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 .
Status of Claims
Claims 24-49 are pending and examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/02/2023 was filed before the mailing date of the First Office Action on the Merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The attempt to incorporate subject matter into this application by reference to WO 2013/030642 and/or EP0678301 is ineffective because such references were added after the filing date of the Application, which is 11/03/2020. An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a) ).
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.
Claims 24-28, 30-33, 35-36, 39, 44, and 46-49 are rejected under 35 U.S.C. 103 as being unpatentable over Bene (U.S. Patent No. 5,725,775 A) in view of Szamosfalvi (U.S. Pre Grant Pub. No. 2008/0015487 A1).
Regarding claim 24, Bene teaches: A Continuous Renal Replacement Therapy (CRRT) apparatus (see at least Fig. 1), the CRRT apparatus comprising:
a filtration unit (see exchanger 1 in Fig. 1) having a primary chamber (see compartment 2 in Fig. 1) and a secondary chamber (see compartment 3 in Fig. 1) separated by a semi- permeable membrane (4 in Fig. 1);
an extracorporeal blood circuit (see Fig. 1) having a blood withdrawal line (see upstream duct 5 in Fig. 1) connected to an inlet of the primary chamber (as shown in Fig. 1, duct 5 connects to compartment 2 at an inlet), and a blood return line (see duct 7 in Fig. 1) connected to an outlet of the primary chamber (as shown in Fig. 1, duct 7 connects to compartment 2 at an outlet), said extracorporeal blood circuit being configured to connect to a patient cardiovascular system (see Fig. 1);
a blood pump (see circulation pump 6) configured to control the flow of blood through the extracorporeal blood circuit (at least inherent);
an effluent fluid line (see duct 18 in Fig. 1) connected to an outlet of the secondary chamber (see Fig. 1);
one or more further fluid lines selected from a fluid line group comprising:
a post-dilution infusion line (see duct 13 in Fig. 1) connected at one end thereof to the blood return line (as shown in Fig. 1, ducts 7 and 13 are connected to one another via bubble trap 8),
a post-dilution bicarbonate infusion line (see duct 21 in Fig. 1) connected at one end thereof to the blood return line (as shown in Fig. 1, ducts 7 and 21 are connected to one another via bubble trap 8),
a dialysis liquid supply line (see duct 14 in Fig. 1) connected at one end thereof to the inlet of the secondary chamber (as shown in Fig. 1, duct 14 connects to compartment 3 at an inlet),
a syringe fluid line connected at one end thereof to the blood withdrawal line;
one or more actuators (see pumps 12, 19, 22 and/or blocking means 15, 16 in Fig. 1) for regulating the flow of fluid through said one or more further fluid lines (at least inherent); and
a control unit (25 in Fig. 1) connected to memory storing one or more mathematical relations (see col. 6, lines 45-49) and to the one or more actuators (see at least col. 4, lines 5-12), the control unit configured to execute a flow-rate setup procedure comprising:
allowing entry of a set value for a prescribed dialysis dose to be delivered (col. 3, line 63 thru col. 4, line 12 teaches that the control unit 25 receives data regarding the desired weight loss flow rate),
allowing entry of a target value for a parameter indicative of a steady state acid-base balance in the blood of a patient (col. 3, line 56 thru col. 4, line 12 teaches that the control unit 35 receives a reference value of the desired concentration of bicarbonate in the blood), and
- determining one or more operating parameters using said one or more mathematical relations, the determining of the one or more operating parameters comprising calculating a set value of three or more fluid flow rates selected from a flow rate group comprising:
a fluid flow rate through the PBP infusion line when the one or more further fluid lines includes the PBP infusion line,
a fluid flow rate through the pre-dilution infusion line when the one or more further fluid lines includes the pre-dilution infusion line,
a fluid flow rate through the post-dilution infusion line when the one or more further fluid lines includes the post-dilution infusion line,
a fluid flow rate through the post-dilution bicarbonate infusion line when the one or more further fluid lines includes the post-dilution bicarbonate infusion line (see at least col. 4, lines 13-18),
a blood fluid flow rate through the extracorporeal blood circuit,
a fluid flow rate through the syringe fluid line when the one or more further fluid lines includes the syringe fluid line,
a fluid flow rate through the dialysis liquid supply line when the one or more further fluid lines includes the dialysis liquid supply line, and
a fluid flow rate through the effluent fluid line (see col. 4, lines 10-12);
wherein calculating each set value of the three or more fluid flow rates is based at least on:
said set value of the prescribed dialysis dose (see col. 3, line 63 thru col. 4, line 12),
said target value for the parameter indicative of a steady state acid-base balance in blood (see [HCO3]DES in col. 3, line 56 thru col. 4, line 12), and
said set value for the prescribed anticoagulant dose.
However, Bene fails to explicitly teach that the CRRT apparatus is configured to perform regional anticoagulation treatments and comprises an anticoagulant infusion line, a source of regional anticoagulant, a pre-dilution infusion line, a pre-blood pump (PBP) infusion line, or a syringe fluid line, that the receiving a patient prescription includes allowing entry of a set value for a prescribed anticoagulant dose to be delivered, determining a fluid flow rate through the anticoagulant infusion line, a fluid flow rate through the PBP infusion line when the one or more further fluid lines includes the PBP infusion line, a fluid flow rate through the pre-dilution infusion line when the one or more further fluid lines includes the pre-dilution infusion line, or a fluid flow rate through the ion balancing infusion line when the one or more further fluid lines includes the ion balancing infusion line, or calculating said set value for the prescribed anticoagulant dose, as required by the claim.
Szamosfalvi teaches an analogous CRRT apparatus (see Figs. 2 and 35) configured for performing regional anticoagulation treatments (see Abstract), comprising:
an anticoagulant infusion line (see pre-filter infusion line 28 in Fig. 2 and para. [0089]) having one end connected to the blood withdrawal line (14; as shown in Fig. 2, line 28 is connected to line 14 via hemofilter 16) in a region of the blood withdrawal line positioned in use upstream from the blood pump (as shown in Fig. 2, lines 14 and 28 connect upstream from pump 22),
a source of regional anticoagulant operably connected to the anticoagulant infusion line (see bag 32 in Fig. 2);
an ion balancing infusion line connected at one end thereof either to the blood return line or to a patient catheter (see bag 40 associated with pump 44 that is connected to line 18; see also para. [0089]),
a pre-dilution infusion line (associated with pump 21 in Fig. 35) connected at one end thereof to the blood withdrawal line (as shown in Fig. 35, the line associated with pump 21 is connected with the blood withdrawal line, which extends from numeral 20 towards pump 22, at hemofilter 16),
a pre-blood pump (PBP) infusion line (associated with pump 21 in Fig. 35) connected at one end thereof to the blood withdrawal line (in Fig. 35, the blood withdrawal line is unlabeled but extends from numeral 20 towards pump 22) in a region of the blood withdrawal line which is positioned in use upstream from the blood pump (as shown in Fig. 35, the line associated with pump 21 is connected with the blood withdrawal line at hemofilter 16), and
- receiving a patient prescription comprising clinical prescription parameters (see para. [0077]), the receiving including:
allowing entry of a set value for a prescribed anticoagulant dose to be delivered (para. [0098] teaches that the prescription will ensure that systemic citrate levels stay at a certain level and that the prescription may be modified so that the steady state citrate level does not exceed a certain level; thereby allowing for a set value of citrate level to be determined);
- determining one or more operating parameters using said one or more mathematical relations, the determining of the one or more operating parameters comprising calculating a set value of three or more fluid flow rates selected from a flow rate group comprising:
a fluid flow rate through the anticoagulant infusion line (see QBCit in para. [0330-0346]),
a fluid flow rate through the ion balancing infusion line when the one or more further fluid lines includes the ion balancing infusion line (see QCA/Mg in para. [0236]);
wherein calculating each set value of the three or more fluid flow rates is based at least on:
said set value for the prescribed anticoagulant dose (para. [0335 and 0346] teach that the calculated citrate dialysance is a function of the arterial flow rate of citrate is calculated).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene to incorporate the teachings of Szamosfalvi by configuring the CRRT apparatus for performing regional anticoagulation treatments by including an anticoagulant infusion line, a source of regional anticoagulant, a pre-dilution infusion line, and a pre-blood pump (PBP) infusion line at least in order to prevent circuit clotting, as taught by Szamosfalvi (see para. [0006]), and by receiving a patient prescription comprising clinical prescription parameters by allowing entry of a set value for a prescribed anticoagulant dose to be delivered at least in order to provide for an automated approach to writing safe anticoagulant prescriptions which do not allow anticoagulant accumulation in a patient, as taught by Szamosfalvi (see para. [0077]), and by calculating a set value of fluid flow rates comprising a fluid flow rate through the anticoagulant infusion line and a fluid flow rate through the ion balancing infusion line when the one or more further fluid lines includes the ion balancing infusion line at least in order to avoid excessive hemoconcentration in the hemofilter during ultrafiltration and thereby greatly reduce the risk of high transmembrane pressures developing, as taught by Szamosfalvi (see para. [0084]), and by calculating the flow rate based on a set value for the prescribed anticoagulant dose at least in order to avoid excessive hemoconcentration in the hemofilter during ultrafiltration and thereby greatly reduce the risk of high transmembrane pressures developing, as taught by Szamosfalvi (see para. [0084]).
Regarding claim 25, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the target value for the parameter indicative of a steady state acid-base balance in the blood of the patient affects the set value of the fluid flow rate through the anticoagulant infusion line when the set value for the blood fluid flow rate through the extracorporeal blood circuit is determined by the control unit as one of the one or more operating parameters (col. 3, line 56 thru col. 4, line 12 of Bene teaches that the control unit 35 receives a reference value of the desired concentration of bicarbonate in the blood), the set value of the fluid flow rate through the anticoagulant infusion line being one of the one or more operating parameters calculated by the control unit (see QBCit in para. [0330-0346] of Szamosfalvi).
Regarding claim 26, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein calculating the set value of three or more fluid flow rates comprises determining of the operating parameters comprising calculating the set value for the fluid flow rate through the anticoagulant infusion line (see QBCit in para. [0330-0346] of Szamosfalvi), wherein the regional anticoagulation dose is a citrate dose indicative of the intensity of the regional anticoagulation (see at least Abstract of Szamosfalvi).
Regarding claim 27, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the regional anticoagulation dose has the same units as a concentration and is the injected amount of anticoagulant per liter of treated blood (mmol/L blood) (see for example Tables 1-6 of Szamosfalvi).
Regarding claim 28, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the control unit is configured to calculate, using a citrate flow rate mathematical relation, the set value for the fluid flow rate through the anticoagulant infusion line as a function of one or more of:
the set value for the regional anticoagulation dose (para. [0335 and 0346] of Szamosfalvi teach that the calculated citrate dialysance is a function of the arterial flow rate of citrate is calculated),
the set value for the fluid flow rate through the anticoagulant infusion line with a blood flow rate see (QBCit in para. [0330-0346] of Szamosfalvi); and
an anticoagulant concentration in the anticoagulant source (see at least para. [0181] of Szamosfalvi).
Regarding claim 30, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the control unit is configured to control an anticoagulant pump to infuse anticoagulant in the blood withdrawal line at the calculated fluid flow rate for the anticoagulant (see para. [0089 and 0201] of Szamosfalvi).
Regarding claim 31, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: comprising the ion balancing infusion line (see line 36 in Fig. 2 of Szamosfalvi) having one end connected either to the blood return line or to a patient catheter (see Fig. 2 showing line 36 connected with line 18) and a source of ion balancing solution connected at an opposite end of the ion balancing infusion line (see bag 40 in Fig. 2), wherein receiving a patient prescription further comprises allowing entry of a set value for an ion re-establishing solution parameter indicative of the intensity of ion balancing (para. [0089] of Szamosfalvi teaches that line 36 is associated with pump 41, which is a volumetric pump; therefore, a certain volume of fluid is measured and pumped), wherein calculating the set value of three or more fluid flow rates comprises calculating the set value of four or more fluid flow rates and determining of the operating parameters comprises calculating the set value for at least the fluid flow rate through the ion balancing infusion line (since pump 41 is a volumetric pump, a certain volume of fluid is measured and pumped which can be used to measure the fluid flow rate through line 36).
Regarding claim 32, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 31. Additionally, Bene in view of Szamosfalvi teaches: wherein the ion re- establishing solution parameter is either:
- a compensation value or compensation percentage of the calcium removed in the filtration unit; or
- a calcium dose in terms of an ion concentration, the calcium dose being calcium concentration in the effluent (para. [0504] of Szamosfalvi teaches that the total calcium content of the effluent fluid is mathematically derived).
Regarding claim 33, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 31. Additionally, Bene in view of Szamosfalvi teaches: wherein the control unit is configured to calculate, using a calcium flow rate mathematical relation, the set value for the fluid flow rate through the ion balancing infusion line as a function of one or more of:
the set value for the ion re-establishing solution parameter;
an effluent flow rate;
a calcium concentration in a source of ion balancing solution (para. [0504] of Szamosfalvi teaches that the total calcium content of the effluent fluid is mathematically derived);
a calcium concentration in an auxiliary container connected to the post-dilution infusion line;
a calcium concentration in a bicarbonate container connected to the post-dilution bicarbonate infusion line.
Regarding claim 35, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein calculating the set value of the fluid flow rate through the ion balancing infusion line is based at least on said target value for the parameter indicative of a steady state acid-base balance in the blood and on said set value of the prescribed dialysis dose (see [HCO3]DES in col. 3, line 56 thru col. 4, line 12 of Bene), wherein the control unit calculates the set value of the fluid flow rate through the ion balancing infusion line using said mathematical relations (para. [0504] of Szamosfalvi teaches that the total calcium content of the effluent fluid is mathematically derived).
Regarding claim 36, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the control unit is configured to control an ion balancing pump to infuse an ion re-establishing solution in the blood return line or into the patient at the fluid flow rate calculated for the ion re-establishing solution (para. [0104] of Szamosfalvi teaches that the RCA system is designed to keep systemic ionized Ca levels at a certain value and the prescription may be modified to keep the ionized calcium flow rate at a certain level).
Regarding claim 39, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein said one or more mathematical relations include a citrate load mathematical relation based on a citrate load to the patient in terms of an amount per unit of time (para. [0837] of Szamosfalvi teaches that concentrations are obtained as a function of time), wherein the citrate load is the difference between a citrate infusion rate through the anticoagulant infusion line and a citrate removal rate to effluent in the eluent line (para. [0259] of Szamosfalvi teaches measurement of conductivity of fresh therapy fluid as well as filter effluent fluid; para. [0080] teaches that conductivity is a function of flow rates).
Regarding claim 44, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein said one or more mathematical relations include a citrate load mathematical relation linking a citrate load with one or more of a citrate dose, the blood flow rate, a citrate clearance, and plasma water flow rate at the inlet of the filtration unit (para. [0091] teaches the determination of arterial plasma flow; see also para. [0106]).
Regarding claim 46, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein calculating the set value for at least the fluid flow rate through the anticoagulant infusion line and/or the fluid flow rate through the ion balancing infusion line, is based on said set value of the prescribed dialysis dose, in case the set value for the blood fluid flow rate through the extracorporeal blood circuit is determined by the control unit as an operating parameter (para. [0104] of Szamosfalvi teaches that the RCA system is designed to keep citrate levels at a certain value and the prescription may be modified to keep the citrate flow rate at a certain level).
Regarding claim 47, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein calculating the set value for at least the fluid flow rate through the anticoagulant infusion line and/or the fluid flow rate through the ion balancing infusion line, is based at least on said target value for the parameter indicative of a steady state acid-base balance in the blood, when the set value for the blood fluid flow rate through the extracorporeal blood circuit is determined by the control unit as an operating parameter (para. [0104] of Szamosfalvi teaches that the RCA system is designed to keep citrate and systemic ionized Ca levels at a certain value and the prescription may be modified to keep the citrate and systemic ionized Ca flow rate at a certain level).
Regarding claim 48, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: the parameter indicative of a steady state acid-base balance in the blood of the patient undergoing a CRRT treatment is a parameter function of a net buffer load in the patient expected at a steady state, wherein the net buffer load is a sum of bicarbonate generation from bicarbonate precursor metabolism, bicarbonate balance in the extracorporeal blood circuit, bicarbonate infusions into the patient and acid infusion in the extracorporeal blood circuit (see para. [0151] of Szamosfalvi).
Regarding claim 49, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein the parameter indicative of a steady state bicarbonate concentration in the blood of the patient is defined imposing a constant value for a normalized net buffer load for the patient at steady state (see para. [0151] of Szamosfalvi).
Claims 29 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Bene (U.S. Patent No. 5,725,775 A) in view of Szamosfalvi (U.S. Pre Grant Pub. No. 2008/0015487 A1), as applied above in claim 24, and further in view of Lannoy (U.S. Pre Grant Pub. No. 2007/0066928 A1).
Regarding claim 29, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. However, neither Bene nor Szamosfalvi explicitly teach a citrate flow rate mathematical relation stored in the memory, as required by the claim.
Lannoy teaches an analogous citrate anti-coagulant supplementation in a blood filtration circuit during CRRT (see Abstract). Lannoy further teaches that a controller 11 may calculate an optimal citrate flow rate as a function of blood flow, citric acid concentration, and trisodium citrate concentration (see para. [0035]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Lannoy by using the mathematical equation
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at least because one of ordinary skill in the art would have reasonably recognized that calculating a flow rate of citrate is a function of the dose of citrate, the total concentration of citrate, and the rate of blood flow, as taught by Lannoy (see para. [0035]).
Regarding claim 34, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 31. However, neither Bene nor Szamosfalvi explicitly teach a calcium flow rate mathematical relation, as required by the claim.
Lannoy teaches that the total calcium concentration is a function of the calcium content before the hemofilter, the calcium contribution from the post-dilution substitution solution, the calcium contribution from the Ca/Mg electrolyte solution, and the calcium lost through the hemofilter (see para. [0082]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Lannoy by including a calcium flow rate mathematical relation that is either
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or
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at least because Lannoy teaches that the calcium flow rate is a function of the calcium content before the hemofilter, the calcium contribution from the post-dilution substitution solution, the calcium contribution from the Ca/Mg electrolyte solution, and the calcium lost through the hemofilter (see para. [0082] of Lannoy). Additionally, one of ordinary skill in the art would have reasonably recognized that when any of the infusion lines is missing, the corresponding flow rate is set to zero at least because when an infusion line is missing, no liquid is flowing through that line.
Claims 37-38, 40-43, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Bene (U.S. Patent No. 5,725,775 A) in view of Szamosfalvi (U.S. Pre Grant Pub. No. 2008/0015487 A1), as applied above in claim 24, and further in view of Pouchoulin (U.S. Pre Grant Pub. No. 2023/0017204 A1).
Regarding claim 37, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. Additionally, Bene in view of Szamosfalvi teaches: wherein said one or more mathematical relations include a net buffer load mathematical relation linking the the parameter indicative of a steady state acid-base balance in the blood with at least one of: an acid infusion (para. [0085] teaches the infusion of citrate, which is an acid).
However, neither Bene nor Szamosfalvi explicitly teach a bicarbonate generated from metabolism of citrate or citrate load, wherein the metabolism of citrate load leads to 3 moles of bicarbonate per mole of citrate at steady state, namely
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, as required by the claim.
Pouchoulin teaches an analogous CRRT apparatus (see Abstract) comprising determining the parameter indicative of a steady state acid-base balance in the blood of the patient based on an estimation of an amount per unit of time of bicarbonate generated from metabolism of citrate infused to the patient, in particular wherein the metabolism of citrate load leads b 3 moles of bicarbonate per mole of citrate at steady state (see para. [0080]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by linking the parameter indicative of a steady state acid-base balance in the blood with a bicarbonate generated from metabolism of citrate at least in order to determine the parameter indicative of a steady state acid-base balance in the blood of the patient, as taught by Pouchoulin (see para. [0080]).
Regarding claim 38, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 37. However, neither Bene nor Szamosfalvi explicitly teach a net buffer load mathematical relation, as required by the claim.
Pouchoulin teaches an analogous CRRT apparatus (see Abstract) comprising a control unit that determines the parameter indicative of a steady state acid-base balance in the blood as a function of the bicarbonate form precursor metabolism, the bicarbonate balance, and the acid infusion (see para. [0078]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by making the net buffer load mathematical relation to be the mathematical formula given in the claim at least because Pouchoulin teaches such a formula and also teaches that such formula determines the parameter indicative of a steady state acid-base balance in the blood of the patient (see para. [0077]). Additionally, one of ordinary skill in the art would have reasonably recognized that when any of the mass transfer rates is missing, the corresponding mass transfer term is absent from the mathematical relation or the corresponding value is set to zero at least because when the mass transfer rate is missing, the mass transfer term would be equal to zero.
Regarding claim 40, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 39. However, neither Bene nor Szamosfalvi explicitly teach citrate load mathematical relation, as required by the claim.
Pouchoulin teaches an analogous CRRT apparatus (see Abstract) comprising a citrate load mathematical relation that is identical to the one claimed (see para. [0174]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by using the cited mathematical relation to determine the injected amount of citrate per liter of blood treated, as taught by Pouchoulin (see para. [0174]). Additionally, one of ordinary skill in the art would have reasonably recognized that when any of the mass transfer rates is missing, the corresponding mass transfer term is absent from the mathematical relation or the corresponding value is set to zero at least because when the mass transfer rate is missing, the mass transfer term would be equal to zero.
Regarding claim 41, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 39. However, neither Bene nor Szamosfalvi explicitly teach that the citrate removal rate to effluent, as required by the claim.
Pouchoulin teaches that the control unit is configured to calculate the citrate load as a function of patient citrate metabolic clearance, the metabolic clearance being determined by the equation
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(see para. [0081]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by configuring the control unit of Bene in view of Szamosfalvi to use the cited mathematical formula to calculate the citrate load as a function of patient citrate metabolic clearance, as taught by Pouchoulin (see para. [0081]).
Regarding claim 42, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. However, neither Bene nor Szamosfalvi explicitly teach a citrate clearance mathematical relation, as required by the claim.
Pouchoulin teaches that the control unit determines citrate clearance according to a mathematical relation (see para. [0084]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by configuring the control unit of Bene in view of Szamosfalvi to use the cited mathematical formula to determine citrate clearance, as taught by Pouchoulin (see para. [0084]). Additionally, one of ordinary skill in the art would have reasonably recognized that when any of the infusion lines or dialysis liquid supply line is missing, the corresponding flow rate term is absent from the mathematical relation or the corresponding value is set to zero at least because when the flow rate is missing, the flow rate would be equal to zero.
Regarding claim 43, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 24. However, neither Bene nor Szamosfalvi explicitly teach wherein a citrate load is alternatively a function of a citrate dose and the blood flow, as required by the claim.
Pouchoulin teaches that the citrate amount is prescribed through the ‘Citrate Dose’ parameter which is the amount of citrate per liter of blood treated (see para. [0202]) and gives the citrate infusion flow rate as a function of the citrate dose and the citrate concentration in the anticoagulant source (see para. [0202-0208]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by making the citrate infusion flow rate a function of the citrate dose and the citrate concentration in the anticoagulant source at least to provide for an amount of citrate in proportion to the amount of calcium to be chelated, as taught by Pouchoulin (see para. [0202]).
Regarding claim 45, Bene in view of Szamosfalvi teaches the invention as discussed above in claim 44. However, neither Bene nor Szamosfalvi explicitly teach a citrate load mathematical relation, as required by the claim.
Pouchoulin teaches that the citrate load is calculate by the formula
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(see para. [0259]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the device of Bene in view of Szamosfalvi to incorporate the teachings of Pouchoulin by choosing the formula described by Pouchoulin (in para. [0259]) at least in order to eliminate citrate concentration parameters and expressing patient citrate load as a function of flow rates and clearances, as taught by Pouchoulin (see para. [0259]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pouchoulin ‘614 (U.S. Pre Grant Pub. No. 2011/0168614 A1) - DEVICE AND PROCEDURE FOR EXTRACORPOREAL BLOOD TREATMENT
Pouchoulin ‘426 (U.S. Pre Grant Pub. No. 2013/0248426 A1) - APPARATUS FOR EXTRACORPOREAL TREATMENT OF BLOOD
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIHAD DAKKAK whose telephone number is (571)272-0567. The examiner can normally be reached Mon-Fri: 9AM - 5PM ET.
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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 (571) 272-7159. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIHAD DAKKAK/ Examiner, Art Unit 3781
/SARAH AL HASHIMI/ Supervisory Patent Examiner, Art Unit 3781