Detailed Action
Applicant's response, filed 08/06/2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied in view of instant application amendments. They constitute the complete set presently being applied to the instant application. Herein, "the previous Office action" refers to the 04/17/2025 Office Action.
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013 , is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/06/2025 has been entered.
Claim Status
Claims 21, 24-26, 34, and 36-37 are currently pending and under examination herein. .
Claims 1-20, 22-23, 27-33, 35, and 38-40 were previously cancelled.
Claims 21, 24-26, 34, and 36-37 are rejected.
Terminal Disclaimer
Regarding the double patenting rejection, the 04/10/2024 terminal disclaimer was recorded, disclaiming the terminal portion of any patent granted on this application, which would extend beyond the expiration date of 17/236,834 and 17/236,847.
Priority
The previously discussed claim for the benefit of priority assigned an effective filing date of 02 December 2020 to claims 21, 24-26, 34, and 36-37. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
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.
Step 1: Statutory categories
Claims 21 and 34, and therein, dependent claims 24-26, and 36-37, remain rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more, in accordance with MPEP § 2106.
Regarding claims 21, 24-26, 34, and 36-37 , limitations are found to recite statutory subject matter (Step 1: YES). Claims are directed to a process (method claims 21, 23-26, 33) and a machine (system claims 34 and 36-37).
Step 2A Prong 1: Judicial Exceptions
The instant claims are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature, or natural phenomenon (Step 2A, Prong 1). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships, and mathematical calculations), certain of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (see MPEP 2106.04(a)(2)). In the instant application, the claims recite the following limitations that equate to an abstract idea, with mental steps and mathematical concepts, and natural phenomena.
Mental steps/Mathematical concepts: the following claims recite
Claims 21 and 34: calculating MDW…determining that the MDW value exceeds a predetermined threshold; subsequent to determining that the MDW value exceeds a predetermined threshold… evaluating infection status based on the values…wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction.
Claims 24 determining that the CRP value exceeds a predetermined threshold.
Claim 36 determining that the MDW value exceeds a predetermined threshold, or wherein the determining comprises determining that the CRP value exceeds a predetermined threshold, or both.
Natural phenomena: the following claims recite
Claims 21 and 34: determining that the individual has an infection based on the values of the first and second parameter…
Under the broadest reasonable interpretation of instant application, detecting infection by MDW and CRP values compared to predetermined thresholds relies on mental processes in conjunction with mathematical concepts, and natural phenomena correlations—all judicial exceptions. It should be noted that there are no bright lines between the types of exceptions, and that many of the concepts identified by the courts as exceptions can fall under several exceptions. “Because abstract ideas, laws of nature, and natural phenomenon "are the basic tools of scientific and technological work", the Supreme Court has expressed concern that monopolizing these tools by granting patent rights may impede innovation rather than promote it. See Alice Corp., 573 U.S. at 216, 110 USPQ2d at 1980; Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012).”
Instant claims direct to mental processes when determining based in biomarker values/levels (MDW, CRP) and whether they exceed threshold. Despite being performed in a system architecture/networked environment (FIG 1, [00034-00039]) with generic modules, devices, and analyzer 102 (FIG 2), these steps (FIG 8, 14, 15) can be performed by a physician of ordinary skill in the art in her own head with generic medical systems and laboratory components [00034-00040].
Instant claims direct to mathematical concepts including quantitative and qualitative/relational methods (determining…exceeds), when determining a diagnosis of infection (data analyzers FIG 4, [00081-00086]). Mathematical operations cited in the written description, include statistics (block 608:linear weighted average, [00080, 00083]), decision rules 500 (FIG 5, [00033, 00058], monocyte indices [00096, 00099], and probability equations [00085]), with graphical representations (violin plots FIGs 16-26 and area under the curve/AUC block 720, [00081]), are utilized to determine biomarker parameters relevant to the detecting infection and compare them to predetermined thresholds. These recitations compare information regarding a sample or test to a control or target data (Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), organizing and manipulating information through mathematical correlations (Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)), and utilize concepts of collecting information, analyzing it and displaying certain results of the collection and analysis (Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)). The courts have identified these concepts and deemed them as practically performed in the human mind with pen and paper, and can include mathematical concepts. Therefore, these limitations fall under the “mental process” and ”mathematical concepts” groupings of abstract idea and are directed to a judicial exception.
The instant claims, which are directed to the collection of data values (MDW, CRP) representing naturally occurring levels of a substance in a body, in combination with their mathematic steps are correlated with a naturally occurring disease or condition, such as influenza and COVID-19 (wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction) (FIG 5-7, 16B, 25-26). The courts have identified the following concepts and products as examples of laws of nature or natural phenomena: the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone, Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018), a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk (Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). Further, in Mayo, the discovery underlying the claims was that when blood levels were above a certain level, harmful effects were more likely and when they were below another level the drug's beneficial effects were lost (Mayo, 566 U.S. at 74—76). The claims provided that particular levels of measured metabolite indicated a need to increase or decrease the amount of drug subsequently administered to the subject. (Id. at 75). However, the claims did not require any actual action be taken based on the measured level of metabolite.(Id. at 75-76). Thus, the claims which required only the observation of a natural law were deemed patent-ineligible. Similarly, the instant claims require only the observation of the natural law, and for this reason too are properly deemed patent-ineligible.
Instant claims correlate human infection (wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction) with innate human (normal/physiologic or abnormal/pathologic) hematologic and metabolic levels. Instant application natural correlations are even further reliant on mental associations as it is dependent on testing of biomarkers, indirect measures of infection, and do not test directly for virus presence, for example, with microbial cultures or nucleic acid or particle levels, and thus, combines mental processes and mathematical concepts with natural laws/phenomena. Similarly, the mathematical formula in Flook, the laws of nature in Mayo, and the isolated DNA in Myriad were all novel or newly discovered, but nonetheless were considered by the Supreme Court to be judicial exceptions because they were "‘basic tools of scientific and technological work’ that lie beyond the domain of patent protection (discovered the BRCA1 and BRCA1 genes in Myriad, 569 U.S. 576, 589, 106 USPQ2d at 1976, 1978; “the novelty of the mathematical algorithm is not a determining factor at all" quoting Mayo, 566 U.S. 71, 101 USPQ2d at 1965); Flook, 437 U.S. at 591-92, 198 USPQ2d at 198); Mayo, 566 U.S. 73-74, 78, 101 USPQ2d 1966, 1968 (noting that the claims embody the researcher's discoveries of laws of nature). The Supreme Court’s cited rationale for considering even "just discovered" judicial exceptions as exceptions stems from the concern that "without this exception, there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’" Myriad, 569 U.S. at 589, 106 USPQ2d at 1978-79 (quoting Mayo, 566 U.S. at 86, 101 USPQ2d at 1971; Myriad, 569 U.S. at 591, 106 USPQ2d at 1979 ("Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry." see MPEP 2106.04.
As such, claims 21, 24-26, 34, and 36-37 recite elements that constitute judicial exceptions: an abstract idea with both mathematical concepts and mental processes, as well as natural phenomena (Step 2A, Prong 1: YES).
Step 2A Prong 2: Integration into Practical Application
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). 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 equate to mere instructions and data use to apply the recited exception in a generic way or in a generic computing environment. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
The following additional elements are considered for integration into practical applications.
Claims 21 and 34 obtaining a first/second parameter associated with the individual… obtaining, where the MDW value is elevated… a monocyte distribution width (MDW) value, a C-reactive protein (CRP) value via initiating an immunoassay analyzer and/or clinical chemistry analyzer to collect measurements for determining the CRP value;
Claims 21 and 34 storing said first and second parameter associated with the individual at a laboratory information system
Claims 21 and 34 laboratory information system; and via the laboratory information system, based on execution of a set of instructions stored on a non-transitory computer readable medium… hematology analyzer adapted to capture measurements of blood cells comprised by the blood sample in a measurement module, an immunoassay analyzer and/or clinical chemistry analyzer to collect measurements for determining CRP, and a system, processor configured with instructions stored on a non-transitory computer readable medium
Claims 25 and 37 wherein the predetermined threshold for MDW is 20.9 channels
Claims 26 and 37 wherein the predetermined threshold for CRP is 22 mg/L
These additional elements do not reflect an improvement to technology or use the recited judicial exception to effect a particular outcome (see MPEP § 2106.05(a)), and are insignificant extra-solution activity or field of use limitations that do not integrate into practical applications (MPEP § 2106.05(g)). The instant claims recite additional elements that amount to mere ordered instructions (obtaining patient samples for biomarker testing in various combinations on a hematology analyzer) and analyzing with generic system of processor/memory of stored instructions to collect parameters without additional structure for the hardware components (system architecture/non-transitory computer-readable medium/networked environment (FIG 1, [00034-00039]) with generic processors, modules, devices, laboratory information system, and hematology analyzer 102 (FIG 2), or defining features (see MPEP § 2106.05(f)). These additional elements do not provide practical integration, as they are generically reciting computing components without improvement or particularity added to a machine, nor do they impose any meaningful limitation on the judicial exceptions (see MPEP 2106.05(a and b). Other additional elements of claim limitations recite generating and processing data (obtaining laboratory values such as WBC and CRP values) These additional elements equate to steps of mere data gathering (laboratory values for use in algorithm methods 500, 600, 700) for input/output into the generic system (MPEP § 2106.05(g)) and so, merely inform the field of use of the invention without indication these affect or alter the judicial exception (see MPEP § 2106.05(h)). As such, these limitations equate to mere instructions and data usage in mental processes and mathematical concepts with generic computing systems. The courts have stated these do not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
Therefore, these claims do not disclose any additional elements which might integrate into a practical application. The system and methods do not recite “particular” limitations that would have more than a nominal or insignificant relationship to the judicial exception. Rather, these limitations merely apply the exception in a generic way and do no integrate the recited exceptions into a practical application (see MPEP 2106.04(d)(2)). As such, claims 21, 24-26, 34, and 36-37 , are directed to judicial exceptions: a natural phenomenon and an abstract idea of mathematical concepts and mental processes (Step 2A, Prong 2: NO).
Step 2B: Inventive Concepts
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). When making a determination whether the additional elements in a claim amount to significantly more than a judicial exception, the additional element (or combination of elements) are considered for whether they are well-understood, routine, conventional activity in the art.
The following additional elements are considered for integration into practical applications.
Claims 21 and 34 obtaining a first parameter associated with the individual… obtaining, where the MDW value is elevated… a monocyte distribution width (MDW) value, a C-reactive protein (CRP) value,
Claims 21 and 34 storing said first and second parameter associated with the individual at a laboratory information system
Claims 21 and 34 laboratory information system; and via the laboratory information system, based on execution of a set of instructions stored on a non-transitory computer readable medium,
Claim 34 a hematology analyzer adapted to capture measurements of blood cells comprised by the blood sample in a measurement module, an immunoassay analyzer and/or clinical chemistry analyzer to collect measurements for determining CRP, and a system, processor configured with instructions stored on a non-transitory computer readable medium
Claims 25 and 37 wherein the predetermined threshold for MDW is 20.9 channels
Claims 26 and 37 wherein the predetermined threshold for CRP is 22 mg/L
These additional elements do not contribute significantly more to well-known and conventional clinical assessments which are routinely performed and utilized by physicians with access to laboratory services and patient medical charts, as of the effective filing date. Under the broadest reasonable interpretation, the above recited limitations equate to analyzing laboratory panels as biomarkers, which are then input to mental and mathematical concepts to prognosticate a natural disease phenomenon--infection status. The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts 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.): determining the level of a biomarker in blood by any means (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017)); detecting DNA or enzymes in a sample (Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017)).
These additional elements merely inform the field of use of the invention without any particularity of components or steps which transform the judicial exception. The courts have identified limitations of merely data gathering (obtaining laboratory values, such as WBC and CRP values for use in algorithm methods 500, 600, 700), (see MPEP § 2106.05(g)), as well-understood, routine, and conventional (performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199; recomputing or readjusting alarm limit values (Bancorp Services v. Sun Life, 687 F.3d 1266, 1278, 103 USPQ2d 1425, 1433 (Fed. Cir. 2012)), receiving or transmitting data, utilizing an intermediary computer to forward information: Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 and OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015); updating an activity log (Ultramercial, 772 F.3d at 716, 112 USPQ2d at 1755). Also, MPEP 2106.05(f) discloses mere instructions to apply the judicial exception (processing samples for laboratory data, then mathematically modeling in an analyzer’s generic processor/memory with stored instructions) cannot provide an inventive concept to the claims(see MPEP § 2106.05(f)). Finally, the instant specification supports conventionality when utilizing commercially available hematology analyzers for these laboratory measurements [0040-0041, 0043, 0051, 0067]. The additional elements do not comprise an inventive concept, when considered individually or as an ordered combination, that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 21, 24-26, 34, and 36-37 remain not patent eligible.
Response to Arguments- 101
The Applicant's arguments [p. 5], filed 08/06/2025, have been fully considered in light of the previously stated reasons in Office Action. Applicant asserts:
A. The claims as amended are believed to more clearly recite that the order of the sensors improve the technology at issue in the claims. That is, independent claims 21 and 34 recite obtaining a first parameter (MDW) via initiation of a hematology analyzer, followed by determining the MDW value exceeds a certain value, and then, subsequent to determining that the MDW value exceeds a predetermined threshold a second parameter (CRP) is determined. As such, the claims are believed to satisfy the requirements of 35 U.S.C. §101 for at least the reason that the claims relate to a particular configuration of analyzers (the hematology analyzer and the immunoassay analyzer and/or clinical chemistry analyzer) and a particular method of using the data from the analyzers (in which a first value is obtained followed by a second value) in order to more accurately determine a risk of mortality. As discussed during the call with the Examiners, the basis for this rationale is provided by the Federal Circuit in Thales Visionix Inc.v. United States.'1 Thales Visionix Inc.v. United States, 850 F.3d 1343 (Fed. Cir.2017): The asserted claims-which recited an inertial tracking system for tracking the motion of an object relative to a moving reference frame- held eligible; the claims were not directed to an abstract idea because they "specif[ied] a particular configuration of inertial sensors and a particular method of using the raw data from the sensors in order to more accurately calculate the position and orientation of an object on a moving platform."
However, it is respectfully submitted that Applicant’s assertion is not persuasive. The fact pattern in Thales Visionix (the particular configuration of inertial sensors and the particular method of using the raw data from the sensors) does not apply to the instant claims because the claimed invention In Thales was a novel technological solution to a technological problem, not merely automating or speeding up steps directed to abstract ideas (mental processes and mathematical concepts to analyze lab value A followed by lab value B) and natural phenomenon (to correlate with human conditions: lab values A+B = an infection…at high risk for one or more of…). Also, while the combination of A and B may improve accuracy over A and C as asserted for determining that the individual has an infection…at high risk for one or more of… these correlations are natural phenomena, a judicial exception. The decision to select laboratory test A then B rather than laboratory test A then C are well within the abilities and choices of a clinician with ordinary skill in the art, and such routine optimization decisions to best diagnose pathological natural correlations are their bread and butter.
Additional elements remain insignificant extra-solution activities, such as merely obtaining data (lab values A or B), without claiming any particularity to testing steps (initiating…collecting… calculating…) or to lab equipment which do not require any sensors. The claimed equipment routinely output/store lab values A or B without any particular physical aspects or required elements (analyzers—whether hematology/immunoassay/clinical chemistry coupled to a laboratory information system) and so, did not provide additional considerations for practical integration or an inventive concept. Instant claims of obtaining lab value A then B (i.e. the data gathering) does not change the hematology analysis or the immunoassay analysis, nor the equipment utilization, therefore, there is no transformation of the computer technology or environment. In Thales, inertial sensors were reconfigured in a non-conventional manner to reduce errors in relative position and orientation measurements of a moving object on a moving reference frame, using mathematical equations (a judicial exception), to position the sensors. Therefore, the conclusion that the courts reached in Thales cannot be extrapolated to the rejected claims, because the math was applied to real world tangible elements AS A RESULT of performing the math.
Making the mental steps and math easier and faster does not change the nature of the judicial exceptions and the type of lab data (whether MDW, CRP, or procalcitonin, WBC, etc.) is routinely determined, analyzed, and applied in the judicial exceptions in order to direct to natural correlations. Finally, the additional elements, when considered individually or as an ordered combination, do not provide practical integration, nor support an inventive concept, and so, do not amount to significantly more than the judicial exception itself. Claims 21, 24-26, 34, and 36-37 are patent ineligible.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
A. Claims 21, 24-26, 34, and 36-37, are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. Claims 24-26, and 36-37 are also rejected because they depend on and/or do not remedy the deficiencies inherited by their parent claims.
This rejection is newly recited in view of instant disclosure amendments.
Claims 21 and 34 recite “determining that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction based on an elevated CRP value,” which is indefinite because it does not set forth how any risk is determined, let alone high risk. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree of risk, and therefore, the metes and bounds are indeterminable.
Claims 21 and 34 recite “based on an elevated CRP value” which is indefinite. The term “elevated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree of elevated with a threshold for comparison, and therefore, the metes and bounds are indeterminable. Applicant can consider incorporating dependent claims 24, 25, and/or 26, into independent claim 21, and further, dependent claims 36 and/or 37 into independent claim 34.
Claims 21 and 34 recite “determining that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction based on an elevated CRP value,” which is indefinite because the claim does not recite the necessary and sufficient information to make the determinations of at high risk based on the collected data. The claim fails to particularly point out and distinctly claim how the data point (CRP) regarding any individual are used to determine or calculate a level of risk for any specific critical condition. It would appear patient health information (whether said individual is critically ill, elderly, has multiple comorbidities, etc.) beyond these the CRP data point is required (i.e. the MDW as well).
Claims 21 and 34 recite “determining that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction based on an elevated CRP value,” which is indefinite because the claim does not recite the necessary and sufficient information to make the determinations of at high risk based on the collected data. The claim fails to particularly point out and distinctly claim how the two collected data points (MDW and CRP) regarding any individual are used to determine or calculate a level of risk for any specific critical condition. It would appear patient health information (whether said individual is critically ill, elderly, has multiple comorbidities, etc.) beyond these two data points is required.
.
Therefore, said limitations are indefinite as claimed. Clarification is required through clearer claim language. Any newly applied objection is necessitated by instant application amendment.
Claim Rejections - 35 USC § 103
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 § 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
Note: citations from the instant application are italicized in the following section.
Independent claims 21 and 34 and dependent claims, 24-26, and 36-37, are rejected under 35 U.S.C. § 103 as being unpatentable over Lin et al. (Lin H et al. (2020) Clinical impact of monocyte distribution width and neutrophil-to lymphocyte ratio for distinguishing COVID-19 and influenza from other upper respiratory tract infections: A pilot study. PLoS ONE 15(11): e0241262, 10 pages; PTO 892 cited, herein referred to as Lin) in view of Mardi D et al. (2010) Mean cell volume of neutrophils and monocytes compared with C‐reactive protein, interleukin‐6 and white blood cell count for prediction of sepsis and nonsystemic bacterial infections. International Journal of Laboratory Hematology 32.4 : 410-418; PTO 892 cited), in further view of Xin MM et al. WO 2019/226260 (priority 23 May 2018).
Any newly applied rejection is necessitated by claim amendment.
Regarding instant method independent claim 21, which provides the steps for system independent claim 34, recites:
obtaining a first parameter associated with the individual, the first parameter comprising a monocyte distribution width (MDW) value; obtaining, where the MDW value is elevated, a second parameter, the second parameter being a C-reactive protein (CRP) value, storing said first and second parameter associated with the individual at a laboratory information system; and via the laboratory information system, based on execution of a set of instructions stored on a non-transitory computer readable medium,
determining that the individual has an viral infection based on the values of first and second parameter.
wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction.
A system… comprising a processor configured with instructions stored on a non-transitory computer readable medium to, when executed, cause the processor to perform…(claim 34 only)
The prior art to Lin teaches:
testing for MDW with a threshold value of MDW >20 (predetermined threshold) as being associated with viral infection patients, both COVID-19 and influenza (Table 2, p5). The area under curve (AUC) of MDW > 20 (for COVID-19 and influenza was 0.703 and 0.6276 (p4 para 3). Monocyte distribution width (MDW) > 20 (odds ratio [OR]: 8.39, p = 0.0110, area under curve [AUC]: 0.703) …could independently distinguish COVID-19 from common upper respiratory tract infections (URIs) (Abstract, p1).
obtaining parameters including MDW and other blood biomarkers (C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR)), to evaluate the likelihood of COVID-19 and distinguish the disease from other respiratory infections (Introduction, p2 para 5-6, p3 para 2, 5, Table 1, p6 para 3).
a system for data collection (a laboratory information system) with patient records (p2-3 para last to para 1: “the electronic database of the web-based physician order entry system of the Taipei Medical University Hospital” of laboratory data, clinical symptoms, etc.). A web/cloud-based database inherently is hosted on a cloud server system, equipped with server processors and non-transitory computer readable medium (claim 34).
However, Lin is silent to further testing regarding CRP, wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction. The instant application discloses a secondary parameter comparison with C-reactive protein/CRP (predetermined criteria 22 mg/L [equivalent to 2.2 mg/dL]).
The prior art to Mardi teaches prediction of sepsis and nonsystemic bacterial infections with monocyte mean cell volume/MMV (analogous to MDW) and CRP [p410, Summary: “observed a significant increase in neutrophil mean cell volume/MNV and MMV in the sepsis group compared with limited infections and controls…compared with CRP (cut-off point 60 mg/dl), MNV at a cut-off of 150 had a comparable sensitivity and specificity and was the most predictive volume conductivity scatter/VCS parameter…MNV and MMV seemed to be potential parameters]. CRP concentrations were the highest in the sepsis group (wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction)and did discriminate from controls (P < 0.001) and patients with nonsystemic infections [p413 Col 1]. Further, Mardi teaches “compared with controls and patients with limited nonsystemic infections, the neutrophils and monocytes in sepsis were significantly increased in the mean volume paralleled by the highest CRP concentrations. A sensitivity and specificity of 76% and 63% were calculated for MNV for prediction of sepsis comparable with that for CRP” [p415 Col 2]. The findings thus support the use of elevated MMV, MDW substitute, and elevated CRP to diagnose infection severity risk classes (sepsis, limited nonsystemic infections, controls), as sepsis increases the risks of mortality, critical care, and organ dysfunction, as disclosed in the instant specification [0027-0028].
The prior art to Xin teaches lab test panels for testing sepsis for analyzing the values of a first/second set of characteristics from blood sample with a set of cutoff values (claims 1 and 4), to produce a representation of a suspicion of sepsis, which can include MDW (reference claim 2, [0044: “received 101 order is to test a sample to determine whether the individual from whom that sample was collected is suffering from sepsis, and the identified 102 test(s) to perform on that sample included determining Cell Population Data (CPD)” [0026], such as monocyte distribution width (MDW)”], and CRP [0069: additionally, the second set of cells may be analyzed for a second characteristic or second set of characteristics, for example, for characterization of a different population of cells (e.g., red blood cells vs. white blood cells, neutrophils vs. monocytes, immature vs. mature cells, etc.), or a different population measurement (e.g., a minimum size, volume, granularity, etc., a standard deviation for a particular measurement, a range for the measurements of a particular type, etc.) or may be a characterization of a different feature of the patient sample than the patient’s cells, such as chemistry, immunoassay, microbiology, etc. (e.g., PCT, CRP, ESR, serum lactate, microbial culture, flu test or other viral indication…].
. Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified Lin’s MDW biomarker use in COVID-19 infection to incorporate Mardi’s and Xin’s use of CRP with MDW or an analogous CPD substitute for detecting sepsis/infection. Combining these prior art elements would have been obvious because CRP was well known in the art as of the effective filing date for evaluation of infection with varying degrees of severity risk. One of ordinary skill in the art would predict combining Lin’s and Mardi’s with Xin’s teachings with a reasonable expectation of success because both inventions are analogously applicable to infection biomarker testing. Therefore, the invention is prima facie obvious.
Regarding instant method and system dependent claims 24-26, and 36-37:
determining that the CRP value exceeds a predetermined threshold (claims 24 and 36).
determining that the MDW value exceeds a predetermined threshold (claims 25 and 36).
wherein the determining comprises determining that the MDW value exceeds a predetermined threshold, or wherein the determining comprises determining that the CRP value exceeds a predetermined threshold, or both (claim 36).
wherein the predetermined threshold for MDW is 20.9 channels, and wherein the predetermined threshold for CRP is 22 mg/L (claims 26 and 37).
The prior art to Lin teaches:
testing for MDW with a threshold value of MDW >20 (predetermined threshold) as being associated with viral infection patients, both COVID-19 and influenza (Table 2, p5). The area under curve (AUC) of MDW > 20 (for COVID-19 and influenza was 0.703 and 0.6276 (p4 para 3). Monocyte distribution width (MDW) > 20 (odds ratio [OR]: 8.39, p = 0.0110, area under curve [AUC]: 0.703) …could independently distinguish COVID-19 from common upper respiratory tract infections (URIs) (Abstract, p1). MDW threshold value range between 20-20.9 can occur through routine optimization.
determined that the CRP levels for COVID-19, influenza, common URI patients were nonsignificant because of different control groups, using a threshold (predetermined threshold), ranging from 1.1 -3.5 mg/dL (CRP is 22 mg/L [ equivalent to 2.2 mg/dL] (Table 1 and p6 para 3)).
However, Lin is silent to testing regarding CRP elevation associated with infection severity.
The prior art to Mardi teaches prediction of sepsis and nonsystemic bacterial infections with monocyte mean cell volume/MMV (MDW) and CRP, wherein use of elevated MDW and elevated CRP can diagnose infection severity risk classes [p410, Summary and p415 Col 2].
Regarding instant method and system claim 33, Lin teaches obtaining one or more parameters by analyzed blood samples for MDW on a Beckman Coulter UniCel DxH 900 analyzer, a quantitative, multi parameter automated hematology analyzer (p3 para 3).
Response to Arguments-103
The Applicant's arguments [p5-7], filed 08/06/2025, have been fully considered in light of the reasons in the prior Office Action, with additions necessitated by claim amendments in the above rejection. Applicant did not offer any arguments on the merits of the 103 rejection,
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
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Note: references to instant application are italicized in the following Double Patent section.
A. Instant claims 21, 24-26, 34, and 36-37 are rejected on the ground of provisional nonstatutory double patenting as being unpatentable over claims 1, 7-8, 10 of patent application US 16/925,943 (Tejidor et al, 2020; herein Tejidor ‘943) (see table) in view of Lin et al. and Mardi, in view of instant application amendments and discussed below.
This is a provisional nonstatutory double patenting rejection.
Instant Application
18/096,449
(2022, US20230165492A1)
16/925,943
(2020, US20210011005A1)
Claims 21 and 34
detecting a viral infection in an individual, comprising:
obtaining a first parameter associated with the individual… obtaining, where the MDW value is elevated… a monocyte distribution width (MDW) value, a C-reactive protein (CRP) value,
determining that the individual has an infection…evaluating infection status based on the values
Claim 1
characterizing an inflammatory response to infection as abnormal based at least in part on detecting the differentially expressed sepsis cell population parameter… apply a first global decision rule, the first global decision rule indicating that the patient is at increased risk of sepsis if all of the analyzed cell population parameters are outside their corresponding non-sepsis reference ranges;
Claim 7
whether the distribution width of measured volumes for a population of monocytes (MDW) within the body fluid sample is within an MDW reference range.
Claim 10
wherein the patient is characterized as at increased risk of sepsis if at least one of the analyzed cell population parameters is outside its corresponding non-sepsis reference range
Claims 24 and 36
determining that the MDW value exceeds a predetermined threshold
Claim 8.
characterized as abnormal if at least one of the analyzed cell population parameters is outside its corresponding reference range and the distribution width of the volume of the monocytes is greater than 19 channels.
Claim 10
characterized as abnormal if at least one of the analyzed cell population parameters is outside its corresponding reference range
Claims 25 and 37
wherein the predetermined threshold for MDW is 20.9 channels.
Claim 8
wherein the inflammatory response to infection is characterized as abnormal if at least one of the analyzed cell population parameters is outside its corresponding reference range and the distribution width of the volume of the monocytes is greater than 19 channels.
Claim 7
within an MDW reference range.
Claims 26 and 37
wherein the predetermined threshold for CRP is 22 mg/L
Claim 1
…indicating that the patient is not at increased risk of sepsis if none of the analyzed cell population parameters is outside of their corresponding non-sepsis reference ranges; and
ii. when at least one analyzed cell population parameter is outside of its corresponding non-sepsis reference range, and at least one analyzed cell population parameter is not outside of its corresponding non-sepsis reference range, apply a local decision rule to determine if the patient is at increased risk of sepsis.
Claim 34
obtaining one or more parameters associated with the individual comprises
exposing a blood sample of the individual to a hematology analyzer.
Claim 1
flowing a body fluid sample associated with the patient through a flow cell, the body fluid sample comprising a heterogenous population of circulating cells; b. determining a set of cell population parameters for the body fluid sample by performing acts comprising: i. using a laser to illuminate the body fluid sample, and ii. using a sensor assembly to detect light from the body fluid sample, as the body fluid sample is flowing through the flow cell; c. analyzing two or more cell population parameters
Claims 36
determining that the MDW/CRP value exceeds a predetermined threshold, or wherein the determining comprises
Claim 1
characterizing an inflammatory response to infection as abnormal based at least in part on detecting the differentially expressed sepsis cell population parameter… apply a first global decision rule, the first global decision rule indicating that the patient is at increased risk of sepsis if all of the analyzed cell population parameters are outside their corresponding non-sepsis reference ranges;
Claim 8. wherein the inflammatory response to infection is characterized as abnormal if at least one of the analyzed cell population parameters is outside its corresponding reference range
However, the Tejidor ‘943 application is silent to using CRP as an additional biomarker for infection (instant claim 36: or wherein the determining comprises determining that the CRP value exceeds a predetermined threshold). Instant application discloses a secondary parameter comparison selected from a group consisting of C-reactive protein/CRP (predetermined criteria 22 mg/L), but ‘943 application instead, performs a third comparison comparing a count of white blood cells (WBC) in the body fluid sample with a WBC reference range [0017] (comparing the secondary parameter with a corresponding predetermined criteria).
The prior art to Lin’s 2020 study teaches using CRP as an additional biomarker for infection:
patient viral infection detection (COVID-19, influenza, and common upper respiratory infections) with MDW and other blood biomarkers (PCT, CRP), thereby, evaluating the likelihood of COVID-19 especially, and distinguishing COVID-19 from other respiratory infections (p2: Introduction).
patient data (laboratory data, clinical symptoms, etc.) was stored and accessed from the electronic database of the hospital web-based physician order entry system (p3: Data collection).
obtaining parameters including MDW and other blood biomarkers (C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR)), to evaluate the likelihood of COVID-19 and distinguish the disease from other respiratory infections (p2 para 5-6: Introduction, and p3 para 2 and 5, Table 1, p6 para 3).
a system for data collection (a laboratory information system) with patient records (p2-3 para last to para 1: “the electronic database of the web-based physician order entry system of the Taipei Medical University Hospital” of laboratory data, clinical symptoms, etc). A web/cloud-based database inherently is hosted on a cloud server system, equipped with server processors and non-transitory computer readable medium.
However, Lin is silent to further testing regarding wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction.
The prior art to Mardi teaches prediction of sepsis and nonsystemic bacterial infections with monocyte mean cell volume/MMV (MDW) and CRP [p410, Summary: “observed a significant increase in neutrophil mean cell volume/MNV and MMV in the sepsis group compared with limited infections and controls…compared with CRP (cut-off point 60 mg/dl), MNV at a cut-off of 150 had a comparable sensitivity and specificity and was the most predictive volume conductivity scatter/VCS parameter…MNV and MMV seemed to be potential parameters]. CRP concentrations were the highest in the sepsis group (wherein an elevated CRP value indicates that the individual is at high risk for one or more of mortality, requiring critical care, and organ dysfunction)and did discriminate from controls (P < 0.001) and patients with nonsystemic infections [p413 Col 1]. Further, Mardi teaches “compared with controls and patients with limited nonsystemic infections, the neutrophils and monocytes in sepsis were significantly increased in the mean volume paralleled by the highest CRP concentrations. A sensitivity and specificity of 76% and 63% were calculated for MNV for prediction of sepsis comparable with that for CRP” [p415 Col 2]. The findings thus support the use of elevated MDW and elevated CRP to diagnose infection severity risk classes (sepsis, limited nonsystemic infections, controls), as sepsis increases the risks of mortality, critical care, and organ dysfunction, as disclosed in the instant specification [0027-0028].
Therefore, it would have been obvious to someone of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified Tejidor ‘943 MDW hematologic biomarker algorithm with Lin’s MDW and CRP biomarker application in COVID-19 viral infection to incorporate Mardi’s use of CRP with MDW equivalent for detecting sepsis infection severity risk Combining these prior art elements would have been obvious because CRP was well known in the art as of the effective filing date for evaluation of infection with varying degrees of severity risk (at high risk for one or more of mortality, requiring critical care, and organ dysfunction). By substituting WBC in Tejidor ‘943 sepsis biomarker panel with CRP, another sepsis biomarker, one of ordinary skill in the art would predict combining Tejidor ‘943 and Lin/Mardi’s CRP teachings with a reasonable expectation of success in predicting and classifying infection risk because said inventions are analogously applicable to sepsis infection biomarker testing. Therefore, the invention is prima facie obvious.
B. Instant claims 21, 24-26, 34, and 36-37 are rejected on the ground of provisional nonstatutory double patenting as being unpatentable over claims 1-4 of US Patent No. US11521706B2 (Xin R et al, 2019; herein Xin ‘706). Reference claim 1: “measuring values of a set of characteristics in the blood sample, the set of characteristics being determined prior to measuring the values; analyzing the values of the set of characteristics to produce a representation of a suspicion of sepsis; and displaying the representation; reference claim 2: “wherein the set of characteristics comprise at least one of a standard deviation of monocyte volume (MDW) or white blood cell count”; reference claim 4: “the set of characteristics is a first set of characteristics, measuring values of a second set of characteristics in the blood sample (CRP), the second set of characteristics being different from the first set of characteristics, comparing the values of the second set of characteristics with a set of cutoff values, and based on the comparison, generating the instruction to analyze the blood sample for sepsis (individual has an infection…at high risk for one or more of mortality, requiring critical care, and organ dysfunction based on an elevated CRP value) the instruction including a command to analyze the values of the first set of characteristics to produce the representation of the suspicion of sepsis Instant application is a species of genus patent Xin ‘706.
Response to Arguments- Double Patenting
The Applicant's arguments [p. 5], filed 08/06/2025, have been fully considered in light of the previously stated reasons in Office Action, and any newly applied rejection/portion is necessitated by instant application amendment. Applicant asserts:
A. Accordingly, Applicant reiterates the deficiencies of Mardi and Lin, as follows:
Mardi does not teach an "MDW equivalent". Rather, Mardi merely references monocyte mean cell volume (MMV) and neutrophil mean cell volume (MNV). Neither MMV nor MNV are equivalent to MDW (monocyte distribution width) as recited in independent claims 21 and 34.
However, it is respectfully submitted that Applicant’s assertion is not persuasive regarding Mardi, wherein MMW was interpreted as a reasonable substitute for MDW as it is an analogous lymphocyte morphometric measurement obtained, collected, and measured with a hematology analyzer, and shown to be correlated with infection as well [Zhu Y et al. 2013: The lymph index: a potential hematological parameter for viral infection. International Journal of Infectious Diseases 17.7 e490-e493; p.e490 Col 1-2 PTO 892 cited. Therefore, MMW can serve as a substitute equivalent known for the same purpose (see MPEP 2144.06: Art Recognized Equivalence for the Same Purpose).
Viral infections induce lymphocyte activation, undifferentiated lymphocyte proliferation, and antibody or cytokine/lymphokine secretion. The immune defense against a viral infection is more dependent on T cells and less dependent on antibodies. Cytotoxic T cells are important in killing virally infected cells…the activated lymphocytes may undergo not only morphologic changes, such as an increase in size, but also alterations in cytoplasmic composition as compared to their normal ‘resting’ counterparts. A Coulter LH750 automated hematology analyzer with VCS (volume, conductivity, and light scatter) technology can determine the intrinsic biophysical properties of over 8000 peripheral leukocytes in their ‘near native state’ using direct current impedance for the cell volume, radio frequency opacity to evaluate conductivity for cytoplasmic chemical composition and nuclear volume, and a laser beam to measure light scatter for cytoplasmic granularity and nuclear structure. It can also measure the degree of cell size variation [as in MDW]. These morphologic measurements are known as cell population data (CPD) [Zhu Y at p.e490 Col 1-2 PTO 892 cited, underline emphasis added].
According to the MPEP 2145 subsection X: D (1), a prior art reference that "teaches away" from the claimed invention is a significant factor to be considered in determining obviousness. However, "the nature of the teaching is highly relevant and must be weighed in substance. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 553, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (Claims were directed to an epoxy resin based printed circuit material. A prior art reference disclosed a polyester-imide resin based printed circuit material, and taught that although epoxy resin based materials have acceptable stability and some degree of flexibility, they are inferior to polyester-imide resin based materials. The court held the claims would have been obvious over the prior art because the reference taught epoxy resin based material was useful for the inventor’s purpose, applicant did not distinguish the claimed epoxy from the prior art epoxy, and applicant asserted no discovery beyond what was known to the art.). Furthermore, "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") (internal quotations omitted) (quoting DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009)); and Schwendimann v. Neenah, Inc., 82 F.4th 1371, 1381, 2023 USPQ2d 1173 (Fed. Cir. 2023) ("Although Oez [the prior art] used a white pigment with a cross-linking polymer, it does not discourage a skilled artisan from using the white pigment without a cross-linking polymer or lead the skilled artisan in a direction divergent from the path taken in the Appealed Patents. Thus, Oez's disclosure is substantial evidence that supports the Board's finding that Oez does not teach away from the proposed combination.")
B. Further, Applicant contends that, taking the reference as a whole, Mardi is more logically construed as teaching away from using CRP as a measure of an infection (whether before or after MDW), teaching that [a]lthough CRP seemed to be a good discriminator for severe bacterial infections also in the present study, its level is determined exclusively by its rate of synthesis. This might be a disadvantage because concentrations could decrease during organ dysfunction at the more sever stages of disease... In addition, immunological testing of CRP and IL-6 concentrations is costly and also time consuming..."2 As such, Mardi would have dissuaded one from skill in the art from using CRP as a measure of anything, such that the skilled artisan would not have combined Mardi with Lin to arrive at the claimed invention. Applicant respectfully submits that the rejection based on double patenting is improper and should be withdrawn.
However, it is respectfully submitted that Applicant’s assertion is not persuasive regarding Mardi teaching away from CRP as a measure of severe disease. In the context of the state of the art as of the instant priority date, CRP and further, lymphocyte cell morphometrics, such as MDW and MMV, are well-known measures of infection and sepsis, including severe sepsis.
Zhu Y, et al. teaches cell population data (CPD), which are morphologic property data of lymphocytes (e.g. lymphocyte volume standard deviation [LV-SD, analogous to MDW], lymph index) measured by a hematology analyzer, can exhibit significant changes in acute hepatitis B virus infection [2013: The lymph index: a potential hematological parameter for viral infection. International Journal of Infectious Diseases 17.7 e490-e493; PTO 892 cited].
Crouser E et al. teaches MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis. [2020: Journal of Intensive Care 8:33; doi.org/10.1186/s40560-020-00446-3; PTO 892 cited].
Uusitalo-Seppälä R et al. teaches CRP as well as PCT and IL-6 are markers for differentiating severe sepsis with OR 1.33 (95% CI 1.01 – 1.75, p =0.045 at p887 Col 1) [2011: Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin, and interleukin-6. Scand J Infect Dis. 2011;43(11–12):883–90.Scand J Infect Dis.; PTO 892 cited].
Conclusion
No claims are allowed.
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/VR/
Examiner
Art Unit 1685
/MARY K ZEMAN/Primary Examiner, Art Unit 1686