10211157 (B.P.A.I. Jun. 29, 2009)

Ex Parte He et al

Board of Patent Appeals and InterferencesJun 29, 2009

10211157 (B.P.A.I. Jun. 29, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte ZHIGANG HE, KEVIN C. WANG, and JIEUN A. KIM __________ Appeal 2008-002333 Application 10/211,157 Technology Center 1600 __________ Decided:1 June 29, 2009 __________ Before TONI R. SCHEINER, DEMETRA J. MILLS, and ERIC GRIMES, Administrative Patent Judges. SCHEINER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims 1-9 and 21- 24, all the claims pending. We have jurisdiction under 35 U.S.C. § 6(b). 1 The two-month time period for filing an appeal or commencing a civil action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date shown on this page of the decision. The time period does not run from the Mail Date (paper delivery) or Notification Date (electronic delivery). Appeal 2008-002333 Application 10/211,157 2 STATEMENT OF THE CASE “The neurotrophin receptor p75NTR (p75) is a membrane glycoprotein that binds all known neurotrophins and has been reported to correlate with and promote axon outgrowth” (Spec. 1: 14-15). “[T]he present inventors have discovered that p75 complexes with the Nogo receptor (NgR) and through NgR mediates inhibitory signaling of the major myelin-derived inhibitors, p75 and NogoA” (Spec. 1: 32 to 2: 2). According to the Specification, inhibiting NgR-p75 binding “reduce[s] axon growth inhibition” (Spec. 3: 9), thereby, “reducing myelin-mediated inhibition of axon regeneration” (id. at 1: 9-10). The claimed invention is directed to assays for measuring NgR-p75 binding, with or without the presence of a modulator of NgR-p75 binding, and assays for characterizing candidate compounds as modulators of NgR-p75 binding (id. at 6: 1-20). Claims 1, 2, 4, and 7 are representative of the subject matter on appeal: 1. A method for assaying Nogo receptor (NgR)-neurotrophin receptor p75NTR (p75) binding, the method comprising the steps of: providing a mixture comprising a p75-binding NgR domain and an NgR-binding p75 domain, wherein each one of the NgR domain and p75 domain is soluble or recombinantly expressed on the surface of a cell; and measuring a resultant binding of the NgR domain to the p75 domain as an indication of the assayed NgR-p75 binding. 2. A method according to claim 1, wherein: the mixture further comprises an inhibitor of NgR-p75 binding, wherein but for the presence of the inhibitor, the mixture provides a control binding of the NgR domain to the p75 domain; and the measuring step measures an inhibitor-biased binding of the NgR domain to the p75 domain lower than the control binding. Appeal 2008-002333 Application 10/211,157 3 4. A method according to claim 2, wherein the inhibitor is selected from the group consisting of: an NgR peptide, a p75 peptide, an NgR peptide- specific antibody fragment and a p75 peptide-specific antibody fragment. 7. A method according to claim 1, wherein the mixture is cell-free. The Examiner relies on the following evidence to show unpatentability: Strittmatter WO 03/031462 A2 Apr. 17, 2003 Kevin C. Wang et al., p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp, 420 NATURE 74-78 (November 2002). Kwang-Mook Jung et al., Regulated Intramembrane Proteolysis of the p75 Neurotrophin Receptor Modulates Its Association with the TrkA Receptor, 278 J. BIOL. CHEM. 42161-42169 (2003). The Examiner rejected claims 1-9 and 21-24 under 35 U.S.C. § 102(e) as anticipated by Strittmatter. THE ISSUE The issue raised by this appeal is whether Appellants have shown that the Examiner erred in finding that Strittmatter describes all the manipulative steps of the presently claimed method, and therefore anticipates the claimed invention. FINDINGS OF FACT FF1 Claim 1 is directed to a method for assaying NgR-p75 binding by providing a mixture comprising a p75-binding NgR domain and an NgR- binding p75 domain, and “measuring a resultant binding of the NgR domain to the p75 domain as an indication of the assayed NgR-p75 binding.” Claim 9 (the only other independent claim) is similar to claim 1, but also includes a Appeal 2008-002333 Application 10/211,157 4 potential modulator of NgR-p75 binding in the assay mixture, and specifies “detecting a resultant modulated binding of the NgR domain to the p75 domain different from . . . control binding as an indication that the agent modulates NgR-p75 binding.” FF2 The Specification teaches that “[a] wide variety of assay formats may be used” to measure NgR-p75 binding, “some wherein (at least) one of the NgR domain and the p75 domain is soluble, wherein (at least) one of the NgR domain and the p75 domain is recombinantly expressed on the surface of a cell, wherein the mixture is cell free, etc.” (Spec. 5: 17-20). FF3 According to the Specification, “[f]or cell-based or in situ assays, metrics typically involve assays of axon growth as evaluated by linear measure, density, host mobility or other function improvement, etc.” (Spec. 5: 29-31, emphasis added). FF4 When screening for an agent that inhibits NgR-p75 binding, “the measuring step characterizes the candidate inhibitor as reducing axon growth inhibition mediated by NgR-p75 binding” (Spec. 6: 7-8). FF5 “The neurotrophin receptor p75NTR (p75) is a membrane glycoprotein that binds all known neurotrophins and has been reported to correlate with and promote axon outgrowth” (Spec. 1: 14-15). FF6 Kwang-Mook Jung et al. teach that “the truncated p75 extracellular domain that contains the NGF-binding region is released into . . . culture medium and biological fluids” by proteolysis (Kwang-Mook Jung et al., 42161, col. 2). Appeal 2008-002333 Application 10/211,157 5 FF7 Strittmatter discloses NgR-derived polypeptides that contain amino acid residues 27-309 of human NgR, and fewer than 115 consecutive amino acids from amino acids 310-445 of NgR (Strittmatter 5: 20-22). Strittmatter also discloses antibodies that bind to an epitope within the CTS domain of NgR, i.e., amino acids 310-445 of NgR (id. at 6: 11-20). FF8 According to Strittmatter, both the NgR-derived polypeptides and the NgR-specific antibodies decrease inhibition of axonal growth when added to a culture of CNS neurons (Strittmatter 6: 14-20). In addition, “the specific activity of a[n] NgR protein or Nogo protein, normalized to a standard unit, between a cell population that has been exposed to the agent to be tested compared to an un-exposed control cell population may be assayed” (id. at 33: 27-29). FF9 The Examiner finds, and Appellants do not dispute, that Strittmatter’s NgR-derived polypeptides and antibodies “are the same NgR fragment and antibody to NgR that are recited in claim 4 of Appellant’s current claims” (Ans.2 3). FF10 The Examiner finds that Strittmatter “teaches contacting neuronal culture, which provides a mixture of both soluble (complete extracellular domain) and membrane bound p75 (as evidenced by Kwang- Mook [Jung] et al, 2003) and NgR, with a fragment of NgR that binds p75” (Ans. 4). FF11 The Examiner finds that Strittmatter, at pages 28-33, also “teaches recombinant expression of NgR in a variety of cell types . . . in 2 All references are to the Examiner’s Answer filed August 10, 2007. Appeal 2008-002333 Application 10/211,157 6 methods for identifying binding partners . . . and agents that modulate activity” (Ans. 5). FF12 The Examiner finds that “the method of Strittmatter has all the steps of the instant method” (Ans. 5), but “Strittmatter does not disclose that the NgR fragment or antibody to the CTS domain [of Nogo] works by blocking NgR-p75 binding” (id.). FF13 Claims 7 and 23 depend from claims 1 and 9, respectively, and require that the mixture comprising the NgR domain and the p75 domain is cell-free. FF14 According to Strittmatter, “cellular extract refers to a preparation or fraction which is made from a lysed or disrupted cell” (Strittmatter 32: 8-9). FF15 The Examiner finds, and Appellants do not dispute, that Strittmatter’s neuronal cell extracts “inherently provide NgR-p75 complexes” (Ans. 6). FF16 Strittmatter describes mixing “a protein of the invention” (i.e., an NgR-derived polypeptide containing amino acid residues 27-309 of human NgR (FF7)), or the entire NgR protein, with an extract of cells derived from human neuronal tissue, in order to detect and identify binding partners of NgR (Strittmatter 31: 27 to 32: 12). FF17 “To aid in separating associated binding partner pairs from the mixed extract, [Strittmatter’s] protein . . . can be immobilized on a solid support . . . Attachment of the protein to a solid support aids in separating peptide-binding partner pairs from other constituents found in the extract. Appeal 2008-002333 Application 10/211,157 7 The identified binding partners can be either a single protein or a complex made up of two or more proteins” (Strittmatter 33: 5-10). FF18 The Examiner finds that Strittmatter’s cellular extracts are “cell-free” mixtures containing NgR and p75, and the use of those cellular extracts “to identify other binding proteins . . . meet[s] the limitations of claim[s] 7 and 23” (Ans. 6). PRINCIPLES OF LAW “Newly discovered results of known processes directed to the same purpose are not patentable because such results are inherent.” Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1376 (Fed. Cir. 2001). Correspondingly, “[a] person of ordinary skill does not need to recognize that a method . . . behaves according to a law of nature in order to fully and effectively practice the method” and “[r]ecitation of a law of nature does not distinguish a claim from prior art[.]” EMI Group N. Am., Inc. v. Cypress Semiconductor Corp., 268 F.3d 1342, 1351 (Fed. Cir. 2001). “The public remains free to make, use, or sell prior art compositions or processes, regardless of whether or not they understand their complete makeup or the underlying scientific principles which allow them to operate.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1348 (Fed. Cir. 1999). ANALYSIS According to the Examiner, Strittmatter discloses “all the steps of the instant method” (Ans. 5), and “[m]easuring a resultant binding of NgR and p75 is inherently accomplished by monitoring axonal growth” (id. at 4), whether or not Strittmatter “disclose[s] that the NgR fragment or antibody to the CTS domain [of NgR] works by blocking NgR-p75 binding” (id. at 5). Appeal 2008-002333 Application 10/211,157 8 Claims 1-6, 8, 9, 21, 22, and 24 Appellants do not dispute the Examiner’s finding that Strittmatter describes all of the manipulative steps of claims 1-6, 8, 9, 21, 22, and 24, including measuring axon growth. Rather, Appellants contend that “Strittmatter’s assays are not constructed to measure or report NgR-p75 specific binding, expressly or inherently, so these assays are not and can not be encompassed by our claims” (App. Br.3 4). Appellants contend that “Strittmatter is oblivious to NgR-p75 binding, so can not possibly describe a method for specifically assaying NgR-p75 binding” (id.), “even if both NgR and p75 happen to be inherently present in a prior art composition, and even if there is some inherent binding between these molecules” (id.). Appellants contend that “the resultant binding . . . must be measured as an indication of the assayed NgR-p75 binding. If NgR-p75 binding is not measured specifically as an indication of the assayed NgR-p75 binding, our claim is inapplicable. To measure binding as an indication of the assayed NgR-p75 binding, the assay must be specific for NgR-p75 binding” (App. Br. 4). Again, Appellants contend that Strittmatter’s assays “are not constructed to measure or report NgR-p75 specific binding” (id.), while Appellants “exemplify the claimed assay . . . [by] showing that when we overexpress HA-tagged P75 and FLAG-tagged NgR into CHO cells, . . . p75 can be co-immunoprecipitated with NgR, but not with a control transmembrane protein” (id.). 3 All references are to the Revised Brief on Appeal filed October 18, 2006. Appeal 2008-002333 Application 10/211,157 9 In other words, Appellants contend that Strittmatter cannot anticipate the claimed invention because Strittmatter does not measure direct binding between NgR and p75, does not recognize or disclose the underlying mechanism affecting the axon growth measured in his assay, and does not contemplate the results of his assays in terms of NgR-p75 binding. Appellants’ arguments are not persuasive. While the Specification teaches that “directly assay[ing] NgR-p75 binding inhibition” is preferred (Spec. 12: 30-31), the present claims are not limited to direct measurement of the interaction between NgR and p75. Since the Specification teaches that axon growth is also a measure of NgR-p75 binding in cell-based or in situ assays (FF2, FF3), the limitations of the claims are met by providing a mixture of NgR and p75 in a cell culture, and measuring axon growth (e.g., claim 1) in the presence of a candidate modulator of axon growth (e.g., claims 2 and 9). Strittmatter identifies agents capable of modulating axon growth inhibition by adding a candidate agent to a cell culture comprising a mixture of NgR and p75, and measuring axon growth (FF3, FF10, FF11, FF12). Moreover, Strittmatter’s modulators are the same modulators described by Appellants as modulators of NgR-p75 binding (FF7, FF9). Appellants have failed to identify a manipulative step in the claimed method that is not also performed in Strittmatter’s method. As discussed above, Appellants’ recognition of the underlying mechanism affecting axon growth inhibition is not sufficient to distinguish the claimed method from Strittmatter’s method. See EMI, 268 F.3d at 1351. Appeal 2008-002333 Application 10/211,157 10 Claims 7 and 23 The Examiner finds that Strittmatter’s neuronal cell extracts are “cell- free” mixtures that “inherently provide NgR-p75 complexes” (Ans. 6, FF15), and that Strittmatter discloses “using cellular extracts . . . to identify other binding proteins” of NgR (id.). Appellants contend that “claims 7 and 23 require providing a cell free mixture of the NgR and p75 domains” (Reply Br.4 3), but “there is no cell- free mixture of NgR and p75 domains in Strittmatter” (id.). Appellants’ argument is not persuasive. The claims merely require providing a mixture of a p75-binding NgR domain and an NgR-binding p75 domain, where the mixture is cell free. Strittmatter combines an NgR polypeptide with a neuronal cell extract in order to detect and identify binding partners of NgR (FF16, FF17). Strittmatter’s cell extracts contain p75 and NgR released from lysed cells (FF14, FF15). Appellants have not explained why the extracts are not “cell free.” CONCLUSIONS OF LAW Appellants have not shown that the Examiner erred in finding that Strittmatter describes all the manipulative steps of the presently claimed method, and therefore anticipates the claimed invention. SUMMARY The rejection of claims 1-9 and 21-24 under 35 U.S.C. § 102(e) is affirmed. 4 All references are to the Second Amended Reply Brief on Appeal, filed August 24, 2007. Appeal 2008-002333 Application 10/211,157 11 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)(1)(iv) (2006). AFFIRMED RICHARD ARON OSMAN 4070 CALLE ISABELLA SAN CLEMENTE CA 92672