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 .
Response to Amendment
The amendments filed on 05/19/2025 has been entered. Claims 16, 20, 21, 22, 24, 25, and 30 have been amended; claims 1-15 have been cancelled. Accordingly, claims 16-26 and 30-31 are pending and under consideration.
Applicant’s amendments to the claims have overcome each and every objection and 35. U.S.C. 112(b) rejection previously set forth in the Non-final Office action mailed on 12/19/2024. Therefore, all claim objections and 35 U.S.C. 112(b) rejections are hereby withdrawn.
Response to Arguments
Applicant’s arguments with respect to claim(s) 16 have been considered but are moot because the new ground of rejection does not rely on the same combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
In light of further search and consideration, claim 16 is now rejected under 35 U.S.C. 103 as being unpatentable over Arzt et al. US 2017/0348474 A1 (previously cited) in view of Muller-Spanka et al. US 2011/0208107 A1 (newly cited) and Hogard et al. US 2015/0314055 A1 (newly cited).
Regarding Applicant’s remarks stating that “Although, in connection with the rejection of dependent claim 20, it is asserted that Puppini et al. teaches a method of removing air bubbles from both compartments of a dialyzer by filling both compartments of the dialyzer with priming fluid. Further, Puppini et al. also teaches that the two compartments of the dialyzer are separated by a gas impermeable membrane (“The blood treatment apparatus has a first compartment and second compartment separated by a semipermeable membrane substantially impermeable to gas.” Puppini et al., Abstract). In other words, Puppini et al. does not teach or suggest a method of providing transitory pressurization steps in priming fluid in a blood side of a membrane gas exchanger in which the gas side of the membrane gas exchanger contains air. As a result, any assertion that one of ordinary skill in the art would look to Puppini et al. to control/remove gas from a gas permeable membrane of a membrane gas exchanger containing air in the gas side and priming fluid in the blood side by performing two or more transitory pressure steps in the priming fluid at a selected time interval is not supported by Puppini et al.” on page 12 of Applicant’s remarks, Examiner acknowledged Applicant’s remarks since Puppini is not relied on for the subject matter challenged in said remarks above. Thus, the remark is considered moot. See rejection of claims below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16-18, 24-26, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Arzt et al. US 2017/0348474 A1 (previously cited, hereinafter Arzt) in view of Muller-Spanka et al. US 2011/0208107 A1 (newly cited, hereinafter Muller-Spanka) and Hogard et al. US 2015/0314055 A1 (newly cited, hereinafter Hogard).
Regarding claim 16, Arzt discloses a method of priming an extracorporeal blood circuit of an apparatus for extracorporeal treatment of blood (Par. 21 – “A method is provided for preparing and venting in a device for extracorporeal blood treatment, such as a heart-lung machine… After the attachment of the filling liquid and the attachment of the table line, the filling procedure is started manually and then takes place fully automatically”), wherein the apparatus 1 (Fig. 5 – patient module 1) for extracorporeal treatment of blood (Par. 21 – “a device for extracorporeal blood treatment”) comprises:
an extracorporeal blood circuit 15+EC (see annotated Fig. 5 below – venous line 15 and extracorporeal blood circuit “EC”; Examiner notes that table set 33 acts in place of a patient during filling, and is provided with venous attachment 32b and arterial attachment 32a, see Par. 63) comprising a first blood line section L1 (see annotated Fig. 5 below) and a second blood line section L2 (see annotated Fig. 5 below);
a blood pump 6 (Fig. 5 – blood pump 6) configured to be coupled to a pump section (see annotated Fig. 5 below – pump section between the reservoir 2 and the oxygenator 3) of the extracorporeal blood circuit 15+EC (see annotated Fig. 5 below – the annotated pump section belongs within the extracorporeal circuit “EC”);
a membrane gas exchanger 3 (Fig. 5 – oxygenator 3) operatively coupled to the extracorporeal blood circuit 15+EC (see annotated Fig. 5 below – the oxygenator is disposed within the extracorporeal circuit “EC”), wherein the membrane gas exchanger 3 (Fig. 5) comprises a blood side (Par. 59 – “the venous side of an oxygenator 3”, and Par. 60 – “an arterial attachment of the oxygenator 3”) in fluid communication with the blood circuit 15+EC (see annotated Fig. 5 below – it can be seen that the oxygenator 3 is connected to the blood pump 6, which is in fluid communication with the circuit “EC”, thus the venous side of oxygenator 3 is also in fluid communication with the circuit “EC”. The arterial side of oxygenator is in communication with circuit “EC” such that it connects with the filter 5) and a gas side (Par. 60 – “the oxygenator 3 also has attachments for an oxygen supply…”), wherein the blood side comprises a blood inlet (Par. 59 – “venous side of an oxygenator 3”; Fig. 5 - the left line that connects pump 6 to oxygenator 3) connected to the first blood line section L1 (see annotated Fig. 5 below – the annotated first blood line section L1 connects to the venous side/left side of the oxygenator 3) and a blood outlet (Par. 60 – “an arterial attachment of the oxygenator 3, a liquid line”; Fig. 5 – the right line that connects oxygenator 3 to filter 5) connected to the second blood line section L2 (see annotated Fig. 5 below – the annotated second blood line section L2 connects to the arterial side of the oxygenator 3);
wherein the method of priming comprises:
- feeding a priming fluid into the extracorporeal blood circuit 15+EC (see annotated Fig. 5 below, and Par. 71 – “The filling liquid from the filling liquid container 45… flows by gravity via the venous side of the system into the reservoir 2 and onwards into the blood pump 6 located at the lower end of the reservoir 2 and then onwards into the filter 5”) and into the blood side of the membrane gas exchanger 3 (Fig. 5 – arrows from filling liquid container 45 starts to flow into the reservoir 2, passes through the blood pump 6 and into the venous side of the oxygenator 3, since “blood pump 6… has… the tangential outlet 62 is connected to the venous side of an oxygenator 3” as discussed in Par. 59) at least until the priming fluid fills the blood side of the membrane gas exchanger 3 while the gas side is filled with air (Par. 113 – “After the filling and venting procedure, the patient is attached as follows. The patient is made ready during the filling procedure… After the system has been filled, the table set filled with the system is separated (severed) at the middle and plugged without air inclusions onto the prepared needles and perfusion commenced”, which indicates that prior to filling and connecting to a patient, the oxygenator 3 has to still be filled with air, including the gas side, because filling liquid has yet to prime the apparatus);
- controlling release of air bubbles (Par. 69 – “controllable valve 21… in the venting line”) from blood flowing in the extracorporeal blood circuit 15+EC (see annotated Fig. 5 below and Par. 71 – circuit “EC” is equipped with valve 21 for venting the patient module) at a blood outlet (see annotated Fig. 5 below – blood outlet) of the membrane gas exchanger 3 (see annotated Fig. 5 below – at the blood outlet of oxygenator 3, the outlet is connected with the filter 5 and valve 21 for venting) by generating transitory pressurization step (Par. 70-71 – “close the first controllable valve 21 (HC1), which is opened after the start of the filling procedure for the venting line of the filter 5, and after the response of the upper filling level sensor 10 in the reservoir 2…”, the action of closing and opening valve 21 as the priming fluid is filled generates pressurization, results in “an air cushion is created”) in the priming fluid in the blood side of the membrane gas exchanger 3 (Fig. 5, and Par. 72 – “The air cushion damps the flow behaviour of the incoming filling liquid…”; Examiner contends that the actuation upon valve 21 results in pressurization of the priming fluid, which results in air cushion as discussed in Par. 72 of Arzt, and since the priming fluid exists within the oxygenator 3, pressurization indeed takes place in the blood side of the oxygenator 3), wherein each transitory pressurization step (Par. 70-71) comprises selectively increasing pressure of the priming fluid in the blood side of the membrane gas exchanger 3 (Par. 71 – “close the first controllable valve 21 (HC1)…”, and Par. 72 – “an air cushion is created in the filter by the closed first controllable valve 21 (HC1) and the therefore closed venting line. The air cushion damps the flow behaviour of the incoming filling liquid”, wherein closing the valve and running the filling liquid to create an air cushion indicate a pressure build up) followed by selectively decreasing pressure of the priming fluid in the blood side of the membrane gas exchanger 3 (Par. 71 – “the first controllable valve 21 (HC1), which is opened after the start of the filling procedure for the venting line of the filter 5, and after the response of the upper filling level sensor 10 in the reservoir 2, in order to control the active filling of the filter 5”, wherein opening the valve relieve the pressure build up, thus decreasing the pressure).
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Annotated Fig. 5 of Arzt
However, Arzt does not explicitly disclose a membrane gas exchanger to exchange gas with blood flowing in the extracorporeal blood circuit, and a gas permeable membrane separating the blood side and the gas side, and wherein the gas side comprises a gas inlet and gas outlet configured to ventilate gas; two or more transitory pressurization steps, after the priming fluid fills the blood side of the membrane gas exchanger and while the gas side remains filled with air to inhibit the gas in the gas side from entering the blood side of the membrane gas exchanger through the gas permeable membrane, wherein each transitory pressurization step of the two or more transitory pressurization steps, and wherein successive pairs of the two or more transitory pressurization steps are separated from each other by a selected time interval.
Muller-Spanka, in the same field of endeavor of cardiopulmonary apparatus (Title), teaches a gas permeable membrane (Par. 64 – “The oxygenator comprises a membrane”) separating the blood side and the gas side (the membrane of an oxygenator is known to separate the blood flow and the gas flow), and wherein the gas side (Fig. 5 – the bottom of oxygenator 64) comprises a gas inlet (Fig. 5 – the O2 inlet on the left of oxygenator 64) and gas outlet (Fig. 5 – the O2 outlet on the right of oxygenator 64) configured to ventilate gas (Fig. 5 – the inlet and outlet of oxygen are capable of ventilate gas).
Hogard, in the same field of endeavor of method of automated priming sequences (Abstract), teaches two or more transitory pressurization steps (Par. 99 – “the pinch valves of the system can be periodically actuated to open and close the saline lines”, wherein as established above, opening and closing a valve can create pressure build up and pressure relief), and wherein successive pairs of the two or more transitory pressurization steps are separated from each other by a selected time interval (Par. 99 – “For example, the pinch valves can be opened and closed every 4-8 seconds to create a pulsing effect of the saline in the lines”; a pair of two or more transitory pressurization is interpreted to be ).
Since Par. 60 of Arzt does disclose that “The oxygenator 3 also has attachments for an oxygen supply (not shown)…”, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have recognized that the oxygen supply made to the oxygenator would create a gas-blood interface in the oxygenator, and this oxygenator is indeed intended to perform gas exchange given the disclosed oxygen supply. Furthermore, Par. 59-60 of Arzt also discuss that “The blood pump 6… has… the tangential outlet 62 is connected to the venous side of an oxygenator 3” and “The oxygenator 3 also has attachments for an oxygen supply”. Therefore, one of ordinary skill in the art would have the technological capability to realize that the cited paragraphs support the fact that both blood and oxygen are delivered within this oxygenator 3, so that oxygen gas can transfer into the extracorporeal blood.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the oxygenator of Arzt to further have the gas permeable membrane and gas inlet/outlet as taught by Muller-Spanka, since it is well-known within the field of oxygenator to have a membrane with gas delivery means to perform oxygenation of blood. Given that the membrane of Muller-Spanka is impermeable to air bubbles (Par. 64 of Muller-Spanka), air present in the oxygenator cannot pass through said membrane. Therefore, the limitation “after the priming fluid fills the blood side of the membrane gas exchanger and while the gas side remains filled with air to inhibit the gas in the gas side from entering the blood side of the membrane gas exchanger through the gas permeable membrane” is met because air in the gas side remains within the gas side given the impermeability of the membrane.
Lastly, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pressurization step of Arzt in view of Muller-Spanka to be two or more separated by a selected time interval as taught by Hogard, in order to promote air removal within the system (Par. 99 of Hogard). The action of periodically closing and opening the valve can “bang” the bubbles loose in the membrane exchanger (Par. 99 of Hogard).
Regarding claim 17, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. The combination further discloses wherein the apparatus 1 for extracorporeal treatment of blood (Fig. 5 of Artz) comprises a blood treatment unit 5 (Fig. 5 of Artz – arterial filter 5) and the extracorporeal blood circuit 15+EC (see annotated Fig. 5 of Artz above) is coupled to the blood treatment unit 5 (Fig. 5 of Artz – filter 5 is disposed within the circuit “EC”), wherein the membrane gas exchanger 3 is located next to the blood treatment unit 5 (Fig. 5 of Artz – oxygenator 3 is to the left of the filter 5).
Regarding claim 18, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 17. The combination further discloses wherein the membrane gas exchanger 3 (Fig. 5 of Artz) is located substantially at the same height of the blood treatment unit 5 (Fig. 5 of Artz – oxygenator 3 is substantially level with the filter 5), and
wherein the method comprises placing a priming fluid waste bag 36 (Fig. 5 of Artz – collecting bag 36) below the membrane gas exchanger 3 (Fig. 5 of Artz – collecting bag 36 is below the oxygenator 3).
Regarding claim 24, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. The combination further discloses wherein generating one or more of the two or more transitory pressurization steps comprises: transiently restricting or occluding flow (Par. 70 of Arzt– “The control unit, for filling and venting the patient module, is configured to close the first controllable valve 21 (HC1), which is opened after the start of the filling procedure for the venting line of the filter 5, and after the response of the upper filling level sensor 10 in the reservoir 2…”) in a portion of the extracorporeal blood circuit 15+EC (see annotated Fig. 5 of Arzt above) downstream of the membrane gas exchanger 3 (Fig. 5 of Arzt) with respect to a flow direction of the priming fluid (Fig. 5 of Arzt – valve 21 is downstream of the oxygenator 3 and downstream of the priming fluid flow as indicated by the arrows in Fig. 5), the transitory pressurization step being a pressure increase with respect to a pressure regimen in place before the transitory pressurization step (Par. 71 of Arzt – “Thus, an air cushion is created in the filter by the closed first controllable valve 21 (HC1) and the therefore closed venting line. The air cushion damps the flow behaviour of the incoming filling liquid”, which indicates that opening and closing the valve 21 pressurizes/increases the pressure the priming fluid and creates air cushions compared to prior the presence of priming fluid or prior to the actuation upon valve 21).
Regarding claim 25, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. The combination further discloses wherein generating one or more of the two or more transitory pressurization steps comprises: keeping the blood pump working (Par. 65 of Arzt – “The filling liquid can therefore pass merely by gravity from the filling liquid container 45 and through the tangential outlet 62 of the pump 6 to the downstream components”, and Par. 70 of Arzt – “The filling liquid from the filling liquid container 45… flows by gravity via the venous side of the system into the reservoir 2 and onwards into the blood pump 6… and then onwards into the filter 5”; Examiner notes that when filling liquid is able to pass from the pump 6 to the downstream components, it is understood to be in a working mode because the outlet 62 is required to be connected “to the venous side of an oxygenator 3” (Par. 58 of Arzt), whereas a stopping pump 6 will have its outlet 62 pointed upwards as seen in Fig. 3-4 so that “air can rise in the direction of the pump outlet 62 during a stop of the pump” (Par. 86)) and closing a clamp 21 (Fig. 5 of Arzt – clamp 21, and Par. 68 of Arzt – “the heart-lung machine is configured such that, after the response of the upper filling level sensor 10, the first controllable valve 21 (HC1) is at least partially closed”, and Par. 70 of Arzt – “The control unit, for filling and venting the patient module, is configured to close the first controllable valve 21”) placed downstream of the membrane gas exchanger 3 (Fig. 5 of Arzt – clamp 21 is downstream of oxygenator 3) with respect to a flow direction of the priming fluid (Fig. 5 of Arzt – arrows indicating the direction of priming fluid flow).
Regarding claim 26, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 25. The combination further discloses wherein said closing the clamp 21 (Fig. 5 of Arzt) placed downstream of the membrane gas exchanger 3 (Fig. 5 of Arzt) comprises repeatedly opening and closing the clamp 21 (Fig. 5 of Arzt and Par. 70 of Arzt – “The control unit, for filling and venting the patient module, is configured to close the first controllable valve 21 (HC1), which is opened after the start of the filling procedure for the venting line of the filter 5, and after the response of the upper filling level sensor 10 in the reservoir 2, in order to control the active filling of the filter 5”, and Par. 99 of Hogard – “valves of the system can be periodically actuated to open and close”).
Examiner notes that once the modification is made as discussed in claim 16, the periodic switching of valve of Hogard will be incorporated into the method of Arzt. Thus, the limitation is met.
Regarding claim 31, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. The combination further discloses comprising, before feeding the priming fluid in the extracorporeal blood circuit 15+EC (see annotated Fig. 5 of Arzt above, and Par. 63 of Arzt discusses the arrangement of module 1 before feeding a priming fluid – “the components in the patient module 1 are arranged in their positions as follows…”) placing the membrane gas exchanger 3 (Fig. 5 of Arzt) close to or at the same height of the blood treatment unit 5 (Fig. 5 of Arzt – oxygenator 3 is close to and at the same height of the filter 5)
and connecting a priming fluid source bag 45 (Fig. 5 of Arzt – filling liquid container 45) and a priming fluid waste bag 36 (Fig. 5 of Arzt – collecting bag 36) to the extracorporeal blood circuit 15+EC (see annotated Fig. 5 of Arzt above – the filling liquid container 45 and the collecting bag are both fluidly connected to the blood circuit 15 and the annotated EC via their attachment to reservoir 2).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Arzt in view of Muller-Spanka in view of Hogard as applied to claim 17 above, and further in view of Hochareon US 2014/0207060 A1 (previously cited, hereinafter Hochareon).
Regarding claim 19, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 17. However, the combination does not disclose wherein the apparatus for extracorporeal treatment of blood comprises a disposable cartridge including the membrane gas exchanger, the blood treatment unit, and at least part of the extracorporeal blood circuit.
Hochareon, in the same field of endeavor of extracorporeal blood apparatus (Par. 57), teaches wherein the apparatus 300 (Fig. 14 – extracorporeal blood conditioning apparatus 300) for extracorporeal treatment of blood (Par. 110 – “A schematic diagram of an extracorporeal blood conditioning apparatus of the present invention is illustrated in FIG. 14…”) comprises a disposable cartridge 310 (Fig. 14 – therapy delivery module 310, and Par. 112 – “In some embodiments, the components of therapy delivery module 310 are contained within a disposable blood circuit cartridge”) including the membrane gas exchanger 314 (Fig. 14 – oxygenation 314, and Par. 111 – “Oxygenation 314 may be provided through a conventional membrane oxygenator…”), the blood treatment unit 312 (Fig. 14-15 - external supplement 312 for supplemental drug or cell therapy, and Par. 112 – “A detailed exemplary flow diagram for therapy delivery module 310 is illustrated in FIG. 15”; Fig. 15 shows that the external supplement 312 is within the module 310), and at least part of the extracorporeal blood circuit (Par. 14-15 – arrows in these figures illustrates the circuit in which blood flows).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus for extracorporeal blood treatment of the combination to further include a disposable cartridge for the gas exchanger, blood treatment unit, and a part of the blood circuit as taught by Hochareon, in order to provide a localized therapy delivery (Par. 111 of Hochareon) and ensure adequate oxygen supply of the target tissue structure (Par. 111 of Hochareon). The localized treatment also prevents or minimize systemic side effects (Par. 14 of Hochareon). Furthermore, it is well-known within the field of extracorporeal blood treatment to have components that are in contact with blood to be disposable, so that operations can replace said components after treatment of a patient and install another module for the next patient’s treatment. Making these parts disposable allows the main housing to be reusable through multiple rounds of treatment.
Claims 20-23 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Arzt in view of Muller-Spanka in view of Hogard as applied to claim 16 above, and further in view of Puppini et al. US 5,893,382 A (previously cited, hereinafter Puppini), as cited in the IDS.
Regarding claim 20, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. However, the combination does not disclose wherein the selected time interval between successive pairs of the two or more transitory pressurization steps is between 10s and 100s.
Puppini, in the same field of endeavor of flushing a membrane apparatus (Title), teaches wherein the selected time interval between successive pairs of the two or more transitory pressurization steps (Col. 2, line 9-12 – “the pressure waves are created by alternately opening and closing occlusion means which are arranged on the flushing circuit on the outlet side (or inlet side, respectively) of the compartment”; see annotated Fig. 2 below – a pair of two transitory pressurization steps includes two peaks and two troughs, the successive pair of two transitory pressurization starts at the next peak) is between 10s and 100s (see annotated Fig. 2 below; as seen in the annotated Fig. 2 below, the peak-to-peak period is within the marked time of 400 and 500; thus, the time interval is below 100 seconds. Furthermore, Examiner further annotated the marked time of 425, 450, and 475 to provide evidence that the annotated peak-to-peak period is indeed above 10 seconds because the interval lasts from around second 410 to over second 450, which is a duration exceeding 10 seconds; thus, the limitation is met).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the transitory pressurization step of the combination to further have pressurization interval between 10s and 100s as taught by Puppini, in order to dislodge air bubbles adhering to a wall of the blood treatment apparatus and to discharge these air bubbles in the flushing liquid (Col. 1, line 66-67 and Col. 2, line 1-3 of Puppini). Furthermore, such pressurization time interval is performed so that the upstream pressure in the pipe remains greater than the pressure the downstream pipe which prevents liquid from flowing back into the blood component unit (Col. 4, line 2-6 of Puppini).
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Annotated Fig. 2 of Puppini
Regarding claim 21, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. However, the combination does not disclose wherein a maximum pressure of the priming fluid at the membrane gas exchanger during one or more of the two or more transitory pressurization step is between 100mmHg and 1000mmHg.
Puppini, in the same field of endeavor of flushing a membrane apparatus (Title), teaches wherein a maximum pressure of the priming fluid (see annotated Fig. 2 above – venous pressure VP in the venous line 15; Examiner contends that the pressure PV in the venous line 15 reflects the pressure at the outlet 8 of blood compartment 3 of dialyser 2) the membrane exchanger 2 (Fig. 1 – dialyser 2) during one or more of the two or more transitory the pressurization step (Fig. 2, and Col. 4, line 54-59 – “(starting from t~350s) one can see an undulating progression of the two pressures, due to the continuing opening and closing of the valve 21. FIG. 2 also shows the course of the pressure curve VP in the venous line 15”) is between 100mmHg and 1000mmHg (see annotated Fig. 2 above – the maximum pressure recorded for PV at the outlet of dialyser 2 is above 200mmHg and less than 1000mmHg, which is within the claimed range; thus, the limitation is met).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the membrane gas exchanger of the combination to have the maximum pressure during pressurization step to be between 100mmHg and 1000mmHg as taught by Puppini, so that the upstream pressure in the pipe remains greater than the pressure the downstream pipe which prevents liquid from flowing back into the blood component unit (Col. 4, line 2-6 of Puppini).
Regarding claim 22, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. However, the combination does not disclose wherein a time length of one or more of the two or more transitory pressurization steps is between 2s and 30s, wherein the time length is a function of a pressure in the blood circuit measured downstream the blood pump or is being fixed.
Puppini, in the same field of endeavor of flushing a membrane apparatus (Title), teaches wherein a time length of each pressurization step (see annotated Fig. 2 above – time length of a pressurization step, which is the action of opening the valve 21 and closing the valve 21), is between 2s and 30s (see annotated Fig. 2 above – the annotated time length takes place within the annotated second 450 and second 475; one of ordinary skill in the art would have recognized that the time increment is 25 seconds, and the annotated time length does not cover the full 25 seconds for a pressurization step; thus, the time length is indeed below 30 seconds and above 2 seconds), wherein the time length of each pressurization step is a function of a pressure in the blood circuit 18 (Fig. 1 – pipe 18) measured 20 (Fig. 1 – sensor 20, and Col. 4, line 35-46 – “When the pressure prevailing in the connecting pipe 18, as measured by the sensor 20, exceeds a predetermined threshold (for example 80 mmHg), the opening of the valve 21 is controlled by the unit 55. The flushing liquid then flows into the discharge pipe 35 where the pump 36 causes it to circulate with the dialysis liquid under preparation. Thereafter, the valve 21 remains activated as a function of the pressure, but its state (open/closed) no longer depends on the absolute value of the pressure in the connecting pipe 18: it is then a function of the pressure difference ∆P…”; this implies that the time at which valve 21 is opened or closed, which is the pressurization step, depends on the measured pressure by sensor 20) downstream the blood pump 12 (Fig. 1 – arterial pump 12; sensor 20 measures pressure downstream of pump 12).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the pressurization step of the combination to further have a time length be between 2s and 30s as taught by Puppini and said time length be a function of pressure as taught by Puppini, so that the upstream pressure in the pipe remains greater than the pressure the downstream pipe which prevents liquid from flowing back into the blood component unit (Col. 4, line 2-6 of Puppini). Monitoring the pressurization step based on the measured pressure within the circuit eliminates the risk of the dialysis/priming liquid under preparation coming into contact with the blood component unit again (Col. 4, line 50-51 of Puppini).
Regarding claim 23, Arzt in view of Muller-Spanka in view of Hogard in view of Puppini discloses the invention of claim 22. The combination further discloses wherein the measured pressure 20 (Fig. 1 of Puppini) is a measured return pressure (Fig. 2 of Puppini, and Col. 3, line 20-24 of Puppini – “The outlet 10 of the dialysis liquid compartment is connected to… a connecting pipe 18 equipped with a sensor 20 for pressure Pi…”, which implies that the pipe 18 and sensor 20 are disposed on a return line; thus, the limitation is met).
Once the combination is made as discussed in claim 22, the method of Arzt will be incorporated the transitory pressurization step based on a function of pressure in the blood circuit measured downstream of the blood pump as taught by Puppini, which is the monitoring operation of pressure sensor 20 on a return line 18 (Fig. 1 of Puppini). Thus, the limitation is met.
Regarding claim 29, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. However, the combination does not explicitly disclose wherein, at the end of priming and before patient connection, a pressure in the blood circuit and in the blood side of the membrane gas exchanger is kept between 20mmHg and 400mmHg.
Puppini, in the same field of endeavor of flushing a membrane apparatus (Title), teaches wherein, at the end of priming and before patient connection (see annotated Fig. 2 above – data point of venous pressure PV at the end of priming), a pressure 51 (Fig. 1 – sensor 51 for venous pressure PV) in the blood circuit 15 (Fig. 1 – venous line 15, and venous pressure PV is monitored via sensor 51) and in the blood side 3 (Fig. 1 – blood compartment 3; Examiner contends one of ordinary skill in the art would have recognized that the pressure in venous line 15 can be equivalent to the pressure at outlet 8 of the blood compartment 3 because “the outlet 8 of the blood compartment is connected to the inlet 9 of the dialysis liquid compartment by means of a venous line 15” (Col. 3, line 17-19)) of the membrane exchanger 2 (Fig. 1 – dialyser 2) is kept between 20mmHg and 400mmHg (see annotated Fig. 2 above – the data point of venous pressure PV at the end of priming is under 400mmHg and noticeably above 20mmHg as the annotated data point is above 200mmHg; thus, the limitation is met).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination to have the pressure within the blood circuit and the blood side of the membrane gas exchanger to be between 20mmHg and 400mmHg at the end of priming as taught by Puppini, in order to facilitate the dislodging of the air bubbles, clinging to the membrane of the blood component and to the walls of the pipes, and their discharge (Col. 4, line 63-65 of Puppini). Puppini also discusses the pressurization step via activation of valve 21 (Fig. 1); therefore, one of ordinary skill in the art would have had the technological capability to realize that maintaining the pressurized environment within the extracorporeal circuit after priming will also maintain the state of being fully free of gas/air bubbles within the circuit, so that the primed circuit can be plugged to the cannulas and the patient and ready for the blood treatment, as discussed in Col. 4, last paragraph, and Col. 5, first paragraph of Puppini.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Arzt in view of Muller-Spanka in view of Hogard as applied to claim 16 above, and further in view of Puppini and Bauer et al. DE 10011208 C1 (previously cited, hereinafter Bauer).
Regarding claim 30, Arzt in view of Muller-Spanka in view of Hogard discloses the invention of claim 16. Arzt in view of Muller-Spanka in view of Hogard further discloses wherein at the end of priming and before patient connection (Par. 112 of Arzt – “After the filling and venting procedure, the patient is attached as follows…”):
wherein a blood circuit portion (Fig. 5 of Arzt – the circuit portion starting from pump 6 to clamp 21, which travels from pump 6, oxygenator 3, filter 5, and ultimately valve 21) between the blood pump 6 (Fig. 5 of Arzt) and a return clamp 21 (Fig. 5 of Arzt) is isolated (Par. 112 of Arzt – ”After the filling and venting procedure… the table set filled with the system is separated (severed) at the middle…”; under broadest interpretation, “a blood circuit portion” being “isolated” is interpreted to mean the circuit being interrupted, such as being severed at the table set as discussed in Par. 112 of Arzt; before connecting to the patient and during priming, the table set 33 can be seen to be continuous and form a loop in order to prime the full extracorporeal circuit; therefore, after filling and venting procedure, the circuit portion between the pump 6 and the valve 21 is considered to be isolated, as it can no longer feed directly from arterial attachment 32a to venous attachment 32b due to the severance at table set 33), no air is allowed to enter into the blood circuit portion (Fig. 5 of Arzt – the circuit portion starting from pump 6 to clamp 21, and Par. 112 – “the table set filled with the system is separated (severed) at the middle and plugged without air inclusions onto the prepared needles…”) and a pressure regimen inside the blood circuit portion is kept constant (Par. 112 of Arzt – “After the system has been filled, the table set filled with the system is separated (severed) at the middle and plugged without air inclusions onto the prepared needles and perfusion commenced”; which implies that once the deaeration of the circuit portion has been completed, said circuit portion is kept the same with the only change being the needles attachment at the table set to the patient).
However, the combination does not disclose wherein at the end of priming and before patient connection: a pressure in the blood circuit and in the blood side of the membrane gas exchanger is kept between 20mmHg and 400mmHg; the blood pump is stopped while a clamp placed on a blood return line downstream of the membrane gas exchanger is kept closed.
Puppini, in the same field of endeavor of flushing a membrane apparatus (Title), teaches wherein at the end of priming and before patient connection (see annotated Fig. 2 above – data point of venous pressure PV at the end of priming):
a pressure 51 (Fig. 1 – sensor 51 for venous pressure PV) in the blood circuit 15 (Fig. 1 – venous line 15, and venous pressure PV is monitored via sensor 51) and in the blood side 3 (Fig. 1 – blood compartment 3; Examiner contends one of ordinary skill in the art would have recognized that the pressure in venous line 15 can be equivalent to the pressure at outlet 8 of the blood compartment 3 because “the outlet 8 of the blood compartment is connected to the inlet 9 of the dialysis liquid compartment by means of a venous line 15” (Col. 3, line 17-19)) of the membrane exchanger 2 (Fig. 1 – dialyser 2) is kept between 20mmHg and 400mmHg (see annotated Fig. 2 above – the data point of venous pressure PV at the end of priming is under 400mmHg and noticeably above 20mmHg as the annotated data point is above 200mmHg; thus, the limitation is met).
Bauer, in the same field of endeavor of filling/rinsing method (Par. 1 in the provided translation), teaches wherein at the end of priming and before patient connection (Par. 47 in the provided translation – “the hemodialysis machine is ready for hemodialysis treatment”):
the blood pump 53 (Fig. 1 – blood pump 53) is stopped (Par. 47 in the provided translation – “with the blood pump 53 stopped”) while a clamp 63 (Fig. 1 – clamp 63) placed on a blood return line 62 (Fig. 1 – withdrawal line 62) downstream of the membrane exchanger 30 (Fig. 1 – hemodialyzer 30; clamp 63 is downstream of hemodialyzer 30 according to the arrows direction) is kept closed (Par. 47 in the provided translation – “the clamp 63 in the withdrawal line 62 closed…”).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination to have the pressure within the blood circuit and the blood side of the membrane gas exchanger to be between 20mmHg and 400mmHg at the end of priming as taught by Puppini, in order to facilitate the dislodging of the air bubbles, clinging to the membrane of the blood component and to the walls of the pipes, and their discharge (Col. 4, line 63-65 of Puppini). Puppini also discusses the pressurization step via activation of valve 21 (Fig. 1); therefore, one of ordinary skill in the art would have had the technological capability to realize that maintaining the pressurized environment within the extracorporeal circuit after priming will also maintain the state of being fully free of gas/air bubbles within the circuit, so that the primed circuit can be plugged to the cannulas and the patient and ready for the blood treatment, as discussed in Col. 4, last paragraph, and Col. 5, first paragraph of Puppini.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the combination to further have the blood pump and downstream clamp be closed at the end of priming as taught by Bauer, in order to maintain an extracorporeal blood circuit filled with sterile fluid (Par. 47 in the provided translation of Bauer) so that the machine is ready for treatment (Par. 47 in the provided translation of Bauer). Furthermore, one of ordinary skill in the art would have had the technological capability to recognize that once the circuit has been pressurized and purged, releasing it to atmospheric environment might once again expose the circuit to air bubbles; thus, sealing off the circuit as taught by Bauer would prevent further air bubbles.
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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/QUYNH DAO LE/Examiner, Art Unit 3781 /JESSICA ARBLE/Primary Examiner, Art Unit 3781
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