Ex Parte Gonzalez-Sapienza et alDownload PDFPatent Trial and Appeal BoardMar 20, 201712097235 (P.T.A.B. Mar. 20, 2017) 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. 12/097,235 06/12/2008 Gualberto Gonzalez-Sapienza 76916-166610US-719172 9055 20350 7590 03/22/2017 KILPATRICK TOWNSEND & STOCKTON LLP Mailstop: IP Docketing - 22 1100 Peachtree Street Suite 2800 Atlanta, GA 30309 EXAMINER COUNTS, GARY W ART UNIT PAPER NUMBER 1678 NOTIFICATION DATE DELIVERY MODE 03/22/2017 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): ipefiling@kilpatricktownsend.com jlhice@kilpatrick.foundationip.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GUALBERTO GONZALEZ- SAPIENZ A, BRUCE HAMMOCK, ANDRES GONZALEZ-TECHERA, LUCIA VANRELL, and HEE JOO KIM,1 Appeal 2016-001220 Application 12/097,235 Technology Center 1600 Before ELIZABETH A. LAVIER, RACHEL H. TOWNSEND, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of detecting an analyte, which have been rejected as obvious, as being indefinite, and for containing new matter. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part and enter a new ground of rejection pursuant to our authority under 37 C.F.R. § 41.50(b). 1 Appellants identify the Real Party in Interest as the Regents of the University of California. (Br. 3.) Appeal 2016-001220 Application 12/097,235 STATEMENT OF THE CASE Immunoassays are a simple, fast, and specific tool for analysis of biological substances. (Spec. 13.) Competitive-format assays are less precise, sensitive, and fast compared to noncompetive formats. (Id.) However, “[f]or the detection of small molecules, a sandwich type noncompetitive ELISA[, enzyme-linked immunosorbent assay,] format is not applicable because once antibody binds to the target molecule, there is no site available for the direct binding of secondary reporter antibody.” (Id. at 14.) The claimed invention is directed to a noncompetitive immunoassay for detecting small molecules. Claims 1, 4—9, and 25 are on appeal. Claims 1 and 25 are representative and read as follows: 1. A method for detecting an analyte, said method comprising: (a) contacting a sample suspected of containing said analyte with a first antibody that specifically binds to the analyte, thereby forming an antibody-analyte complex; (b) contacting the antibody-analyte complex with an affinity agent comprising a phage protein fused to a heterologous polypeptide, wherein the heterologous polypeptide specifically binds to the analyte of the antibody-analyte complex, thereby forming an antibody-analyte-affmity agent complex; and (c) detecting the antibody-analyte-affmity agent complex, thereby detecting the analyte, wherein the analyte has a molecular weight of less than about 1360 Da. 25. The method of claim 1, wherein the heterologous peptide specifically binds to both the analyte and the antibody of the antibody-analyte complex. (Br. 25-26.) 2 Appeal 2016-001220 Application 12/097,235 The following grounds of rejection by the Examiner are before us on review: 1. Claim 25 under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement. 2. Claim 25 under 35 U.S.C. § 112, second paragraph, as being indefinite. 3. Claim 1 under 35 U.S.C. § 103(a) as unpatentable over Monforte2 and Grassi.3 4. Claim 4 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Thompson.4 5. Claims 5 and 6 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Kay.5 6. Claims 7—9 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, Kay, and McCafferty.6 7. Claim 25 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Self.7 2 Joseph A. Monforte, WO 02/48403 A2, published June 20, 2002. 3 Jacques Grassi et al., Two different approaches for developing immunometric assays of haptens, 42 (9) Clin. Chem., 1532—1536 (1996). 4 Thompson et al., US 4,731,326, issued Mar. 15, 1988. 5 Kay et al., US 5,498,538, issued Mar. 12, 1996. 6 McCafferty et al., US 6,806,079 Bl, issued Oct. 19, 2004 7 Colin H. Self et al., High-Performance Assays of Small Molecules: Enhanced Sensitivity, Rapidity, and Convenience Demonstrated with a Noncompetitive Immunometric Anti-Immune Complex Assay System for Digoxin, 40 (11) Clin. Chem., 2035-2041 (1994). 3 Appeal 2016-001220 Application 12/097,235 DISCUSSION New Matter The Examiner finds that the language in claim 25 “wherein the heterologous peptide specifically binds to both the analyte and the antibody of the antibody-analyte complex” (emphasis added) “was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.” (Non-Final Action 7.)8 According to the Examiner, while the Specification at paragraphs 6, 23, 30, and 39 describe a heterologous polypeptide specifically binds to the antibody- analyte complex, “[tjhere is no description in the specification disclosing the heterologous peptide specifically binds to both the analyte and the antibody of the antibody-analyte complex.” (Id.) We disagree with the Examiner’s conclusion. Appellants’ Specification provides the following definition for the term peptide: “The terms ‘polypeptide,’ ‘peptide’ and ‘protein’ are used interchangeably herein to refer to a polymer of amino acid residues.” (Spec. 142.) Furthermore, the Specification explains that an “[ajntibody” is a type of polypeptide, i.e., a “polypeptide encoded by an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen.” (Spec. 134.) The Specification states that the phrase “specifically [ ] binds” when referring to an antibody “refers to a binding reaction that is determinative of Office Action mailed March 3, 2014. 4 Appeal 2016-001220 Application 12/097,235 the presence of the antibody’s binding target (e.g., a small molecule, protein epitope, or a phage protein) in a heterogeneous population of analytes (e.g., small molecules, phage proteins, and other biologies).” (Spec. 138.) Paragraph 6 of Appellants’ Specification states that once the antibody- small molecule complex is formed by contacting a sample suspected of containing the small molecule “with an antibody that specifically binds to the [small] molecule,” the complex is contacted with the affinity agent comprising a phage protein fused to a heterologous polypeptide “that specifically binds to the antibody-small molecule complex.” Figure 1 depicts the foregoing specific binding of antibody to small molecule and heterologous polypeptide to antibody-small molecule complex as follows: (Fig. 1.) As can be seen from the figure, the “peptide” is shown to be in contact with both the analyte and the antibody to which the analyte is specifically bound. Thus, this figure depicts “specific binding” to the analyte and antibody of the analyte-antibody complex. Thus, we agree with Appellants (Br. 17—18), that the Specification and figures provide sufficient detail from which one of skill in the art could reasonably conclude that the 5 Appeal 2016-001220 Application 12/097,235 inventor was in possession of the invention recited in claim 25. Consequently, we reverse the Examiner’s rejection of claim 25 under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement because it contains new matter. Indefiniteness The Examiner finds that “[cjlaim 25 appears to contradict claim 1” because claim 1 requires the polypeptide to specifically bind to the analyte of the antibody-analyte complex, whereas claim 25 recites that the polypeptide specifically binds to “both the analyte and the antibody of the antibody-analyte complex.” (Non-Final Action 8.) We disagree with the Examiner’s finding that claim 25 contradicts claim 1 and the Examiner’s conclusion based thereon that claim 25 is indefinite. In particular, as Appellants explain, claim 25 would only contradict claim 1 if “specifically binds” is interpreted “as closed-ended language such that claim 1 . . . reads ‘the heterologous polypeptide specifically binds to the analyte and only the analyte. ’” (Br. 18—19.) We agree with Appellants that claim 1 is not so limited. Claim 1 is open-ended, using the transition phrase “comprising,” and the contacting step recited in “(b)” does not include any limiting language regarding the specific binding. Moreover, Appellants’ definition of “specifically binds” provided in the Specification at paragraph 38 does not limit claim 1 ’s recitation of specific binding of the heterologous polypeptide to binding that is only to the analyte of the antibody-analyte complex. While it is certainly the case that specific binding can be to the antibody alone, the definition simply notes that such binding is a binding reaction that is determinative of the present of the 6 Appeal 2016-001220 Application 12/097,235 “antibody’s binding target,” and, further describes that the target can be to a fusion protein rather than individual components of the fusion protein. (Spec. 138.) We find the claimed analyte-antibody complex is akin to a “fusion protein” as described in Appellants’ Specification at paragraph 38. Thus, we agree with Appellants that there is no contradiction between claim 1 and claim 25. Rather, claim 1 broadly encompasses specific binding by an antibody to the analyte alone or to the antibody-analyte complex. Consequently, we reverse the Examiner’s rejection of claim 25 under 35 U.S.C. § 112, second paragraph as being indefinite. Obviousness Because the Examiner’s obviousness rejection of claims 1 and 4—9 turn on the same issue, we will consider those rejections together. The Examiner’s obviousness rejection of claim 25 will be addressed separately. Claims 1 and 4—9 The Examiner finds that Monforte discloses a sandwich assay for determining an analyte of interest as claimed except for disclosing detection of analytes that have a molecular weight of less than about 1360 Da. (Non- Final Action 10—11.) The Examiner finds, however, that Grassi teaches “two-site immunometric assay (sandwich assays)” using antibodies for determining analytes that have a molecular weight of less than about 1360 Da. (Non-Final Action 11.) According to the Examiner, it would have been obvious to use the antibodies taught by Grassi in the assay of Monforte: because Grassi et al shows that it is known in the art of sandwich assays to incorporate antibodies into sandwich formats for the detection of substance P (SP) (1347 Da), neurokinin [A] (NKA) (1133 Da) or angiotensin II (1048 Da) and shows that the use of such reagents provide for highly 7 Appeal 2016-001220 Application 12/097,235 sensitive and specific sandwich immunoassays for small molecules. (Non-Final Action 11.) Appellants argue that the Examiner’s rejection is in error because claim 1 requires “binding of the heterologous polypeptide to the analyte of the antibody-analyte complex” and in Grassi’s “sandwich assay” the second antibody that binds to the small molecule analyte does not bind to the antibody-analyte complex because the analyte is no longer bound as part of the antigen-antibody complex. (Br. 21.) We agree with Appellants. While it is true that Grassi teaches a multistep “sandwich” assay method for detecting small molecules in which an antibody-analyte complex is formed by specific binding of the analyte to a first antibody, the binding of the second “detection” antibody depends upon the deconstruction of the antibody-analyte complex prior to binding. (Grassi 1534.) The assay works because the analyte is covalently cross-linked to the solid phase antibody to which it is specifically bound and then the antibody-analyte complex is “dissociat[ed] and (or) denature[d]” so that the “hapten-antibody complex releases the hapten epitope (epitope release) from the antibody binding site.” (Id.) Because the hapten epitope is no longer specifically bound to the solid phase antibody, but the hapten is still cross-linked to that antibody at a different site, a labeled version of the same antibody that is attached to a solid phase is able to specifically bind the hapten for detection. (Id.) In other words, the antibody-analyte complex that was formed by specific binding of the antibody to analyte is no longer present for the labeled 8 Appeal 2016-001220 Application 12/097,235 antibody to bind to. Thus, if one were to use the Grassi reagents in the Monforte process, the labeled antibody would not “bind[] to the analyte of the antibody-analyte complex” as required by claim 1. None of the secondary references relied upon by the Examiner with respect to claims 4—9 remedies this deficiency. When a prima facie case of obviousness has not been established, the rejection must be reversed. In re Fine, 837 F.2d 1071, 1075 (Fed. Cir. 1988). In light of the foregoing, we reverse the Examiner’s rejection of claims 1 and 4—9 as being obvious over Monforte and Grassi with or without Thompson, and/or Kay, and McCafferty. Claim 25 Claim 25 requires the heterologous peptide “specifically binds to both the analyte and the antibody of the antibody-analyte complex.” The Examiner finds that Self discloses an immunometric assay for detection of small molecule analytes such as digoxin (780 Da). (Non-Final Action 14.) The Examiner finds that the secondary antibodies that Self uses “bind to both the antigen/antibody complex.” (Id.) According to the Examiner, [i]t would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate antibodies such as taught by Self et al into the method and affinity agent of Monforte for the detection of digoxin because Self et al shows that it is known in the art of sandwich assays to incorporate antibodies into sandwich formats for the detection of digoxin and shows that the use of such reagents provides for rapid and robust assay of small molecules similar to those realized for larger molecules. (Id. at 14—15.) 9 Appeal 2016-001220 Application 12/097,235 We agree with the Examiner that claim 25 would have been obvious from Monforte and Self. Appellants contend that Self does not describe binding of a heterologous polypeptide “to the analyte itself.” (Br. 23.) We disagree. As discussed above in the new matter discussion, in light of Appellants’ Specification, a heterologous polypeptide can be an antibody. Moreover, claim 25 requires that the heterologous polypeptide bind to both the analyte and antibody of the antibody-analyte complex. Self describes an immunoassay that uses an anti-immune complex antibody to detect the analyte of interest. (Self 2035.) As Self explains, the “anti-immune complex assay is based on the interaction of a receptor such as a primary antibody with its ligand, such that new binding sites, recognizable by a secondary antibody, are formed.” (Self 2035 (abs.).) The “secondary (anti-immune complex) antibody is produced that specifically binds primary anti-hapten antibody that is combined with hapten but does not bind primary antibody or hapten alone.” (Self 2035.) Thus, we find that Self teaches an antibody that specifically binds to both the analyte and the antibody of the antibody-analyte complex as required by claim 25. Self teaches that this assay for small molecules provides a “high performance assay” that is simple, rapid, sensitive and precise. (Id.) Consequently, we agree with the Examiner that the prior art provides a reason to combine the reagents of Self with Monforte’s process employing phage displaying a binding component fused to the phage and that there would have been a reasonable expectation of success at least for the detection of the small molecule digoxin. For the foregoing reasons, 10 Appeal 2016-001220 Application 12/097,235 Appellants do not persuade us that the Examiner erred in rejecting claim 25 for obviousness over Monforte, Grassi, and Self. We note that the Examiner does not rely on Grassi for this rejection. (Non- Final Action 14—15.) In affirming a multiple reference rejection under 35 U.S.C. § 103, the Board may rely on fewer than all of the references relied on by the Examiner in an obviousness rationale without designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961). New Ground of Rejection Claim 1 is rejected as unpatentable under 35 U.S.C. § 103 as obvious over Monforte and Self. We adopt the factual findings by the Examiner with respect to Monforte and Self. (Non-Final Action 10-11, 14—15.) As discussed above, with regard to the Examiner’s indefmiteness rejection of claim 25 (which we reverse), claim 1 broadly encompasses specific binding by an antibody to the analyte alone or to the antibody-analyte complex. Claim 25 specifically requires the binding be to the antibody-analyte complex. The test of obviousness is “whether the teachings of the prior art, taken as a whole, would have made obvious the claimed invention.” In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). For the same reasons the Examiner found claim 25 obvious from the teachings of Monforte and Self, which we affirm above, we find claim 1 is also obvious. In particular, as the Examiner noted, It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate antibodies such as taught by Self et al into the method and affinity agent of Monforte for the detection of digoxin because Self et al shows that it is known in the art of sandwich assays to incorporate antibodies into sandwich formats for the detection of digoxin 11 Appeal 2016-001220 Application 12/097,235 and shows that the use of such reagents provides for rapid and robust assay of small molecules similar to those realized for larger molecules. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating antibodies such as taught by Self [et] al into the method and affinity agent of Monforte for the detection of digoxin. (Non-Final Action 14—15.) We have applied the new rejection only to independent claim 1 and leave it to the Examiner to determine, in any future prosecution, whether the rejection should be applied to any of claims 4—9. See MPEP § 1213.02 (“[Sjince the exercise of authority under 37 CFR 41.50(b) is discretionary, no inference should be drawn from a failure to exercise that discretion.”). SUMMARY We reverse the rejection of claim 25 under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement. We reverse the rejection of claim 25 under 35 U.S.C. § 112, second paragraph, as being indefinite. We reverse the rejection of claim 1 under 35 U.S.C. § 103 (a) as unpatentable over Monforte and Grassi. We reverse the rejection of claim 4 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Thompson. We reverse the rejection of claims 5 and 6 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Kay. We reverse the rejection of claims 7—9 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, Kay, and McCafferty. We affirm the rejection of claim 25 under 35 U.S.C. § 103(a) as unpatentable over Monforte, Grassi, and Self. 12 Appeal 2016-001220 Application 12/097,235 We enter a new ground of rejection over claim 1; namely claim 1 is unpatentable under 35 U.S.C. § 103(a) as being obvious over Monforte and Self. TIME PERIOD FOR RESPONSE This decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of rejection pursuant to this paragraph shall not be considered final for judicial review.” 37 C.F.R. § 41.50(b) also provides that the Appellants, 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: (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 prosecution 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). AFFIRMED-IN-PART; 37 C.F.R, $ 41.50(b) 13 Copy with citationCopy as parenthetical citation