CHILDREN'S MEDICAL CENTER CORPORATION

Patent Trials and Appeals BoardDec 10, 2021

2021001313 (P.T.A.B. Dec. 10, 2021)

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. 14/768,970 08/19/2015 Richard S. Lee C1233.70062US01 8953 23628 7590 12/10/2021 WOLF GREENFIELD & SACKS, P.C. 600 ATLANTIC AVENUE BOSTON, MA 02210-2206 EXAMINER BORIN, MICHAEL L ART UNIT PAPER NUMBER 1631 NOTIFICATION DATE DELIVERY MODE 12/10/2021 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_eOfficeAction@WolfGreenfield.com WGS_eOfficeAction@WolfGreenfield.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RICHARD S. LEE and JOHN FROEHLICH Appeal 2021-0013131 Application 14/768,970 Technology Center 1600 Before DEBORAH KATZ, JOHN G. NEW, and ROBERT A. POLLOCK, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 37, 41, 42, and 46–50. Specifically, claims 37, 41, 42, and 46–50 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Swamy et al. (US 2004/0248317 A1, December 9, 2004) (“Swamy”), M. Gilette and S. A. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies Children’s Medical Center Corporation as the real party-in-interest. App. Br. 2. Appeal 2021-001313 Application 14/768,970 2 Carr, Quantitative analysis of peptides and proteins in biomedicine by targeted mass spectrometry, 10(1) NATURE METHODS 28–34 (December 27, 2012) (“Gilette”), and C. Bruce et al., Probabilistic Enrichment of Phosphopeptides by Their Mass Defect, 78(13) ANAL. CHEMISTRY 4374– 4382 (2006) (“Bruce”). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE, and enter a New Ground of Rejection. NATURE OF THE CLAIMED SUBJECT MATTER Appellant’s claimed invention is directed to a device and system for discriminating between peptide and glycopeptide signals in mass spectrometry. Spec. p. 8, ll. 17–20. REPRESENTATIVE CLAIM Independent claim 37 is representative of the claims on appeal and recites: 37. A device comprising at least one computer processor and memory storing computer-executable instructions that, when executed by the at least one computer processor, perform a method of identifying glycopeptides in a sample, the method comprising: defining at least one glycopeptide-rich acquisition enhancement zone (GRAEZ) region for classifying mass spectroscopy data, wherein each GRAEZ region is bounded by ranges of nominal mass and defect mass; receiving mass spectroscopy data for the sample, wherein the mass spectroscopy data includes mass information for each of a plurality of ion species detected in the sample, wherein the mass information includes a nominal mass value and a defect mass value for the ion species; Appeal 2021-001313 Application 14/768,970 3 classifying, by the at least one computer processor, each of the plurality of detected ion species to identify a subset of ion species associated with a glycopeptide, wherein classifying each of the plurality of detected ion species comprises: determining, whether the ion species falls within one of the at least one GRAEZ regions based on the mass information for the ion species; and including the ion species in the subset when it is determined that the ion species falls within one of the at least one GRAEZ regions; and performing targeted tandem mass spectrometry on each of the ions identified in the subset to identify the glycopeptides in the sample. App. Br. 13. ISSUES AND ANALYSIS We decline to adopt the Examiner's findings of fact, reasoning, and conclusion that the appealed claims are prima facie obvious over the combined prior art, and we enter a New Ground of Rejection. We address the arguments raised by Appellant below. Issue 1 Appellant argues that the Examiner erred by finding that the combination of Swamy, Gilette, and Bruce teach or suggest all of the limitations of the independent claims. App. Br. 7–11. Analysis The Examiner finds that Swamy teaches a system for using mass spectrometry to identify a glycopeptide in a peptide sample. Final Act. 3 Appeal 2021-001313 Application 14/768,970 4 (citing Swamy p. 17–18 (cls. 1, 5–7, 12, 30–32), ¶¶ 13, 18, 23, 62). More particularly, the Examiner finds that Swamy teaches scoring mass- spectrometry data using a glycosylation threshold based on an idealized glycopeptide spectrum. Id. (citing Swamy ¶¶ 87, 119). The Examiner finds that Swamy’s scoring includes identifying a “pentasaccharide core” region of the spectrum, and that the pentasaccharide core region is equivalent to the claimed “glycopeptide-rich acquisition enhancement zone” (“GRAEZ”) region. Id. The Examiner finds that Swamy does not teach including defect mass values in the scoring method. See Final Act. 4. However, the Examiner finds that Bruce teaches using defect mass to identify phosphopeptides in mass spectrometry. See id. at 4–5; see also Ans. 4 (citing Bruce pp. 4375, 4382). The Examiner finds that using defect mass values allows selecting and ranking phosphopeptides for subsequent phosphorylation mapping. See Final Act. 5. The Examiner finds that a person of ordinary skill in the art would have been motivated to apply Bruce’s technique using defect mass to identify other modified polypeptides, including glycopeptides as taught by Swamy, with a reasonable expectation of success. See id. The Examiner also finds that Swamy does not teach performing targeted mass spectrometry on identified ions. See Final Act. 3–4; Ans. 5. However, the Examiner finds that Gilette teaches applying targeted mass spectrometry to increase sensitivity and quantitative detection of peptides and their post-translational modifications. Final Act. 4 (citing Gilette pp. 28–34). The Examiner finds that it would have been obvious to one of ordinary skill to apply Gilette’s targeted mass spectrometry to Swamy’s subset of glycopeptides. Id. Accordingly, the Examiner concludes that the claims would have been prima facie obvious over the prior art. See id. at 5. Appeal 2021-001313 Application 14/768,970 5 Appellant contends that Swamy’s pentasaccharide core region does not correspond to the claimed GRAEZ region. See App. Br. 9–10. Specifically, Appellant contends that Swamy’s pentasaccharide core region is bounded by ranges of nominal mass of the detected ions and not ranges of nominal mass and defect mass as claimed. See id. at 9 (citing Swamy Fig. 5, ¶¶ 112–117). We agree with Appellant that Swamy’s pentasaccharide core region is not bounded by ranges of nominal mass and defect mass, in contrast with the claimed GRAEZ region. Although we agree with the Examiner that Swamy teaches identifying glycopeptides using mass spectrometry, Swamy’s method relies on correlating the nominal mass of identified fragments to a typical glycopeptide spectrum and not the defect mass. See Swamy ¶ 24, Fig. 5. The Examiner has not provided any findings as to why Swamy’s pentasaccharide core region, bounded by nominal mass only, “is viewed as equivalent” to the claimed GRAEZ region, bounded by ranges of nominal mass and defect mass. Rejections on obviousness grounds cannot be sustained by mere conclusory statements. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Accordingly, the Examiner has not met the burden of establishing prima facie obviousness, and we reverse the rejection. NEW GROUND OF REJECTION We enter a New Ground of Rejection. Independent claim 37 is rejected under 35 U.S.C. § 103(a) as obvious over Bruce, Swamy, and Gilette. Bruce teaches using defect mass with tandem mass spectrometry to differentiate between peptides and modified peptides, e.g., phosphopeptides. Appeal 2021-001313 Application 14/768,970 6 See Bruce 4375, 4382; see also Lehman2 at 1335 (“deltamass value can be used for scoring the specificity of the peptide mass with respect to protein identification and for glycopeptide identification”). Bruce teaches a first step of calculating a peptide’s mass defect from its experimental monoisotopic mass, and a second step of determining “whether the combination of mass and mass defect values for this peptide belongs in a region of high phosphorylation probability.” Bruce at 4382. Bruce’s region of high phosphorylation probability is bounded by ranges of nominal mass and defect mass. See id. at 4379 (Figs. 3B–3D illustrating a phosphorylation probability map as a function of monoisotopic mass and defect mass). Accordingly, Bruce teaches a region that is identical to the claimed GRAEZ region, albeit phosphopeptide-rich rather than glycopeptide-rich. See id. As discussed above, the Examiner finds that Bruce teaches a method of applying defect mass to identify and quantify modified peptides. See supra. The Examiner further finds a reason to combine Bruce with Swamy and Gilette to identify glycopeptides using targeted tandem mass spectrometry. See id. Bruce teaches that, although the “algorithm for identifying peptides with a high probability of phosphorylation is based on the mass defect of the phosphate group, the mass defect of other atoms within amino acid residues influences the magnitude of the overall mass defect of each peptide.” Bruce 4381. Bruce specifically teaches that oxygen-rich glycopeptides would also have a more negative defect mass compared to unmodified peptides; thus, oxygen-rich glycopeptides will have 2 W. D. Lehman et al., The information encrypted in accurate peptide masses—improved protein identification and assistance in glycopeptide identification and characterization, 35 J. MASS SPECTROMETRY 1335–1341 (2000) (of record). Appeal 2021-001313 Application 14/768,970 7 a greater probability of being picked up by Bruce’s method. Id. Accordingly, Bruce expressly teaches a reason to modify the algorithm to identify glycopeptides using mass spectrometry as taught by Swamy. Both Bruce and Swamy teach that their computerized analytical tools may be combined with other programs to determine an abundance of a biomolecule in a biological sample using mass spectrometry. See Bruce 4382; see also Swamy ¶ 11. Accordingly, we find that a person of ordinary skill in the art would have a reasonable expectation of success in combining the references. We consequently reject claim 37 as being obvious over Bruce, Swamy and Gilette. We have entered a New Ground of Rejection for only the independent claim and leave it to the Examiner to evaluate the patentability of the other claims in view of this combination or in combination with other newly found or previously cited references. CONCLUSION The rejection of claims 37, 41, 42, and 46–50 under 35 U.S.C. § 103 is reversed. We have entered a new ground of rejection pursuant to 37 C.F.R. § 41.50(b) as to claim 37. 37 C.F.R. § 41.50(b) provides that “[a] new ground of rejection … shall not be considered final for judicial review.” 37 C.F.R. § 41.50(b) also provides that Appellant, WITHIN TWO MONTHS FROM THE DATE OF THE DECISION, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: Appeal 2021-001313 Application 14/768,970 8 (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new evidence relating to the claims so rejected, or both, and have the matter reconsidered by the examiner, in which event the proceeding will be remanded to the examiner … . (2) Request rehearing. Request that the proceeding be reheard under § 41.52 by the Board upon the same record. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R. § 1.136(a)(1)(iv). REVERSED 37 C.F.R. § 41.50(b) Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed New Grounds 37, 41, 42, 46– 50 103 Swamy, Gilette, Bruce 37, 41, 42, 46–50 37