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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/21/2026 has been entered.
Claims 1-16, 21-24 are pending. Claims 1-8 are withdrawn. Claims 9-16, 21-24 have been considered on the merits. All arguments and amendments have been considered.
Claim Interpretation
The claims are drawn to a system comprising a cartridge containing a reagent comprising a polycation, and one or more processing devices. Independent claim 9 is amended to include the limitation of “the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less…”. For examination purposes, a reagent comprising a heparin inhibitor comprising a polycation present in the claimed concentration range is a reagent which enables the system to detect apixaban as claimed.
The intended use and function of the claimed reagent and system does not patentably distinguish the system, per se, since such undisclosed use and function is inherent to the reagent of the system. In order to be limiting, the intended use and function must create a structural difference between the claimed reagent and system and the reagent and system of the prior art. In the instant case, the intended use and function fails to create a structural difference, thus, it is not limiting. Please note that when applicant claims a reagent and system in terms of function, and the reagent and system of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112). Moreover, the claimed function must be inherent to the reference system. The discovery of a previously unappreciated property of a prior art reagent and system, or of a scientific explanation for the prior art's functioning, does not render the old system patentably new. Thus, the claiming of a new use, functions or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (MPEP 2112).
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 9-16, 21, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schafer et al. (US20220093223A1, IDS) in view of Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11).
Schafer teach a system to identify direct oral factor Xa (DOAC) inhibitors in a sample, wherein the DOAC is apixaban, rivaroxaban or edoxaban (0023, 0024, 0028). The system (ROTEM® device) allows one to perform viscoelastic tests to monitor the blood coagulation process and to detect anticoagulants with minor effects on clotting time, these tests are known as ROTEM® TFTEM and EXTEM® (0024, 0028, 0031). The system comprises a cartridge which receives the blood sample for carrying out the viscoelastic tests (0009, 0056). The system receives parameters from the tests and uses them to detect the presence and effects of DOAC’s (0032). The system comprises processing devices, i.e. software modules, analyzer instruments, computing devices and ROTEM devices, for performing operations including clotting parameters based on the test sample with a reagent to identify the presence of DOAC’s (0013, 0024, 0033, 0040, 0055, 0064). The test sample is a blood sample (0024, 0056, 0058) and the reagent for performing the test comprises a reduced tissue factor (0028), calcium chloride, and polybrene as a heparin inhibitor (0031).
Regarding claim 10, the direct oral factor Xa inhibitor comprises apixaban, rivaroxaban or edoxaban (0024, 0028).
Regarding claim 11, the results comprise identifying the DOAC inhibitor (0028, 0032, 0036, 0057).
Regarding claim 12, the results include estimated concentrations of the DOAC inhibitor (0057).
Regarding claims 13 and 22, the polycation is polybrene (0031).
Regarding claim 15, the reagent comprises calcium chloride (0031).
Regarding claim 16, the clotting parameter includes time to clot or clotting time (CT) (0005, 0026, 0028, 0031, 0036, for example).
Regarding claim 21, the reagent comprises a diluted/reduced tissue factor (0028).
Therefore, the system comprises a cartridge to receive a blood sample comprising a DOAC, specifically taught are the DOACS apixaban, rivaroxaban or edoxaban. The cartridge contains a reagent to be mixed with the sample, and the reagent comprises a polycation, specifically polybrene as a heparin inhibitor, i.e., a reagent enabling the system to detect apixaban as claimed. The system also comprises one or more processing devices for performing operations to include a clotting parameter to identify a DOAC in the sample.
Schafer does not teach the assay concentration range of the polycation, i.e. polybrene to be within a range of 1-100 µg/mL according to claims 1 and 14.
Jakimczuk teach assays for monitoring the anticoagulant activity of rivaroxaban in the presence of heparin using polybrene and find that polybrene at concentrations of 10 and 50 µg/mL neutralize heparin and enoxaparin and enable the accurate measuring of anti-factor Xa activity and thrombin time in rivaroxaban containing samples (abstract, section 2.2- 2.4, 3.4). The polybrene concentrations were selected to not affect the results of the coagulation tests, to neutralize heparin and to allow accurate monitoring of rivaroxaban (discussion section, p. 7, last parag.-p. 9). The reference teaches that while they only assessed rivaroxaban as a representative DOAC, it would be expected that apixaban and edoxaban would behave likewise due to their similar mechanism of action to rivaroxaban (p. 9, 1st full parag.).
Therefore, it would have been obvious before the effective filing date of the claimed invention to use the polycation, polybrene, at a concentration range of 1-100 µg/mL, as Jakimczuk teach that concentrations falling within the claimed range allow one to effectively neutralize heparin in a test sample and accurately monitor clotting parameters relating to the presence of DOAC’s. Further, a phosita would have a reasonable expectation that the system as a whole performs operations (as claimed) which can be used to identify DOACS including apixaban, rivaroxaban or edoxaban.
Regarding the limitation of “the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less…”, a reagent comprising a heparin inhibitor comprising a polycation is taken to be reagent which enables the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less. The prior art references teach a system comprising the claimed reagent which comprises the polycation at concentrations within applicants claimed range.
Therefore, the system of Schafer with the reagent of Jakimczuk would be a system enabled to identify a presence or concentration of the DOAC as claimed. The reagent of the prior art references is one which would enable the system to detect apixaban as claimed.
The intended use and function of the claimed reagent and system does not patentably distinguish the system, per se, since such undisclosed use and function is inherent to the reagent of the system. In order to be limiting, the intended use and function must create a structural difference between the claimed reagent and system and the reagent and system of the prior art. In the instant case, the intended use and function fails to create a structural difference, thus, it is not limiting. Please note that when applicant claims a reagent and system in terms of function, and the reagent and system of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112). Moreover, the claimed function must be inherent to the reference system. The discovery of a previously unappreciated property of a prior art reagent and system, or of a scientific explanation for the prior art's functioning, does not render the old system patentably new. Thus, the claiming of a new use, functions or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (MPEP 2112).
Claim(s) 9-16, 21, 22, 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over McCluskey et al. (US10175225, IDS) in view of Schafer et al. (US20220093223A1, IDS) and Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11).
Regarding claims 9, 13, and 22, McCluskey teaches a blood coagulation testing system comprising a cartridge to receive a test sample (col. 1, lines 60-col. 3, lines 1-27, for example). The cartridge contains a reagent to mix with the test sample, wherein the reagent comprising a heparin inhibitor comprising a polycation, specifically polybrene (col. 15, lines 42-col. 16, lines 1-4). The system comprises one or more processing devices for performing thromboelastometry and rotary thromboelastometry (known as TEM® and ROTEM®) operations comprising using clotting parameters to determine time to clot and clot formation time for the test sample (col. 1, lines 60-col. 3, lines 1-27, col. 6, lines 65-col. 7, lines 1-20, col. 20, lines 61-67, for example).
Regarding claim 15, the reagent comprises calcium chloride (col. 15, lines 42-col. 16, lines 1-4).
Regarding claim 21, the reagent comprises a tissue factor (col. 15, lines 42-44, 65, 66, col.16, lines 3, 4).
Regarding claim 22, the polycation is polybrene (col. 15, lines 42-col. 16, lines 1-4).
Regarding claims 24, the reagent is a bead and are lyophilized materials (col. 15, lines 36-42).
The processing devices of claim 9 are not claimed according to structure, but rather a function. When looking to applicants’ specification to determine the structure corresponding to the function, applicants’ specification states
[0050] An example system that may be used to implement the low tissue factor assay includes, but is not limited to, the system described in U.S. Pat. No. 10,175,225 (“Blood Testing System and Method”) that issued on Jan. 8, 2019, the contents of which are incorporated herein by reference. U.S. Pat. No. 10,175,225 describes a blood testing system that includes an analyzer console and one or more cartridges for performing tests, including a low tissue factor assay that may be used for identifying, and estimating an amount of, direct oral factor Xa inhibitors in a test sample using a reagent that includes a diluted tissue factor, CaCl.sub.2, and a heparin inhibitor including a polycation, such as polybrene or other polycations described above.
[0053] The diagnostic test instruments/clinical analyzers and assays described herein may be controlled using computing systems or any other appropriate computing device having one or more processing devices, such as one or more microprocessors, one or more microcontrollers, or programmable logic such as one or more field-programmable gate arrays (FGPAs) or one or more application-specific integrated circuits (ASICs).
Thus, the devices of McCluskey are taken to be devices which would perform the operations as claimed if the sample potentially contained the DOAC’s apixaban of claims 1, 11 and 12, and rivaroxaban, betrixaban or edoxaban of claim 10 because the disclosed system comprises a cartridge to receive a test sample, a reagent comprising a heparin inhibitor comprising a polycation, and one or more processing devices for performing thromboelastometry and rotary thromboelastometry (known as TEM® and ROTEM®) operations comprising using clotting parameters to determine time to clot and clot formation time for the test sample according to claims 9 and 16 (col. 1, lines 60-col. 3, lines 1-27, col. 6, lines 65-col. 7, lines 1-20, col. 20, lines 61-67, for example). Therefore, the system of McCluskey would be one enabled for identifying DOAC’s.
McCluskey differs from the claimed invention in that they do not teach specifically teach the processing device identifies the presence of the direct oral factor Xa inhibitors apixaban of claims 1, 11 and 12, and rivaroxaban, betrixaban or edoxaban of claim 10.
Schafer teach a system to identify direct oral factor Xa (DOAC) inhibitors in a sample, wherein the DOAC is apixaban, rivaroxaban or edoxaban (0023, 0024, 0028). The system (ROTEM® device) allows one to perform viscoelastic tests to monitor the blood coagulation process and to detect anticoagulants with minor effects on clotting time, these tests are known as ROTEM® TFTEM and EXTEM® (0024, 0028, 0031). The system comprises a cartridge which receives the blood sample for carrying out the viscoelastic tests (0009, 0056). The system receives parameters from the tests and uses them to detect the presence and effects of DOAC’s (0032). The system comprises processing devices, i.e. software modules, analyzer instruments, computing devices and ROTEM devices, for performing operations including clotting parameters based on the test sample with a reagent to identify the presence of DOAC’s (0013, 0024, 0033, 0040, 0055, 0064). The test sample is a blood sample (0024, 0056, 0058) and the reagent for performing the test comprises a reduced tissue factor (0028), calcium chloride, and polybrene as a heparin inhibitor (0031).
Regarding claim 10, the direct oral factor Xa inhibitor comprises apixaban, rivaroxaban or edoxaban (0024, 0028).
Regarding claim 11, the results comprise identifying the DOAC inhibitor (0028, 0032, 0036, 0057).
Regarding claim 12, the results include estimated concentrations of the DOAC inhibitor (0057).
Regarding claim 16, the clotting parameter includes time to clot or clotting time (CT) (0005, 0026, 0028, 0031, 0036, for example).
Therefore, the system comprises a cartridge to receive a blood sample comprising a DOAC, specifically taught are the DOACS apixaban, rivaroxaban or edoxaban. The cartridge contains a reagent to be mixed with the sample, and the reagent comprises a polycation, specifically polybrene as a heparin inhibitor, i.e., a reagent enabling the system to detect apixaban as claimed. The system also comprises one or more processing devices for performing operations to include a clotting parameter to identify a DOAC in the sample.
Thus, before the effective filing date of the claimed invention, one of ordinary skill in the art would have had a reasonable expectation of successfully using the system comprising a cartridge and processing devices of Schafer and McCluskey for performing the operations directed to the measuring or detecting the potential presence of direct oral factor Xa inhibitors given the combined art teachings of ROTEM systems comprising cartridges and processing devices for measuring clotting parameters as well as measuring said parameters in samples having DOAC’s present. The prior art systems are disclosed to comprise cartridges for receiving samples and a reagent comprising the claimed reagent components and devices for performing the disclosed function. Thus, it would have been obvious to one of ordinary skill in the art that the devices would perform the claimed clotting parameter operations when the DOAC’s are present.
McCluskey does not teach the assay concentration range of the polycation, i.e. polybrene to be within a range of 1-100 µg/mL according to claim 14.
Jakimczuk teach assays for monitoring the anticoagulant activity of rivaroxaban in the presence of heparin using polybrene and find that polybrene at concentrations of 10 and 50 µg/mL neutralize heparin and enoxaparin and enable the accurate measuring of anti-factor Xa activity and thrombin time in rivaroxaban containing samples (abstract, section 2.2- 2.4, 3.4). The polybrene concentrations were selected to not affect the results of the coagulation tests, to neutralize heparin and to allow accurate monitoring of rivaroxaban (discussion section, p. 7, last parag.-p. 9). The reference teaches that while they only assessed rivaroxaban as a representative DOAC, it would be expected that apixaban and edoxaban would behave likewise due to their similar mechanism of action to rivaroxaban (p. 9, 1st full parag.).
Therefore, it would have been obvious before the effective filing date of the claimed invention to use the polycation, polybrene, at a concentration range of 1-100 µg/mL, as Jakimczuk teach that concentrations falling within the claimed range allow one to effectively neutralize heparin in a test sample and accurately monitor clotting parameters relating to the presence of DOAC’s. Further, a phosita would have a reasonable expectation that the system as a whole performs operations (as claimed) which can be used to identify DOACS including apixaban, rivaroxaban or edoxaban.
Regarding the limitation of “the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less…”, a reagent comprising a heparin inhibitor comprising a polycation is taken to be reagent which enables the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less. The prior art references teach a system comprising the claimed reagent which comprises the polycation at concentrations within applicants claimed range.
Therefore, the systems of McCluskey and Schafer with the reagent of Jakimczuk would be a system enabled to identify a presence or concentration of the DOAC as claimed. The reagent of the prior art references is one which would enable the system to detect apixaban as claimed.
The intended use and function of the claimed reagent and system does not patentably distinguish the system, per se, since such undisclosed use and function is inherent to the reagent of the system. In order to be limiting, the intended use and function must create a structural difference between the claimed reagent and system and the reagent and system of the prior art. In the instant case, the intended use and function fails to create a structural difference, thus, it is not limiting. Please note that when applicant claims a reagent and system in terms of function, and the reagent and system of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112). Moreover, the claimed function must be inherent to the reference system. The discovery of a previously unappreciated property of a prior art reagent and system, or of a scientific explanation for the prior art's functioning, does not render the old system patentably new. Thus, the claiming of a new use, functions or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (MPEP 2112).
Claim(s) 9-16, 21, 22, 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Viola et al. (US20180306774, IDS) in view of Schafer et al. (US20220093223A1, IDS) and Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11).
Regarding claims 9, 16, Viola teach a system comprising a cartridge configured to receive a test sample and the cartridge contains a reagent (0007-0009, 0100) comprising a heparin inhibitor comprising a polycation, i.e. polybrene (0051, 0060, 0099, 0149) and calcium (0056) to mix with the test sample and one or more processing devices to perform operations, i.e. viscoelastic tests to assess the coagulation process (0062, 0063, 0098, 0102) including clot time measurements (0144, 0151, 0152). The system is disclosed to be a thromboelastometry-based system (0062).
Regarding claim 9, the reagent comprises a factor Xa inhibitor (0099).
Regarding claims 13 and 22, the polycation is polybrene (0051, 0099).
Regarding claim 21, the reagent comprises a tissue factor (0045, 0099).
Regarding claim 24, the reagent can be a bead/sphere, in lyophilized forms, or as dried surface coatings (0101).
The processing devices of claim 9 are not claimed according to structure, but rather a function. When looking to applicants specification to determine the structure corresponding to the function, applicants specification states
[0052] In another non-limiting example, the low tissue factor assay may be performed using the system described in U.S. Patent Publication No. 2018/0306774 (“Disposable System for Analysis of Hemostatic Function”) that published on Oct. 25, 2018, the contents of which are incorporated herein by reference. This patent publication describes the Ouantra® hemostasis analyzer. The low tissue factor assays may have a turnaround time of 15 to 20 minutes in some examples, making them suitable for point-of-care (POC) applications.
[0053] The diagnostic test instruments/clinical analyzers and assays described herein may be controlled using computing systems or any other appropriate computing device having one or more processing devices, such as one or more microprocessors, one or more microcontrollers, or programmable logic such as one or more field-programmable gate arrays (FGPAs) or one or more application-specific integrated circuits (ASICs).
Thus, the devices of Viola are taken to be devices which would perform the operations as claimed if the sample potentially contained the DOAC’s apixaban of claims 1, 11 and 12, and rivaroxaban, betrixaban or edoxaban of claim 10 because system comprises a cartridge to receive a test sample, a reagent comprising a heparin inhibitor comprising a polycation, and one or more processing devices for performing viscoelastic tests to assess the coagulation process (0062, 0063, 0098, 0102) including clot time measurements (0144, 0151, 0152). The system is disclosed to be a thromboelastometry-based system (0062). Therefore, the system of Viola would be one enabled for identifying DOAC’s.
Viola differs from the claimed invention in that they do not teach specifically teach the processing device identifies the presence of the direct oral factor Xa inhibitors apixaban of claims 1, 11 and 12, and rivaroxaban, betrixaban or edoxaban of claim 10. The reference also does not teach the reagent to comprise calcium chloride according to claim 15.
Schafer teach a system to identify direct oral factor Xa (DOAC) inhibitors in a sample, wherein the DOAC is apixaban, rivaroxaban or edoxaban (0023, 0024, 0028). The system (ROTEM® device) allows one to perform viscoelastic tests to monitor the blood coagulation process and to detect anticoagulants with minor effects on clotting time, these tests are known as ROTEM® TFTEM and EXTEM® (0024, 0028, 0031). The system comprises a cartridge which receives the blood sample for carrying out the viscoelastic tests (0009, 0056). The system receives parameters from the tests and uses them to detect the presence and effects of DOAC’s (0032). The system comprises processing devices, i.e. software modules, analyzer instruments, computing devices and ROTEM devices, for performing operations including clotting parameters based on the test sample with a reagent to identify the presence of DOAC’s (0013, 0024, 0033, 0040, 0055, 0064). The test sample is a blood sample (0024, 0056, 0058) and the reagent for performing the test comprises a reduced tissue factor (0028), calcium chloride, and polybrene as a heparin inhibitor (0031).
Regarding claim 10, the direct oral factor Xa inhibitor comprises apixaban, rivaroxaban or edoxaban (0024, 0028).
Regarding claim 11, the results comprise identifying the DOAC inhibitor (0028, 0032, 0036, 0057).
Regarding claim 12, the results include estimated concentrations of the DOAC inhibitor (0057).
Regarding claim 15, the reagent comprises calcium chloride (0031).
Regarding claim 16, the clotting parameter includes time to clot or clotting time (CT) (0005, 0026, 0028, 0031, 0036, for example).
Therefore, the system comprises a cartridge to receive a blood sample comprising a DOAC, specifically taught are the DOACS apixaban, rivaroxaban or edoxaban. The cartridge contains a reagent to be mixed with the sample, and the reagent comprises a polycation, specifically polybrene as a heparin inhibitor, i.e., a reagent enabling the system to detect apixaban as claimed. The system also comprises one or more processing devices for performing operations to include a clotting parameter to identify a DOAC in the sample.
Thus, before the effective filing date of the claimed invention, one of ordinary skill in the art would have had a reasonable expectation of successfully using the system comprising a cartridge, reagent, and processing devices of Viola and Schafer for performing the operations directed to the measuring or detecting the potential presence of direct oral factor Xa inhibitors given the combined art teachings of ROTEM systems comprising cartridges and processing devices for measuring clotting parameters as well as measuring said parameters in samples having DOAC’s present. The prior art systems are disclosed to comprise cartridges for receiving samples and a reagent comprising the claimed reagent components and devices for performing the disclosed function. Thus, it would have been obvious to one of ordinary skill in the art that the devices would perform the claimed clotting parameter operations when the DOAC’s are present.
Viola does not teach the assay concentration range of the polycation, i.e. polybrene to be within a range of 1-100 µg/mL according to claims 1 and 14.
Jakimczuk teach assays for monitoring the anticoagulant activity of rivaroxaban in the presence of heparin using polybrene and find that polybrene at concentrations of 10 and 50 µg/mL neutralize heparin and enoxaparin and enable the accurate measuring of anti-factor Xa activity and thrombin time in rivaroxaban containing samples (abstract, section 2.2- 2.4, 3.4). The polybrene concentrations were selected to not affect the results of the coagulation tests, to neutralize heparin and to allow accurate monitoring of rivaroxaban (discussion section, p. 7, last parag.-p. 9). The reference teaches that while they only assessed rivaroxaban as a representative DOAC, it would be expected that apixaban and edoxaban would behave likewise due to their similar mechanism of action to rivaroxaban (p. 9, 1st full parag.).
Therefore, it would have been obvious before the effective filing date of the claimed invention to use the polycation, polybrene, at a concentration range of 1-100 µg/mL, as Jakimczuk teach that concentrations falling within the claimed range allow one to effectively neutralize heparin in a test sample and accurately monitor clotting parameters relating to the presence of DOAC’s. Further, a phosita would have a reasonable expectation that the system as a whole performs operations (as claimed) which can be used to identify DOACS including apixaban, rivaroxaban or edoxaban.
Regarding the limitation of “the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less…”, a reagent comprising a heparin inhibitor comprising a polycation is taken to be reagent which enables the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less. The prior art references teach a system comprising the claimed reagent which comprises the polycation at concentrations within applicants claimed range.
Therefore, the systems of Viola and Schafer with the reagent of Jakimczuk would be a system enabled to identify a presence or concentration of the DOAC as claimed. The reagent of the prior art references is one which would enable the system to detect apixaban as claimed.
The intended use and function of the claimed reagent and system does not patentably distinguish the system, per se, since such undisclosed use and function is inherent to the reagent of the system. In order to be limiting, the intended use and function must create a structural difference between the claimed reagent and system and the reagent and system of the prior art. In the instant case, the intended use and function fails to create a structural difference, thus, it is not limiting. Please note that when applicant claims a reagent and system in terms of function, and the reagent and system of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112). Moreover, the claimed function must be inherent to the reference system. The discovery of a previously unappreciated property of a prior art reagent and system, or of a scientific explanation for the prior art's functioning, does not render the old system patentably new. Thus, the claiming of a new use, functions or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (MPEP 2112).
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Viola et al. (US20180306774, IDS) in view of Schafer et al. (US20220093223A1, IDS) and Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11) as applied to claims 9-16, 21, 22, 24 above, and further in view of Barrett et al. (Clinical and Applied Thrombosis/Hemostasis, vol. 19, p. 522-528, 2013). and Greenburg et al. (American Journal of Clinical Pathology, vol. 86, p. 484-489., 1986).
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable McCluskey et al. (US10175225, IDS) in view of Schafer et al. (US20220093223A1, IDS) and Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11) as applied to claims 9-16, 21, 22, 24 above, and further in view of Barrett et al. (Clinical and Applied Thrombosis/Hemostasis, vol. 19, p. 522-528, 2013). and Greenburg et al. (American Journal of Clinical Pathology, vol. 86, p. 484-489., 1986).
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable Schafer et al. (US20220093223A1, IDS) in view of Jakimczuk et al. (J. of Clin. Med, 3/16/2022, p. 1-11) as applied to claims 9-16, 21, 22 above, and further in view of Barrett et al. (Clinical and Applied Thrombosis/Hemostasis, vol. 19, p. 522-528, 2013). and Greenburg et al. (American Journal of Clinical Pathology, vol. 86, p. 484-489., 1986).
Each of Viola, McCluskey and Schafer teach the system of claim 9 comprising a calcium ion.
While the calcium ion assay concentration within a range of 9-15 mM is not taught by the prior art references, this is taken to be a result effective variable which can be optimized depending on the assay, amount of DOAC’s present, and/or to optimize (increasing or decreasing) clotting time in the assay. Support is provided by Barrett and Greenburg. Barrett teaches that calcium chloride concentrations added to assays for monitoring the anticoagulant activity of DOAC’s can be optimized depending on drug concentrations and to increase assay range and sensitivity (abstract, p. 523, for example). Greenburg additionally teaches that effect of calcium chloride on clotting time, that increasing concentration prolonged activated partial thromboplastin time (p.484, whole page, Discussion p. 487-488). Thus, the concentration is taken to be optimizable by one of ordinary skill in the art.
Response to Arguments
Applicant's arguments filed 9/21/2026 have been fully considered but they are not persuasive. Applicants’ arguments are only directed at the Schafer and Jakimczuk references.
As addressed above, the amendment to claim 9, drawn to a system comprising a cartridge containing a reagent comprising a polycation, and one or more processing devices. Independent claim 9 is amended to include the limitation of “the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter or less…”.
Thus, a reagent comprising a heparin inhibitor comprising a polycation present in the claimed concentration range is a reagent which enables the system to detect apixaban as claimed.
The intended use and function of the claimed reagent and system does not patentably distinguish the system, per se, since such undisclosed use and function is inherent to the reagent of the system. In order to be limiting, the intended use and function must create a structural difference between the claimed reagent and system and the reagent and system of the prior art. In the instant case, the intended use and function fails to create a structural difference, thus, it is not limiting. Please note that when applicant claims a reagent and system in terms of function, and the reagent and system of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103 (MPEP 2112). Moreover, the claimed function must be inherent to the reference system. The discovery of a previously unappreciated property of a prior art reagent and system, or of a scientific explanation for the prior art's functioning, does not render the old system patentably new. Thus, the claiming of a new use, functions or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. (MPEP 2112).
Applicant argues that Schafer teaches that the TFTEM CT assays is sensitive to low levels of DOAC (apixaban) but does not disclose the assay being sensitive to apixaban at a concentration of 25 ng/mL or less in the test sample.
Applicant is reminded that the claims are drawn to a system and not an assay method. The current claim language reads that “the reagent comprising a heparin inhibitor comprising a polycation, the reagent enabling the system to detect…”. Thus, as currently claimed, a reagent comprising a heparin inhibitor comprising a polycation according to claim 9, is a reagent enabling to system to detect. Thus, combined art teachings of a system having the claimed system components would be one which is enabled to “perform the function”.
Applicants argue that the amendment should not be treated as a statement of intended use but rather this language defines a functional capability inseparable from the structural and compositional characteristics of the claimed system and its reagent component. Applicants further cite MPEP 2114 that features of an apparatus may be recited structurally or functionally…when a functional limitation requires the apparatus to have particular structural capabilities, it narrows the scope of the claim and should be accorded patentable weight. Applicants state that the inquiry is always whether the claim language products a structural difference over the prior art, not whether it is phrased in functional terms.
Applicants argue that the language "enabling," directly ties the reagent's properties to the system's ability to achieve a specific, quantified detection sensitivity. Moreover, the 25 ng/mL detection threshold is not an arbitrary or aspirational label. To "enable" detection of apixaban at such a low concentration, the reagent possesses specific chemical and physical properties, for example, a polycation along with a heparin inhibitor, that distinguish the reagent from reagents that can only detect apixaban at higher concentrations. These limitations thus creates a structural difference over any prior art system that uses a generically similar reagent but cannot achieve this threshold. Accordingly, the limitation "the reagent enabling the system to detect the apixaban at a concentration of 25 nanograms/milliliter (ng/mL) or less" is not a statement of intended use. It is a functional limitation that imposes a specific, quantified performance requirement on the system's reagent, which requires the reagent to possess a particular composition.
It is the Examiners position that the prior art of record teaches the claimed reagent, i.e. a reagent comprising a heparin inhibitor comprising a polycation, specifically polybrene. Applicants have failed to distinguish a structural difference between the claimed reagent and that of the prior art. The reagent of the prior art possesses specific chemical and physical properties, for example, a polycation, which does not distinguish it structurally from the reagent claimed and thus the reagent would possess the same functional limitation, thus enabling the system to perform the function.
Applicants argue that Jakimczuk was cited for its alleged disclosure of "monitoring the anticoagulant activity of rivaroxaban in the presence of heparin using polybrene” and is not understood to remedy the foregoing deficiencies of Schaefer regarding detection of apixaban. Accordingly, even if Jakimczuk were combined with Schafer, the resulting hypothetical combination would fail to disclose or to suggest the features of claim 1.
It is the Examiners position that, Jakimczuk teach assays for monitoring the anticoagulant activity of rivaroxaban in the presence of heparin using polybrene and find that polybrene at concentrations of 10 and 50 µg/mL neutralize heparin and enoxaparin and enable the accurate measuring of anti-factor Xa activity and thrombin time in rivaroxaban containing samples (abstract, section 2.2- 2.4, 3.4). The polybrene concentrations were selected to not affect the results of the coagulation tests, to neutralize heparin and to allow accurate monitoring of rivaroxaban (discussion section, p. 7, last parag.-p. 9). The reference teaches that while they only assessed rivaroxaban as a representative DOAC, it would be expected that apixaban and edoxaban would behave likewise due to their similar mechanism of action to rivaroxaban (p. 9, 1st full parag.). Further, in light of the teachings of the systems and reagent of the combined prior art refences, one of ordinary skill in the art would have a reasonable expectation of success that the systems and reagents could be used to detect all of the claimed DOAC’s as the art teaches that the claimed systems and reagent can be applied to the claimed DOAC’s, i.e., apixaban, rivaroxaban, or edoxaban. A system of the prior art having the claimed structural components, i.e. an apparatus dictated by its structure and composition, would have the claimed functional properties, by virtue of its structure and composition. This rational is the same as applied by applicant on p. 9 of their arguments.
“The reasoning in Oda applies in this application. Just as the operating temperature range in Oda was not merely a description of the environment in which the bimetal apparatus might be used, but rather a property of the apparatus itself dictated by its material composition, the detection-sensitivity feature recited in claim 9 is not merely a description of the analyte concentration at which the claimed system might be employed. Rather, the phrase "the reagent enabling the system to detect the apixaban at a concentration of 25 ng/mL or less" defines a functional property of the system's reagent, determined by the reagent's specific composition… In both cases, the limitations describe what the apparatus/system is and what it can do by virtue of its structure and composition, not merely what it is intended for”.
Applicants arguments are not found persuasive.
Conclusion
THIS ACTION IS MADE FINAL. 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 TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
