ideas in this instance) then Step 2A, Prong Two provides that the claims be examined further to determine whether the judicial exception is integrated into a practical application [see MPEP § 2106.04(d)]. A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
MPEP § 2106.04(d)(I) lists the following five example considerations for evaluating whether a judicial exception is integrated into a practical application:
(1) 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).
(2) 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).
(3) 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).
(4) Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c).
(5) 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).
The claims recite additional elements as follows:
Additional elements of data gathering: Claims 1, 10, 11, 13-15, 22-23, 25, and 26 recite the additional element of "receiving data." Data gathering steps are additional elements which perform functions of inputting, collecting, and outputting the data needed to carry out the abstract idea. These steps are considered insignificant extra-solution activity and are not sufficient to integrate an abstract idea into a practical application as they do not impose any meaningful limitation on the abstract idea or how it is performed, nor do they provide an improvement to technology [see MPEP § 2106.04(d)(I)].
Additional element of therapy: Claims 10, 11, 22, and 23 recite "administering or adjusting treatment for diabetes or prediabetes"; claims 12 and 24 recite "administering a dose of iron supplementation"; claim 15 recites " administering treatment to the subject for a morbidity." The claims do not yet recite a particular therapy as the claims lack a level of specificity for the treatment (claims 10, 11, 22, and 23), for the disease (claims 12 and 24), and for both treatment and disease (claim 15). As such, the treatment limitations in claims 10-12, 15, and 22-24 are not elevated to a particular treatment, and therefore are insufficient to integrate the abstract ideas into a practical application (see MPEP § 2106.04(d)(2)).
Note, regarding the therapy steps of "method" claims 10, 12, 15, 22, and 24, when a physical step such as "administering..." or "adjusting..." is recited as contingent, then it is only interpreted as an additional element for embodiments in which the contingency is true and the step actually is required. This interpretation applies to process claims. Machine or manufacture claims requiring equivalent process instructions, on the other hand, still require the result of the contingency be provided for in the structure of the claim, e.g. in instructions, regardless of the eventual evaluation of the contingency.
Additional elements of computer components: Claims 13, 14, 25, and 26 recite the additional elements of "processor(s)," "memory," and/or "non-transitory computer-readable storage medium (CRM)." The claims require only generic computer components, which do not improve computer technology, and do not integrate the recited judicial exception into a practical application (see MPEP § 2106.04(d)(1) and MPEP § 2106.05(f)).
Step 2A Prong Two summary: Claims 1-26 have been further analyzed with respect to Step 2A, Prong Two, and no additional elements have been found, alone or in combination, that would integrate the judicial exception into a practical application. (Step 2A, Prong Two: No).
Step 2B analysis:
Because the additional claim elements do not integrate the judicial exception of abstract ideas into a practical application, claims 1-26 are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept. An inventive concept is furnished by an element or combination of elements that is recited in the claim in addition to the judicial exception, and is sufficient to ensure that the claim, as a whole, amounts to significantly more than the judicial exception itself (see MPEP § 2106.05).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are well-understood, routine, and conventional. Those additional elements are as follows:
Additional elements of data gathering, inputting, and outputting steps: The additional elements of receiving data (claims 1, 10, 11, 13-15, 22-23, 25, and 26), do not cause the claims to rise to the level of significantly more than the judicial exception. The courts have recognized receiving or transmitting data over a network; storing and retrieving information in memory; determining the level of a biomarker in blood by any means; [see MPEP§2106.05(d)(II)], as well-understood, routine, conventional activity when they are claimed in a merely generic manner (e.g., at a high level of generality) or as extra-solution activity. Therefore, the additional elements of data gathering are routine, well-understood, and conventional, and do not provide an inventive concept needed to amount to significantly more than the judicial exception.
Additional elements of treatment: Claims 10, 11, 22, and 23 recite "administering or adjusting treatment for diabetes or prediabetes"; claims 12 and 24 recite "administering a dose of iron supplementation"; claim 15 recites " administering treatment to the subject for a morbidity." These additional elements are shown to be well-known, routine, and conventional in the art as follows:
Chaudhury, (Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Frontiers in endocrinology, vol. 8:6, pages 1-12; cited on the attached PTO-892), discusses the pharmacologic management of Type 2 Diabetes (T2D) (p.3-10, and throughout document); HbA1C level in diagnosing, monitoring, adjusting management of T2D (p.2-3; p.4, col.1).
Wang, (Iron deficiency and other types of anemia in infants and children. American family physician, vol. 93(4), pages 270-278 (2016); cited on the attached PTO-892), discusses iron supplementation and differential diagnosis of anemia (p.272-274 , text; p.273, tables 3&4.)
Additional elements of computer components: The additional elements of processor(s), memory, and/or non-transitory CRM of claims 13, 14, 25, and 26, do not cause the claims to rise to the level of significantly more than the judicial exception; these are conventional computer components and as such do not provide an inventive concept.
Further regarding the conventionality of additional elements, the MPEP at 2106.05(b) and 2106.05(d) presents several points relevant to conventional computers and data gathering steps in regard to Step 2A Prong 2 and Step 2B, including:
• A general purpose computer that applies a judicial exception, such as an abstract idea, by use of conventional computer functions, does not qualify as a particular machine (see 2106.05(b)(I)), as in the case of claim 13, 14, 25, and 26, which are interpreted to recite conventional computer components.
• Integral use of a machine to achieve performance of a method may integrate the recited judicial exception into a practical application or provide significantly more, in contrast to where the machine is merely an object on which the method operates, which does not integrate the exception into a practical application or provide significantly more (see 2106.05(b)(II). In instant claims 13, 14, 25, and 26, the recited processors, memory, and CRM are used in receiving and calculating, etc.; as such, they act only as tools to perform the steps of calculating, and do not integrate the judicial exception into a practical application or provide significantly more.
• Use of a machine that contributes only nominally or insignificantly to the execution of the claimed method (e.g., in a data gathering step or in a field-of-use limitation) would not integrate a judicial exception or provide significantly more (see 2106.05(b)(III). The processors, memory, and CRM of claim 13, 14, 25, and 26 used in receiving and calculating do not impose meaningful limitations on the claims.
• The courts have recognized "receiving or transmitting data over a network," "performing repetitive calculations," and "storing and retrieving information in memory," as well-understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)(II)). The receiving of data in claims 1, 10, 11, 13-15, 22-23, 25, and 26 is recited in a generic manner.
All limitations of claims 1-26 have been analyzed with respect to Step 2B, and none provides a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception, and thus do not transform the judicial exception into a patent eligible application of the exceptions. Step2B: NO. Therefore, claims 1-26, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter.
Response to Applicant Arguments - 35 USC § 101
Applicant's arguments filed 06/01/2026 have been fully considered but they are not yet persuasive.
Applicant asserts (remarks, p.11-13) (bold emphasis added):
• ..."the claims, as amended, "integrate [a] judicial exception into a practical application"... (p.11, ¶ 5).
• "the claims are not directed to merely this alleged judicial exception...The claim recitations represent a technological improvement to models of RBC population dynamics." (p.12, ¶ 4).
• "Modeling the RBC population in this way has several advantages, including: (1) the (v, h) space is densely sampled during each routine CBC, (2)
b(v, h, t) can be directly sampled with each CBC, (3) physiologic knowledge of
the dynamics of (v, h) can guide the functional form of dP/dt ... (4) P(v, h, t) and b(v, h, t) can be repeatedly sampled more frequently"... (p.12, ¶ 5).
• ..." the claims are not directed to merely this concept. Instead, the
claims are directed to a specific technological improvement"... (p.13, ¶ 1).
The arguments are not yet persuasive specifically because regarding the first consideration for improvement to technology or a technical field at MPEP 2106.04(d)(1), as the specific technological improvement is not clear in the remarks. Additionally, when considering the arguments concerning "Modeling the RBC population in this way has several advantages"..., it is not clear that those advantages must result from the claims as recited for all embodiments. Further, the record, including the Specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field, and the claims do not yet clearly result in such an improvement.
Regarding showing an improvement to technology, a detailed explanation of a technical improvement may help to overcome a 101 rejection, (see MPEP 2106.04(d) and (d)(1), as well as MPEP 2106.05(a)). The explanation might include a concise statement of the improvement, including improvement over the previous state of the technology field; identification of the technology field; explanation of how the claims deliver the improvement and that reasonably all embodiments within the claim scope also will result in the asserted improvement, and extension of the explanation to persuasively demonstrate the nexus of integration of the judicial exceptions into a practical application. As further examples, argument may clearly and adequately explain cause and effect leading to improvement or, for example, when such cause and effect explanation is not possible, then may include evidence (e.g. experimental data) comparing a claimed result to conventional results. Also, arguments and evidence may be extrinsic to the original disclosure, including references available after the priority date, as long as it is clear that an argument applies to all embodiments of a properly supported claim. In the present invention, the nexus between the JEs and the improvement is vague, and the 06/01/2026 arguments do not persuasively explain the improvement.
Claim Rejections - 35 USC § 103
The rejection of claims 1-26 under U.S.C. 103 in the 12/04/2025 Office action as being unpatentable over Golub in view of Patel is withdrawn.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-8, 10-20, and 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Golub, (American journal of hematology, vol. 89(5), pages 459-466 (2014); cited on the 10/05/2022 IDS) in view of Malka (Science translational medicine, vol. 8(359):359ra130, pages 1-10 (2016) ; cited on the 10/05/2022 IDS)in view of Patel (American journal of hematology, vol. 90(5), pages 422-428 (2015); cited on the 10/05/2022 IDS).
Note: For clear and concise communication, portions of this new 103 rejection as compared to the withdrawn rejection (especially those involving the newly cited Malka reference) are underlined below.
Regarding the claim 1, 13-15, 25, and 26 steps for "receiving data" of a first and a second CBC, including RBC volume and hemoglobin and Golub teaches obtaining blood samples from rhesus macaque infants at birth, 4, 6, 12, and 22.5 months, and performing complete blood count (CBC) to obtain distributions of single-RBC and single reticulocyte volume and hemoglobin concentration (p.460, col.1).
Regarding the claim 1, 13-15, 25, and 26 step for "calculating…parameters …based on volume and hemoglobin, the …parameters including …a rate of change in RBC clearance rate …or rate of change in RBC production rate," Golub teaches RBC population dynamics for monkeys and humans were modeled using single-cell measurements of RBC volume and hemoglobin concentration and a published mathematical model (p.460, col.1). Golub teaches "the model (eq. (1)) describes the volume and hemoglobin dynamics of a typical RBC (dv/dt, dh/dt) as a function (f) of its current volume and hemoglobin and accounting for fluctuations in these rates over time (n). The dynamics of the full RBC population dP/dt include production of reticulocytes (b) and clearance of senescent cells (c) (p.462, col.1.)
Regarding the claim 1, 13-15, 25, and 26 step for " a pathophysiological state"... , Golub, at p.463, cols.1-2, teaches finding "a significant difference in the RBC clearance threshold (vc) (in Fig. 2G, p.462.) The detailed mechanism for RBC clearance in general is not well understood and is unlikely to be determined by volume or hemoglobin content alone, but because the clearance signal is highly correlated with these quantities, comparisons are made of empirical clearance thresholds between the groups in terms of volume and hemoglobin content. … (the study) finds that RBCs in iron deficient (ID) animals continue to circulate at significantly lower volumes and hemoglobin contents than in iron sufficient (IS) animals, even after normalizing for the lower MCV and MCH in the ID cohort. In IS animals, most RBCs have been removed before their volume reaches 77% of the animal’s MCV, while in ID animals the clearance threshold is lower, and cells continue to mature and circulate beyond this point (p.463, cols.1-2.)
Regarding the claim 2 recitation for " determining… a RBC clearance rate, a RBC production rate, or a RBC age distribution," Golub teaches the dynamics of the full RBC population dP/dt include production of reticulocytes (b) and clearance of senescent cells (c); …Fig. 2A shows the schematic of RBC maturation and its parameterization by the model (p.462, col.1, and fig.2.)
Regarding the claim 3 recitation for determining a rate of change in white blood cell count, a rate of change in platelet count, a rate of blood loss, or a rate of bone marrow cellular output, Golub teaches reticulocytes (top right of panel A) are released from the bone marrow
into the circulation (p.462, fig. 2A.)
Regarding the claims 4 and 16 recitation of determining …information indicative of a degree of morbidity of the subject, including information indicative of presence of an infection, presence of malignancy, presence of anemia, and/or presence of diabetes, Golub shows in utero iron deficiency is associated with persistent delay in RBC clearance in 2-year-old rhesus monkeys (p.463, fig.3); the single-RBC volume and hemoglobin distributions for IS (panel A, fig. 3) and ID (panel B, fig. 3) animals.
Regarding the claims 5 and 17 recitation of parameters include a rate of RBC volume change and/or a variation of RBC volume change, the claims 6 and 18 recitation of parameters include a rate of RBC hemoglobin reduction and/or a variation of RBC hemoglobin reduction, and the claims 7 and 19 recitation of calculating parameters includes calculating a probability density of RBC volume, RBC hemoglobin content, and/or RBC age as a function of time, Golub teaches probability densities (fig.3) and single-RBC volume and hemoglobin distributions for an iron sufficient (IS) (panel A, fig. 3) and an iron deficient (ID) (panel B, fig. 3) animal (p.463, fig. 3.)
Regarding the claims 8 and 20 expression:" -∇·(Pf)+ ∇·(D∇P) + b(v, h) - d(v, h)," Golub teaches a similar model equation, "-∇·(Pf)+ ∇·(D∇P) + b(v, h) - d(v, h)·P," which describes the volume and hemoglobin dynamics of a typical RBC as a function of its current volume and hemoglobin, accounting for fluctuations in those rates over time (p.462, col.1-2.)
Regarding the claims 12 and 24 recitation of administering a dose of iron supplementation to the subject in response to a determination that the change in the RBC clearance rate does not meet a predefined threshold, Golub, at p.463, cols.1-2, teaches finding a significant difference in the RBC clearance threshold (i.e., between ID and IS animals) …comparisons can be made of empirical clearance thresholds between the groups (ID and IS) in terms of volume and hemoglobin content. … (the study) finds that RBCs in ID animals continue to circulate at significantly lower volumes and hemoglobin contents than they do in IS animals, even after normalizing for the lower MCV and MCH in the ID cohort (p.463, cols.1-2.) Additionally, Golub shows iron supplementation (p.460, col.1.)
Golub does not teach determining an RBC age distribution and a mean RBC age based on the one or more parameters of claim 1, 13-15, and 25-26 (taught by Malka and Patel).
Golub does not teach determining a pathophysiological state of the subject based on the RBC age distribution of claims 1, 13-14. (Taught by Malka.)
Golub does not teach administering (or indicating) treatment to the subject for a morbidity based on the RBC age distribution and in response to a determination that at least one of the one or more parameters does not meet a predefined threshold of claims 15, 25, and 26. (Taught by Patel and Malka.)
Golub does not teach HbA1c measurements and administering/ adjusting treatments for diabetes of claims 10, 11, 22, and 23 (taught by Patel).
Regarding claim 1, 13-15, and 25-26, the recited determining an RBC age distribution and a mean RBC age based on the one or more parameters reads on "We combined a mechanistic mathematical model of hemoglobin glycation and red blood cell kinetics with large sets of within-patient glucose measurements to derive patient-specific estimates of nonglycemic determinants of HbA1c, including mean red blood cell age. We found that between-patient variation in derived mean red blood cell age explains all glucose-independent variation in HbA1c" (Malka, p.1, abstract); and "The RBC ages are assumed to be uniformly distributed between 0 and 2 (Malka, p.6, col.2, ¶ 5).
Regarding claim 1 and 13-14, the recited determining a pathophysiological state of the subject based on the RBC age distribution reads on "The clinical HbA1c measurement is the average over a uniform distribution of RBC ages ranging between 0 and 2 ∙ MRBC days" (Malka, p.7, col.2, ¶ 1); and "The difference in AG (average concentration of blood glucose) between a nondiabetic (HbA1c < 6.5%) and a diabetic with suboptimal disease control (HbA1c > 7.0%) can be ~15 mg/dl (Malka, p.3, col.2, ¶ 3). Here, Malka shows the pathophysiological state of increased HbA1c percentage, as determined based on (in part) RBC age distribution.
Regarding claims 15 and 25-26, the recited administering (or indicating) treatment to the subject for a morbidity based on the RBC age distribution and in response to a determination that at least one of the one or more parameters does not meet a predefined threshold reads on "The clinical HbA1c measurement is the average over a uniform distribution of RBC ages ranging between 0 and 2 ∙ MRBC days" (Malka, p.7, col.2, ¶ 1); and "The difference in AG (average concentration of blood glucose) between a nondiabetic (HbA1c < 6.5%) and a diabetic with suboptimal disease control (HbA1c > 7.0%) can be ~15 mg/dl (Malka, p.3, col.2, ¶ 3). Here, Malka links the pathophysiological state of increased (over a threshold) HbA1c percentage, as determined based on (in part) RBC age distribution. It would be obvious to administer or adjust treatment based on the HbAlc level which was determined, in part, based on the RBC age distribution.
Also taught by Patel: Regarding the recited administering (or indicating) treatment to the subject for a morbidity based on the RBC age distribution and in response to a determination that at least one of the one or more parameters does not meet a predefined threshold of claims 15 and 25-26, Patel teaches the glycated hemoglobin fraction (hemoglobin Ale or HbAlc) is routinely measured to assess glucose control in diabetic patients; ... and further, tested the prediction that elevated RDW is associated with elevated mean RBC age by measuring Ve and HbAlc in nondiabetics (p.424, col.l-p.425, col.2), such that it would be obvious to administer or adjust
diabetes treatment based on the HbAlc level.
Also taught by Patel: Regarding the recited determining an RBC age distribution and a mean RBC age based on the one or more parameters (of claims 1, 13-15, and 25-26) reads on the red contour lines representing RBC age distribution in Figure 1A (Patel, p.424); and "We therefore sought to test this model-generated prediction of increased mean RBC age by estimating mean RBC age and vc (RBC clearance) (Patel, p.424, col.1, ¶ 1).
Regarding the claims 10, 11, 22, and 23 recitations for receiving an HbA1c measurement, determining an HbA1c level indicative of diabetes or prediabetes for the subject by adjusting a nominal HbA1c level based on the RBC age distribution; and administering (adjusting in claims 11 and 23) treatment for diabetes or prediabetes to the subject in response to a determination that the HbA1c measurement for the subject exceeds the HbA1c level for the subject, Patel teaches the glycated hemoglobin fraction (hemoglobin A1c or HbA1c) is routinely measured to assess glucose control in diabetic patients; …and further, tested the prediction that elevated RDW is associated with elevated mean RBC age by measuring vc and HbA1c in non-diabetics (p.424, col.1-p.425, col.2), such that it would be obvious to administer or adjust treatment based on the HbA1c level.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the method for modeling RBC population dynamics by calculating and determining parameters using CBC data of Golub with the use of CBC data in determining of pathophysiological states and analysis of HbA1c measurements of Patel, with the determination of RBC age distribution used in determining a pathophysiological state of Malka, to come to a method using CBC data and/or HbA1c measurements to model RBC dynamics and inform or adjust treatments in pathophysiological states. One would be motivated to combine, as Golub states disease phenotypes, such as risk of diabetes, involve mechanisms that are challenging to elucidate… mathematical modeling can decompose these complex phenotypes (p.465, col.1, while Patel states future studies…will enable model improvements which will likely enhance predictive accuracy (p.427, col.1.) Additionally, Malka developed a model of glycation kinetics and derived a patient-specific correction factor (MRBC) to improve the accuracy of AG (average concentration of blood glucose) estimation from HbA1c (p.4, col.2). One of ordinary skill would have had a reasonable expectation of success in combining, as Golub, Patel, and Malka are generally drawn to related teaching of modeling RBC population dynamics, and as such the combination would have been obvious.
Response to Applicant Arguments - 35 USC § 103
Applicant's arguments filed 06/01/2026 have been fully considered but they are not yet persuasive.
Applicant asserts (remarks, p.13) (bold emphasis added): ..."the cited references do not describe ‘determining a pathophysiological state of the subject based on the RBC age distribution’ as recited by amended independent claim 1" (p.13, ¶ 4).
The argument is not persuasive as a new 103 has been asserted above, necessitated by amendment, in which the recited determining a pathophysiological state of the subject based on the RBC age distribution (of claims 1 and 13-14) reads on "The clinical HbA1c measurement is the average over a uniform distribution of RBC ages ranging between 0 and 2 ∙ MRBC days" (Malka, p.7, col.2, ¶ 1); and "The difference in AG (average concentration of blood glucose) between a nondiabetic (HbA1c < 6.5%) and a diabetic with suboptimal disease control (HbA1c > 7.0%) can be ~15 mg/dl (Malka, p.3, col.2, ¶ 3). Here, Malka shows the pathophysiological state of increased HbA1c percentage, as determined based on (in part) RBC age distribution.
Conclusion
No claim is allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 Meredith A Vassell whose telephone number is (571)272-1771. The examiner can normally be reached 8:30 - 4:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KARLHEINZ SKOWRONEK can be reached at (571)272-9047.
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.
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.
/M.A.V./Examiner, Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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