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 Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 12-14 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Keaney et al. (US 2018/0214826 A1).
Regarding claim 12, Keaney discloses a method of filtering a suspension of red blood cells (Abstract; ¶0031-0037), comprising: introducing a wash solution to the suspension of red blood cells (¶0036: the whole blood may be diluted by an anticoagulant) such that a combined volume is retained within a first compartment (Fig. 2A, feat. 202; ¶0052-0053: Blood 203 is applied to retentate channel 202); applying a sweeping action upon the volume (¶0032 and 0038: pump 126 pulls blood from retentate channel 202 across filter module 102 to provide sufficient sweeping); applying a pressure upon the volume while applying the sweeping action such that the volume is urged through a filter membrane at a predetermined filtration rate (¶0038-0039: pump 126 pulls blood from retentate channel 202 across filter module 102); maintaining the filtration rate over a predetermined period of time such that hemolysis is maintained below a threshold level (¶0038-0039: the system controls the transmembrane pressure and resulting filtration rate to prevent or reduce hemolysis); and collecting the volume within a second compartment (Fig. 2A, feat. 208; ¶0052-0053).
Regarding claim 13, Keaney discloses the method of claim 12. Keaney further discloses that introducing the wash solution comprises introducing the wash solution such that the volume has 10% hematocrit level (¶0036, 0040, and 0086: the cells suspension may be diluted to a hematocrit level of 10%).
Regarding claim 17, Keaney discloses the method of claim 12. Keaney further discloses that the system controls the flow rates to ensure that the characteristic red blood cell passage rate through the filter is not exceeded and filtration can be maintained for at least an hour (¶0032 and 0109). This touches the claimed range of less the 30 minutes to an hour, and therefore anticipates it. Please see MPEP §2131.03(II).
Regarding claim 18, Keaney discloses the method of claim 12. Keaney further discloses that the pump flow rates may be controlled to prevent hemolysis (¶0038), and therefore maintain less than 1% hemolysis. Therefore, Keaney further discloses that maintaining the filtration rate comprises maintaining the hemolysis threshold level below 1%.
Regarding claim 19, Keaney discloses the method of claim 12. Keaney further discloses that maintaining the filtration rate comprises removing extracellular solute from the volume (¶0038: circulating tumor cells are removed from the blood volume).
Regarding claim 20, Keaney discloses the method of claim 19. Keaney further discloses that removing extracellular solutes comprises removing over 99% of the extracellular solutes from the volume (¶0031, 0038, and 0055-0057).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4-6, and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Guigan (US 5,188,583 A) in view of Schlutz (US 3,982,691 A).
Regarding claim 1, Guigan discloses an apparatus for centrifuging a suspension of red blood cells (Figs. 1-12, feat. 1; Col. 1, line 36 – Col. 2, line 20; Col. 2, lines 43-45), comprising a reservoir positioned within a housing and located along an axis of rotation, wherein the reservoir defines a port for receiving the suspension of red blood cells (Figs. 1-2, feat. 20; Col. 3, lines 6-20); a wash reservoir located below around the reservoir (Figs. 1-2, feats. 21-28; Col. 3, lines 6-29); a pack compartment located circumferentially about the reservoir (Figs. 1-2, feats. 51-58; Col. 3, lines 34-51) and in fluid communication with the wash reservoir through a fluid lumen extending from a top portion of the wash reservoir (Figs. 1, 2, and 9, feats. 50; Col. 3, line 58 – Col. 4, line 2); a supernatant compartment in fluid communication with the pack compartment and located circumferentially between the wash reservoir and the pack compartment (Figs. 1, 2, and 10, feats. 41-48; Col. 3, line 52 – Col. 4, line 2); and a waste reservoir located below the wash reservoir and in fluid communication with the supernatant compartment (Figs. 2, 11, and 12, feat. 7; Col. 3, lines 52 – Col. 4, line 13).
Guigan does not disclose that the fluid lumen extending from the top portion of the wash reservoir extends to a bottom portion of the pack compartment.
Schlutz teaches a centrifugal separation and washing device (Figs. 1-4; Col. 3, lines 21-41) comprising a chamber for receiving red blood cells (Figs. 1 and 4, feat. 11; Col. 7, lines 15-37) comprising a plurality of compartments (Figs. 1 and 4, feat. 10) in which the red blood cells collect and collapse (Fig. 4, feat. 43; Col. 8, lines 6-54). The device further comprises a plurality of recesses or conduits (Figs. 1 and 4, feat. 2; Col. 7, lines 15-37) disposed in a bottom plate (1) which are each in fluid communication with the bottom and apex of each of the compartments (Figs. 1 and 4, feat. 9) via openings (5) in an intermediate plate (6). Schlutz teaches that the conduits (Figs. 1 and 4, feat. 2) allow the blood cells and washing fluid to be introduced at the point of maximum centrifugal force, which allows the washing fluid to contact substantially all of the compacted blood cells and higher efficiency (Col. 8, line 40 – Col. 9, line 20). The apparatus of Guigan includes a lumen opening at the top portion of the wash reservoir (Guigan: Figs. 1, 2, and 9, feat. 50), and modifying the apparatus of Guigan to have a lumen that extends to the bottom of the pack compartment as taught by Schlutz would cause the fluid lumen to extend from a top portion of the wash reservoir and a bottom portion of the pack compartment. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the apparatus disclosed by Guigan so that the fluid lumen extending from the top portion of the wash reservoir extends to a bottom portion of the pack compartment in order to allow the blood cells and washing fluid to be introduced at the point of maximum centrifugal force, which allows the washing fluid to contact substantially all of the compacted blood cells and higher efficiency as taught by Schlutz.
Regarding claim 2, Guigan in view of Schlutz discloses the apparatus of claim 1. Guigan further discloses that the reservoir defines an excess red blood cell hold region (Figs. 1-2, feat. 20; Col. 3, lines 6-20).
Regarding claim 4, Guigan in view of Schlutz discloses the apparatus of claim 1. Guigan further discloses that the supernatant compartment comprises a wall having a surface angled relative to the axis of rotation (Figs. 1, 2, and 10, feats. 41-48; Col. 3, line 52 – Col. 4, line 2).
Regarding claim 5, Guigan in view of Schlutz discloses the apparatus of claim 1. Guigan further discloses that the supernatant compartment is in fluid communication with the waste reservoir via a fluid lumen (Figs. 2, 3, and 11, feat. 61; Col. 3, line 52 – Col. 4, line 13).
Regarding claim 6, Guigan discloses a method for centrifuging a suspension of red blood cells (Col. 1, line 36 – Col. 2, line 20; Col. 3, line 58 – Col. 4, line 13), comprising: introducing the suspension of red blood cells within a reservoir (Figs. 1-2, feat. 20; Col. 3, lines 6-20) such that the suspension drains from the reservoir and into a pack compartment (Figs. 1-2, feat. 51; Col. 3, lines 34-51) circumferentially positioned about the reservoir (Figs. 9-12; Col. 3, line 58 – Col. 4, line 13: the suspension drains from reservoir 20 to pack compartments 51-58 via wash compartments 21-28); rotating the suspension within the circumferential pack compartment (Fig. 10; Col. 3, lines 58-64); and stopping a rotation of the suspension such that waste from the supernatant compartment (Figs. 1, 2, and 10, feats. 41-48; Col. 3, line 52 – Col. 4, line 2) drains into a waste compartment (Figs. 2, 11, and 12, feat. 7; Col. 3, lines 52 – Col. 4, line 13) and a RBC pack remains within the pack compartment (Figs. 10-12, feats. 51-58 and 71; Col. 3, line 64 – Col. 4, line 13).
Guigan does not disclose that rotating the suspension within the circumferential pack compartment causes wash solution within a wash compartment flows radially outwards and up through the pack compartment and into a supernatant compartment.
As discussed above, Schlutz teaches a centrifugal separation and washing device (Figs. 1-4; Col. 3, lines 21-41) comprising a chamber for receiving red blood cells (Figs. 1 and 4, feat. 11; Col. 7, lines 15-37) comprising a plurality of compartments (Figs. 1 and 4, feat. 10) in which the red blood cells collect and compact (Fig. 4, feat. 43; Col. 8, lines 6-54). The device further comprises a plurality of radially oriented recesses or conduits (Figs. 1 and 4, feat. 2; Col. 7, lines 15-37) disposed in a bottom plate (1) which are each in fluid communication with the bottom and apex of each of the compartments (Figs. 1 and 4, feat. 9) via openings (5) in an intermediate plate (6) such that the wash fluid flows radially outward and up through the red blood cels (Fig. 4). The wash fluid is driven through the red blood cells by a combination of the centrifugal force and a pressure head (Col. 8, lines 27-53) and is collected by a waste conduit (Fig. 4, feat. 41). Schlutz teaches that the conduits (Figs. 1 and 4, feat. 2) allow the blood cells and washing fluid to be introduced at the point of maximum centrifugal force, which allows the washing fluid to contact substantially all of the compacted blood cells and higher efficiency (Col. 8, line 40 – Col. 9, line 20). The apparatus of Guigan includes a lumen opening at the top portion of the wash reservoir (Guigan: Figs. 1, 2, and 9, feat. 50), and modifying the apparatus of Guigan to have a lumen that extends to the bottom of the pack compartment as taught by Schlutz would cause the fluid lumen to extend from a top portion of the wash reservoir and a bottom portion of the pack compartment and cause the wash fluid to flow radially outward and up through the pack compartment to a supernatant compartment. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the apparatus and method of Guigan so that rotating the suspension within the circumferential pack compartment causes wash solution within a wash compartment flows radially outwards and up through the pack compartment and into a supernatant compartment in order to allow the blood cells and washing fluid to be introduced at the point of maximum centrifugal force, which allows the washing fluid to contact substantially all of the compacted blood cells and higher efficiency as taught by Schlutz.
Regarding claim 8, Guigan in view of Schlutz discloses the method of claim 6. Guigan further discloses that introducing the suspension comprises introducing the red blood cells within the reservoir located along an axis of rotation of the reservoir (Figs. 2 and 7-12, feats. 2 and 20; Col. 2, lines 43-45; Col. 3, lines 21-30).
Regarding claim 9, Guigan in view of Schlutz discloses the method of claim 6. As discussed above, Schlutz teaches a device comprising a plurality of radially oriented recesses or conduits (Figs. 1 and 4, feat. 2; Col. 7, lines 15-37) disposed in a bottom plate (1) which are each in fluid communication with the bottom and apex of each of the compartments (Figs. 1 and 4, feat. 9) via openings (5) in an intermediate plate (6) such that the wash fluid flows radially outward and up through the red blood cels (Fig. 4). Therefore, Guigan in view of Schlutz further discloses that rotating the suspension comprises flowing the wash solution through one or more openings which flow into a bottom of the pack compartment.
Regarding claim 10, Guigan in view of Schlutz discloses the method of claim 6. Guigan further discloses that the supernatant compartment (Figs. 1, 2, and 10, feats. 41-48; Col. 3, line 52 – Col. 4, line 2) is located circumferentially within the pack compartment (Figs. 1-2, feats. 51-58; Col. 3, lines 34-51).
Regarding claim 11, Guigan in view of Schlutz discloses the method of claim 6. Guigan further discloses that the waste reservoir (Figs. 2, 11, and 12, feat. 7; Col. 3, lines 52 – Col. 4, line 13) is located circumferentially below the wash compartment (Figs. 1-2, feats. 21-28; Col. 3, lines 6-29).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Guigan (US 5,188,583 A) in view of Schlutz (US 3,982,691 A) and in further view of Leach (US 2016/0288139 A1).
Regarding claim 3, Guigan in view of Schlutz discloses the apparatus of claim 1, but does not disclose a valve positioned along the top portion of the wash reservoir.
Leach teaches a cell washing apparatus (Figs. 2-8, feat. 100; ¶0025-0029) comprising a valve (134; ¶0029) at the top portion of a wash reservoir (124; ¶0029 and 0035). The valve advantageously controls fluid outflow from the wash reservoir based on the speed of the centrifuge (¶0029). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the apparatus disclosed by Guigan in view of Schultz so that it comprises a valve positioned along the top portion of the wash reservoir in order to control fluid outflow from the wash reservoir as taught by Leach.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Guigan (US 5,188,583 A) in view of Schlutz (US 3,982,691 A) and in further view of Unger et al. (US 5,114,396 A).
Regarding claim 7, Guigan in view of Schlutz discloses the method of claim 6, but does not disclose repeating each of the steps from one to four times.
Unger teaches a red blood cell washing system (Figs. 1-3, feat. 1; Col. 2, line 65 – Col. 3, line 8) and method (Figs. 4a-4j; Col. 4, line 53 – Col. 5, line 42) in which the third to sixth steps, which comprise accelerating, decelerating, and stopping the centrifuge (Figs. 4c-4f; Col. 5, lines 6-38), are repeated as many times as required to make the red blood cells clinically acceptable (Col. 5, lines 39-42). Unger teaches that between 3 and 4 repetitions are typically required (Col. 5, lines 39-42). The 3 to 4 repetitions lies within the claimed range of 1 to 4 repetitions, and therefore a prima facie case of obviousness exists for the claimed range. Please see MPEP §2144.05(I). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Guigan in view of Schlutz so that it further comprises repeating each of the steps from one to four times in order to ensure that the red blood cells are clinically acceptable as taught by Unger.
Claims 14 is rejected under 35 U.S.C. 103 as being unpatentable over Keaney et al. (US 2018/0214826 A1) in view of Nierich (WO 2021/187988 A2).
Regarding claim 14, Keaney discloses the method of claim 12. Keaney further discloses that applying the sweeping action comprises passing the volume over a polycarbonate or polyethylene membrane (Fig. 2, feat. 212; ¶0038 and 0056). Keaney does not disclose that the membrane is track etched.
Nierich teaches a blood filtration apparatus and method for autologous blood transfusion (Figs. 1-2, feat. 3; Page 1, lines 4-8; Page 18, lines 23-34) comprising a filter membrane (3). Nierich teaches that the filter membrane may be a track-etched membrane because the pores of track etched membranes advantageously have predicable diameters and directions, leading to a membrane with predictable porosity, as well as being devoid of burrs, leading to a smooth finish preventing cell damage (Page 12, lines 1-14). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Keaney so that the membrane is a track etched membrane so that the membrane has predictable porosity and prevent cell damage as taught by Nierich.
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Keaney et al. (US 2018/0214826 A1).
Regarding claim 15, Keaney discloses the method of claim 12. Keaney further teaches that the system regulates the flow rate so that the applied transmembrane pressure is less than 100 torr (approximately 1.93 psi) in order to avoid filter fouling (¶0038-0042). This overlaps the claimed range of 0.5 to 10 psi of pressure, and therefore there is a prima facie obvious case for the claimed range. Please see MPEP §21440.5(I). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Keaney so that applying the pressure comprises applying 0.5 to 10 psi of pressure upon the volume in order to avoid filter fouling.
Regarding claim 16, Keaney discloses the method of claim 12. Keaney further teaches that the filter membrane (Fig. 2A, feat. 212) may have a pore size between 1 and 10 microns in order to prevent the passage of circulating tumor cells (CTCs) (¶0055-0057). This range overlaps the claimed range of 0.8 to 1.2 microns, and therefore there is a prima facie obvious case for the claimed range. Please see MPEP §21440.5(I). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Keaney so that applying the pressure further comprises urging the volume through the filter membrane having a pore size of 0.8 to 1.2 micron in order to prevent the passage of circulating tumor cells.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Keaney et al. (US 2018/0214826 A1) in view of Unger et al. (US 5,114,396 A).
Regarding claim 21, Keaney discloses the method of claim 12. Keaney further discloses that the fluid at the outlet end of the retentate channel may be repetitively recirculated along with additional whole blood for reprocessing by the filter (¶0037 and 0043-0044). Keaney is silent with respect to the number of times that the steps of the method are repeated to recirculate the fluid.
Unger teaches a red blood cell washing system (Figs. 1-3, feat. 1; Col. 2, line 65 – Col. 3, line 8) and method (Figs. 4a-4j; Col. 4, line 53 – Col. 5, line 42) in which the third to sixth steps, which comprise accelerating, decelerating, and stopping the centrifuge (Figs. 4c-4f; Col. 5, lines 6-38), are repeated as many times as required to make the red blood cells clinically acceptable (Col. 5, lines 39-42). Unger teaches that between 3 and 4 repetitions are typically required (Col. 5, lines 39-42). The 3 to 4 repetitions lies within the claimed range of 1 to 4 repetitions, and therefore a prima facie case of obviousness exists for the claimed range. Please see MPEP §2144.05(I). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method disclosed by Keaney so that it further comprises repeating each of the steps from one to four times in order to ensure that the red blood cells are clinically acceptable as taught by Unger.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Dorian (US 2018/0154374 A1) discloses a red blood cell washing system comprising an access port at the bottom of the centrifuge chamber.
Dorian (US 2018/0154286 A1) discloses a red blood cell centrifuge system.
Sartory (US 3,825,175 A) discloses a centrifugal particle elutriator.
Schlutz (US 4,091,989 A) discloses a centrifugal blood separator.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARJUNA P CHATRATHI whose telephone number is (571)272-8063. The examiner can normally be reached M-F 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sarah Al-Hashimi can be reached at 5712727159. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARJUNA P CHATRATHI/Examiner, Art Unit 3781
/SARAH AL HASHIMI/Supervisory Patent Examiner, Art Unit 3781