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 § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Boggs; Daniel R. et al. (US 20130267884 A1) with incorporation of Giesler; Richard C. et al. (US 5868696 A) in view of Langley; Robert W. et al. (US 5817042 A) in view of Szamosfalvi; Balazs et al. (US 20090221948 A1).
Regarding claim 11, Boggs discloses a system for carrying out an apheresis procedure (¶ [0001], [0002], [0007], a blood processing system is provided comprising a blood separation device; ¶ [0023], FIG. 1 schematically illustrates a processing system, generally indicated at 2);
comprising: a) a durable, reusable hardware device including a cell separator drive unit (¶ [0029] FIG. 2 illustrates a centrifugal processing device, generally indicated at 100 … a commercial centrifuge sold by Fenwal, Inc. as the Amicus.RTM. separator … not limited to but including U.S. Pat. No. 5,868,696, to Giesler et al., issued Feb. 9, 1999, which is incorporated herein by reference);
one or more pumps (¶ [0031], For example, the panel 108 includes three pumping and valving stations … at 110, 112 and 114, in FIG. 2 … Each illustrated pump 122, 124, 126, 128, 130, 132 is a peristaltic pump); and
a controller (¶ [0028] In FIG. 1, such controller 24 may include a main controller, generally indicated at 36, such as a programmable controller);
b) a disposable fluid circuit configured for mounting onto said hardware device, said fluid circuit including a separation chamber (¶ [0030] As shown in FIG. 2, the centrifugal processing device 100 includes a separation assembly, specifically a centrifuge rotor assembly, generally within the housing indicated at 102, and is configured to control fluid flow through a disposable fluid processing set, (generally indicated 104 in FIG. 3), used in association with the processing device 100);
a venous access device for establishing flow communication between an apheresis subject and said separation chamber (¶ [0034], The set 104 includes a double needle … and may include single needle and other types of processing sets);
said circuit including a line defining a flow path for introducing blood from said apheresis subject to said separation chamber and a line for infusing a separated blood component from said chamber to said apheresis subject (¶ [0034], The set 104 includes a double needle (one for withdrawal of fluid from a patient and one for return of fluid to the patient) processing assembly); and
c) wherein said controller is configured to (a) determine a blood volume of an apheresis subject (¶ [0051] Turning to FIG. 7, the data entry process is initiated by first determining the required patient data, including gender, height, and weight, entering that information so that the patient's initial total blood volume, V.sub.0, may be calculated. This is done using, e.g., the generally accepted equations developed by Nadler et al.);
(b) establish an optimal rate of infusion of a separated blood component to said subject (¶ [0010] In another aspect, the operating flow rates are all adjusted proportionally to not exceed the allowable citrate infusion rate and still maintain the flow rate ratios that will achieve the procedure objectives; ¶ [0044], determining a plasma flow rate for returning plasma to the patient … and determining a return rate as limited by citrate infusion to the patient; ¶ [0092] Next, the controller checks whether the citrate infusion rate expected from the calculated values whole blood, replacement fluid, and plasma flow rates is above CIR.sub.MAX);
(c) effect the operation of said one or more pumps at said optimal infusion rate (¶ [0099], If the operator saves the data entry inputs and they are deemed achievable by the controller, the calculations of pump rates and time are applied to the exchange procedure).
Regarding the blood introduction line and component infusion line, Boggs incorporates Giesler; Richard C. et al. (US 5868696 A) (¶ [0034] The disposable set 104 is preferably adapted to be loaded onto a separation assembly, such as shown and disclosed in U.S. Pat. No. 5,868,696, incorporated by reference above).
Giesler discloses further details of a disposable circuit including a blood introduction line and component infusion line (col. 14, lines 30-40, FIG. 19 shows a single needle platelet collection system 28 (FIGS. 2; 3; and 11 also show the single needle system 28 in association with the tray 26 and centrifuge assembly 12). FIG. 20 shows a two needle platelet collection system 30).
Boggs does not explicitly configure the controller to (a) determine the subject’s body water volume. Langley discloses a method and apparatus for an apheresis procedure (col. 1, lines 15-25; col. 4, lines 5-10; col. 6, lines 45-50 The flow paths for a hypothetical blood apheresis procedure are shown in FIG. 1.);
comprising: a) a controller (col. 7, lines 35-40, microprocessor based controller 80);
b) a fluid circuit including a separation chamber (col. 7, lines 5-15, extracorporeal tubing set 81 … The separator system 26 may be a centrifuge of the continuous flow type, such as the centrifuge used with the SPECTRA.TM. brand apheresis system);
c) wherein said controller is configured to (a) determine the body water volume of an apheresis subject (col. 8, lines 45-55, FIG. 2 schematically illustrates the more general multi-compartment model of the present invention … The second compartment V.sub.i 84 conceptually correlates to the donor/patient's intracellular fluid and the remaining part of the donor/patient's interstitial fluid; col. 9, lines 20-40, V.sub.I =b V.sub.TB … Where … V.sub.TB =the donor/patient total blood volume in ml. … a,b,K=constants empirically determined by correlating the model to measured citrate concentrations in human subjects);
(b) establish an optimal rate of infusion to said subject and (c) effect the operation of said one or more pumps at said optimal infusion rate (col. 12, lines 10-20, Where the infusion rate of anticoagulated blood to the donor/patient is being varied to rapidly achieve and maintain the maximum citrate concentration tolerable in the donor/patient, the rate of anticoagulant addition to the inlet line 12 may be adjusted to achieve the appropriate ratio of inlet flow rate to anticoagulant flow rate R, as follows).
Langley more accurately predicts how much citrate a patient can tolerate with a compartment model in order to calculate a maximum blood infusion rate (col. 9, lines 5-15, The citrate kinetics illustrated in FIG. 2 are calculated over time … as described by the following equations; col. 12, lines 35-40, FIG. 3 graphically illustrates that using the optimized anticoagulant infusion rate profile of the simplified single compartment model, results in a rapid donor/patient citrate accumulation that then remains at or below the MADEC for the remainder of the procedure time). One would be motivated to modify Boggs by determining a subject’s body water volume as taught by Langley in order to more accurately calculate an ideal infusion rate. Therefore, it would have been obvious to modify Boggs with Langley’s body water volume calculation in order to reduce the error in the infusion rate.
Boggs and Langley do not explicitly disclose that the controller (b) establishes an optimal rate of infusion of a component to said subject based on the determined body water volume of the subject. Szamosfalvi discloses a system and method for regional citrate anticoagulation (RCA) (¶ [0003], [0070] With reference first to FIG. 2, a system for CRRT … System 10);
comprising: a) a durable, reusable hardware device including one or more pumps (¶ [0070], blood pump 22 may be precise … An ultrafiltration pump 26; ¶ [0072] With continuing reference to FIG. 2 … Pre-filter infusion line 28 may supply a pre-dilution solution, such as a citrate-containing anticoagulation solution as described below, from a pre-filter source (e.g., bag 32). A pre-filter replacement fluid pump 34); and
a controller (¶ [0069], The system may include a combination of various CRRT and dialysis machine hardware components, a software control module);
b) a disposable fluid circuit (¶ [0070], System 10 includes a CRRT circuit 12; ¶ [0078] Disposable, sterile fluid circuits may be utilized according to the present invention); and
c) wherein said controller is configured to (a) determine the body water volume of a subject (¶ [0143] a) Sex, height, age, weight (if Watson volume and V.sub.E calculations are desired; minimum data is weight));
(b) establish an optimal rate of infusion of a component to said subject based on the determined body water volume of the subject; and (c) effect the operation of said one or more pumps at said optimal infusion rate (¶ [0079] System 10 … may be used to safely provide citrate anticoagulation to any extracorporeal blood circuit; ¶ [0081] The kinetic program analyzes the CVVH prescription (fluid compositions and flow rates as well as blood flow rate) and the sensor data when available. It also utilizes anthropomorphic data to predict the citrate volume of distribution in the patient; ¶ [0379] As also explained, the kinetic curve of systemic plasma citrate concentration can be used to derive the exact value of the liver clearance of citrate as well as the volume of distribution of citrate, V.sub.E. Using the above parameters, systemic citrate levels can be accurately predicted at any future T time point. The calcium and citrate pump as well as the entire prescription including the therapy fluid bicarbonate concentration (when flexible) can then be completely controlled by the machine software).
Szamosfalvi considers the patient’s body water volume when calculating a citrate infusion rate, in order to compensate for how citrate distributes in the patient’s body (¶ [0081], It also utilizes anthropomorphic data to predict the citrate volume of distribution in the patient; ¶ [0129], Both calcium and citrate do not distribute into the RBC volume; ¶ [0195], As also explained, the kinetic curve of systemic plasma citrate concentration can be used to derive the exact value of the liver clearance of citrate as well as the volume of distribution of citrate, V.sub.E. Using the above parameters, systemic citrate levels can be accurately predicted at any future T time point). One would be motivated to modify Boggs and Langley with Szamosfalvi’s body water volume-adjusted infusion rate to more accurately the patient’s citrate levels. Therefore, it would have been obvious to modify Boggs and Langley with Szamosfalvi’s body water volume-adjusted infusion rate in order to more reliably prevent adverse reactions to citrate.
Regarding claims 12-17 and 20, Boggs discloses a system wherein said fluid circuit is configured for attachment to a source of a citrate anticoagulant and further includes a line defining a flow path for combining anticoagulant with blood withdrawn from the apheresis subject (¶ [0038], Anticoagulant from the anticoagulant container 172 may be pumped to the first flow path 190 by the upper or anticoagulant pump 124);
wherein the volume of citrate anticoagulant combined with said blood is based on the amount of blood withdrawn from the apheresis subject (¶ [0094] where ACR is the whole blood to anticoagulant solution volume ratio defined by ACR = Q WB / Q AC);
wherein said anticoagulant source comprises a container of citrate anticoagulant associated with a weight scale (¶ [0032], One or more weight scales 142, 144, 146, 148, 150 may be associated with the controller 138 … to allow for weight measurement of such containers during and/or after the processing procedure);
wherein said separation chamber includes a fluid outlet through which a separated blood component flows, said system further comprising a return line defining a flow path between said outlet and said apheresis subject (¶ [0040] Outlet flow paths 202 and 208 may allow separated blood components, such as red blood cells, plasma and/or platelets, to separately exit the processing chamber 160);
wherein said controller is further configured to determine the volume of citrate in said separated blood component (¶ [0044], determining a return rate as limited by citrate infusion to the patient; ¶ [0092] Next, the controller checks whether the citrate infusion rate expected from the calculated values whole blood, replacement fluid, and plasma flow rates is above CIR.sub.MAX);
wherein said return line is associated with a return pump and said controller is further configured to effect operation of said return pump and infuse said separated blood component at said optimal infusion rate (¶ [0099], If the operator saves the data entry inputs and they are deemed achievable by the controller, the calculations of pump rates and time are applied to the exchange procedure);
wherein said separation chamber comprises a centrifuge or a spinning membrane (¶ [0039], The first flow path 190 preferably communicates with the processing chamber 160 so as to allow the withdrawn whole blood from the patient to be separated into selected constituent blood components, such as red blood cells, platelets and/or plasma).
Regarding claims 18 and 19, Boggs discloses a controller configured to determine said amount of blood volume based on one or more of an apheresis subject's age, weight, height, and gender (¶ [0051] Turning to FIG. 7, the data entry process is initiated by first determining the required patient data, including gender, height, and weight, entering that information so that the patient's initial total blood volume, V.sub.0, may be calculated).
Boggs does not explicitly determine an amount of body water. Langley discloses a controller configured to determine said amount of body water by determining at least one of the total plasma volume and extracellular fluid volume of the apheresis subject (col. 8, lines 50-55, The second compartment V.sub.i 84 conceptually correlates to the donor/patient's intracellular fluid and the remaining part of the donor/patient's interstitial fluid; col. 9, lines 20-50, The following relationships completely define the donor/patient citrate model schematized in FIG. 2).
Langley refines an estimate of a patient’s citrate tolerance in order to accelerate an infusion procedure. Regarding the rationale and motivation to modify Boggs with Langley’s compartment model and body water calculation, see the discussion of claim 11 above.
Response to Arguments
Applicant’s arguments filed 02 September 2026 regarding the rejection of claims 11-20 as amended, under 35 USC § 103 over Boggs, Giesler and Langley, have been fully considered and are persuasive. After further consideration, the amended claims are rejected on new grounds under 35 USC § 103 over Boggs, Giesler, Langley and Szamosfalvi (see above).
Applicant submits that accordingly, because Boggs neither determines nor utilizes body water volume, Boggs does not disclose or suggest establishing an optimal rate of infusion of a separated blood component based on a determined body water volume of the subject (remarks p. 6-7). Examiner acknowledges that Boggs is silent regarding a step of calculating a body water volume.
Applicant asserts that body water volume is neither an input nor an output of Langley's method (remarks p. 7). Applicant contends that Langley does not measure, estimate, or determine the subject's body water volume (remarks p. 7).
Examiner notes that Langley calculates parameters related to body water volume (col. 8, lines 45-55, FIG. 2 schematically illustrates the more general multi-compartment model of the present invention … The second compartment V.sub.i 84 conceptually correlates to the donor/patient's intracellular fluid and the remaining part of the donor/patient's interstitial fluid; col. 9, lines 20-40, V.sub.I =b V.sub.TB … Where … V.sub.TB =the donor/patient total blood volume in ml. … a,b,K=constants empirically determined by correlating the model to measured citrate concentrations in human subjects).
Szamosfalvi is cited in the new grounds of rejection as teaching a method that calculates a body water volume and adjusts a pump speed based on the body water volume. Szamosfalvi considers where citrate distributes in the patient’s body, which excludes RBC’s (¶ [0129], Both calcium and citrate do not distribute into the RBC volume). Szamosfalvi’s model more accurately predicts where citrate will travel in the patient’s body and therefore how its concentration will change (¶ [0195], Using the above parameters, systemic citrate levels can be accurately predicted at any future T time point).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Paolini; Francesco et al. US 20110118647 A1
Fontanazzi; Francesco et al. US 20140074008 A1
Sternby; Jan US 6258027 B1
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 extension fee 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 date of this final action.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Rebecca Eisenberg can be reached at 571-270-5879. The fax phone number for the organization where this application is assigned is 571-273-8300.
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/Adam Marcetich/
Primary Examiner, Art Unit 3781
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