Cornelis Hack et al.Download PDFPatent Trials and Appeals BoardDec 24, 20212021001235 (P.T.A.B. Dec. 24, 2021) Copy Citation 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. 14/240,903 06/09/2014 Cornelis Erik Hack P6041926PCT/US 2225 132452 7590 12/24/2021 N.V. Nederlandsch Octrooibureau New Babylon City Offices Anna van Buerenplein 21a The Hague, 2595 DA NETHERLANDS EXAMINER DILLAHUNT, SANDRA E ART UNIT PAPER NUMBER 1646 NOTIFICATION DATE DELIVERY MODE 12/24/2021 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): USPTO@nlo.eu shultz@nlo.eu uspractice@nlo.eu PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte CORNELIS ERIK HACK and CAFER YILDIZ ____________ Appeal 2021-001235 Application 14/240,903 Technology Center 1600 ____________ Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and ULRIKE W. JENKS, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 16, 18, 20, 21, 25, and 27 (Appeal Br. 2). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as “UMC Utrecht Holding B. V.” (Appellant’s November 5, 2020, Appeal Brief (Appeal Br.) 2). Appeal 2021-001235 Application 14/240,903 2 STATEMENT OF THE CASE Appellant’s disclosure relates to “a method . . . to boost thrombin activity to stimulate blood clotting” (Spec.2 1). Claim 16 is reproduced below: 16. A method for treating or reducing the risk of bleeding in a human hemophilia patient comprising administering to the patient an effective amount of an inhibitor of antithrombin III that is an antibody or antibody fragment that specifically binds to antithrombin III, wherein, activity of the antibody or antibody fragment inhibitor is characterized as follows: (a) when the antibody inhibitor is added to pooled plasma from a healthy subject and mixed with thrombin or factor Xa to form a mixture, the mixture prevents, by more than 20%, a reduction in activity of the thrombin and factor Xa by the plasma in an in vitro assay of thrombin activity and factor Xa-activity, compared to the reduction in the activity of the thrombin or the factor Xa in a mixture containing the same pooled plasma but in the absence of the added inhibitor; and (b) the activity described in (a) is correlated with the ability of the antibody or fragment, when administered to said patient, to bind to antithrombin III and to treat or reduce the risk of bleeding in said patient. (Appeal Br. 11.) Claims 16, 18, 20, 21, 25, and 27 stand rejected under the written description provision of 35 U.S.C. § 112, first paragraph. 2 Appellant’s February 25, 2014, Specification. Appeal 2021-001235 Application 14/240,903 3 ISSUE Does the preponderance of evidence on this record support Examiner’s finding that Appellant’s Specification fails to provide written descriptive support for the claimed invention? ANALYSIS The method of Appellant’s claim 16, reproduced above, comprises, inter alia, the administration of an effective amount of an antibody or antibody fragment that specifically binds to and is an inhibitor of antithrombin III. In addition, Appellant’s claim 16 requires that: (a) when the antibody inhibitor is added to pooled plasma from a healthy subject and mixed with thrombin or factor Xa to form a mixture, the mixture prevents, by more than 20%, a reduction in activity of the thrombin and factor Xa by the plasma in an in vitro assay of thrombin activity and factor Xa-activity, compared to the reduction in the activity of the thrombin or the factor Xa in a mixture containing the same pooled plasma but in the absence of the added inhibitor; and (b) the activity described in (a) is correlated with the ability of the antibody or fragment, when administered to said patient, to bind to antithrombin III and to treat or reduce the risk of bleeding in said patient. (see generally Ans.3 4 (Examiner finds that Appellant’s claim 16 “broadly encompass[es] a genus of antibodies described solely by their function of binding to antithrombin III and preventing, by more than 20%, a reduction in activity of the thrombin and factor Xaa when added to pooled plasma, as measured by an in vitro assay of thrombin or Xaa activity”).) Examiner finds that Appellant’s Specification “discloses two anti- antithrombin III polyclonal antibodies; however, no antibody is described by 3 Examiner’s September 3, 2020, Answer. Appeal 2021-001235 Application 14/240,903 4 CDRs or other sequences” (id. at 5–6). Appellant’s antibodies, and fragments thereof, are instead described only by their function (id. at 6). Examiner finds that “functional characteristics of antibodies (including binding specificity and affinity) are dictated on their structure” and that “[a]mino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin” (id. at 6 (citing Vajdos4)). Examiner finds that amino acid modification of “any given CDR” has unpredictable effects on antibody binding (Ans. 6 (citing Brown5)). Examiner further finds that Appellant’s Specification provides no description of how binding of an antibody in any specific region of antithrombin III would lead to inhibition or blocking of its activity. It is possible that binding to antithrombin III at some antigen sequences will not result in inhibited activity, as they may not affect conformation, protein binding or other aspects of antithrombin III activity. Without demonstration that any antibody that binds antithrombin III would result in neutralization of antithrombin III activity, one of ordinary skill in the art could not predict the potential neutralizing capability of any given antibody. Antibodies are capable of binding to any number of possible epitopes on a 4 Vajdos et al., Comprehensive Functional Maps of the Antigen-binding Site of an Anti-ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis, 320 J. Mol. Biol. 415–428 (2002). 5 Brown et al., Tolerance to Single, but Not Multiple, Amino Acid Replacements in Antibody VH CDR2: A Means of Minimizing B Cell Wastage from Somatic Hypermutation?, 156 J. Immunol. 3285–3291 (1996). Appeal 2021-001235 Application 14/240,903 5 given protein, and not all of those interactions will result in lost activity for the antigen protein. (Ans. 6–7 (citing Knoller6).) In sum, Examiner finds, “with the exception of two polyclonal antibodies,” Appellant’s Specification “does not disclose any antibody having the claimed functions” and, thus, Appellant’s claim 16 “encompass[es] a vast genus of antibodies that have no correlation between their structure and function” (id. at 4). Examiner, therefore, finds that Appellant’s Specification fails to provide written descriptive support for the entire genus encompassed by Appellant’s claim 16 (id.). “[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). To be complete, we note that the written description standard set out in Ariad applies to antibodies. See Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1376–79 (Fed. Cir. 2017) (applying the Ariad standard to antibodies claimed based on their binding and blocking activities); see also AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1298–1300 (Fed. Cir. 2014) (same). A “sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” 6 Knoller et al., Monoclonal Antibodies Against Antithrombin III: Identification of Their Epitopes and Effects on Antithrombin III Activities, 180 Eur. J. Biochem. 319–326 (1989). Appeal 2021-001235 Application 14/240,903 6 Ariad, 598 F.3d at 1350. “[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials.” Id. Although “functional claim language can meet the written description requirement when the art has established a correlation between structure and function,” “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.” Id. In addition, although Appellant's claim 16 is directed to a method rather than a product, we note that the same standard applies with regard to the written description requirement. As the Rochester Court made clear: Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004). For the foregoing reasons, we agree with Examiner’s finding the Appellant’s Specification fails to provide written descriptive support for the genus of antibodies, and fragments thereof, that fall within the scope of Appellant’s claim 16. “One shows that one is ‘in possession’ of the invention by describing the invention, with all its claimed limitations, not that which makes it obvious. . . . One does that by such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention.” Appeal 2021-001235 Application 14/240,903 7 Lockwood v. Am. Airlines Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (emphasis omitted); see also Ariad, 598 F.3d at 1352 (Although those of ordinary skill in this art may understand how to prepare antibodies, “it is the specification itself that must demonstrate possession. And while the description requirement does not demand any particular form of disclosure, . . . or that the specification recite the claimed invention in haec verba, a description that merely renders the invention obvious does not satisfy the requirement.”). Therefore, we are not persuaded by Appellant’s contentions that the disclosed methods of making and screening antibodies provide a description of the claimed antibodies (see Appeal Br. 6–10). We acknowledge Appellant’s contention that antibodies that bind antithrombin III were known in the art (see Appeal Br. 7–8). For example, Appellant contends that “Knoller describes two antibodies, A36 and B108, that interfere with antithrombin III inhibition of thrombin” (Appeal Br. 7 (citing Knoller 323–324)). We note, however, that, in contrast to Appellant’s contention to the contrary, Knoller supports Examiner’s findings. In particular, Knoller discloses that although “A36 could prevent heparin-enhanced AT activity only if it was reacted with AT prior to the addition of heparin;” “B108 enhanced AT activity in the absence or in the presence of heparin” and a third antibody, A10, “had no effect” (Knoller 324). Appellant fails to direct attention to a disclosure in its Specification, or in Knoller, that describes the structural differences between these three antibodies that result in each antibody’s functional differences. As discussed above, regardless of whether a claim is directed to a method or product, the same standard applies with regard to the written description requirement. See Rochester, 358 F.3d at 926. Therefore, we are Appeal 2021-001235 Application 14/240,903 8 not persuaded by Appellant’s contention that its claim 16 is directed to a method not an antibody or genus of antibodies (Appeal Br. 7). CONCLUSION The preponderance of evidence on this record supports Examiner’s finding that Appellant’s Specification fails to provide written descriptive support for the claimed invention. The rejection of claim 16 under the written description provision of 35 U.S.C. § 112, first paragraph, is affirmed. Claims 18, 20, 21, 25, and 27 are not separately argued and fall with claim 16. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 16, 18, 20, 21, 25, 27 112, first paragraph Written Description 16, 18, 20, 21, 25, 27 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) (2019). AFFIRMED Copy with citationCopy as parenthetical citation