DETAILED ACTION
This action is in response to the amendments and remarks filed on 09/22/2025, in which claims 1, 3-4 and 13-14 have been amended and claims 1-5 and 7-18 are pending and ready for examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation “the cassette comprises substantially all wetting components for the filtration unit.” However it is not clear how this is possible because the filtration unit and the cassette are separate items that interact, and further because the filtration unit comprises a sample inlet and sample outlet, which are wetting components.
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 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 1-3 and 7-13 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013144090 (hereinafter “Oranth”, per equivalent publication US 2015/0083665), in further view of US 20050205498 by (hereinafter “Sowemimo-Coker”) and US 2007/0056894 A1 (hereinafter “Connors”).
Regarding claim 1 Oranth discloses a tangential flow filtration (TFF) system (Fig. 1), comprising:
a filtration unit (see Fig. 1 & Title) comprising a housing (not pictured but the TFF is disclosed to include a housing [0011]) with a sample inlet 25, a sample outlet 16, a first actuator (12a/13), and a second actuator (12b/13); third actuator (any of the other actuators 12a,b/13 for reservoirs 19a,b) and
a filter 3 is in fluid communication with the sample inlet and the sample outlet,
a first reservoir 18a in fluid communication with the filter, the first reservoir being arranged to couple to the first actuator for imparting flow to a feed solution in a first direction through the filter [0051];
a second reservoir 18b in fluid communication with the filter, the second reservoir being arranged to couple to the second actuator for imparting flow to a feed solution in a second direction through said filter, wherein the second direction opposes the first direction [0051];
a third reservoir 20 arranged to receive an amount of permeate solution, wherein the third reservoir is in fluid communication with the sample outlet when connected to the filtration unit; see Figs. 1-3, [0048]-[0054].
Oranth does not disclose (1) one or more valves, (2) the third reservoir being arranged to couple to the third actuator for imparting a suction force substantially simultaneously to the actuation of the first and/or the second actuators a cassette adapted to fit the filtration unit, or (3) a cassette comprising the filter that is connected to the filtration unit, wherein the cassette is disposable and housed by a connector being removably adjointable to the filtration unit, or (4) wherein the cassette is connected to the filtration unit, the filter is in fluid communication with an air inlet arranged to allow a flow of air through at least said filter to purge any residue left therein following filtering, or wherein the air is forced through a fiber wall to a filter outlet and/or through a filter inlet to the filter outlet.
However, with regard to (1) one or more valves; Oranth further teaches that similar blood separation systems comprise one or more valves in order to control the flow of fluid within the filtration unit (“Normally, a flow filtration system is used which comprises a circuitry with the tangential flow filtration module, a reservoir containing the fluid sample, one or more pressure sensors, valves and a pump to drive the fluid sample through the circuitry.” [0006]). Further Sowemimo-Coker discloses a similar cell-containing fluid sample concentration tangential flow filtration system (Abstract, [0031], Figs. 5-6), comprising first 9 and second 36 reservoirs (which are syringes that include a plunger) which pump fluid back and forth over a filter, wherein valves are provided for each of the syringes to allow flow control such as to allow backflushing the filter [0158].
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filling date to combine the filtration unit of Oranth with one or more valves as taught by Sowemimo-Coker, to yield the predictable results of controlling the flow of fluid within the filtration unit, such as starting and stopping the fluid flowing into or out the filter and allowing backflushing control. MPEP 2143.A.
With regard to (2) a third reservoir which can impart a suction force, Sowemimo-Coker discloses a similar cell-containing fluid sample concentration tangential flow filtration system (Abstract, [0031], Figs. 5-6), comprising first 9 and second 36 reservoirs (which are syringes that include a plunger) which pump fluid back and forth over a filter, and a third reservoir 26 in fluid communication with the filter and the sample outlet and arranged to receive an amount of cell-free solution which permeates the filter [0106], [0159].
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the filtration system of Oranth by substituting for the third reservoir a syringe with plunger as disclosed by Sowemimo-Coker because this involves the simple substitution of known reservoirs for collecting permeate fluid from a tangential flow filtration unit to yield the predictable results of collecting the filter permeate, which is a cell-free solution.
The third reservoir of Oranth in view of Sowemimo-Coker being a syringe with plunger, it is thus inherently capable of imparting a suction force substantially simultaneously to the actuation of the first and/or the second actuators a cassette adapted to fit the filtration unit, as claimed. See MPEP 2112.01 with regard to inherency.
With regard to the third reservoir being arranged to couple to the third actuator, Oranth discloses all of the syringe reservoirs are connected to actuators so that they can be controlled [0051], [0061]-[0072]. Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the filtration system of Oranth in view of Sowemimo-Coker by additionally including a third actuator coupled to the third reservoir in order to control the third syringe reservoir using the controller during filtration.
With regard to (3) a cassette that is removably coupled to the filtration unit, Oranth discloses “[i]t is also possible that an external fluid reservoir is connected to the system, e.g. to one of the conduits of the fluidic channel, so that the fluid being withdrawn in the TFF-module is refilled from the external reservoir.” [0031], and thus anticipates connecting the filtration system to fluid sources external to the disclosed device. Further Connors discloses a filtration system that uses cassettes comprising filters and fluid channels (conduits) that are held in a holder which provides fluid connections to supply the cassette with feed solution and remove retentate and filtrate solutions (Figs. 6a,b,c, 10), and wherein the cassette may be disposable [0017], and may have non-flowing ports (i.e. connectors) for aligning the cassette in the holder [0050].
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the filtration system of Oranth in view of Sowemimo-Coker by forming it as a disposable cassette that fits into a cassette holder that has ports to supply feed and remove retentate and filtrate, and connectors to align the cassette in the holder as disclosed by Connors because this is a known filtration system arrangement that allows filtration using multiple cassettes and for processing more fluid than would fit in the syringe reservoirs.
This thus results in a cassette comprising the filter that is connected to the holder (i.e. the filtration unit which necessarily comprises a sample/feed inlet and a sample/filtrate/retentate outlet), wherein the cassette is disposable and housed by a connector being removably adjointable to the filtration unit. Where the actuators are clearly not disposable and thus would have been obvious to provide with the reusable holder/filtration unit, and where the syringes are obvious to supply as detachable components which connect to the cassette, because syringes are well-known to be single use with a detachable connector for attachment to a needle or fluid conduit and thus would have been obvious to be supplied as single use items which detachably connect to fluid conduits, i.e. of the cassette.
With regard to (4) an air inlet, Sowemimo-Coker discloses a similar tangential flow filtration system, as detailed supra, wherein the filter is backflushed with a liquid solution (platelet recovery solution B, 5% saline solution) and then 13-cc air in order to collect cells separated/trapped thereon (Fig. 4 and 9-10, [0092], [0105], [0158], [0162], [0190]).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the apparatus of Oranth in view of Sowemimo-Coker and Cannon by additionally fluidly connecting the filter with one or more flush solution inlets arranged to allow a flow of a flush solution through at least the filter to flush any residue (i.e. cells) left therein and an air inlet arranged to allow a flow of air through at least the filter (i.e. which accomplishes the claimed limitation “to purge any residue left therein following flushing”) as taught in Sowemimo-Coker because collecting cells is known means of using such a tangential flow filtration device and thus this involves the obvious improvement of the device using a means known for a similar device in order to allow collection of the materials entrapped on the membrane, i.e. cells.
Note: With regard to the limitations that the fluid is “cell-containing” and “cell-free”; these are functional limitations which attempt to define this apparatus claim’s structure in terms of its functional abilities. Claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function (see MPEP 2114), and thus the prior art need only disclose structure capable of achieving the recited function(s) to read on the functional limitations. It is specifically noted that the claim thus does not positively claim a cell-containing or cell-free fluid. These functional limitations do not further define over the prior art because the structure disclosed by Oranth in view of Sowemimo-Coker and Connors would be capable of the noted functional limitation(s), i.e. even though the specific functions are not disclosed.
Regarding claim 2-3 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, wherein the cassette of Connors is disposable and not disclosed to have any actuators or valves, and therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to form the cartridge so that it is free of actuators and values, to reduce cost of the disposable cassette. And thus the cassette is considered to comprises substantially all wetting components for the filtration unit (where the syringes may be considered part of the cassette or separate).
Regarding claim 7 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, but does not disclose wherein the filter comprises, a hollow fibrous material comprising a fiber wall projecting from a filter inlet to a filter outlet, permitting a flow of cell-containing solution through said filter inlet and/or outlet and a flow of cell-free solution through said fiber wall.
However Oranth discloses the filter comprises a semipermeable membrane (17) projecting from a filter inlet (14) to a filter outlet (15), and the filter (3) being configured permit a flow of cell-containing solution through the filter inlet and/or outlet and a flow of cell-free solution through said filter [0031], [0070].
Oranth in view of Sowemimo-Coker and Connors is silent as to where the filter comprises a hollow fibrous material comprising a fiber wall.
However, Sowemimo-Coker further teaches a cassette for filtering a cell containing solution [0031], where the filter comprises a hollow fibrous material ([0106]) comprising a fiber wall (30) projecting from a filter inlet (23) to a filter outlet (27) the filter (30) being configured permit a flow of cell-containing solution through the filter inlet and/or outlet and a flow of cell-free solution through the fiber wall [0106].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date to substitute one known element, the flat membrane of Oranth in view of Sowemimo-Coker and Connors, for another, the hollow fiber membrane as taught by Sowemimo-Coker because this involves the simple substitution go known tangential flow filtration filters for concentration cell solutions to yield the predictable results of concentrating cells in a cross-flow filter.
Regarding claim 8 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, wherein the connector is arranged to adjoin the filtration unit by a transverse movement of the connector with respect to the filtration unit following an insertion axis in a direction substantially perpendicular or parallel to a centerline of the filter, wherein said transverse movement comprises sliding of the connector in a receiving portion of the filtration unit; Connors Figs. 6a,b,c and 10; [0067]-[0070].
Regarding claim 9 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, but does not disclose wherein, when the cassette is connected to the filtration unit, the filter is in fluid communication with one or more flush solution inlets arranged to allow a flow of flush solution through at least said filter to flush any residue left therein following filtering, wherein the flush solution is forced through a fiber wall to a filter outlet and/or through a filter inlet to the filter outlet, and wherein the flush solution is selected from water based buffer solutions with pH of from 6.5 to 7.5, selected from water based salt solutions comprising sodium phosphate, sodium chloride, potassium chloride and/or potassium phosphate or phosphate buffer saline.
With regard to a flush solution and an air inlet, Sowemimo-Coker discloses a similar tangential flow filtration system, as detailed supra, wherein the filter is backflushed with a liquid solution (platelet recovery solution B, 5% saline solution) and then 13-cc air in order to collect cells separated/trapped thereon (Fig. 4 and 9-10, [0092], [0105], [0158], [0162], [0190]).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the apparatus of Oranth in view of Sowemimo-Coker and Cannon by additionally fluidly connecting the filter with one or more flush solution inlets arranged to allow a flow of a flush solution through at least the filter to flush any residue (i.e. cells) left therein and an air inlet arranged to allow a flow of air through at least the filter (i.e. which accomplishes the claimed limitation “to purge any residue left therein following flushing”) as taught in Sowemimo-Coker because collecting cells is known means of using such a tangential flow filtration device and thus this involves the obvious improvement of the device using a means known for a similar device in order to allow collection of the materials entrapped on the membrane, i.e. cells.
Note: With regard to the limitations “wherein the flush solution is forced through a fiber wall to a filter outlet and/or through a filter inlet to the filter outlet, and wherein the flush solution is selected from water based buffer solutions with pH of from 6.5 to 7.5, selected from water based salt solutions comprising sodium phosphate, sodium chloride, potassium chloride and/or potassium phosphate or phosphate buffer saline”; these are functional limitations which attempt to define this apparatus claim’s structure in terms of its functional abilities. Claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function (see MPEP 2114), and thus the prior art need only disclose structure capable of achieving the recited function(s) to read on the functional limitations. These functional limitations do not further define over the prior art because the structure disclosed by Oranth in view of Sowemimo-Coker and Connors would be capable of the noted functional limitation(s), i.e. even though the specific functions are not disclosed.
Regarding claim 10 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, wherein the first actuator is arranged to apply a first force onto the cell-containing solution in the first reservoir and the second actuator is arranged to apply a second force onto the cell- containing solution in the second reservoir, wherein the first force is greater than the second force when imparting flow in the first direction, and wherein the first force is less than the second force when imparting flow in the second direction [0051], and wherein the first and second actuators may be considered to comprise a drive (12a,b/13) and a plunger (shown in figures and inherent to each of the syringes), the plunger being arranged to reciprocate within the respective first and second reservoirs [0051], and wherein the drive comprises a stepper motor [0065], wherein the stepper motor of the first actuator is arranged to provide a first rate of displacement and the stepper motor of the second actuator is arranged to provide a second rate of displacement and wherein said first and second displacements are in opposite directions and of a different magnitude adjusted such that friction between the plungers and reservoirs are compensated (These limaitons are seen as inherent to the stepper motors and control unit disclosed Oranth [0051], [0061]-[0072], see MPEP 2112.01 with regard to inherency; but are functional limitations which are not further defining of structure limitations. Claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function, see MPEP 2114).
Note: With regard to the limitations “wherein the difference between the flow rate of the cell- containing composition out of the first reservoir and the flow rate of said cell- containing composition into the second reservoir is equal to the flow rate of cell-free solution through the fiber wall of the filter”; these are functional limitations which attempt to define this apparatus claim’s structure in terms of its functional abilities. Claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function (see MPEP 2114), and thus the prior art need only disclose structure capable of achieving the recited function(s) to read on the functional limitations. These functional limitations do not further define over the prior art because the structure disclosed by Oranth in view of Sowemimo-Coker and Connors would be capable of the noted functional limitation(s), i.e. even though the specific functions are not disclosed.
Regarding claim 11 Oranth in view of Sowemimo-Coker and Connors discloses a method of filtering a cell-containing solution using the filtration system of claim 1, comprising the steps of:
allowing an amount of cell-containing solution (the fluid sample may contain bacteria and viruses to be concentrated [0005], [0074]) to flow through the sample inlet and into the first reservoir: actuating the first actuator to push the cell-containing solution through the filter in a first direction; actuating a second actuator to push the cell-containing solution through the filter in a second direction; [0051], [0061]-[0072];
collecting a sample of cell-free solution (i.e. in reservoir 20 and which is obviously cell free since the objective is to concentrate the samples) filtered by the filter; and
wherein the first direction is opposite the second direction [0051]; see Figs. 1-3, [0048]-[0054], [0061]-[0074].
Oranth does not disclose (1) connecting the cassette to the filtration unit.
However, it would have been obvious to start the filtration process with connecting the cassette to the filtration unit as the filtration process would not be possible if they are not first connected.
Regarding claim 12 Oranth in view of Sowemimo-Coker and Connors discloses the method of claim 11, wherein a first force is applied by the first actuator and a second force is applied by the second actuator and said first force is greater than said second force when imparting flow in the first direction, and wherein said first force is less than said second force when imparting flow in the second direction; (Oranth [0051], [0061]-[0072] discloses that pressure between the actuators is controlled to provide constant pressure as it is pumped back and forth and compensates for liquid removed by the filter and thus inherently discloses the process claimed in claim 12, See MPEP 2112.01 with regard to inherency.).
Regarding claim 13 Oranth in view of Sowemimo-Coker and Connors discloses the method of claim 11, wherein the first and second actuators comprise a drive and a plunger (shown in figures and inherent to each of the syringes), the plunger being arranged to reciprocate within the respective first and second reservoirs, and wherein the drive consists of a stepper motor [0065], wherein the stepper motor of the first actuator is arranged to provide a first rate of displacement and the stepper motor of the second actuator is arranged to provide a second rate of displacement and wherein said first and second displacements are in opposite directions and of a different magnitude adjusted such that friction between the plungers and reservoirs are compensated, wherein the difference between the flow rate of the cell-containing composition out of the first reservoir and the flow rate of said cell-containing composition into the second reservoir is equal to the flow rate of cell-free solution through the fiber wall of the filter (Oranth [0051], [0061]-[0072] discloses that pressure between the actuators is controlled to provide constant pressure as it is pumped back and forth including specific control to compensate for permeate flux and permeate volume, and thus inherently discloses the process claimed in claim 13). See MPEP 2112.01 with regard to inherency.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Oranth in view of Sowemimo-Coker and Connors further in view of US 20170246591 A1 (hereinafter “de los Reyes”).
Regarding claim 4 Oranth in view of Sowemimo-Coker and Connors discloses the filtration system of claim 1, wherein the cassette further comprises one or more conduits (supra) to allow flow of fluids between the cassette and the holder/filtration unit. It is not specifically disclosed that the cassette is arranged that when connected to the filtration unit, said one or more conduits engage with one or more valves to provide a closable connection capable of regulating the flow through said one or more conduits between an open and a closed position.
However, de los Reyes discloses a similar cassette filter system which comprises a staging plate (holder) that regulates flow through a plurality of cassettes, wherein a retentate valve in the staging plate is fluidly coupled to a retentate port which is fluidly coupled to a channel in the at least one cassette ([0020, [0071], Claim 12), i.e. to control retentate fluid flowing out of the cassette and control backpressure.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date, to modify the filtration system of Oranth in view of Sowemimo-Coker and Connors, by including a retentate valve in the cassette holder retentate conduit as disclosed by de los Reyes, to control retentate flow out of the cassette(s) and control backpressure in the filter cassette.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Oranth in view of Sowemimo-Coker, Connors and de los Reyes further in view of US 2002/0146817 A1 (hereinafter “Cannon”).
Regarding claim 5 Oranth in view of Sowemimo-Coker, Connors and de los Reyes discloses the filtration system of claim 1, but does not disclose wherein the one or more valves comprise one or more pinch valves.
However, Cannon teaches fluid treatment apparatus comprising a housing (see Fig. 3, outer shell or housing 7) with one or more valves (see Fig. 3, valves for diverting media flow 11); said one or more valves comprising a pinch valve (see ¶ [0053] “The first, second, third, or fourth valves may be pinch valves”) in order to prevent and/or divert the flow of a fluid (see ¶ [0013 “least one valve adapted to prevent or divert media flow”).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date to substitute one known element, the valves of the combination of Oranth in view of Sowemimo-Coker, Connors and de los Reyes for another, the pinch valve as taught by Cannon, to yield the predictable results of controlling the flow of fluid within the filtration unit.
Claim 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Oranth in view of Connors and Sowemimo-Coker.
Regarding claim 14 Oranth discloses a method of filtering a cell-containing solution (the (the fluid sample may contain bacteria and viruses to be concentrated [0005], [0074]) comprising the steps of:
providing a filtration unit comprising a filter 3, a first reservoir 18a, and a second reservoir 18b and a third reservoir (19a or 19b) fixed in position relative to one another:
the filtration unit comprising a housing (not pictured but the TFF is disclosed to include a housing [0011]) with a sample inlet 25, a sample outlet 16, a first actuator 12a, and a second actuator 12b, and a third actuator (other 12a or 12b);
allowing an amount of cell-containing solution (the fluid sample may contain bacteria and viruses to be concentrated [0005], [0074]) to flow through the sample inlet and into the first reservoir: actuating the first actuator to engage with the first reservoir to impart flow to the cell-containing solution in a first direction through the filter and to push the cell-containing solution through the filter in the first direction; actuating a second actuator to engage with the second reservoir to impart flow to a cell-containing solution in a second direction through the filter and to push the cell-containing solution through the filter in the second direction [0051];
collecting a sample of cell-free solution filtered by the filter (i.e. in reservoir 20 and which is obviously cell free since the objective is to concentrate the samples); and
wherein the first direction is opposite the second direction [0051]; see Figs. 1-3, [0048]-[0054], [0061]-[0074].
Oranth does not disclose (1) the filtration unit comprises one or more valves or (2) connecting a disposable cassette to the filtration unit; the disposable cassette being a unitary structure free of moving parts removably coupled to a filtration unit as a single unit, the disposable cassette including the filter and reservoirs, and removing the disposable cassette from the filtration unit as a single unit for disposal thereof after filtration, or (3) wherein the cassette is connected to the filtration unit, the filter is in fluid communication with an air inlet arranged to allow a flow of air through at least said filter to purge any residue left therein following filtering, or wherein the air is forced through a fiber wall to a filter outlet and/or through a filter inlet to the filter outlet.
With regard to (1) the filtration unit comprises one or more valves; Oranth further teaches that similar blood separation systems comprise one or more valves in order to control the flow of fluid within the filtration unit (“Normally, a flow filtration system is used which comprises a circuitry with the tangential flow filtration module, a reservoir containing the fluid sample, one or more pressure sensors, valves and a pump to drive the fluid sample through the circuitry.” [0006]). Further Sowemimo-Coker discloses a similar cell-containing fluid sample concentration tangential flow filtration system (Abstract, [0031], Figs. 5-6), comprising first 9 and second 36 reservoirs (which are syringes that include a plunger) which pump fluid back and forth over a filter, wherein valves are provided for each of the syringes to allow flow control such as to allow backflushing the filter [0158].
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filling date to combine the filtration unit of Oranth with one or more valves as taught by Sowemimo-Coker, to yield the predictable results of controlling the flow of fluid within the filtration unit, such as starting and stopping the fluid flowing into or out the filter and allowing backflushing control. MPEP 2143.A.
With regard to (2) connecting a cassette that is removably coupled to the filtration unit, Oranth discloses “[i]t is also possible that an external fluid reservoir is connected to the system, e.g. to one of the conduits of the fluidic channel, so that the fluid being withdrawn in the TFF-module is refilled from the external reservoir.” [0031], and thus anticipates connecting the filtration system to fluid sources external to the disclosed device. Further Connors discloses a filtration system that uses cassettes comprising filters and fluid channels (conduits) that are held in a holder which provides fluid connections to supply the cassette with feed solution and remove retentate and filtrate solutions (Figs. 6a,b,c, 10), and wherein the cassette may be disposable [0017], and may have non-flowing ports (i.e. connectors) for aligning the cassette in the holder [0050].
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the filtration system of Oranth by forming it as a disposable cassette that fits into a cassette holder that has ports to supply feed and remove retentate and filtrate, and connectors to align the cassette in the holder as disclosed by Connors because this is a known filtration system arrangement that allows filtration using multiple cassettes and for processing more fluid than would fit in the syringe reservoirs.
This thus results in a cassette comprising the filter that is connected to the holder (i.e. the filtration unit which necessarily comprises a sample/feed inlet and a sample/filtrate/retentate outlet), wherein the cassette is a single disposable unit and housed by a connector being removably adjointable to the filtration unit. Where the actuators are clearly not disposable and thus would have been obvious to provide with the reusable holder/filtration unit, and where the syringes are obvious to supply as detachable components which connect to the cassette, because syringes are well-known to be single use with a detachable connector for attachment to a needle or fluid conduit and thus would have been obvious to be supplied as single use items which detachably connect to fluid conduits, i.e. of the cassette. The cassettes would have been further obvious to provide as a unitary structure free of moving parts since the cassettes of Connors are unitary structures that do not comprise moving parts and to reduce costs and complexity of the disposable cassette. Where the syringes may be considered part of the cassette or separate, as they are detachable.
Where, it would have been obvious to start the filtration process with connecting the cassette to the filtration unit as the filtration process would not be possible if they are not first connected, a to disconnect the disposable cassette from the filtration unit as a single unit so that it may be disposed of after filtration since it is disposable.
With regard to (3) an air inlet, Sowemimo-Coker discloses a similar tangential flow filtration system, as detailed supra, wherein the filter is backflushed with a liquid solution (platelet recovery solution B, 5% saline solution) and then 13-cc air in order to collect cells separated/trapped thereon (Fig. 4 and 9-10, [0092], [0105], [0158], [0162], [0190]).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the apparatus of Oranth in view of Connors by additionally fluidly connecting the filter with one or more flush solution inlets arranged to allow a flow of a flush solution through at least the filter to flush any residue (i.e. cells) left therein and an air inlet arranged to allow a flow of air through at least the filter (i.e. which accomplishes the claimed limitation “to purge any residue left therein following flushing”) as taught in Sowemimo-Coker because collecting cells is known means of using such a tangential flow filtration device and thus this involves the obvious improvement of the device using a means known for a similar device in order to allow collection of the materials entrapped on the membrane, i.e. cells.
Regarding claim 15 Oranth in view of Connors and Sowemimo-Coker discloses the method according to claim 14, wherein a first force is applied by the first actuator and a second force is applied by the second actuator, and the first force is greater than the second force when imparting flow in the first direction, and wherein the first force is less than the second force when imparting flow in the second direction; (Oranth [0051], [0061]-[0072] discloses that pressure between the actuators is controlled to provide constant pressure as it is pumped back and forth and thus inherently discloses the process claimed in claim 15). See MPEP 2112.01 with regard to inherency.
Regarding claim 16 Oranth in view of Connors and Sowemimo-Coker discloses the method according to claim 14, wherein the first and second actuators comprise a drive 12a, 12b and a plunger, the plunger being arranged to reciprocate within the respective first and second reservoirs, and wherein the drive of the first actuator is arranged to provide a first rate of displacement and the drive of the second actuator is arranged to provide a second rate of displacement and wherein the first and second displacements are in opposite directions and of a different magnitude adjusted such that friction between the plungers and reservoirs are compensated, wherein the difference between the flow rate of the cell-containing solution out of the first reservoir and the flow rate of the cell-containing solution into the second reservoir is equal to the flow rate of cell-free solution through a fiber wall of the filter; (Oranth [0051], [0061]-[0072] discloses that pressure between the actuators is controlled to provide constant pressure as it is pumped back and forth and compensates for liquid removed by the filter and thus inherently discloses the process claimed in claim 16). See MPEP 2112.01 with regard to inherency.
Regarding claim 17 Oranth in view of Connors and Sowemimo-Coker discloses the filtration system according to claim 14, wherein the difference between the flow rate of the cell-containing solution out of the first reservoir and the flow rate of the cell-containing solution into the second reservoir is equal to the flow rate of cell-free solution through a fiber wall of the filter; (Oranth [0051], [0061]-[0072] discloses that pressure between the actuators is controlled to provide constant pressure as it is pumped back and forth and compensates for liquid removed by the filter and thus inherently discloses the process claimed in claim 17). See MPEP 2112.01 with regard to inherency.
Regarding claim 18 Oranth in view of Connors and Sowemimo-Coker discloses the filtration system according to claim 14, wherein the drive of the first actuator comprises a first stepper motor and the drive of the second actuator comprises a second stepper motor (each of the actuators is pictured to have a motor 12a, which is disclosed to be a stepping motor [0065]).
Response to Amendment
The previous 35 U.S.C. 112(b) rejections of claims 1-2 and 4-18 are withdrawn in view of the Applicants’ arguments and amendments.
Response to Arguments
Applicant's arguments filed 09/22/2025 have been fully considered but they are not persuasive.
In response to Applicants’ argument that Oranth teaches against a system having redundant circuits, valves, and sensors and therefore it would not have been obvious to include valves; the Examiner disagrees. Applicants argue [0006] of Oranth teaches against a system having redundant circuits, valves, and sensors, and that “[b]ecause ORANTH is concerned with processing small amounts of fluid volume, one of ordinary skill in the art would not look to modify ORANTH with a series of valves and reservoirs, as the Examiner states at page 5 of the Office Action.” However, [0006] of Oranth is only seen to teach away from systems having a loop circuitry and an internal reservoir, and does not teach away from valves or a separate third reservoir/syringe as claimed, and where valves are seen as obvious to include in any fluid handling system absent reason to exclude them. Sowemimo-Coker is now additionally cited to address the obviousness of including valves.
In response to Applicants’ argument that because Oranth is silent to the need for any purging and any purging of residue using air any motivation to add such a feature or structure would be impermissible hindsight; the Examiner disagrees. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Specifically, the motivation to add air purging is provided by the disclosure of Sowemimo-Coker, as detailed in the rejection and which Applicants have not addressed. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to Applicants’ argument that using a third reservoir imparting a suction force substantially simultaneously to an actuation of the first and/or second actuators would change the operation of Oranth and is thus not obvious; the Examiner disagrees. It should first be noted that it is not impermissible to change the operation of the reference Oranth, but rather it is impermissible to change the operation of the device such that it renders it unsuitable for its intended purpose; see MPEP 2143.01(V). Oranth discloses only one of the pairs of piston pumps (i.e. first and second reservoirs) is used to drive the fluid and one time, however this does not restrict a third pump from actuating when one of the first or second reservoir/pumps is actuated, and does not require simultaneous actuation of the first and second reservoir/pumps; and thus addition of third reservoir/pump and its simultaneous actuation with the first or second reservoir/pumps dos not change the operation of the device such that it renders it unsuitable for its intended purpose; and is thus proper.
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.
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/ERIC J MCCULLOUGH/ Examiner, Art Unit 1773
/BENJAMIN L LEBRON/ Supervisory Patent Examiner, Art Unit 1773