Best ABT , Inc.

Patent Trials and Appeals Board

Mar 8, 2022

2021002686 (P.T.A.B. Mar. 8, 2022)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/618,772 02/10/2015 Atilio Anzellotti 6844 95603 7590 03/08/2022 Best Medical International, Inc. Patent Counsel 7643 Fullerton Road Springfield, VA 22153 EXAMINER DONOHUE, SEAN R ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 03/08/2022 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): patents@teambest.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ATILIO ANZELLOTTI, AARON MCFARLAND, CLIVE BROWN-PROCTOR, DANIEL HILLESHEIM, and MARK KHACHATURIAN1 Appeal 2021-002686 Application 14/618,772 Technology Center 1600 Before ERIC B. GRIMES, ULRIKE W. JENKS, and JOHN G. NEW, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a testing method, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. STATEMENT OF THE CASE As with any medical application involving the use of radioactive materials, quality control is important in the 1 Appellant identifies the real party in interest as Best ABT, Inc. Appeal Br. 3. “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42. Appeal 2021-002686 Application 14/618,772 2 synthesis and use of PET biomarker radiopharmaceuticals. . . . The final radiopharmaceutical solution should be tested for the presence and levels of volatile organics, such as ethanol or methyl cyanide, that may remain from synthesis process. . . . Further, the radiochemical purity of the final solution should be tested to ensure that it is sufficiently high for the solution to be useful. Other tests, such as tests of radionuclide purity, tests for the presence of bacterial endotoxins, and tests of the sterility of the synthesis system, are known in the art. Spec. ¶ 7. The “invention relates to conducting quality control tests on radiopharmaceuticals for use in positron emission tomography (PET).” Id. ¶ 1. Claims 24-50 are on appeal. Claim 24, the only independent claim, is reproduced below: 24. A method of conducting quality control testing for a radiopharmaceutical before delivery of the radiopharmaceutical to a patient, the method comprising: generating a radiopharmaceutical including a radioisotope and at least one volatile organic contaminant to form a radiopharmaceutical solution including the radioisotope and the at least one volatile organic contaminant; determining the radioactivity of the radiopharmaceutical in the radiopharmaceutical solution; separating the radiopharmaceutical solution into a first portion, a second portion, and a third portion; determining endotoxicity of the first portion; determining a first ultraviolet spectra of the second portion before passing the second portion through a high performance liquid chromatography column; separating the second portion into a number of separated chemical species with the high performance liquid chromatography column; Appeal 2021-002686 Application 14/618,772 3 determining the refractive index of each of the number of the separated chemical species; determining the radioactivity of each of the number of separated chemical species; determining that the radiopharmaceutical passes quality control testing when the refractive index of the radiopharmaceutical indicates that the radiopharmaceutical includes 400 parts per million or less of the volatile organic contaminant; and passing the third portion through a sample line that is in liquid communication with a plurality of testing devices, said sample line including apparatus to divert a sample volume of the radiopharmaceutical solution to each of said plurality of testing devices, wherein said apparatus includes a multipart valve, a plurality of ports arranged in series, or a plurality of load loops arranged in series, and wherein the plurality of testing devices in liquid communication with said sample line are able to conduct tests on sample volumes of the radiopharmaceutical solution from the third portion of the radiopharmaceutical solution while the second portion of the radiopharmaceutical solution is passing through the high performance liquid chromatography column, wherein the plurality of testing devices is selected from the group consisting of a phase transfer catalyst device, a multi- channel analyzer for radionucleic purity, a dose calibrator for radioactivity level measurement, an endotoxin measurement device or an electronic conductivity device, and wherein the testing occurs on the sample volumes that include a totality of the radiopharmaceutical solution. Appeal Br. 20-21 (Claims Appendix). Appeal 2021-002686 Application 14/618,772 4 The claims stand rejected as follows: Claims 24-29, 31-35, 37, 40-44, 46, and 48-50 under 35 U.S.C. § 103 as obvious based on Nutt I2 and Nutt II3 (Non-Final Action4 5); Claims 24-37, 40-44, 46, and 48-50 under 35 U.S.C. § 103 as obvious based on Nutt I, Nutt II, Ball,5 and Koziorowski6 (Non-Final Action 9); Claims 24-29, 31-35, 37-44, and 46-50 under 35 U.S.C. § 103 as obvious based on Nutt I, Nutt II, Mathis,7 and Kuznetsova8 (Non-Final Action 10); and Claims 24-29, 31-35, 37, 40-46, and 48-50 under 35 U.S.C. § 103 as obvious based on Nutt I, Nutt II, and Mock9 (Non-Final Action 11). OPINION Claim Interpretation Claim 24 concludes with the limitation that “the testing occurs on the sample volumes that include a totality of the radiopharmaceutical solution.” 2 US 2013/0130309 A1, published May 23, 2013. 3 US 2011/0070158 A1, published March 24, 2011. 4 Office Action mailed July 23, 2019. The Final Office Action mailed February 18, 2020, refers to the Non-Final Action for an explanation of the rejections. 5 US 2010/0145630 A1, published June 10, 2010. 6 A simple method for the quality control of [18F]FDG, APPLIED RADIATION AND ISOTOPES 68:1740-1742 (2010). 7 Overall Radio-HPLC Design, in ANALYTICAL AND CHROMATOGRAPHY TECHNIQUES IN RADIOPHARMACEUTICAL CHEMISTRY 125-148 (D.M Wieland et al. eds., 1986). 8 Preparation and Quality Control of [N-Methyl-11C]choline for Routine PET Application, RADIOCHEMISTRY 45(4):377-381 (2003). 9 A Color Spot Test for the Detection of Kryptofix 2.2.2 in [18F]FDG Preparations, NUCLEAR MEDICINE & BIOLOGY 24:193-195 (1997). Appeal 2021-002686 Application 14/618,772 5 Appellant and the Examiner disagree on whether the prior art teaches or would have suggested this limitation. Thus, we begin by construing the disputed claim language. “While the Board must give the terms their broadest reasonable construction, the construction cannot be divorced from the specification and the record evidence.” In re NTP, Inc., 654 F.3d 1279, 1288 (Fed. Cir. 2011). The “broadest reasonable interpretation in light of the specification . . . is an interpretation that corresponds with what and how the inventor describes his invention in the specification, i.e., an interpretation that is ‘consistent with the specification.’” In re Smith Intl., Inc., 871 F.3d 1375, 1382-83 (Fed. Cir. 2017). The preamble of claim 24 states that the method’s purpose is for “conducting quality control testing for a radiopharmaceutical before delivery of the radiopharmaceutical to a patient.” The body of the claim begins with “generating a radiopharmaceutical including a radioisotope and at least one volatile organic contaminant to form a radiopharmaceutical solution including the radioisotope and the at least one volatile organic contaminant,” then “separating the radiopharmaceutical solution into a first portion, a second portion, and a third portion.” Claim 24. Claim 24 thus distinguishes between “a radiopharmaceutical” that is intended for delivery to a patient, and “a radiopharmaceutical solution,” which is separated into three portions that are subjected to testing. Claim 24 also states that “the testing occurs on the sample volumes that include a totality of the radiopharmaceutical solution.” Appeal 2021-002686 Application 14/618,772 6 Thus, in the context of claim 24 as a whole, “the radiopharmaceutical solution” refers to a sample of “the radiopharmaceutical,” and is used for the tests that are recited for the “first portion,” “second portion,” and “third portion.” The results of those tests thus provide quality control testing of “the radiopharmaceutical” as a whole “before delivery of the radiopharmaceutical to a patient.” This interpretation is consistent with the Specification’s description of the claimed method. The Specification states, for example, that purified radiopharmaceutical solution (“solution” here is not used in the same sense as in the claims) is collected in a product collection vial, from which a first portion of the purified radiopharmaceutical solution is directed . . . to a QCM [quality control module] 50. From the product collection vial 210, a second portion of the purified radiopharmaceutical solution is directed . . . into a sterility sample vial 230. A first part of the second portion . . . remains in the sterility sample vial 220 [sic], and a second part of the second portion of the purified radiopharmaceutical solution in the sterility sample vial 230 travels . . . into a product injection vial 250. The second part of the second portion . . . is generally the radiopharmaceutical solution that will be administered to one or more patients. Spec. ¶ 51. Thus, the portion of the radiopharmaceutical solution that is used for quality control testing represents a sample of the overall radiopharmaceutical, and is different from the part that will be administered to patients. See also id. ¶ 59 (“The example embodiment of an HPLC-based QCM 50 illustrated in Figure 4 is to test a first portion of purified radiopharmaceutical solution (hereinafter ‘the sample radiopharmaceutical solution’ or simply ‘sample.’)”). Appeal 2021-002686 Application 14/618,772 7 Obviousness Claims 24-29, 31-35, 37, 40-44, 46, and 48-50 stand rejected as obvious based on Nutt I and Nutt II. The Examiner finds that Nutt I teaches a “method of conducting quality control comprising generating a radiopharmaceutical (FDG) including at least one radioisotope (F-18) and a volatile organic component (MeCN).” Non-Final Action 5. The Examiner finds that the method taught by Nutt I includes many of the limitations of claim 24 (id. at 6), but does not include passing a third portion through a sample line that is in fluid communication with a plurality of testing devices, . . . wherein the plurality of testing devices in liquid communication with the sample line are able to conduct tests on sample volumes of radiopharmaceutical from the third portion while the second portion is passing through the HPLC column. Id. at 7. The Examiner finds, however, that Nutt II teaches “a quality control module for biomarker generator system” that includes a sample card that “allow[s] operators to conduct quality control tests in reduced time using microscale test samples from [a] radiopharmaceutical solution.” Id. The Examiner finds that Nutt II teaches that, “to test for color and clarity, a light source shines white light through the sample in the test vessel” and “[a]n electronic eye (colorimetric detector) detects the light that has passed through the sample and measures the lights intensity and color.” Id. The Examiner finds that Nutt II also teaches that, “to test for kryptofix, the sample is placed on a gel comprising silica gel with iodoplatinate . . . and a color recognition sensor measures the resultant color of the sample.” Id. at 7-8. Finally, the Examiner finds that Nutt II teaches that, “to test for volatile organics, a heat source heats the sample in the test vessel to 150°C so that Appeal 2021-002686 Application 14/618,772 8 the aqueous gas components, now in gas form, enter the adjacent gas chromatograph.” Id. at 8. The Examiner concludes that it would have been obvious to include the sample card of Nutt II in the method of Nutt I in order to “enable conducting multiple quality control tests in reduced time using microscale test samples from the radiopharmaceutical solution.” Id. The Examiner reasons that it would have been obvious to modify the method of Nutt [I] by further detecting the presence of K 222 [i.e., kryptofix], a phase transfer catalyst, using silica gel and iodoplatinate before determining the visible light absorbance of the mixture as taught by Nutt [II] because it would advantageously enable determining the presence of K222 in the final radiopharmaceutical formulation after radiosynthesis of [18F]FDG. Id. The Examiner also concludes that it would have been obvious “to modify the method of Nutt [I] by further determining the ratio of the separated chemical species [18F]FDG to radioactivity of the radiopharmaceutical as taught by Nutt [II] because it would advantageously enable determining the percent radiochemical yield.” Id. We agree with the Examiner that the method of claim 24 would have been obvious based on Nutt I and Nutt II. The Examiner finds that Nutt I teaches a method that includes all of the limitations of claim 24 except for those directed to the “third portion.” We agree. Nutt I discloses “quality control systems incorporating high performance liquid chromatography (HPLC) to perform quality control testing on a radiopharmaceutical solution.” Nutt I ¶ 13. Nutt I describes “an HPLC-based QCM 50 . . . to test a first portion of purified radiopharmaceutical solution (hereinafter ‘the Appeal 2021-002686 Application 14/618,772 9 sample radiopharmaceutical solution’ or simply ‘sample’) from a DSM.” Id. ¶ 43. Nutt I describes a quality control testing method for a radiopharmaceutical comprising reacting said radioisotope and said at least one reagent to produce . . . a raw state radiopharmaceutical solution containing undesirable chemical entities; . . . directing a first aliquot of the clarified radiopharmaceutical solution into a first sample collection vessel . . . for measurement of the radioactivity of the clarified radiopharmaceutical solution; directing a second aliquot of the clarified radiopharmaceutical solution into a second sample collection vessel . . . for endotoxicity testing; directing a third aliquot of the clarified radiopharmaceutical solution into a high performance liquid chromatography column to separate molecularly distinct species within the third aliquot . . . ; measuring the optical qualities of the third aliquot of the sample radiopharmaceutical solution by means of an ultraviolet-light detector; using a refractive index detector to measure the amount of each separated molecularly distinct species from said high performance liquid chromatography column; and measuring the radioactivity of each separated molecularly distinct species from said high performance liquid chromatography column. Nutt I ¶ 19 (emphasis added). See also id. ¶ 58: [T]he RI [refractive index] detector 505 also measures the residual concentration in the sample radiopharmaceutical solution of solvents such as acetonitrile and ethanol. Generally, a purified radiopharmaceutical solution will be considered to pass quality control testing if the residual concentration of acetonitrile in the sample radiopharmaceutical solution is less than or equal to 400 ppm. As the Examiner noted, Nutt I does not teach the limitations of claim 24 related to the “third portion.” However, Nutt II teaches “a PET biomarker production system includ[ing] a radioisotope generator, a Appeal 2021-002686 Application 14/618,772 10 radiopharmaceutical production module, and a quality control module.” Nutt II ¶ 13. Nutt II teaches that, “[o]nce the radiopharmaceutical solution has passed through the filter 170, some of the solution is diverted into the sample card 40, which contains a number of sample vessels 402a-e.” Id. ¶ 28. Figure 4 of Nutt II is reproduced below: Figure 4 shows “a flow diagram of one embodiment of the sample card interacting with one embodiment of the quality control module (QCM).” Id. ¶ 21. More specifically, Figure 4 shows that “the radiopharmaceutical samples travel from the sample vessels 402a-e into the test vessels 502, 602, 702, 802, and 902 within the QCM 50. Within the QCM 50, instruments exist to perform a number of automated quality control tests for each run of radiopharmaceutical.” Id. ¶ 29. Appeal 2021-002686 Application 14/618,772 11 Nutt II states that its QCM conducts several tests. For example, “[t]o test for color and clarity, a light source 504 shines white light through the sample in the test vessel 502. An electronic eye 506 then detects the light that has passed through the sample and measures that light’s intensity and color against reference samples.” Id. ¶ 30. Appellant’s Specification states that the disclosed quality control system can include a number of testing devices, including “an electronic eye device [to] measure the electronic conductivity of said radiopharmaceutical.” Spec. ¶ 78. Thus, the QCM of Nutt II reasonably appears to include “an electronic conductivity device” (i.e., an electronic eye) as recited in claim 24. Nutt II also states that, [t]o test for the presence of kryptofix, the sample in the test vessel 802 is placed on a gel 804 comprising silica gel with iodoplatinate. The sample and gel 804 are then warmed, and a color recognition sensor 806 measures the resultant color of the sample, with a yellow color indicating the presence of kryptofix. Nutt II ¶ 33. Appellant’s Specification states that, when the disclosed system “includes a component or components for detecting the presence of residual phase transfer catalyst in the finished radiopharmaceutical solution, an iodine reagent is mixed with a sample solution containing the phase transfer catalyst Kryptofix 2.2.2; this mixture causes a red suspension to form, which can be observed visually.” Spec. ¶ 79 (emphasis added). Thus, the QCM of Nutt II reasonably appears to include “a phase transfer catalyst device,” as recited in claim 24. Based on the above teachings, it would have been obvious to a person of ordinary skill in the art to modify the quality control module (QCM) of Appeal 2021-002686 Application 14/618,772 12 Nutt I to carry out the additional testing described by Nutt II on a third aliquot of the testing sample of Nutt I, while the second aliquot of Nutt I is undergoing the HPLC analysis described by Nutt I. Motivation to combine the teachings of the references is provided by Nutt II, which teaches that the additional quality control tests allow assaying for color and clarity of the radiopharmaceutical, as well as the presence of residual kryptofix phase transfer catalyst. Thus, the method of claim 24 would have been obvious to a skilled artisan based on Nutt I and Nutt II. Appellant argues, however, that Nutt I and Nutt II fail to teach the features of “conducting tests on sample volumes of the radiopharmaceutical solution from the third portion of the radiopharmaceutical solution while the second portion of the radiopharmaceutical solution is passing through the high performance liquid chromatography column . . . wherein the testing occurs on the sample volumes that include a totality of the radiopharmaceutical solution.” Appeal Br. 11 (alteration in original). Appellant argues that, “[i]ndeed, Nutt II expressly teaches away from the features of ‘wherein the testing occurs on the sample volumes that include the totality of the radiopharmaceutical solution,’” because “Nutt II is concerned with performing quality control test[s] on every dose rather than on a pharmaceutical solution as an entire batch or the sample volumes that include a totality of the radiopharmaceutical solution. Accordingly, Nutt II teaches away from testing on sample volumes of a portion of an entire batch.” Id. This argument is unpersuasive. As discussed above, the broadest reasonable interpretation of “testing [that] occurs on the sample volumes that include a totality of the radiopharmaceutical solution” requires only that the part of the radiopharmaceutical that is separated for use in quality control Appeal 2021-002686 Application 14/618,772 13 testing-i.e., “the radiopharmaceutical solution”-is used in its totality for that testing. Nutt I discloses this limitation. Nutt I states that its “HPLC-based QCM 50 . . . is to test a first portion of purified radiopharmaceutical solution (hereinafter ‘the sample radiopharmaceutical solution’ or simply ‘sample’).” Nutt 1 ¶ 43. Nutt I states that “a portion of the sample radiopharmaceutical solution . . . is loaded . . . into a first QCM pathway 527.” Id. ¶ 44. “Another portion of the sample radiopharmaceutical solution . . . enter[s] a second QCM pathway 523; this second portion . . . passes through the second QCM pathway 523 into an endotoxin testing sample vessel 521.” Id. Nutt I states that “[a]ny remainder third portion of the sample radiopharmaceutical solution . . . enter[s] a third QCM pathway 529, which conveys the remainder third portion of the sample radiopharmaceutical solution to a waste vessel 507.” Id. Thus, Nutt I discloses that the quality control testing in its method uses sample volumes that include the totality of the part of its radiopharmaceutical that is diverted for quality control testing. Appellant’s Specification describes the limitation in question in the same manner as Nutt I. See Spec. ¶¶ 59-60. Appellant also argues that “there is no motivation for one of ordinary skill in the art to combine the disclosures of Nutt I and Nutt II.” Appeal Br. 12. Appellant argues that “any teaching that might suggest the combination of Nutt I with Nutt II likely appears to stem from Appellant’s own disclosure rather than the teachings of the applied references of Nutt I and Nutt II.” Id. at 13. Appeal 2021-002686 Application 14/618,772 14 This argument is also unpersuasive. Both Nutt I and Nutt II are directed to quality control testing of radiopharmaceuticals for use in PET scans. See Nutt I ¶ 13, Nutt II ¶ 13. Nutt II suggests additional quality control tests that are useful for radiopharmaceuticals, including tests for color and clarity, and for residual phase transfer catalyst (kryptofix). Thus, a person skilled in the art of making radiopharmaceuticals for use in PET scans would have recognized that the method of Nutt I would be improved by modifying it to include the additional quality control assays disclosed by Nutt II. We agree with the Examiner that the cited references provide ample reason to combine their respective teachings. In summary, we affirm the rejection of claim 24 under 35 U.S.C. § 103 based on Nutt I and Nutt II. Claims 25-29, 31-35, 37, 40-44, 46, and 48-50 fall with claim 24 because they were not argued separately. 37 C.F.R. § 41.37(c)(1)(iv). Claims 24-37, 40-44, 46, and 48-50 stand rejected under 35 U.S.C. § 103 based on Nutt I, Nutt II, Ball, and Koziorowski. Claims 24-29, 31-35, 37-44, and 46-50 stand rejected under 35 U.S.C. § 103 based on Nutt I, Nutt II, Mathis, and Kuznetsova. Claims 24-29, 31-35, 37, 40-46, and 48-50 stand rejected under 35 U.S.C. § 103 based on Nutt I, Nutt II, and Mock. Appellant has waived arguments directed to Ball, Koziorowski, Mathis, Kuznetsova, or Mock. See Appeal Br. 14-19. We therefore affirm the remaining rejections for the reasons discussed above. Appeal 2021-002686 Application 14/618,772 15 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 24-29, 31- 35, 37, 40- 44, 46, 48- 50 103 Nutt I, Nutt II 24-29, 31- 35, 37, 40- 44, 46, 48- 50 24-37, 40- 44, 46, 48- 50 103 Nutt I, Nutt II, Ball, Koziorowski 24-37, 40- 44, 46, 48- 50 24-29, 31- 35, 37-44, 46-50 103 Nutt I, Nutt II, Mathis, Kuznetsova 24-29, 31- 35, 37-44, 46-50 24-29, 31- 35, 37, 40- 46, 48-50 103 Nutt I, Nutt II, Mock 24-29, 31- 35, 37, 40- 46, 48-50 Overall Outcome 24-50 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED