Ex Parte Robertson et alDownload PDFPatent Trial and Appeal BoardApr 29, 201311814516 (P.T.A.B. Apr. 29, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte JOHN FORSYTH RUSSELL ROBERTSON, ANTHONY BARNES, ANDREA MURRAY, and CAROLINE CHAPMAN __________ Appeal 2011-008044 Application 11/814,516 Technology Center 1600 __________ Before DONALD E. ADAMS, ERIC GRIMES, and GEORGIANNA W. BRADEN, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a diagnostic method, which have been rejected for anticipation and obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. STATEMENT OF THE CASE The Specification states that ―it has become apparent that antibodies, and in particular autoantibodies, can also serve as biological markers of disease or disease susceptibility‖ (Spec. 1:21-23). The Specification also Appeal 2011-008044 Application 11/814,516 2 states that ―difficulties can arise in devising a standardised assay methodology appropriate for the whole population of subjects to be screened because the absolute amounts of antibody present vary dramatically from individual to individual. This can produce a high incidence of false negative results.‖ (Id. at 3:18-22.) The Specification discloses that the ―reliability of assays based on detection of antibodies, particularly autoantibodies, as biological markers of disease can be improved dramatically by inclusion of an antigen titration step‖ (id. at 3:33-36). Such an approach is contrary to prior art methods which titrate antigen merely to construct a calibration curve to allow identification of the most appropriate antigen concentration to be used for detecting antibodies in actual patient samples. In these methods only a single point measurement is proposed for actual diagnosis. (Id. at 4:2-7.) Claims 1-20, 36-42, and 47-49 are on appeal. Claim 1 is representative and reads as follows: 1. A method of detecting a disease state or disease susceptibility in a mammalian subject, comprising detecting an antibody in a bodily fluid test sample from the subject wherein the antibody is a biological marker of a disease state or disease susceptibility, the method comprising: (a) contacting the test sample with a plurality of different amounts of an antigen specific for the antibody, (b) detecting the amount of specific binding between the antibody and the antigen, (c) plotting or calculating a curve of the amount of specific binding versus the amount of antigen for each amount of antigen used in step (a), and (d) comparing the curve of the test sample with a control sample curve, Appeal 2011-008044 Application 11/814,516 3 wherein a difference in the test sample curve when compared with the control sample curve indicates the presence of a disease state or susceptibility in the subject. The Examiner has rejected claims 1-3, 36, 37, 41, 42, and 47-49 under 35 U.S.C. § 102(b) as anticipated by Paré 1 (Answer 4), and has rejected all of the claims on appeal under 35 U.S.C. § 103(a) as obvious based on either Montenarh 2 or Zhang, 3 combined with Paré (Answer 5). The same issue is dispositive with respect to both rejections. The Examiner finds that Paré discloses a method that includes all of the steps of claim 1 in its Figure 3 and accompanying description (id. at 4-5). In particular, the Examiner finds that Figure 3 shows results from a test sample as claimed. Figure 3 clearly analyzes distinct test samples. Figure 3 shows a detection assay demonstrating differences in specific binding of various concentrations of Neospora tachyzoite antigen to autoantibody against Neospora tachyzoite antigen in serum of subjects with Neospora infection as compared to [such] binding . . . in serum of subjects that are not infected with Neospora. (Id. at 9.) Appellants argue that ―Paré uses different concentrations of bovine Neospora tachyzoite (BPA 1) antigen, as shown in Figure 3, to optimize the 1 Paré et al., An enzyme-linked immunosorbent assay (ELISA) for serological diagnosis of Neospora sp. infection in cattle, 7 J. VET. DIAGN. INVEST. 352- 359 (1995). 2 Montenarh et al., p53 autoantibodies in the sera, cyst and ascitic fluids of patients with ovarian cancer, 13 INTERNATIONAL JOURNAL OF ONCOLOGY 605-610 (1998). 3 Zhang et al., Enhancement of Antibody Detection in Cancer Using Panel of Recombinant Tumor-associated Antigens, 12 CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION 136-143 (2003). Appeal 2011-008044 Application 11/814,516 4 assay . . . . An optimization technique is not a multi-point assay to detect disease or disease susceptibility in a test sample.‖ (Appeal Br. 5.) Appellants argue that ―[o]ne skilled in the art would know that the use of a titration curve, as shown in Figure 3, for the purpose of optimizing antigen concentration in an assay is common in ELISA development and would not consider this titration curve to be a multi-point assay to obtain information about a test sample‖ (id. at 6-7). That is, Appellants argue that while Paré‘s Figure 3 shows results from a positive control and a negative control at different antigen concentrations (id. at 7), ―Figure 3 fails to show results from a test sample as claimed in Claims 1, 36 and 48 for the detection of disease state or susceptibility‖ (id. at 8). Appellants argue that ―Figure 3 merely shows control data used to optimize the assay . . . . One skilled in the art would clearly understand that the ultimate ELISA taught by Paré for test sample analysis is a single point assay using 200 ng/well of antigen.‖ (Id.) We agree with Appellants that the claims on appeal do not read on the ELISA optimization described by Paré. Claim 1 is directed to a ―method of detecting a disease state or disease susceptibility‖ by ―detecting an antibody in a bodily fluid test sample.‖ This language is in the preamble of the claim, but ―[i]f the claim preamble, when read in the context of the entire claim, recites limitations of the claim, or, if the claim preamble is ‗necessary to give life, meaning, and vitality‘ to the claim, then the claim preamble should be construed as if in the balance of the claim.‖ Pitney Bowes, Inc. v. Hewlett- Packard Co., 182 F.3d 1298, 1305 (Fed. Cir. 1999). Appeal 2011-008044 Application 11/814,516 5 Here, the claim language supports Appellants‘ interpretation of the claimed method as requiring a test sample that is different from a positive control; i.e., a test sample that is not known in advance to contain the antibody of interest. The point of carrying out the claimed method is to ―detect[ ] a disease state or disease susceptibility‖ by determining whether a test sample contains an antibody that is a marker of the disease or susceptibility. By contrast, carrying out the recited steps on a positive control – a sample already known to contain the antibody of interest – would not be ―detecting a disease state‖ because a positive control by definition is a sample in which the disease state has been previously detected. ―The effect preamble language should be given can be resolved only on review of the entirety of the patent to gain an understanding of what the inventors actually invented and intended to encompass by the claim.‖ Corning Glass Works v. Sumitomo Electric U.S.A., Inc., 868 F.2d 1251, 1257 (Fed. Cir. 1989). Here, the Specification also supports interpreting the claim to require the test sample to be one that is not already known to contain the antibody of interest. The Specification describes its methods as improving ―the clinical utility and reliability of assays based on detection of antibodies, particularly autoantibodies, as biological markers of disease‖ (Spec. 3:12-15). That is, ―[b]y testing the sample suspected of containing antibodies against a series of different amounts of antigen and constructing a titration curve it is possible to reliably identify true positive screening results independently of the absolute amount of antibody present in the sample‖ (id. at 3:16 to 4:2, emphasis added). The Specification contrasts the disclosed methods to Appeal 2011-008044 Application 11/814,516 6 ―prior art methods which titrate antigen merely to construct a calibration curve to allow identification of the most appropriate antigen concentration to be used for detecting antibodies in actual patient samples‖ (id. at 4:2-6); i.e., methods like that described by Paré. ―[P]reamble language will limit the claim if it recites not merely a context in which the invention may be used, but the essence of the invention without which performance of the recited steps is nothing but an academic exercise.‖ Boehringer Ingelheim Vetmedica v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003) (concluding that ―growing‖ and ―isolating‖ recited in the preamble were entitled to weight because they ―are the raison d’etre of the claimed process itself. Divorced from the process of growing and isolating virus, the claimed method reduces to nothing more than a process for producing cytopathic effects in sheets of cultured MA-104 cells—a process whose absence of fathomable utility rather suggests the academic exercise.‖). In this case, as in Boehringer Ingelheim, reading the manipulative steps of claim 1 as divorced from a method of actually detecting a disease state or susceptibility would reduce the claimed method to the academic exercise of confirming the presence of antibodies in a sample that is already known to contain them. Interpreting claim 1 as a whole and in light of the Specification, we conclude that its preamble limits the claimed method to one in which the ―test sample‖ is not a positive control; i.e., not a sample that already known to contain the antibody that is a biological marker of a disease state or disease susceptibility. Paré discloses contacting positive control samples with a plurality of different amounts of an antigen, but it does not disclose Appeal 2011-008044 Application 11/814,516 7 carrying out the assay with a test sample that is not already known to contain the antibody of interest. 4 Paré therefore does not anticipate claim 1. The other independent claims on appeal are also limited to assays carried out on test samples that are not positive controls. Claim 48, like claim 1, is directed to a ―method of detecting a disease state or disease susceptibility‖ by detecting binding between an autoantibody and a tumor marker protein (see Appeal Br. 18 (Claims Appendix)). Claim 19 is directed to a ―method of identifying an anti-cancer treatment for a human patient, comprising detecting one or more autoantibodies specific for tumour marker proteins in a bodily fluid test sample from the patient,‖ and claim 36 is directed to a ―method of detecting an antibody in a test sample comprising a bodily fluid from a mammalian subject wherein said antibody is a biological marker of a disease state or disease susceptibility‖ (id. at 16). For the reasons discussed above, the preambles of each of the independent claims on appeal are entitled to weight in interpreting the scope of the claims, and in each case the claimed method is limited to one that uses a test sample that is not a positive control. Such a method is not disclosed by Paré, nor has the Examiner shown that it would have been obvious based on Montenarh or Zhang, in combination with Paré. 4 Paré also discloses contacting negative control samples with a plurality of different amounts of an antigen, but claim 1 clearly distinguishes the test sample from a negative control, since it requires comparing the test sample curve with a control sample curve and determining the presence of a disease state or disease susceptibility based on a difference between the two curves. Appeal 2011-008044 Application 11/814,516 8 SUMMARY We reverse both of the rejections on appeal. REVERSED cdc Copy with citationCopy as parenthetical citation