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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/23/2026 has been entered.
Claim Status
Claims 1-24 are pending and are examined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 5, 6, and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brady (US Patent 6,878,127).
Regarding Claim 1, Brady teaches a two-stage filter blood sample preparation (Fig. 13 device 82, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94. Col. 27, lines 1-10) system comprising:
a two-stage filter component which contains a first filter and a second filter for preparing a blood sample having a volume (Fig. 13 device 82),
wherein the first filter and second filter have a pore size (a first compartment 84, which contains the adsorption medium 34 and a second compartment 86, which contains a different medium 88, which can comprise an adsorption medium or an ion exchange medium), and
the pore size of the first filter is larger than the pore size of the second filter (the polymeric particles 76 of the medium 34 are predominantly mesoporous, with a pore size ranging from 2 to 70 nm, and preferably from 5 to 50 nm. For example, the size of the pores can be within the range of 20 to 150 nm, and preferably between 30 and 100 nm. The polymeric particles 96 are thus predominantly macroporous. The order of passage through the mediums 34 and 88 can be reversed. Col. 20, lines 47-49. This would make the pore size of the first filter is larger than the pore size of the second filter); and
a filter support for retaining the first filter and a second filter (partition 90),
each filter having a first and a second face, wherein the second face of the first filter is retained opposite a first face of the second filter (A partition 90 in the device 82 (e.g., made of a mesh material to accommodate fluid flow) separates the first compartment 84 from the second compartment 86.);
an inlet component comprising an inlet port for receiving a blood sample on a first face of the first filter (inlet 92); and
an outlet component comprising an outlet port for releasing a filtered blood sample from a second face of the second filter (outlet 94),
wherein no more than two filters, the first filter and the second filter, are positioned between the inlet component and the outlet component; or wherein no more than two filters, the first filter and the second filter, arc uscd to separate components of the blood sample when a blood sample is passed through the inlet port to the outlet port (Fig. 13, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.).
Regarding Claim 2, Brady teaches the blood sample preparation system of claim 1, wherein the volume of the blood sample is greater than about 100 µl (the volume of the blood sample is directed to intended use of the device and can be greater than 100 ul).
Regarding Claim 5, Brady teaches the blood sample preparation system of claim 2, wherein the volume of the blood sample is about 500 microliters to about 5 mL (the volume of the blood sample is directed to intended use of the device and can be greater than 100 ul).
Regarding Claim 6, Brady teaches the blood sample preparation system of claim 1, wherein the pore size of the second filter is about 1 micron and/or wherein the pore size of the first filter is about 3 microns (the polymeric particles 76 of the medium 34 are predominantly mesoporous, with a pore size ranging from 2 to 70 nm, and preferably from 5 to 50 nm. For example, the size of the pores can be within the range of 20 to 150 nm, and preferably between 30 and 100 nm. The polymeric particles 96 are thus predominantly macroporous. The order of passage through the mediums 34 and 88 can be reversed. Col. 20, lines 47-49. This would make the pore size of the first filter is larger than the pore size of the second filter).
Regarding Claim 17, Brady teaches a method of filtering a blood sample, comprising: providing a blood sample through the inlet port of the two-stage filtering component of claim 1; and filtering the blood sample through the two-stage filtering component to form a filtered blood sample (Fig. 13, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 3, 4, 8, 18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), as applied to claims 1 and 17 above, in view of Kelso (US Pub 2012/0024788).
Regarding Claim 3, Brady teaches the blood sample preparation system of claim 1.
Brady is silent to a microfluidic amplification component for amplification of nucleic acid from the blood sample, wherein the microfluidic amplification component is in fluid connection with the filter component.
Kelso teaches in the related art of blood filtering. [0059] a device of the present invention, a collection element, and/or a collection module is integrated with downstream processes wherein the microfluidic amplification component is in fluid connection with the filter component (e.g., a cartridge or other device for HIV viral RNA extraction, purification and amplification).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a microfluidic amplification as taught by Kelso, in fluid connection with the filter component of Brady, to allow for viral RNA extraction.
Regarding Claim 4, Brady teaches the blood sample preparation system of claim 3.
Brady is silent to comprising a DNA purification component.
Kelso teaches in the related art of blood filtering. The component would be the para-magnetic particles. [0059] a collection element provides a matrix for storage (e.g., long term storage) of para-magnetic particles (PMPs). In some embodiments, PMPs which are used for capture nucleic acids (e.g., viral RNA) and subsequent processing. In some embodiments, a collection element allows the PMPs to be extracted out of the membrane using a magnetic force (e.g., generated by a permanent magnet or an electro-magnet).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added PMPs, as taught by Kelso, to the system of Brady to allow for capturing nucleic acids.
Regarding Claim 8, Brady teaches the system of claim 3.
Brady is silent to the microfluidic amplification component comprises a polymerase chain reaction chamber for amplifying nucleic acid.
Kelso teaches the sample in Tube-2 was then processed using the IPF method (SEE FIG. 15). The sample from Tube-2 was added to the larger chamber of the cartridge and mixed for 4 minutes using the automated system. 50 µL of elution buffer was aliquoted into the smaller chamber of the IPF cartridge and the two aqueous fluids were overlaid with CHILLOUT liquid wax (Biorad laboratories; SEE FIG. 15). The automated system aggregated the PMPs for 2 minutes using the external magnet and moved the aggregate from the lysis buffer to the elution buffer.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the microfluidic amplification component comprises a polymerase chain reaction chamber for amplifying nucleic acid, as taught by Kelso in the system of Brady to allow for amplifying a nucleic acid.
Regarding Claim 18, Brady teaches the method of claim 17.
Brady is silent to amplifying the nucleic acid target from the filtered blood sample.
Kelso teaches [0061] Membranes were selected based on manufacturer's recommendations, ability to separate plasma from 100-200 µL of whole blood without clogging, pore size, and filter capacity, [0078] (VIVID filter separates cells and the ACCUWIK separates plasma. These would therefore indicate that each of these filters has a different pore size. [0080] The cell separation module containing the filtered material can then be properly discarded. Filtration is done by size since filtered material would be too big to pass though the filter. [0059] a collection element, and/or a collection module is integrated with downstream processes (e.g., a cartridge or other device for HIV viral RNA extraction, purification and amplification).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of amplifying the nucleic acid target from the filtered blood sample, as taught by Kelso, to the method of Brady, to allow for preparing a blood sample for PCR and then further diagnostics on that sample.
Regarding Claim 20, Brady teaches a method of filtering a blood sample and amplifying a nucleic acid target from the blood sample, comprising: providing a blood sample through the inlet port of the two-stage filtering component of claim 1; filtering the blood sample through the two-stage filtering component to form a filtered blood sample (see teachings of claim 1, (Fig. 13, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.).
Brady is silent to purifying nucleic acid from the filtered blood sample to form a purified nucleic acid sample; and amplifying the nucleic acid target from the purified nucleic sample.
Kelso teaches [0048] devices purify blood plasma. [0059] para-magnetic particles for capturing nucleic acids [0076] TABLE-US-00003 TABLE 3 SAMPLES AND CYCLE THRESHOLD (CT) OBTAINED BY ADDING SAMPLES TO AMBION ELUTION BUFFER, PURIFYING THE RNA USING THE IPF METHOD. [0059] a collection element, and/or a collection module is integrated with downstream processes (e.g., a cartridge or other device for HIV viral RNA extraction, purification and amplification.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the step of purifying nucleic acid from the filtered blood sample to form a purified nucleic acid sample; and amplifying the nucleic acid target from the purified nucleic sample, as taught by Kelso to the method of Brady, to allow for a pure nucleic acid to be analyzed from a blood sample.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), as applied to claim 1 above, in view of Pabst (US Patent 4,592,848).
Regarding Claim 7, Brady teaches the blood sample preparation system of claim 1, wherein the pore size of the first filter is about 3 microns (the upper filter plate pair 36, 36A may be designed to prevent particles which are 4 microns or larger in cross section from passing through the elements).
Brady is silent to a peristaltic pump for delivering the blood sample to the blood sample preparation system through the inlet port.
Pabst teaches in the related art of filtering a biological sample. Three hundred milliliters of plasma containing precipitate were fitered at a flow rate of 30 milliliters per minute using a Cole-Parmer peristaltic pump. Pressure at the inlet of the fiber was monitored using a pressure gauge. The maximum pump pressure possible was 25 psi. A nitrogen pressure source for the expander tube at port 38 was set at 25 psi. The hose connections to the pump and filter were made using silicone tubing. Col. 10, lines 57-61.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added a peristaltic pump, as taught by Pabst, for delivering the blood sample to the blood sample preparation system through the inlet port in the system of Brady, to allow for continuous flow of the sample for filtration.
Claims 9, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), in view of Kelso (US Pub 2012/0024788; previously cited) as applied to claims 3, 4, 8, 18 and 20 above, and further in view of Inoue (US Pub 2012/0107822).
Regarding Claims 9, 10, and 11, modified Brady teaches the blood sample preparation system of claim 3, wherein no more than two filters, the first filter and the second filter, separate components of the blood sample when a blood sample is passed through the inlet port to the outlet port (Fig. 13, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.).
Modified Brady is silent to the microfluidic amplification component further comprises at least two inlets for the polymerase chain reaction chamber for providing reagents to the polymerase chain reaction chamber, the microfluidic amplification component further comprises an extraction chamber disposed between the at least two inlets and the polymerase chain reaction chamber for extracting nucleic acid from the blood sample, optionally the microfluidic amplification component further comprises an outlet from the polymerase chain reaction chamber for disposal of waste products, optionally wherein the microfluidic component further comprises at least one valve for controlling flow of reagent to and from the polymerase chain reaction chamber.
Inoue teaches in the related art of microfluidic devices. [0032] FIG. 1, PCR system 100 may include a mixing chip 110, an interface chip 120, and a PCR microfluidic chip 140. Reagents and primers may be mixed in the mixing chip 110 at the desired ratio and may be delivered to the interface chip 120, via ports 108 and 112. The DNA-containing PCR solution may then be delivered to PCR microfluidic chip 140 that includes one or more microchannels 142 in which amplification will take place via the PCR technique. [0034] In some embodiments, a function of mixing chip 110 is to proportionally mix primers 104 and other reagents 102 common to the desired assay. The common reagents 102 and primers 104 are drawn into a mixing region 106 via channel 105 and then held there for an amount of time, after which, the resulting mixture (a.k.a., "reagent/primer mixture"), which may or may not be homogeneous, is drawn into an exit channel 107 connected to exit port 108. The examiner also notes that the term “Extraction chamber” is not limited to extracting since no structure is provided in the claim to specify what would make the chamber be an extraction chamber versus a general chamber. So, the term extraction chamber is any chamber that would be capable of having an extraction take place within the chamber.
The examiner notes that the structures following the term “optionally” are not required as part of the claimed system.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added at least two inlets for the polymerase chain reaction chamber for providing reagents to the polymerase chain reaction chamber, an extraction chamber disposed between the at least two inlets and the polymerase chain reaction chamber for extracting nucleic acid from the blood sample, and an outlet from the polymerase chain reaction chamber for disposal of waste products, as taught by Inoue, to the system of modified Brady, to allow for PCR to take place within the device.
Claims 12, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), in view of Kelso (US Pub 2012/0024788; previously cited), as applied to claim 8 above, and further in view of Mathies (US Pub 7,766,033; previously cited).
Regarding Claims 12, 13, and 14, modified Brady teaches the blood sample preparation system of claim 8, wherein no more than two filters, the first filter and the second filter, separate components of the blood sample when a blood sample is passed through the inlet port to the outlet port (Fig. 13, In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.).
Modified Brady is silent to at least one valve is a solenoid valve, and the solenoid valve comprises a sensing tip.
Mathies teaches in the related art of microfluidic devices. See Abstract. The latching valve structure of claim 11 wherein the demultiplexer has n-rows of membrane valves operated by n-solenoid valves to address 2n independent latching valve structures. See Background/Summary. The latching valve structures 30 and 60 were characterized using variable-duration pressure (e.g., 40 kPa) and vacuum (e.g., -85 kPa) pulses from a computer-controlled solenoid valve. The pressures reported are relative to atmospheric pressure and were measured using a strain gauge pressure transducer. The pneumatic logic device of the present invention may be fabricated as discussed above. For device characterization, pneumatic inputs were supplied by the actuation of computer controlled solenoid valves for the evaluation of individual microvalves, logic gates, and the adder circuits. Separate pumps were used to supply logic high and logic low pressures to the solenoid valves.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added at least one valve (solenoid valve) with a sensing tip, as taught by Mathies, to the system of modified Brady, to provide for controlling microfluidic flow and performing complexation pneumatic logical operations, as taught by Mathies, in Col. 1, lines 18-20.
Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), in view of Kelso (US Pub 2012/0024788; previously cited), as applied to claim 8 above, and further in view of Kornilovich (US Pub 2012/0244604).
Regarding Claims 15 and 16, modified Brady teaches the blood sample preparation system of claim 8.
Modified Brady is silent to the microfluidic amplification component further comprises an actuator and the actuator comprises a membrane.
Kornilovich teaches a polymerase chain reaction (PCR) system includes a mixture chamber, a denature chamber, an annealing chamber, an extension chamber, and a product chamber, that are fluidically coupled to one another through a plurality of microfluidic channels. An inertial pump is associated with each microfluidic channel, and each inertial pump includes a fluid actuator integrated asymmetrically within its associated microfluidic channel. See Abstract. [0060] FIG. 9 shows an inertial pump integrated in a microfluidic channel that is suitable for implementing in a PCR architecture of a PCR microchip 102, according to an embodiment of the disclosure. Referring generally to FIG. 9, the pumping effect of an inertial pump 900 is based on the action (i.e., fluid displacements) of a fluid actuator 902 located asymmetrically within a fluidic channel 904. See membrane.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added an actuator (comprising a membrane), as taught by Kornilovich, to the amplification component in the device of modified Brady, to allow for selective activation to circulate fluid between the chambers in a controlled cycle, as taught by Kornilovich, in the Abstract.
Claims 19, 21, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), as applied to claims 1 and 17 above, in view of Hoffmann (US Pub 2021/0180116).
Regarding Claims 19, 21, and 22, Brady teaches the method of claim 17 and the blood sample preparation system of claim 1. Brady teaches the polymeric particles 76 of the medium 34 are predominantly mesoporous, with a pore size ranging from 2 to 70 nm, and preferably from 5 to 50 nm. For example, the size of the pores can be within the range of 20 to 150 nm, and preferably between 30 and 100 nm. The polymeric particles 96 are thus predominantly macroporous. The order of passage through the mediums 34 and 88 can be reversed. Col. 20, lines 47-49.
However, Brady is silent to the pore size of the first filter and the second filter range from about 1 um to about 25 um and the pore size of the second filter is about 1 micron to about 3 microns and wherein the pore size of the first filter is about 3 microns to about 5 microns.
Hoffmann teaches in the related art of filters. [0058] In addition to the above disclosed pore sizes and materials, other embodiments of the asymmetric membrane may be successfully prepared using other combinations of pore size (range from 200 nm to 30 μm) and other materials (polyester or PET). FIGS. 9a-d are top-down view SEM images of other asymmetric membranes 450, 452, 453, 455 that were prepare in accordance with the fabrication methods disclosed herein. The scale bars is each image are 5 μm. FIG. 9a is an SEM image of an example asymmetric PC membrane 450 prepared with a micropore width of 10 μm and nanopore width of 200 nm. FIG. 9b is an SEM image of an example asymmetric PC membrane 452 prepared with a micropore width of 25 μm and nanopore width of 1 μm.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pore size of the first filter and the second filter range from about 1 um to about 25 um and the pore size of the second filter is about 1 micron to about 3 microns and wherein the pore size of the first filter is about 3 microns to about 5 microns, as taught by Hoffmann, in the filter in the system, as taught by Brady, to allow for collecting particles of larger sizes in a 2 layers of filters, as taught by Hoffman, in the Abstract.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), as applied to claim 1 above, in view of Allen (US Patent 6,039,868).
Regarding Claim 23, Brady teaches the blood sample preparation system of claim 1.
Brady is silent to the first filter and the second filter comprise polycarbonate.
Allen teaches in the related art of filters. A preferred size-exclusion filter membrane is polycarbonate. Col. 4, lines 64-65.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used polycarbonate, as taught by Allen, for the material of the first filter and the second filter, in the system, as taught by Brady, to allow for a standard and cost-effective filtering material to be utilized.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Brady (US Patent 6,878,127), as applied to claim 1 above, in view of Kolb (US Pub 2018/0125464).
Regarding Claim 24, Brady teaches the blood sample preparation system of claim 1.
Brady is silent to the first filter and/or second filter are 70 microns to 240 microns thick.
Kolb teaches in the related art of clinical specimens. [0019] the filter matrix can range from around 50 μm thick to around 2000 μm thick.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected a filter that has a thickness of 70 microns to 240 microns, as taught by Kolb, in the system of Brady, to allow for a suitable size, as taught by Kolb, in [0019].
Response to Arguments
Applicant’s arguments, see pages 1-10, filed 9/23/26, with respect to the rejections of claims have been fully considered. Upon further consideration, the 102 and 103 rejections in view of Kaali over claim 1 are withdrawn and a new ground of rejection is made in view of Brady (US Patent 6,878,127). Brady teaches only 2 filters and blood passing through the 2 filters from the inlet to the outlet in Col. 27, lines 1-10 in Fig. 13, “In use, the blood is conveyed into the device 82 through an inlet 92. The blood passes in succession through the adsorption medium 34 and the different, second medium 88. The blood exits the device 82 through an outlet 94.”
Additionally, upon further consideration, the examiner also notes the prior art of Allen was withdrawn over independent claim 1 (previously cited as an alternative rejection of claim 1).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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 JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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