DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-24 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, 17, 19, 21, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kaali (US Patent 5,185,086).
Regarding Claim 1, Kaali teaches a blood sample preparation system comprising: a two-stage filter component comprising at least a first filter and a second filter for preparing a blood sample having a volume, wherein the first filter and second filter have a pore size, and 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, 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; an inlet component comprising an inlet port for receiving a blood sample on a first face of the first filter; and an outlet component comprising an outlet port for releasing a filtered blood sample from a second face of the second filter (Fig. 2 generally rectangular, box-like treatment vessel 31 fabricated from plastic or other electrical insulating material closed by an insulating top 32 and an insulating bottom 33. A fluid inlet conduit 34 is provided in top 32 and an outlet conduit 35 is provided in bottom 33. The near sides and top of vessel 31 have been broken away to show the construction of the mechanical filter elements 36, 36A and 37, 37A all of which are fabricated from platinum or other relatively inert electrically conductive material which is compatible with human blood, and/or body fluids, and/or synthetic fluids, and/or tissue. As shown in Fig. 2, the upper set of filter plate elements 36 and 36A are relatively coarse compared to the lower set of filter plate elements 37 and 37A. Again, for example, 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 while the lower set of elements 37, 37A may be designed to prevent the passage of particles 0.2 microns or larger from passing through. Again, as a matter of design, the passages through the sets of filter plates elements 36, 36A and 37, 37A may be axially aligned. See Col. 4, lines 62-68 and Col. 5, lines 1-20.).
wherein no more than two filters, the first filter and the second filter, are used to separate components of the blood sample (this limitation is directed to intended use of the device).
Regarding Claim 2, Kaali 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, Kaali 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, Kaali 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 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).
Regarding Claim 17, Kaali 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 (A method and system for the treatment of blood and/or other body fluids (such as amniotic fluids) as well as synthetic fluids such as tissue culture medium whereby a fluid to be treated is mechanically filtered for elimination of particles contained therein which exceed 0.2 microns in size (or some other minutely small size) and in addition subjecting the fluid being treated to electric field forces in the microwatt/milliwatt region induced by relatively low voltage of a few volts and low current density which does not exceed values which could impair the biological usefulness and characteristics of the blood or other fluid being treated. A fluid inlet conduit 34 is provided in top 32 and an outlet conduit 35 is provided in bottom 33.).
Regarding Claim 19, Kaali teaches the method of claim 17, wherein the pore size of the first filter and the second filter range from about 1 um to about 25 um ( 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 while the lower set of elements 37, 37A may be designed to prevent the passage of particles 0.2 microns or larger from passing through.).
Regarding Claim 21, Kaali teaches the blood sample preparation system of claim 1, wherein the pore size of the second filter is about 1 micron to about 3 microns (Again, for example, 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).
Regarding Claim 22, Kaali teaches the blood sample preparation system of claim 1, wherein the pore size of the first filter is about 3 microns to about 5 microns (while the lower set of elements 37, 37A may be designed to prevent the passage of particles 0.2 microns or larger from passing through.).
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 Kaali (US Patent 5,185,086) as applied to claims 1 and 17 above, in view of Kelso (US Pub 2012/0024788).
Regarding Claim 3, Kaali teaches the blood sample preparation system of claim 1 further comprising 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 Kaali, to allow for viral RNA extraction.
Regarding Claim 4, Kaali teaches the blood sample preparation system of claim 3.
Kaali 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 Kaali to allow for capturing nucleic acids.
Regarding Claim 8, Kaali teaches the system of claim 3.
Kaali 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 Kaali to allow for amplifying a nucleic acid.
Regarding Claim 18, Kaali teaches the method of claim 17.
Kaali 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 Kaali, to allow for preparing a blood sample for PCR and then further diagnostics on that sample.
Regarding Claim 20, Kaali 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, A fluid inlet conduit 34 is provided in top 32 and an outlet conduit 35 is provided in bottom 33.);
Kaali 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 Kaali, 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 Kaali (US Patent 5,185,086) as applied to claim 1 above, in view of Pabst (US Patent 4,592,848).
Regarding Claim 7, Kaali 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).
Kaali 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 Kaali, 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 Kaali (US Patent 5,185,086), 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 Kaali teaches the blood sample preparation system of claim 3.
Modified Kaali 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, the microfluidic amplification component further comprises an outlet from the polymerase chain reaction chamber for disposal of waste products.
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.
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 Kaali, 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 Kaali (US Patent 5,185,086), 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 Kaali teaches the blood sample preparation system of claim 8.
Modified Kaali is silent to wherein the microfluidic amplification component further comprises at least one valve for controlling flow of reagents to and from the polymerase chain reaction chamber, the 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 Kaali, 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 Kaali (US Patent 5,185,086), 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 Kaali teaches the blood sample preparation system of claim 8.
Modified Kaali 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 Kaali, to allow for selective activation to circulate fluid between the chambers in a controlled cycle, as taught by Kornilovich, in the Abstract.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Kaali (US Patent 5,185,086) as applied to claim 1 above, in view of Kolb (US Pub 2018/0125464).
Regarding Claim 24, Kaali teaches the blood sample preparation system of claim 1.
Kaali 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 Kaali, to allow for a suitable size, as taught by Kolb, in [0019].
Claims 1 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Allen (US Patent 6,039,868) in view of Kelso (US Pub 2012/0024788).
The examiner notes this is an additional rejection over claim 1.
Regarding Claim 1, Allen teaches a blood sample preparation system comprising: a two-stage filter component comprising at least a first filter and a second filter for preparing a blood sample having a volume, wherein the first filter and second filter have a pore size, and a filter support for retaining the first filter and a second filter, 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; an inlet component comprising an inlet port for receiving a blood sample on a first face of the first filter; and an outlet component comprising an outlet port for releasing a filtered blood sample from a second face of the second filter (Referring now to FIGS. 1-3, a blood separation device 10 comprises a flexible tube 12 having an internal lumen 14. A needle assembly 16 is attached at an inlet end of the tube 12 and a filter member 18 is attached at an outlet end of the tube. A shield 20 having a flange 22 at its base is disposed around the needle assembly 16 and attached to the inlet end of flexible tube 12. The shield 20 is opened at its upper end 24 so that it can receive a conventional blood collection device, such as a vacuum collection device, which can be introduced over the needle assembly 16, as described in more detail hereinafter. The filter assembly 18 houses a three-layer filter element including individual glass fiber layers 26, 28, and 30 and final size exclusion membrane 31 below the glass fiber layers. The filter assembly 18 includes two separable halves 32 and 34 to facilitate assembly after the glass fiber layers 26, 28 and 30 and size exclusion membrane 31 have been introduced. A plasma outlet port 36 is provided at the base of the filter member 18 to permit directed transfer of the plasma to a desired assay device or substrate. Preferably, the size exclusion membrane is sealed tightly against the bottom glass fiber layer 30 to inhibit leakage of blood and plasma past the membrane. The examiner additionally notes that Allen teaches Materials and constructions for two-stage filter systems suitable for use. Col. 5, lines 12-13.).
wherein no more than two filters, the first filter and the second filter, are used to separate components of the blood sample (this limitation is directed to intended use of the device).
Allen is silent to and the pore size of the first filter is larger than the pore size of the second filter.
Kelso teaches [0066] The efficiency of separation is governed by several factors. Capillary number or pore size of the collection membrane affects the efficiency of extraction. The smaller the pore size, the greater the efficiency of extraction, which would indicate greater efficiency by the use of 111 membrane compared to 142. While the separation membrane should separate plasma without gelling fouled or clogged, its capacity should be minimal A membrane with a high liquid capacity would lead to lower efficiency of extraction in the collection 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 configured the pore size of the first filter is larger than the pore size of the second filter, as taught by Kelso, in the filter component in the system of Allen, to allow for separation and then further extraction in the same component.
Regarding Claim 23, Allen teaches the blood sample preparation system of claim 1, wherein the first filter and the second filter comprise polycarbonate (A preferred size-exclusion filter membrane is polycarbonate. Col. 4, lines 64-65.).
Response to Arguments
Applicant’s arguments, see page 6, filed 3/2/26, with respect to claim objections have been fully considered and are persuasive. The objections to the claims has been withdrawn.
Applicant's arguments, see pages 6-10, filed 3/2/26 have been fully considered but they are not persuasive.
First, Applicant argues on page 6 regarding the 102 rejection that “only two filters, the first filter and the second filter, are used to separate components of the blood sample.”
In response, the examiner notes that the specification does not limit the claimed system to only a first filter and a second filter. Further, the limitation states that a “first filter and a second filter are used to separate components of the blood sample” which is directed to intended use and would not limit the claim to other filters being in the system. The blood sample is also not part of the system and separating the components of the blood sample is an intended use of the system. Therefore, the rejection is maintained.
Second, Applicant argues that on page 9 that the prior art of Allen teaches a device that employs at least 4 layers (3 chromatographic layers and 1 size exclusion filter) which is different mechanistically and structurally from applicant’s device.”
In response, the examiner notes that the specification does not limit the claimed system to only a first filter and a second filter. Further, the limitation states that a “first filter and a second filter are used” which is directed to intended use and would not limit the claim to other filters being in the system. The blood sample is also not part of the system and separating the components of the blood sample is an intended use of the system. The examiner additionally notes that Allen teaches Materials and constructions for two-stage filter systems suitable for use. Therefore, the rejection is maintained.
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 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