Ex Parte Chan et al

Patent Trials and Appeals BoardJul 9, 2019

13102993 - (D) (P.T.A.B. Jul. 9, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/102,993 05/06/2011 109855 7590 07/11/2019 Quest Diagnostics Attn: Legal Department 33608 Ortega Highway San Juan Capistrano, CA 92675 FIRST NAMED INVENTOR Sum Chan 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 034827-0503 8300 EXAMINER EOM, ROBERT J ART UNIT PAPER NUMBER 1797 NOTIFICATION DATE DELIVERY MODE 07/11/2019 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): ipdocketing@foley.com joshua.e.kim@questdiagnostics.com joel.s.white@questdiagnostics.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte SUM CHAN, DARREN A. CARNS, MICHAEL P. CAULFIELD, RICHARD E. REITZ, MILDRED M. REDOR-GOLDMAN, and SEYED A. SADJADI Appeal 2018-009183 Application 13/102,993 Technology Center 1700 Before ROMULO H. DELMENDO, DONNA M. PRAISS, and N. WHITNEY WILSON, Administrative Patent Judges. WILSON, Administrative Patent Judge. DECISION ON APPEAL Appellants1 appeal under 35 U.S.C. Â§ 134(a) from the Examiner's March 10, 2017 decision finally rejecting claims 16-23 and 27 ("Final Act."). We have jurisdiction over the appeal under 35 U.S.C. Â§ 6(b). We affirm. 1 Appellants identify Quest Diagnostics Investments Incorporated as the real party in interest (Appeal Br. 1 ). Appeal 2018-009183 Application 13/102,993 CLAIMED SUBJECT MATTER Appellants' disclosure relates, inter alia, to a method for determining the amount of lamotrigine in a test sample by tandem mass spectrometry (Spec. ,-J,-J 2, 40-44). Lamotrigine is an antiepileptic drug used to control certain kinds of seizures (Spec. ,-J 22). The method involves (1) purifying lamotrigine from the test sample; (2) ionizing lamotrigine purified from said sample to produce lamotrigine precursor ions detectable by mass spectrometry, wherein said precursor ions have a mass to charge ratio (m/z) of about 255.9; (3) fragmenting said precursor ion into one or more fragment ions detectable by mass spectrometry, wherein one of said fragment ions has m/z of about 210.8; and (4) detecting the amount of one or more of the parent and fragment ions of steps (2) and (3) ions by mass spectrometry (id. ,-J,-J 40-44). The amount of ions detected is related to the amount of lamotrigine in the test sample, which comprises blood, plasma, or serum (id. ,-J 46). Details of the claimed invention are set forth in independent claim 16, which is reproduced below from the Claims Appendix to the Appeal Brief (emphasis added): 16. A method for determining the amount of lamotrigine in a test sample by tandem mass spectrometry, comprising: (a) purifying lamotrigine from said test sample; (b) ionizing lamotrigine purified from said sample to produce lamotrigine precursor ions detectable by mass spectrometry, wherein said precursor ions have a mass to charge ratio (m/z) of about 255.9; ( c) fragmenting said precursor ion into one or more fragment ions detectable by mass spectrometry, wherein one of said fragment ions has m/z of about 210.8; and ( d) detecting the amount of one or more of the parent and fragment ions of steps (b) and ( c) ions by mass spectrometry, 2 Appeal 2018-009183 Application 13/102,993 wherein the amount of ions detected is related to the amount of lamotrigine in the test sample; wherein the test sample comprises blood, plasma, or serum. REJECTIONS (1) Claims 16-23 and 27 are rejected under 35 U.S.C. Â§ 101 on the grounds that the claimed invention is directed to a judicial exception. (2) Claims 16, 17, 22, 23, and 27 are rejected under 35 U.S.C. Â§ 103 (a) as unpatentable over Doig2 in view of Dasgupta3 and Decaestecker4, as evidenced by Luo. 5 2 M.V. Doig & R. A. Clare, USE OF THERMOSPRAY LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY TO AID IN THE IDENTIFICATION OF URINARY METABOLITES OF A NOVEL ANTIEPILEPTIC DRUG, LAMOTRIGINE, 554 J. of Chromatography 181-89 (1991). 3 Amitava Dasgupta & Amy P. Hart, LAMOTRIGINE ANALYSIS IN PLASMA BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY AFTER CONVERSION TO A TERT.-BUTYLDIMETHYLSILYLDERIVATIVE, 693 J. of Chromatography B 101- 07 (1997). 4 Tineke N. Decaestecker et al., EVALUATION OF AUTOMATED SINGLE MASS SPECTROMETRY TO TANDEM MASS SPECTROMETRY FUNCTION SWITCHING FOR COMPREHENSIVE DRUG PROFILING ANALYSIS USING A QUADRUPOLE TIME-OF- FLIGHT MASS SPECTROMETER, 14 Rapid Commc 'ns In Mass Spectrometry 1787-92 (2000). 5 Yi Luo, IDENTIFICATION, QUANTIFICATION AND CONFIRMATION OF AMOTRIGINE IN EQUINE PLASMA BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY, TIP Approved SOP PETRL SOP 526.0 LC/MS/MS (2005). 3 Appeal 2018-009183 Application 13/102,993 (3) Claims 19-21 are rejected under 35 U.S.C. Â§103(a) as unpatentable over Doig in view of Dasgupta and Decaestecker, as evidenced by Luo, and further in view ofMasahiko6 as evidenced by Jemal7 or Wu. 8 DISCUSSION Rejection 1 - Â§ 101 Legal background. An invention is patent-eligible if it claims a "new and useful process, machine, manufacture, or composition of matter." 35 U.S.C. Â§ 101. However, the Supreme Court has interpretedÂ§ 101 to include implicit exceptions: "[l]aws of nature, natural phenomena, and abstract ideas" are not patentable. E.g., Alice Corp. v. CLS Bank Int 'l, 573 U.S. 208,216 (2014). In determining whether a claim falls within an excluded category, the Supreme Court's two-step framework, described in Mayo and Alice guides our analysis. Id. at 217-18 ( citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 75-77 (2012)). In accordance with that framework, we first determine what concept the claim is "directed to." See Alice, 573 6 Takino Masahiko et al., ANALYSIS OF DRUGS FROM PLASMA BY COLUMN SWITCHING-LC/ESI-MS WITH TURBULENT-FLOW CHROMATOGRAPHY, 49 Shitsuryo Bunseki Sago Toronkai Koen Yoshishu, 284-85 (2001). We refer, as do the Examiner and Appellants, to the English-language abstract of record. 7 Mohammed Jemal, HIGH-THROUGHPUT QUANTITATIVE BIOANALYSIS BY LC/MS/MS," 14 Biomedical Chromatography 422-29 (2000). 8 Jing-Tao Wu et al., DIRECT PLASMA SAMPLE INJECTION IN MULTIPLE- COMPONENT LC-MS-MS ASSAYS FOR HIGH-THROUGHPUT PHARMACOKINETIC SCREENING, 72 Analytical Chemistry 61-67 (2000). 4 Appeal 2018-009183 Application 13/102,993 U.S. at 219 ("On their face, the claims before us are drawn to the concept of intermediated settlement, i.e., the use of a third party to mitigate settlement risk."); see also Bilski v. Kappas, 561 U.S. 593, 611 (2010) ("Claims 1 and 4 in petitioners' application explain the basic concept of hedging, or protecting against risk."). Concepts determined to be abstract ideas, and thus patent ineligible, include certain methods of organizing human activity, such as fundamental economic practices (Alice, 573 U.S. at 219-20; Bilski, 561 U.S. at 611); mathematical formulas (Parker v. Flook, 437 U.S. 584, 594-95 (1978)); and mental processes (Gottschalkv. Benson, 409 U.S. 63, 67 (1972)). Concepts determined to be patent eligible include physical and chemical processes, such as "molding rubber products" (Diamond v. Diehr, 450 U.S. 175, 191 (1981 )); "tanning, dyeing, making water-proof cloth, vulcanizing India rubber, smelting ores" (id. at 182 n.7 (quoting Corning v. Burden, 56 U.S. 252, 267-68 (1854))); and manufacturing flour (Benson, 409 U.S. at 69 (citing Cochrane v. Deener, 94 U.S. 780, 785 (1876))). In Diehr, the claim at issue recited a mathematical formula, but the Supreme Court held that "a claim drawn to subject matter otherwise statutory does not become nonstatutory simply because it uses a mathematical formula." Diehr, 450 U.S. at 187; see also id. at 191 ("We view respondents' claims as nothing more than a process for molding rubber products and not as an attempt to patent a mathematical formula."). Having said that, the Supreme Court also indicated that a claim "seeking patent protection for that formula in the abstract ... is not accorded the protection of our patent laws, ... and this principle cannot be circumvented by attempting to limit the use of the formula to a particular technological 5 Appeal 2018-009183 Application 13/102,993 environment." Id. ( citing Benson and Flook); see, e.g., id. at 187 ("It is now commonplace that an application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection."). If the claim is "directed to" an abstract idea, the analysis moves to the second step of the Alice and Mayo framework, where "we must examine the elements of the claim to determine whether it contains an 'inventive concept' sufficient to 'transform' the claimed abstract idea into a patent- eligible application." Alice, 573 U.S. at 221 ( quotation marks omitted). "A claim that recites an abstract idea must include 'additional features' to ensure 'that the [claim] is more than a drafting effort designed to monopolize the [ abstract idea]."' Id. ( alterations in original) ( quoting Mayo, 566 U.S. at 77). "[M]erely requir[ing] generic computer implementation[] fail[s] to transform that abstract idea into a patent-eligible invention." Id. The PTO has published revised guidance on the application ofÂ§ 101. 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50 (Jan. 7, 2019) ("Guidance"). Under the Guidance, we first look to whether the claim recites: (1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and (2) additional elements that integrate the judicial exception into a practical application (see MPEP Â§Â§ 2106.05(a)-(c), (e)-(h)). Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim: 6 Appeal 2018-009183 Application 13/102,993 (3) adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field (see MPEP Â§ 2106.0S(d)); or (4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception. See Guidance. We will focus our analysis on claim 16, which is the only independent claim on appeal, and the only claim argued by Appellants. Claim 16 Guidance Step 1 There is no dispute that claim 16 falls within a statutory category, as it recites a method for determining the amount of lamotrigine in a test sample. Guidance Step 2A, Prong 1 Under Step 2A of the Guidance, we first consider whether the claims recite a judicial exception. Claim 16 recites a number of steps, including, for example (a) "purifying lamotrigine from said test sample," (b) "ionizing lamotrigine purified from said sample to produce lamotrigine precursor ions detectable by mass spectrometry," ( c) "fragmenting said precursor ion into one or more fragment ions detectable by mass spectrometry," ( d) "detecting the amount of one or more of the parent and fragment ions of steps (b) and (c) ions by mass spectrometry," and (e) "wherein the amount of ions detected [in step ( d)] is related to the amount of lamotrigine in the test sample." While steps (a)-(d) recite physical manipulation of a sample and measurements resulting from such manipulation, the "wherein" clause ( e) recites a relationship between the measurements of step ( d) and the amount of lamotrigine in the test sample. Such a relationship is arguably a law of nature, which drives a conclusion that the claim recites a law of nature. For 7 Appeal 2018-009183 Application 13/102,993 purposes of this decision we will assume, arguendo, that the claim recites a law of nature. Guidance Step 2A, Prong 2 Having determined that the claims recite a judicial exception, our analysis under the Guidance turns to determining whether there are additional elements that integrate the exception into a practical application. See MPEP Â§Â§ 2106.05(a)-(c), (e)-(h). The additional elements in claim 16 are: (a) "purifying lamotrigine from said test sample," (b) "ionizing lamotrigine purified from said sample to produce lamotrigine precursor ions detectable by mass spectrometry," where the precursor ions have an m/z value of 255.9; (c) "fragmenting said precursor ion into one or more fragment ions detectable by mass spectrometry," where the fragment ions have an m/z value of 210.8, and (d) "detecting the amount of one or more of the parent and fragment ions of steps (b) and ( c) ions by mass spectrometry. These additional elements include some very specific requirements (in particular the specific m/z requirements), such that they cannot be considered as having an overall high level of generality. These additional elements integrate the law of nature into a practical application of being able to measure the concentration of lamotrigine in a patient's blood. We agree with Appellants that the claim here is similar to the claim in Rapid Litig. Mgmt. v. CellzDirect, 827 F.3d 1042 (Fed. Cir. 2016). In that case, the c1airn at issue related to a process for "'producing a desired preparation of rnulti-cryopreserved hepatocytes, said hepatocytes being capable of being frozen and thawed at least two times." CellzDirect, 827 8 Appeal 2018-009183 Application 13/102,993 F.3d at l 046. The claim recited a number of different, manipulative steps to which the hepatocytes were subjected, and the process resulted in '"a better way of preserving hepatocytes!' CellzDirect, 827 F. 3d at 1048. Similarly, in this case the sample is subjected to a number of different manipulative steps, which results in what is described as a better way of detennining the amount of Iamotrigine in a test sample by tandem mass spectrometry. Because we determine, based on the analysis under Step 2A, Prong l and Step 2A Prong 2, that the claimed invention is not directed to patent ineligible subject matter, we need not and do not address the rest of the steps recited in the Guidance. \Ve reverse the rejection under Â§101. Rejections (2) and (3) - Â§ 103 The Examiner finds that Doig teaches the "use of thermospray liquids chromatography-mass spectrometry to aid in the identification of urinary metabolites of a novel antiepileptic drug, Lamotrigine" (Final Act. 3, citing Doig, Title). The Examiner further finds that Doig teaches the base peak of an m/z value of 256, and that purification occurs by thermospray liquids chromatography (Final Act. 3). The Examiner states that Doig does not teach (1) detecting lamotrigine in blood or plasma, or (2) using tandem mass spectrometry (Final Act. 3, 4). The Examiner finds that Dasgupta teaches purification and detection of lamotrigine using GS-MS in human serum, such as blood or plasma (Final Act. 3-4). Therefore, according to the Examiner, it would have been obvious to have modified Doig's method by applying it to blood or plasma 9 Appeal 2018-009183 Application 13/102,993 because this would allow direct measurement of the lamotrigine in the patient's body (Final Act. 4). The Examiner also finds that Decaestecker teaches the use of tandem mass spectroscopy, and that applying this technique to Doig' s process would have been obvious because it provides a "wealth of information" in a single acquisition (Final Act. 4, citing Decaestecker, Abstract, p. 1791 ). The Examiner further finds that Decaestecker discloses that the collision energy for the MS test should be optimized for the analysis of drugs between 10 and 3 6 e V, a range which encompasses Appellants' use of 32 eV. Finally, the Examiner finds that Luo teaches that the daughter ion of lamotrigine has an m/z of 211, with a CE of 30 eV. Therefore, according to the Examiner: The Applicants used CE value within the known optimized range of CE in MS/MS tandem spectrometry of drugs, as specifically indicated by Decaestecker, and obtained the daughter ion with the largest peak at ml z 210. 8 (211) as evidenced by Luo, as the inherent property of lamotrigine. To express this again, the values of m/z for the fragments of the molecules are defined by their structure and are inherent to the structure of the molecule. Therefore, m/z 210.8 for lamotrigine fragment is inherent to its tandem MS/MS spectrum with CE around 30 eV, as evidenced by Luo. Also, as it is evidenced by Luo's methodology, see Principle and Method, signal with m/z 211 (210.8) is the strongest, see Table 7, and thus would be the most obvious to use for monitoring lamotrigine fragmentation by MS/MS spectrometry. (Final Act. 5). Appellants argue that the prior art fails to teach or suggest the claimed fragmentation and detection of a fragment ion having an m/z of about 210.8 10 Appeal 2018-009183 Application 13/102,993 (Appeal Br. 12). In particular, Appellants contend that although the Examiner relies on Luo as evidencing that if an e V of 32 is used, a daughter ion having an ml z of 210. 8 will inherently result, the Examiner has misapplied the laws on inherency. Id. Appellants' argument is not persuasive. "[I]n order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis[,] the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art." PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1195-96 (Fed. Cir. 2014). To properly rely on the doctrine of inherency in a rejection, "the examiner must provide a basis in fact and/or technical reasoning to reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art." Ex parte Levy, 17 USPQ2d 1461, 1464 (BPAI 1990). In this instance, the Examiner has explained that, based on the teachings of Decaestecker, a person of skill in the art would have sought an optimized CE value for the mass spectrometry analysis for lamotrigine in the range of 10-3 6 e V. The optimization process is described by Decaestecker as producing at least 10% of the [M + Ht ion and some diagnostic fragment ions and would yield, as evidenced by Luo, a CE value of about 30. Luo also evidences that the use of this CE value would necessarily arrive at the daughter fragment with an m/z of210.8. Although, as noted by Appellants, Luo is not prior art to the application on appeal, it is properly used as evidence that the use of a CE 11 Appeal 2018-009183 Application 13/102,993 value of 32 would result in a daughter ion having the claimed m/z value of 210.8. Although, as shown by Appellants (Reply Br. 7-8), the prior art discloses a number of different fragments having different m/z values, Decaestecker teaches that optimization of the CE value can provide better results, such as the value which would necessarily result in a daughter ion having the claimed m/z value of 210.8. The evidence of record supports the Examiner's determination that the prior art teaches or suggests the use of such a CE, through the optimization process described by Decaestecker. Accordingly, we agree with the Examiner that the prior art suggests the use of conditions which would inherently result in the production of daughter ions having an m/z value of210.8. Because Appellants do not direct us to any objective evidence of non- obviousness such as unexpected results beyond those that would result from routine optimization, we determine that, based on the preponderance of the evidence of record, Appellants have not demonstrated reversible error in the obviousness rejection of claim 16. Because Appellants do not offer separate arguments for the remaining claims (see, Appeal Br. 11 ), we also affirm the rejections of those claims. CONCLUSION We REVERSE the rejection of claims 16-23 and 27 under 35 U.S.C. Â§ 101 on the grounds that the claimed invention is directed to a judicial exception. 12 Appeal 2018-009183 Application 13/102,993 We AFFIRM the rejection of claims 16, 17, 22, 23, and 27 under 35 U.S.C. Â§103(a) as unpatentable over Doig in view of Dasgupta and Decaestecker, as evidenced by Luo. We AFFIRM the rejection of claims 19-21 under 35 U.S.C. Â§103(a) as unpatentable over Doig in view of Dasgupta and Decaestecker, as evidenced by Luo, and further in view ofMasahiko as evidenced by Jemal or Wu. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ l .136(a)(l )(iv). AFFIRMED 13