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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/28/2025 has been entered.
Claim Interpretation
Regarding limitations recited in claims 15-16, 19-20, 22-26, and 30, which are directed to a manner of operating the disclosed sample analyzer, it is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See: MPEP § 2114 and 2115.
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.
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.
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) 1-2, 4-5, 7-9, 11-12, 15-16, 19-20, 22-26, and 29-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chupp et al. (USP 5,631,165), in view of Boulassel et al. (Accuracy of Platelet Counting by Optical and Impedance Methods in Patients with Thrombocytopaenia and Microcytosis).
Regarding claim 1, Chupp discloses a sample analyzing method for measuring red blood cells and platelets in a blood sample (C54/L27-C55/L23, see: C. RBC and Platelet Sample Processing), wherein the method comprises:
preparing a first test sample solution containing a blood sample to be tested and a diluent (C54/L28-33, see: a portion of patient sample… is mixed with a volume of diluent/sheath reagent…);
flowing the first test sample solution in a flow cell having an aperture with electrodes, and detecting electrical signals generated when particles in the first test sample solution pass through the aperture (C54/L40-43, see: the diluted sample is transferred to impedance transducer);
obtaining, according to the electrical signals, a first measurement result of red blood cells and platelets in the first test sample solution (C54/L43-44, see: platelets are sized and counted in impedance transducer);
determining, according to the first measurement result, that a number of the platelets in the first test sample solution is less than a predetermined threshold (C54/L49-51, see: the impedance count being used as a diagnostic tool for monitoring instrument performance; C54/L52-59, see: a lower threshold is set which distinguished platelets from noise, and an upper threshold is set which distinguishes platelets from RBCs);
preparing a second test sample solution containing the blood sample to be tested and a diluent or preparing a second test sample solution from the first test sample solution (C54/L44-45, see: Platelets are also transferred to and counted in the optical transducer; C54/L66-67, see: The diluted sample from the RBC cup is also transferred to the optical transducer…);
irradiating the second test sample solution with light in an optical detection area (C54/L44-45, see: Platelets are also transferred to and counted in the optical transducer; C54/L66-67, see: The diluted sample from the RBC cup is also transferred to the optical transducer…);
collecting at least two types of scattered light signals generated by particles in the second test sample solution under light irradiation (C55/L1-4, see: The platelets are determined… using the PSS (polarized side scatter) and IAS (intermediate angle scatter) optical parameters); and
obtaining, according to the at least two types of scattered light signals, a second measurement result of red blood cells and platelets in the second test sample solution (C54/L44-45, see: Platelets are also transferred to and counted in the optical transducer; C55/L4-6, see: The pulses from detectors are processed, digitized and stored…).
Chupp does not explicitly disclose conditionally performing optical detection based on the abnormality of the measurement of electrical signals.
Boulassel teaches it was well known in the art that impedance methods based method of counting significantly overestimated platelet counts compared to optical methods, particularly for patients with conditions associated with microcytosis (pg. 468/Conclusion). It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention to use the accuracy of the impedance based measurements to determine if the optical measurements disclosed in the method disclosed by Chupp are necessary, as taught by Boulassel, in order to provide for consistent platelet count accuracy without the need for redundant analytical tests.
Regarding claim 2, Chupp further discloses the first measurement result and/or the second measurement result comprise(s) a result of at least one parameter selected from a red blood cell count, a platelet count, a mean corpuscular volume, a mean platelet volume, and a red blood cell distribution width, or a result of a parameter calculated from a combination thereof (C54/L43-44, see: platelets are sized and counted in impedance transducer; C54/L44-45, see: Platelets are also transferred to and counted in the optical transducer).
Regarding claim 4, Chupp further discloses the diluent is capable of maintaining morphology of red blood cells and platelets (C54/L33-35, see: The diluent/sheath reagent is appropriate both as a sheath carrier…).
Regarding claim 5, Chupp further discloses the at least two types of scattered light signals comprise at least two types of axial light loss, forward-scattered light signals, medium-angle-scattered light signals, high-angle- scattered light signals, side-scattered light signals, and backward-scattered light signals (C55/L1-4, see: The platelets are determined… using the PSS (polarized side scatter) and IAS (intermediate angle scatter) optical parameters).
Regarding claim 7, Chupp further discloses the at least two types of scattered light signals comprise at least one type of the forward-scattered signals, the medium-angle-scattered signals, and the high-angle-scattered signals (C55/L1-4, see: The platelets are determined… using the PSS (polarized side scatter) and IAS (intermediate angle scatter) optical parameters).
Regarding claim 8, Chupp further discloses the at least two types of scattered light signals comprise the forward-scattered signals and the medium-angle-scattered signals, or the forward-scattered signals and the high-angle-scattered signals (C42/L44-C43/L11, see: one or more detectors are preferably placed in the forward light path for measuring forward intermediate angle scattering and small angle forward scattering; C55/L1-4, see: The platelets are determined… using the PSS (polarized side scatter) and IAS (intermediate angle scatter) optical parameters).
Regarding claim 9, Chupp further discloses the light irradiation is polarized light irradiation, and the at least two types of scattered light signals comprise at least two types of signals in specific states of polarization of axial light loss, forward-scattered light signals, medium-angle-scattered light signals, high-angle-scattered light signals, side-scattered light signals, and backward-scattered light signals that are generated by the particles in the second test sample solution under the polarized light irradiation (C55/L1-4, see: The platelets are determined… using the PSS (polarized side scatter) and IAS (intermediate angle scatter) optical parameters).
Regarding claim 11, Chupp further discloses the step of obtaining, according to the at least two types of scattered light signals, a second measurement result of red blood cells and platelets in the second test sample solution comprises: generating, according to the at least two types of scattered light signals, a two-dimensional or three-dimensional scattergram of the particles in the second test sample solution (Fig. 45A-D); and obtaining, based on the two-dimensional or three-dimensional scattergram, the second measurement result of the red blood cells and the platelets in the second test sample solution (C55/L10-11, see: The count reported from the optical transducer is platelet concentration (PLT)).
Regarding claim 12, Chupp further discloses if it is determined, according to the first measurement result, that the red blood cells and/or the platelets in the blood sample to be tested are abnormal, obtaining, according to the first measurement result and the second measurement result, a final measurement result of the red blood cells and the platelets in the blood sample to be tested, or determining the second measurement result as a final measurement result of the red blood cells and the platelets in the blood sample to be tested (C54/L49-51, see: the impedance count being used as a diagnostic tool for monitoring instrument performance); if it is determined, according to the first measurement result, that the red blood cells and/or the platelets in the blood sample to be tested are normal, determining the first measurement result as a final measurement result of the red blood cells and the platelets in the blood sample to be tested (C54/L44-45, see: Platelets are also transferred to and counted in the optical transducer; C54/L66-67, see: The diluted sample from the RBC cup is also transferred to the optical transducer…); and outputting the final measurement result of the red blood cells and the platelets of the blood sample to be tested (C55/L10-11, see: The count reported from the optical transducer is platelet concentration (PLT)).
Regarding claim 29, Chupp further discloses if it is determined, according to the first measurement result, that a number of the platelets in the first test sample solution is less than a predetermined threshold, there is no clear boundary between a PLT histogram and an RBC histogram that are obtained according to the electrical signals, and there is a clear boundary between a PLT particle population and an RBC particle population on a scattergram that is generated according to the at least two types of scattered light signals (C54/L28-C55/L23, see: RBC histogram and platelet histogram, wherein a lower threshold is set which distinguished platelets from noise, and an upper threshold is set which distinguishes platelets from RBCs and platelets are determined in two dimensional feature space using polarized side scatter).
Regarding claim 15, Chupp discloses a sample analyzer (Fig. 1, 4-5, 10, 16-17, 19-24; C54/L27-C55/L23), comprising:
a sampling apparatus (Fig. 4A) having a pipette with a pipette nozzle (see: aspiration prove 156) and having a driving apparatus for driving the pipette to quantitatively aspirate a blood sample through the pipette nozzle (see: drive assembly 158 for moving the aspiration probe assembly 148 along a slide assembly 160);
a sample preparation apparatus (Fig. 5) having a reaction cell (see: tubing network 182) and a liquid supply part (Fig. 5, see: cup 134 where the patient sample which is deposited by means of aspiration prove is mixed with a volume of diluent/sheath reagent), wherein the reaction cell is configured to receive the blood sample aspirated by the sampling apparatus (see: tubing network 182 coupled to cup 134), and the liquid supply part is configured to supply a diluent to the reaction cell, such that the blood sample aspirated by the sampling apparatus is mixed in the reaction cell with the diluent supplied by the liquid supply part, to prepare a test sample solution (C54/L28-33, see: a portion of patient sample… is mixed with a volume of diluent/sheath reagent…);
an impedance detection apparatus (Fig. 5, see: impedance transducer 174; Fig. 17) comprising a first flow cell having an aperture (see: orifice 314) with electrodes (see: sample introduction nozzle 316 which doubles as the upstream side electrode, and secondary electrode 318), wherein the impedance detection apparatus is configured to detect DC impedances generated when particles in the test sample solution pass through the aperture, and output electrical signals reflecting information about the passage of the particles through the aperture (C39/L35-C40-57);
an optical detection apparatus (Fig. 5, see: optical transducer 170; Fig. 16, 19-24) having a light source (see: laser light source 352), a second flow cell (see: flow cell 170), and optical collectors (see: detectors 400, 402, 404), wherein the particles in the test sample solution that has been treated with the diluent are capable of flowing in the flow cell, light emitted by the light source irradiates the particles in the second flow cell to generate at least two types of scattered light signals, and the optical collectors are configured to collect the at least two types of scattered light signals (C41/L32-C45/L26);
a transfer apparatus (Fig. 10A-B) configured to transfer the test sample solution that has been treated with the diluent in the reaction cell to the impedance detection apparatus and the optical detection apparatus (see: valves 210, 212); and
a processor communicatively connected to the sampling apparatus, the sample preparation apparatus, the impedance detection apparatus, the optical detection apparatus, and the transfer apparatus (Fig. 1, see: analyzer module 64 and data station module 69; C11/L25-67).
Regarding the functional capabilities the instantly recited sample analyzer of claim 15 is configured to perform, the Applicants are directed towards the above rejection of claim 1 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 16 is configured to perform, the Applicants are directed towards the above rejection of claim 2 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 19 is configured to perform, the Applicants are directed towards the above rejection of claim 4 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 20 is configured to perform, the Applicants are directed towards the above rejection of claim 5 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 22 is configured to perform, the Applicants are directed towards the above rejection of claim 7 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 23 is configured to perform, the Applicants are directed towards the above rejection of claim 9 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 24 is configured to perform, the Applicants are directed towards the above rejection of claim 9 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 25 is configured to perform, the Applicants are directed towards the above rejection of claim 11 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 26 is configured to perform, the Applicants are directed towards the above rejection of claim 12 which explains the Examiner’s interpretation of the analogous prior art method.
Regarding the functional capabilities the instantly recited sample analyzer of claim 30 is configured to perform, the Applicants are directed towards the above rejection of claim 29 which explains the Examiner’s interpretation of the analogous prior art method.
Response to Arguments
Applicant's arguments filed 08/28/2025 have been fully considered but they are not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one having ordinary skill in the art, before the effective filing date of the claimed invention, would have been motivated to provide for consistent platelet count accuracy without the need for redundant analytical tests.
The Applicants are further advised that Chupp et al. teaches all of the limitations of the instantly recited method and sample analyzer, save for the “conditionally performing optical detection based on the abnormality of the measurement of electrical signals”. Chupp explicitly discloses comparing the impedance measurements to an upper threshold to distinguish the platelets from RBCs and performing polarized side scatter optical transducer measurements to provide a platelet count for determining platelet concentration (C54/L28-C55/L23).
For the above reasons, the previous ground of rejection have been maintained, with minor updates to address the presented claim amendments.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J EOM whose telephone number is (571)270-7075. The examiner can normally be reached Monday-Friday (9:00AM-5:00PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at 5712721254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT J EOM/Primary Examiner, Art Unit 1797