Ex Parte Holmquist et al

Patent Trial and Appeal BoardApr 21, 2016

12964717 (P.T.A.B. Apr. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. 12/964,717 109855 7590 Quest Diagnostics 1311 Calle Batido FILING DATE 12/09/2010 04/25/2016 San Clemente, CA 92673 FIRST NAMED INVENTOR Brett Holmquist 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. 034827-1021 5269 EXAMINER SODERQUIST, ARLEN ART UNIT PAPER NUMBER 1797 NOTIFICATION DATE DELIVERY MODE 04/25/2016 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 BRETT HOLMQUIST and NIGEL CLARKE Appeal2014-004789 Application 12/964,717 Technology Center 1700 Before ADRIENE LEPIANE HANLON, JEFFREY T. SMITH, and MICHELLE N. ANKENBRAND, Administrative Patent Judges. ANKENBRAND, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Appellants 1 appeal under 35 U.S.C. Â§ 134(a) from the Examiner's rejection of claims 1--44. We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. The Invention Appellants' invention relates to methods for detecting derivatized vitamin D by mass spectroscopy. Spec. Abstract. Claim 1 is representative of the claims on appeal, and is reproduced below from the Claims Appendix 1 Appellants identify Quest Diagnostics Investments Incorporated as the real party in interest. Id. at 1. Appeal2014-004789 Application 12/964,717 to the Appeal Brief: 1. A method for detennining the amount of non- rnetabolized vitamin D in a sample by tandem rnass spectrometry, the rnethod comprising the steps of (i) subjecting Cookson-type-derivatized non-metabolized vitamin D from the sample to an ionization source to generate one or more precursor ions detectable by mass spectrometry; (ii) fragmenting at least one of said precursor ions to generate one or more fragment ions detectable by mass spectrometry; (iii) determining the amount of one or more precursor and fragment ions by mass spectrometry; and (iv) relating the amount of ions determined in step (iii) to the amount of a non-metabolized vitamin Din the sample, wherein the sample is subjected to a Cookson-type derivatization reagent under conditions sufficient to generate Cookson-type-derivatized non-metabolized vitamin D prior to step (1). App. Br. 13 (Claims App'x). The References Zimmer et al., Comparison of turbulent-flow chromatography with automated solid-phase extraction in 96-well plates and liquid-liquid extraction used as plasma sample preparation techniques for liquid chromatography-tandem mass spectrometry, 854 J. CHROMATOGRAPHY A 23, 23-3 5 ( 1999) ("Zimmer"). Naoaki Murao et al., Ferrocene-based Diels-Alder derivatization for the determination of 1 a-hydroxyvitamin DJ in rat plasma by high- performance liquid chromatography-electrospray tandem mass spectrometry, 346 ANALYTICAL BIOCHEMISTRY 158, 161-163 (2005) ("Murao"). Feliciano Priego Capote et al., Identification and determination of fat- soluble vitamins and metabolites in human serum by liquid chromatography/triple quadrupole mass spectrometry with multiple reaction 2 Appeal2014-004789 Application 12/964,717 monitoring, 21 RAPID COMM. ivIASS SPECTROMETRY 17 45, 17 45-17 54 (2007) ("Capote"). Pavel A. Aronov et al., Metabolic profiling of major vitamin D metabolites using Diels-Alder derivatization and ultra-performance liquid chromatography-tandem mass spectrometry, 391 ANALYTICAL BIOANALYTICALCHEMISTRY 1917, 1917-1930 (2008) ("Aronov"). The Rejections 1. Claims 1 and 7-23 are rejected under 35 U.S.C. Â§ 103(a) as unpatentable over the combination of Aronov and Capote; 2. Claims 2, 3, 5, and 6 are rejected under 35 U.S.C. Â§ 103(a) as unpatentable over the combination of Aronov, Capote, and Murao; and 3. Claims 4 and 24--44 are rejected under 35 U.S.C. Â§ 103(a) as unpatentable over the combination of Aronov, Capote, and Zimmer or the combination of Aronov, Capote, Murao, and Zimmer. OPINION After having considered each of Appellants' contentions and the evidence presented in this Appeal, we determine that Appellants have not identified reversible error in the Examiner's rejections of claims 1--44 under 35 U.S.C. Â§ 103. Thus, we affirm these rejections for the reasons expressed in the Final Action, Answer, and below. Rejection 1 Appellants argue the claims as a group. See App. Br. 8-11. Therefore, we limit our discussion to representative claim 1. Claims 7-23 stand or fall with claim 1. See 37 C.F.R. Â§ 41.37(c)(l)(iv) (2013). Appellants argue that Aronov teaches away from measuring non- metabolized vitamin D with a mass spectrometry-based quantitation method. 3 Appeal2014-004789 Application 12/964,717 App. Br. 8-10. In particular, Appellants point to a portion of Aronov, which discloses that the authors omitted derivatized non-metabolized vitamin D from the method because they obtained poor recoveries of the non- metabolized vitamin D. Id. at 9-10. Appellants contend that the omission reflects Aronov' s "conviction that the methods tested in the article were not suitable for measurement of non-metabolized vitamin D." Id. at 10. We are not persuaded. "A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant." In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). As the Examiner points out, Aronov focuses on the metabolites rather than non-metabolized vitamin D, but does not teach that it was or would have been impossible to quantitatively measure non-metabolized vitamin D. Ans. 6, 9. Indeed, Aronov discloses that non-metabolized vitamin Dis recovered from the extraction step of the method, albeit to a much lesser extent than more polar forms of vitamin D. Aronov 1925. Aronov further teaches that derivatized non-metabolized vitamin Dis detectable with tandem mass spectrometry, as Table 1 illustrates that both precursor and product ions are formed for derivatized non-metabolized vitamin D2 and D3. Id. at 1920, Table 1. And Aronov explains that although usually it is not necessary to analyze blood levels of vitamin D2 and D3 (i.e., non-metabolized vitamin D), such a need exists in supplementation studies. Id. at 1918. Thus, Aronov expresses a preference for using the described method to profile derivatized metabolites, but would not have discouraged the skilled artisan from using the method to 4 Appeal2014-004789 Application 12/964,717 profile derivatized non-metabolized vitamin D, e.g., for supplementation studies. Appellants argue that Capote would not have provided one of ordinary skill in the art with a reason to use Aronov's method to profile non- metabolized vitamin D because Capote's teachings are focused on vitamin D metabolites and Capote "discloses nothing regarding how to achieve measurement of non-metabolized vitamin D." App. Br. 10-11. In this same regard, Appellants argue that the Examiner's rationale for combining the prior art teachings amounts to impermissible hindsight. Id. at 11. We are not persuaded, as the method described in Capote is directed to identifying and determining "fat-soluble vitamins Ki, K3, A, D2, D3 and E ... and metabolites 25-hydroxyvitamin D2 and D3 and 1,25- dihydroxyvitamin D3 in human serum by liquid chromatography/electrospray ionization tandem mass spectrometry." Capote 1745 (Abstract). Capote's method, therefore, focuses on both metabolized and non-metabolized vitamin D. Further, as the Examiner finds, Capote explains that the measurement of both vitamin D metabolites, "as well as the non-hydroxylated [i.e., non-metabolized] forms is important to ascertain vitamin D status." Id.; Final Act. 3--4. To that end, Capote discloses identification and quantification methods and data-including chromatograms, limit of detection data, and limit of quantification data-for non-metabolized vitamin D2 and D3. See Capote Figs. 1-5, Tables 2--4. Appellants' argument that Capote "is all about metabolized vitamin D," therefore, is without merit. We also find Appellants' hindsight argument without merit. If the Examiner articulates reasoning having rational underpinnings for making a 5 Appeal2014-004789 Application 12/964,717 proposed modification or combination of prior art teachings, then that articulated reasoning demonstrates the combination is not based on impermissible hindsight. See In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). Here, the Examiner finds that it would have been obvious to measure non-metabolized vitamin Dusing Aronov's method, given Capote's teachings that measuring the non-metabolized forms is important to ascertain vitamin D status and having a complete profile is of great interest in clinical practice and metabolomics. Final Act. 4. Based on our foregoing discussion of Aronov and Capote, we are persuaded that the Examiner's articulated reasons for combining the teachings support the conclusion of obviousness. Accordingly, we affirm the rejection of claims 1 and 7-23 under 35 U.S.C. Â§ 103. Re} ections 2 and 3 When addressing the claims subject to these rejections, the Examiner applied Aronov, Capote and additional references. See Final Act. 4--5. Appellants, however, do not direct us to any error in the Examiner's findings or conclusions as to the additional references, Murao and Zimmer. Rather, Appellants argue that, like Capote, the additional references, do not remedy the deficiency in Aronov. App. Br. 12. For the reasons discussed above, we find no deficiency in the combined teachings of Aronov and Capote that requires curing by Murao and/or Zimmer. Thus, we also affirm the rejections of claims 2---6 and 24--44 under 35 U.S.C. Â§ 103. 6 Appeal2014-004789 Application 12/964,717 DECISION/ORDER The Examiner's rejections of claims 1--44 under 35 U.S.C. Â§ 103(a) are affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a). AFFIRMED 7