Ex Parte Krivitski et alDownload PDFPatent Trial and Appeal BoardJul 31, 201311370721 (P.T.A.B. Jul. 31, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte NIKOLAI KRIVITSKI and NAVEEN THURAMALLA ____________ Appeal 2012-002102 Application 11/370,721 Technology Center 3700 ____________ Before ERIC GRIMES, LORA M. GREEN, and ULRIKE W. JENKS, Administrative Patent Judges. JENKS, Administrative Patent Judge DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. § 134 involving claims directed to a method of determining cardiac output by measuring blood parameters in an extracorporeal closed fluid system. The Examiner has rejected the claims as lacking written descriptive support, anticipation, and obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We affirm the prior art rejections. 1 Appellants state that the real party in interest is Transonic Systems, Inc. (App. Br. 2). Appeal 2012-002102 Application 11/370,721 2 STATEMENT OF THE CASE Claims 1-27 are on appeal, and can be found in the Claims Appendix of the Appeal Brief (App. Br. 32-39). Claims 1, 22, and 25 are illustrative of the claims on appeal, and read as follows (emphasis added): 1. A method for determining cardiac output comprising the steps of: a) establishing an extracorporeal closed fluid circuit between an arterial cannula and a venous cannula in a patient; b) establishing a constant fixed flow of blood through the extracorporeal closed fluid circuit from the arterial cannula to the venous cannula, using a pump; c) injecting an indicator intravenously; d) taking a reading of a blood parameter in the extracorporeal closed fluid circuit after the indicator has flowed at least once through the cardiopulmonary circulatory system of the patient to which the arterial and venous cannula are attached; and e) determining cardiac output from the read blood parameter independent of the constant fixed flow of blood through the extracorporeal fluid circuit. 22. A system for determining cardiac flow in a patient comprising: a) a closed fluid circuit connecting an arterial cannula and a venous cannula in a patient; b) a least one sensor on the closed fluid circuit positioned to sense a physical parameter of a fluid flowing in the closed fluid circuit from the arterial cannula to the venous cannula, the physical parameter corresponding to passage of an indicator through a cardiopulmonary circulatory system of the patient; c) at least one closable access port on the closed fluid circuit, the access port configured to allow fluid access to the closed fluid circuit; d) at least one flow regulator to establish a constant fixed flow of blood through the closed fluid circuit; and e) a processor connected to the at least one sensor configured to receive signals from the at least one sensor and Appeal 2012-002102 Application 11/370,721 3 determine cardiac flow when blood flows from the arterial cannula to the venous cannula with the indicator that has been injected into the at least one closable access port and passed at least once through the cardiopulmonary circulatory system of the patient. 25. A method of determining a cardiac output of a patient, the method comprising: (a) establishing a predetermined constant flow in a closed extracorporeal circuit withdrawing blood from an arterial portion of a patient cardiopulmonary system and returning the withdrawn blood to a venous portion of the patient cardiopulmonary system; and (b) determining a cardiac output of the patient independent of the predetermined constant flow, the cardiac output corresponding to a sensed change in a blood parameter in the closed extracorporeal circuit, the sensed change resulting from a dilution indicator passing through the patient cardiopulmonary system and a portion of the dilution indicator passing into the closed extracorporeal circuit. The Examiner has rejected the claims as follows: I. claims 1, 3, 22, and 27 under 35 U.S.C. § 112 first paragraph as lacking written descriptive support; II. claim 25 under 35 U.S.C. § 102(e) as being anticipated by Krivitski; 2 III. claims 1-21 and 26 under 35 U.S.C. § 103(a) as being unpatentable over Krivitski and Mohl; 3 IV. claims 22-24 and 27 under 35 U.S.C. § 103(a) as unpatentable over Krivitski in view of Buckberg 4 2 Nikolai M. Krivitski et al., US 2004/0158133 Al, published Aug. 12, 2004. 3 Werner Mohl, US 6,506,146 Bl, issued Jan. 14, 2003. 4 Gerald D. Buckberg et al., US 5,011,469, issued Apr. 30, 1991. Appeal 2012-002102 Application 11/370,721 4 I. The Issue: New Matter The Examiner takes the position that the Specification does not provide support for the limitations of “constant fixed flow” or “independent of constant fixed flow of blood” (Ans. 5). Furthermore, the Examiner takes the position that “[a] standard rate does not equate to constant or fixed” (id. at 11). Appellants contend that “the original disclosure stated the pump caused the blood to flow at a predetermined rate. Appellant respectfully submits such disclosure is sufficient to reasonably convey to one of ordinary skill in the art that the blood flow in the extracorporeal circuit was a constant fixed rate.” (App. Br. 14.) The issue is: Has the Examiner shown that the disclosure as originally filed does not provide descriptive support for the limitation of “constant fixed flow”? Findings of Fact FF 1. Original claim 3 provides “wherein the step of establishing the regulated blood flow comprises the step of starting a pump to cause the blood to flow at a predetermined rate.” (Spec. 17-18.) FF 2. The Specification provides that cardiac output is calculated based on the following equation: “Q represents the rate of cardiac output, V represents the volume of the indicator and S represents the area under the dilution curve.” (Spec. 8- 9: ¶ 0026.) FF 3. The Specification also provides, as a preferred embodiment, the following equation: Appeal 2012-002102 Application 11/370,721 5 Q, V, and S are the same as above (FF 2). “K is a calibration constant designed to relate the voltage signal received from the sensor to the concentration of indicator in the blood as it passes the sensor.” (Spec. 10: ¶ 0028.) Analysis With respect to the limitation “constant fixed flow” we agree with the Appellants‟ position that the original disclosure of setting the pump to a predetermined flow provides descriptive support for the presently claimed recitation of “constant fixed flow.” While the Examiner is correct that the specific language of the claims was not disclosed ipsis verbis in the Specification, ipsis verbis support is not required. Fujikawa v. Wattanasin, 93 F.3d 1559, 1570 (Fed. Cir. 1996). Here, the Specification as originally filed recites setting the blood flow to a predetermined rate. Furthermore, Appellants contend that the disclosed dilution principles support and are consistent with constant flow as recited in the claims (App. Br. 15). Appellants assert that one of ordinary skill in the art would “immediately recognize this equation implies a regulated – constant – flow” (id.). Given the totality of the disclosure (FFs 1-3) we agree with Appellants that the Specification sufficiently supports the “constant fixed flow” limitation as recited in the pending claims. With respect to the limitation “independent of the constant fixed flow of blood,” Appellants contend that the Specification provides “three examples of determining cardiac output independent of the flow rate through the extracorporeal circuit.” (App. Br. 19.) Appellants point to three equations in the Specification as providing descriptive support for Appeal 2012-002102 Application 11/370,721 6 determining cardiac output independent of the constant fixed flow rate (App. Br. 17-19). According to Appellants the same equation that provides support to establish constant fixed flow through the extracorporeal circuit, Q = V/S (FF 2; App. Br. 15), also provides support for the limitation “independent of the constant fixed flow of blood.” Appellants are correct that literally these equations as written do not list flow volume as one of the measured parameters (FFs 2-3). As the equations do not list flow volume as one of the measured parameters, it appears that these equations are seemingly independent of flow parameters. The Examiner reiterates “that the term regulated is not an equivalent term to constant fixed” and that “[a] standard rate does not equate to constant fixed.” (Ans. 11.) What is missing from the Answer, however, is an explanation from the Examiner as to why Appellants‟ reliance on these equations would not provide descriptive support for the claimed limitation of “independent of the constant fixed flow of blood.” Accordingly, the Examiner has not shown that the Specification fails to sufficiently support the “independent of constant fixed flow of blood” limitation as recited in the pending claims. We reverse the new matter rejections. II. The Issue: Anticipation of Claim 25 by Krivitski Claim 25 is directed to a method of determining cardiac output similar to that of claim 1, except that claim 25 does not require allowing the indicator to pass at least once through the patient‟s cardiopulmonary system before assessing a change in a blood parameter. The Examiner takes the position that “Krivitski discloses a method for determining cardiac output including the steps of establishing an extracorporeal closed fluid circuit Appeal 2012-002102 Application 11/370,721 7 between an arterial cannula and a venous cannula in a patient.” (Ans. 5.) An extracorporeal circuit is established in a “tubing system where blood flows, as well as disclosed as usable with dialysis which also meets the claim limitation of creating a constant flow in a closed fluid circuit.” (Id. at 11.) The issue is: Does the preponderance of the evidence of record support the Examiner‟s finding that Krivitski anticipates claim 25? Findings of Fact FF 4. Krivitski disclosed a method comprising “connecting an arterial tubing portion of a dialysis system to withdraw blood from a patient and connecting a venous tubing portion of the dialysis system to deliver filtered blood to the patient.” (Krivitski, 6: claim 1.) FF 5. Krivitski disclosed that “[d]ialysis machines of some brands turn ultrafiltration off during dialysis session several times to conduct internal self-calibration. Advantageously, these self-calibrating procedures can be used for calibration of the sensitivity optical probe to the relative concentration change.” (Krivitski, 4-5: ¶ 0069.) FF 6. Krivitski disclosed that cardiac output may be determined by dilution technique measuring photometric properties: The measurement may be made in an extracorporeal blood system in which optical measuring probes are secured, for example, to tubing leading to exterior blood treatment equipment such as hemodialysis machine, extracorporeal artery-vein passive shunt, or the like. Thereafter, a bolus, or known volume, of an indicator material is injected into the bloodstream, and measurements are made of changes in the photometric properties of the blood to determine the passage of the bolus past the optical probe 10. (Krivitski, 5: ¶ 0074; Ans. 6.) Appeal 2012-002102 Application 11/370,721 8 FF 7. Krivitski disclosed that cardiac output of a patient‟s heart may be calculated as follows: CO is the cardiac output; “Vind is total volume of injected indicator; Sb-ind is the area under a dilution curve representing the total optical density changes in the blood column over a time period; and Ks is the calibration coefficient for a particular set of tubing and probe” (Krivitski, 5: ¶¶ 0077-0078; Ans. 6). FF 8. The Examiner finds that “Krivitski teaches that an extracorporeal circuit is established in the prior art of record as can be seen in paragraphs 0020-0021 where there is tubing system where blood flows, as well as disclosed as usable with dialysis which also meets the claim limitation of creating a constant flow in a closed fluid circuit.” (Ans. 11.) FF 9. The Examiner finds that “Krivitski inherently uses a pump in the device in order to maintain the system as it is used to provide dialysis to patients, and provides a constant fixed flow.” (Ans. 11-12.) Principle of Law To anticipate a reference must expressly or inherently disclose “within the four corners of the document not only all of the limitations claimed but also all of the limitations arranged or combined in the same way as recited in the claim.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (2008). Analysis Appellants contend that Krivitski does not disclose each and every element of the claim. Specifically, that Krivitski does not disclose Appeal 2012-002102 Application 11/370,721 9 “„establishing a predetermined constant flow in a closed extracorporeal circuit.‟” (App. Br. 22.) We are not persuaded by Appellants‟ contention that Krivitski does not disclose all the limitations of claim 25. The Examiner reasons that Krivitski disclosed a tubing system “usable with dialysis which also meets the claim limitation of creating a constant flow in a closed fluid circuit” (FF 8). The Examiner concluded that a dialysis system inherently provides constant flow (FF 9) and thereby meets the claim limitation of “predetermined constant flow” as required by claim 25. See In re Best, 562 F.2d 1252, 1254-55 (CCPA 1977): [W]here the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on. … Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. Appellants have not provided persuasive rebuttal evidence that the system of Krivitski, used to provide dialysis to a patient, would not provide a “predetermined constant flow” as found by the Examiner (Ans. 11). The Examiner‟s finding of inherency for the “predetermined constant flow” limitation is additionally supported by the finding that Krivitski disclosed the use of a closed extracorporeal circuit for “determining cardiac output from [a] measured blood parameter” (Ans. 5). As the Examiner points out, Krivitski disclosed that the cardiac output of a patient can be Appeal 2012-002102 Application 11/370,721 10 calculated based on the total volume of the injected dilution indicator (Ans. 6; FF 6), by using the area under the dilution curve in conjunction with the use of a calibration coefficient for a particular tubing (FFs 6, 7). Here, Krivitski calculates the cardiac output using the same measured parameters and equations (FFs 6-7) as those disclosed in the Specification (FFs 2-3). Appellants concede that the examples and methods of calculating cardiac output as disclosed in the Specification (FFs 2-3) using the equation the equation Q= V/S provides support for the limitation of “determining cardiac output of the patient independent of the predetermined flow through the extracorporeal system” (App. Br. 19), and that one “of ordinary skill in the art would immediately recognize this equation (FF 2) implies a regulated - constant – flow” (id. at 15, see also Reply Br. 3). Krivitski uses essentially the same equation to determine cardiac output (FF 7), thus, the reference disclosed “constant flow.” The “very essence of inherency is that one of ordinary skill in the art would recognize that a reference unavoidably teaches the property in question.” Agilent Technologies, Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009) (emphasis added). Based on the evidence, we find that the Examiner has met the burden of presenting a prima facie case of anticipation. We affirm the rejection of claim 25. III. The Issue: Obviousness over Krivitski in view of Mohl The Examiner takes the position that Krivitski disclosed methods of determining cardiac output by calculating blood flow using the equation Q=KV/S wherein Q represents cardiac blood flow, V represents the amount of indicator injected, K equals a calibration coefficient and S is Appeal 2012-002102 Application 11/370,721 11 representative of the integral of the time rate of change (area under a dilution curve) in concentration of blood to indicator (saline solution) injected when the indicator is detected as present in the blood. (Ans. 6.) The Examiner concedes that Krivitski fails to specifically recite a pump, however, the Examiner finds that “Krivitski inherently uses a pump in the device in order to maintain the system as it is used to provide dialysis to patients, and provides a constant fixed flow” (id. at 11-12). The Examiner relies on Mohl “to positively claim the use of a pump within a [blood flow] system” (id. at 12). The issue is: Does the preponderance of evidence of record support the Examiner‟s conclusion that the combination of Krivitski and Mohl renders the claims obvious? Principle of Law The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 425 (CCPA 1981). Analysis Appellants assert that Mohl teaches away from the combination with Krivitski because it would lead one of ordinary skill in the art to use “variable flow as opposed to the claimed constant fixed” flow in the combined device leaving the device inoperable. (Reply Br. 8.) We are not persuaded. The Examiner finds that “Krivitski inherently uses a pump in the device in order to maintain the system as it is used to Appeal 2012-002102 Application 11/370,721 12 provide dialysis to patients, and provides a constant fixed flow” (Ans. 11-12; FFs 4-7). See In re Best, 562 F.2d at 1254-55. Appellants have not provided persuasive rebuttal evidence that the system of Krivitski, used to provide dialysis to a patient, would not provide constant flow through the use of a pump as found by the Examiner. The Examiner‟s finding of inherency for the limitation of “predetermined constant flow” is also supported by the finding that Krivitski calculates cardiac output using the general formula CO = K ∙ V/S (FF 7) where CO is cardiac output. Appellants concede that the examples and methods of calculating cardiac output as disclosed in the Specification (FFs 2-3) using the equation the equation Q = K ∙ V/S not only shows constant flow; the same equation also provides support for the limitation “independent of the constant fixed flow” (App. Br. 18), and also that one “of ordinary skill in the art would immediately recognize this equation (FF 2) implies a regulated - constant – flow” (id. at 15, see also Reply Br. 3). Krivitski uses this same equation to determine cardiac output (FF 7), thus, the reference disclosed the limitations of “constant fixed flow” and “independent of the constant fixed flow.” The Examiner looks to Mohl for the positive recitation of using a pump in an extracorporeal blood flow system (Ans. 12). Even though Mohl is primarily directed to providing extracorporeal blood flow on a discontinuous or pulsed basis, Mohl also provides for continuous flow by suggesting “optionally one continuously conveying external suction means or pump being used” (Mohl, col. 3, ll. 13-14). We find that Mohl disclosed the use of a pump in an extracorporeal circulatory system that can be configured to run continuously. The Examiner finds that Krivitski Appeal 2012-002102 Application 11/370,721 13 inherently uses a pump in the device (Ans. 11-12; see also FF 5). The mere substitution of one pump for another pump would be obvious to one of ordinary skill in the art. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Appellants have not pointed to any persuasive evidence that suggests that dialysis systems generally, or specifically the system of Krivitski, does not utilize a pump for the blood filtration process. We are also not persuaded by Appellants‟ contention that Mohl teaches away from the combination. Mohl not only suggests applying variable flow to the extracorporeal system but also optionally provides for continuous flow by conveying continuous external suction or pump (Mohl, col. 3, ll. 13-14). It is well settled that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or even non-preferred embodiments. See In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971). We find that the preponderance of the evidence of record supports the Examiner‟s conclusion of obviousness and we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) over Krivitski in view of Mohl. As claims 2-21 and 26 have not been argued separately, they fall together with claim 1. 37 C.F.R. § 41.37(c)(1)(vii). IV. The Issue: Obviousness over Krivitski in view of Buckberg Claim 22 is directed to a system comprising components suitable for carrying out a method like that of claim 1; claim 22 additionally requires a “closable access port” and a “flow regulator.” The Examiner takes the position that “Krivitski [disclosed] a system for a closed fluid circuit between an arterial cannula and a venous cannula in a patient . . . but fails to Appeal 2012-002102 Application 11/370,721 14 teach a flow regulator to establish and regulate the flow of blood through the closed circuit.” (Ans. 9.) “Buckberg teaches a regulated flow of blood through the closed circuit from the arterial cannula to the venous cannula . . . using a flow regulator.” (Id. at 10.) The Examiner finds that “Krivitski inherently uses a pump in the device in order to maintain the system as it is used to provide dialysis to patients, and provides a constant fixed flow. Buckberg is relied upon to show that it is known to use a flow regulator within an extracorporeal system and not used to illustrate a constant fixed flow.” (Id. at 12.) The issue is: Does the preponderance of evidence of record support the Examiner‟s conclusion that the combination of Krivitski and Buckberg renders the claims obvious? Findings of Fact FF 10. Buckberg disclosed a peripheral cardiopulmonary bypass system. “The peristaltic pump 118 is desirable in that the pumping mechanism does not actually contact the blood, thus eliminating a source of contamination and allowing reuse of the pump.” (Buckberg, col. 12, ll. 7- 10; Ans. 10.) FF 11. Buckberg disclosed that: To accommodate possible fluctuations in the volume of the flow required, and to regulate the blood volume of the patient, a reservoir, preferably compliant, is provided bridging the pump, with an inlet to the reservoir being connected to the pump outlet, and an outlet from the reservoir being connected between the venous catheter connection and the pump. Inflow and outflow valves in the connections permit circulating blood volume and therefore blood flow rates to be controlled. (Buckberg, col. 4, ll. 33-41.) Appeal 2012-002102 Application 11/370,721 15 Analysis Appellants assert that “Krivitski is recognized as failing to disclose the constant flow through the extracorporeal circuit, and Buckberg does not cure this deficiency.” (App. Br. 28.) “[D]etermining a cardiac output cannot be predicated upon bypassing all the blood flow around the heart, and then attempting to measure cardiac output.” (Id. at 29.) Appellants assert that “neither of the cited references disclose or suggest the limitation of „establishing a constant fixed flow through the closed fluid circuit.‟” (Id. at 30.) We are not persuaded. The Examiner finds that “Krivitski inherently uses a pump in the device in order to maintain the system as it is used to provide dialysis to patients, and provides a constant fixed flow” (Ans. 11-12; FFs 4-7). See In re Best, 562 F.2d at 1254-55. Appellants have not provided persuasive rebuttal evidence to show that the system of Krivitski, used to provide dialysis to a patient, would not provide constant flow through the use of a pump found by the Examiner. The Examiner‟s finding of inherency for the limitation of “constant fixed flow” is further supported in that Krivitski teaches two major ways of calibrating a conventional hemodialysis system. One such method relies on the dilution method (FFs 5-7) and the other relies on changing the rate of ultrafiltration by a known amount. “When the ultrafiltration rate is altered, the venous flow rate becomes greater by ultrafiltration rate change QUF. The change in the ultrafiltration rate produces a decreasing hemoglobin concentration.” (Krivitski 4: ¶ 0061.) The ability to change the flow through the ultrafiltration system further supports the Examiner‟s position that Krivitski inherently discloses a dialysis system having a pump. In Appeal 2012-002102 Application 11/370,721 16 addition, the Examiner finds that Krivitski calculates cardiac output using the general formula CO = K ∙ V/S (FF 7) where CO is cardiac output. As conceded by Appellants, the general formula Q= K ∙ V/S shows constant flow (App. Br. 15-19). Because Krivitski‟s cardiac output calculation relies on constant fixed flow (FF 7) in conjunction with an extracorporeal circuit (FF 4), we are not persuaded by Appellants‟ contentions that the references do not disclose the limitation “constant fixed flow.” We agree with the Examiner‟s finding that Buckberg disclosed the use of a pump (FF 10) as well as the use of flow regulators (FF 11) to control the blood flow in a closed extracorporeal circuit. Buckberg disclosed the use of a peristaltic pump and teaches that the use of such a pump is desirable because the pumping mechanism does not make direct contact with blood and therefore the pump can be utilized multiple times without the fear of contamination (FFs 10-11). “The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference,” but what the combined teachings of the references suggest. In re Keller, 642 F.2d at 425. The Examiner relies on Krivitski for teaching an extracorporeal circuit and measuring cardiac output while “Buckberg is relied upon to show that it is known to use a flow regulator within an extracorporeal system and not used to illustrate a constant fixed flow.” (Ans. 12.) We are not persuaded by Appellants‟ contention that the combination does not teach “a constant fixed flow of blood though the extracorporeal closed fluid circuit” (App. Br. 30) because we agree with the Examiner‟s finding that Krivitski provides this limitation by calculating the Appeal 2012-002102 Application 11/370,721 17 cardiac output using the general formula CO = K ∙ V/S (FF 7) in the closed extracorporeal dialysis system (FF 4). We find that the preponderance of the evidence of record supports the Examiner‟s conclusion of obviousness and we affirm the rejection of claim 22 under 35 U.S.C. § 103(a) over Krivitski in view of Buckberg. As claims 23, 24, and 27 have not been argued separately, they fall together with claim 22. 37 C.F.R. § 41.37(c)(1)(vii). SUMMARY We reverse the rejection of claims 1, 3, 22, and 27 under 35 U.S.C. § 112 first paragraph as lacking written descriptive support. We affirm the rejection of claim 25 under 35 U.S.C. § 102(e) as being anticipated by Krivitski. We affirm the rejection of claims 1-21 and 26 under 35 U.S.C. § 103(a) as being unpatentable over Krivitski and Mohl. We affirm the rejection of claims 22-24 and 27 under 35 U.S.C. § 103(a) as unpatentable over Krivitski in view of Buckberg. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED cdc Copy with citationCopy as parenthetical citation