Bruno Colin et al.Download PDFPatent Trials and Appeals BoardMar 18, 20212020004646 (P.T.A.B. Mar. 18, 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. 12/918,159 08/18/2010 Bruno Colin 146497 6449 25944 7590 03/18/2021 OLIFF PLC P.O. BOX 320850 ALEXANDRIA, VA 22320-4850 EXAMINER PYLA, PAUL D ART UNIT PAPER NUMBER 1653 NOTIFICATION DATE DELIVERY MODE 03/18/2021 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): OfficeAction25944@oliff.com jarmstrong@oliff.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte BRUNO COLIN, DAVID MOSTICONE, JEAN-CLAUDE RAYMOND, THIERRY SOFIA, and ANTOINE VIMONT ____________ Appeal 2020-004646 Application 12/918,159 Technology Center 1600 ____________ Before DONALD E. ADAMS, RYAN H. FLAX, and JAMIE T. WISZ, 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 59–87 (see Ans.2 3). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 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 “bioMérieux” (Appellant’s December 5, 2019, Appeal Brief (Appeal Br.) 1). 2 Examiner’s April 2, 2020, Answer. Appeal 2020-004646 Application 12/918,159 2 STATEMENT OF THE CASE Appellant’s disclosure relates to “method for identifying one or more microorganisms by means of an agglutination reaction carried out simultaneously with the enrichment of the sample in microorganisms” (Spec.3 1). Appellant’s independent claims 59, 77, and 82 are reproduced below: 59. A method for detecting whether at least one microorganism is present in a sample, comprising: subjecting a mixture including the sample, a sensitized solid support, and a culture medium in a container to culturing conditions for 4 to 96 hours so as to culture the microorganism when present in the sample such that the microorganism is multiplied; and measuring in real time an amount of binding of the microorganism to the sensitized solid support at a plurality of time points during the 4 to 96 hours of culturing; wherein: the microorganism is a unicellular organism; the sensitized solid support includes (i) a solid support, and (ii) an antigen, antibody, phage, phage protein, antiligand, or ligand that enables binding between the microorganism and the sensitized solid support; binding of the microorganism to the sensitized solid support indicates that the microorganism is present in the sample; and the binding of the microorganism to the sensitized solid support takes place simultaneously with the multiplication of the microorganism when present in the sample. (Appeal Brief A-1 (emphasis added).) 3 Appellant’s August 18, 2010, Specification. Appeal 2020-004646 Application 12/918,159 3 77. A method for detecting whether at least one microorganism is present in a sample, comprising: subjecting a mixture including the sample, a sensitized solid support, and a culture medium in a container to culturing conditions for 4 to 96 hours so as to culture the microorganism when present in the sample such that the microorganism is multiplied; and periodically measuring in real time an amount of binding of the microorganism to the sensitized solid support during culturing; wherein: the microorganism is a unicellular organism; the sensitized solid support includes (i) a solid support, and (ii) an antigen, antibody, phage, phage protein, antiligand, or ligand that enables direct binding between the microorganism and the sensitized solid support; binding of the microorganism to the sensitized solid support indicates that the microorganism is present in the sample; and the binding of the microorganism to the sensitized solid support takes place simultaneously with the multiplication of the microorganism when present in the sample. (Appeal Brief A-3–A-4 (emphasis added).) 82. A method for detecting whether at least one microorganism is present in a sample, comprising: subjecting a mixture including the sample, a sensitized solid support, and a culture medium in a container to culturing conditions for 4 to 96 hours so as to culture the microorganism when present in the sample such that the microorganism is multiplied; and periodically measuring in real time an amount of binding of the microorganism to the sensitized solid support during culturing; wherein: Appeal 2020-004646 Application 12/918,159 4 the microorganism comprises a species of Listeria; the sensitized solid support includes (i) a solid support, and (ii) an antibody that enables direct binding between the microorganism and the sensitized solid support; binding of the microorganism to the sensitized solid support indicates that the microorganism is present in the sample; and the binding of the microorganism to the sensitized solid support takes place simultaneously with the multiplication of the microorganism when present in the sample. (Appeal Br. A-4–A-5 (emphasis added).) Grounds of rejection before this Panel for review: I. Claims 59, 60, and 62–87 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns,4 Manafi,5 Atrache,6 and Hansen.7 II. Claims 59, 71, and 77 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi, Atrache, Hansen, and Sun.8 4 Burns et al., US 2006/0246535 A1, published Nov. 2, 2006. 5 Manafi et al., Fluorogenic and Chromogenic Substrates Used in Bacterial Diagnostics, 55 MICROBIOLOGICAL REVIEWS 335–48 (1991). 6 Atrache et al., US 5,415,997, issued May 16, 1995. 7 Hansen, US 5,286,452, issued Feb. 15, 1994. 8 Sun et al., FOOD-BORNE PATHOGENS, Use of bioluminescent Salmonella for assessing the efficiency of constructed phage-based biosorbent, 27 JIMB 126–28 (2001). Appeal 2020-004646 Application 12/918,159 5 III. Claim 61 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi, Atrache, Hansen, and McCoy.9 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Burns discloses “agglutination methods for detecting microorganisms in solutions or suspensions,” which are “based in part on the discovery that agglutination methods utilizing the selectivity of antigen binding sites of antibodies are sensitive enough to selectively detect microorganism contaminants, without first culturing the microorganisms” (Burns ¶¶ 3 and 26 (emphasis added)). FF 2. Burns discloses: [M]ethods of detecting a microorganism . . . in an aqueous solution or suspension where the aqueous solution or suspension does not comprise precultured microorganisms. The methods first comprise mixing the solution or suspension with microspheres coated with antibodies or antibody fragments comprising an antigen binding site selective for the microorganism. This creates a microsphere- solution/suspension mixture. The method then comprises evaluating the microsphere-solution/suspension mixture for agglutination. In these methods, the presence of agglutination 9 McCoy, US 2007/0218522 A1, published Sept. 20, 2007. Appeal 2020-004646 Application 12/918,159 6 indicates that the solution or suspension contains the microorganism. (Burns ¶ 37 (emphasis added); see also id. ¶ 60 (emphasis added) (Burns discloses that “it is within the scope of the invention that these multiple antibody/antibody fragment microbeads could be used with a bacteria that has been precultured from the substrate where contamination is suspected.”).) FF 3. Burns discloses that “nonlimiting examples” of aqueous solution or suspension within the scope of its invention: [I]nclude environmental sources such as sewage, streams, rivers, lakes, ground water, irrigation water, municipal water supplies, tap water, and wells; food or animal feed including extracts of solid food or feed; medical products including liquid medicines and solutions and suspensions or extracts of solid medicines; and vertebrate (including mammalian, e.g., human) body fluids and products such as urine, bile, stool, peritoneal washings, sputum, bronchial aspirate, cerebrospinal fluid, pus, blood, and extracts of those fluids; and blood products such as plasma, serum, and blood products that are substantially purified from other blood products, such as red blood cells, platelets, factor IX, factor VII, albumin, and antibodies. Blood products, particularly blood cells and platelets, are preferred, since there is an acute need for rapid tests for detecting contaminating microorganisms in these products. (Burns ¶ 38.) FF 4. Burns uses the term “microorganism” to mean “a microscopic prokaryotic, archeal, or eukaryotic organism that is suspected of contaminating the aqueous solution or suspension, including bacteria, fungi and parasitic species that are capable of infecting vertebrates,” wherein the term “‘[m]icroorganism’ does not include viruses” (Burns ¶ 39). Appeal 2020-004646 Application 12/918,159 7 FF 5. Burns discloses that the term “‘selective’ means the ability of the antibody or antigen binding site to noncovalently bind to the microorganism but not other related microorganisms” (Burns ¶ 39; see id. ¶ 40 (Burns discloses that “[i]t is understood that antibodies selective for any particular species of bacteria could be produced without undue experimentation. Preferred are bacteria that are known pathogenic contaminants. Non- limiting examples include . . . Listeria spp.”)). FF 6. Burns discloses that its “methods are useful with any type of microsphere known in the art, for example red blood cells (‘hemagglutination’). Preferably, the microspheres are latex microspheres, since these are widely used in agglutination methods and techniques to bind antibodies to latex microspheres, either covalently or noncovalently, are well developed” (Burns ¶ 44). FF 7. Burns discloses that its “methods can be used with any agglutination format, for example a hanging drop slide . . ., or in wells of multiwell plates, such as a typical 96-well microtiter plate,” wherein “agglutination of the microspheres can be assessed visually with the naked eye or through a microscope . . . or using an instrument that measures light scattering” (Burns ¶¶ 48–49). FF 8. Burns discloses that its methods are “not narrowly limited to any particular type of antibody or antibody fragment comprising an antigen binding site. Thus any type of antibody or fragment known in the art . . . can be used,” wherein “[t]he antibodies can also comprise a detectible label, such as a radioactive, fluorescent, hapten (e.g., digoxigenin), or ligand (e.g., biotin) labels, which could aid in detecting agglutination” (Burns ¶ 51). Appeal 2020-004646 Application 12/918,159 8 FF 9. Examiner finds that Burns fails to disclose “the measuring in real- time an amount of binding of the microorganism to the support at a plurality of time points during the 4-96 hour (4-16 hours for claim 75) of culture time” (Ans. 11). FF 10. Atrache “relates to methods for detecting low levels of a particular microorganism, or microorganisms from a mixed culture or sample using antibodies and solid immunosorbent supports without the need for a preliminary or further growth step in selective media” (Atrache 1:12–17 (emphasis added)). FF 11. Atrache discloses: [A] method for detecting low levels of a particular microorganism . . . in a sample which method comprises: exposing the sample to a solid support to which are adsorbed antibodies specific for the microorganism or microorganisms being detected, said antibodies being capable of selective capture and immobilisation of the microorganism or microorganisms without compromising the ability of the microorganism or microorganisms to replicate; washing the support to remove unbound materials; adding sterile nutrient broth to the support; incubating the support in the nutrient broth at a temperature and for a time relative to the generation time of the microorganism or microorganisms sufficient to allow the microorganism or microorganisms to reach a detectable level; washing the support and then performing an immunoassay on the support using an immunoreagent specific for the microorganism or microorganisms being detected. (Atrache 3:57–4:7) FF 12. Atrache discloses microorganisms, within the scope of its disclosure, include Listeria species” (Atrache 4:18–18). FF 13. Atrache discloses: The exposure of the sample to the antibody-coated support is generally for 1 hour or less. The wash steps are preferably Appeal 2020-004646 Application 12/918,159 9 performed using sterile saline buffer, more preferably Tris- saline buffer. Virtually any nutrient broth may be used in the method, however, preferred broths are tryptone soya broth and M broth. The incubation in nutrient medium may be overnight and is usually at 37° C. (Atrache 4:19–26.) FF 14. Manafi discloses techniques “for detection and differentiation of bacteria,” “based on the utilization of chromogenic and fluorogenic substrates for detection of activities of specific enzymes. These sensitive methods have led to improved accuracy and faster detection and may be performed by using the primary isolation media, thus bypassing the need for time-consuming isolation procedures prior to identification” (Manafi 335; see id. (Manafi reviews “recent publications, with particular emphasis on methods for specific detection of Escherichia coli”)). FF 15. Hansen “relates to optical analytical methods based on rates of particle agglutination” (Hansen 1:8–12). FF 16. Hansen discloses that “[a]n important aspect of particle agglutination . . . is that scattered light intensity measured as a function of time can be the basis for a very sensitive kinetic immunoassay” (Hansen 2:54–58). FF 17. Hansen discloses: [A] quantitative, kinetic, particle agglutination method for simultaneously measuring the concentrations of several analytes in a single fluid sample. The method entails the use of a novel high resolution optical flow particle analyzer instrument wherein detection by a single light detector of unidirectional low angle forward light scatter from differently sized and/or refractive indexed coated monomeric particles and their multimeric aggregates, is the basis of a stable kinetic method designed for simultaneous assays of multiple analytes in a single sample. The expressions “particles”, “spheres”, Appeal 2020-004646 Application 12/918,159 10 “microspheres” and “beads” are used interchangeably herein and are intended to refer to polymeric (e.g., latex, polystyrene) spherical particles of generally uniform diameter and refractive index relative to the surrounding medium. (Hansen 8:8–23; see id. at 12:45–49 (Hansen’s “procedure involves suspending in an assay reagent solution appropriate to the particular analytes being estimated antibody-coated monomeric spheres of different diameter or refractive index.”).) FF 18. Hansen discloses that its method “may be used to measure either agglutination or inhibition of agglutination of coated particle,” wherein “[c]omponents of the reaction mixture may be added concurrently or sequentially” (Hansen 13:22–26). FF 19. Examiner finds that “if Burns, Manafi, Atrache and Hansen do not teach that the agglutination detectable signal reaction implements a phage- bacterial protein reaction,” Sun makes up for this deficiency (see Ans. 22; see also 22–24). FF 20. Examiner finds that the combination of “Burns, Manafi, Atrache and Hansen do not explicitly teach that the microorganisms are counted according to the most probable number method” and relies on McCoy to make up for this deficiency (see Ans. 24; see also 24–26). ANALYSIS I Based on the combination of Burns, Manafi, Atrache, and Hansen, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious to use Atrache’s “incubation times and temperatures,” in the method of Burns, Manafi, Atrache, and Hansen, to “provide an improved assay where slow growing or hard to detect Appeal 2020-004646 Application 12/918,159 11 microorganisms (e.g., Listeria monocytogenes) can be tested which expands the range of the assay to such microorgamsms” (Ans. 20; see FF 1–18). Examiner further concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious “to add the culture medium a chromogenic or fluorescent enzymatic substrate that directly detects an enzymatic activity of the microorganism (when present in the sample) independent of agglutination so as to provide a robust assay that can detect microorganisms based direct contact of produced enzymes” and “replace the kinetic assay of Hansen for the endpoint assay in Burns . . . [to] provide an improved assay where slow growing or hard to detect microorganisms can be tested and analyzed real-time with multiple data points during the analysis” (Ans. 20–21.) We are not persuaded Burns discloses methods of detecting a microorganism in an aqueous solution or suspension that has, or has not, been precultured (FF 2 (emphasis added)). Atrache discloses a method, wherein at least one microorganism, in a sample, is captured with a solid support comprising adsorbed antibodies specific for the microorganism being detected to form a microorganism-solid support complex, washing the complex to remove unbound materials, incubating the complex in a nutrient broth, at a temperature and for a time relative to the generation time of the microorganism or microorganisms sufficient to allow the microorganism or microorganisms to reach a detectable level, washing the complex, and then performing an immunoassay on the complex using an immunoreagent specific for the microorganism or microorganisms being detected (FF 11; see also FF 10 (Altrache discloses “methods for detecting low levels of a particular microorganism, or Appeal 2020-004646 Application 12/918,159 12 microorganisms from a mixed culture or sample using antibodies and solid immunosorbent supports without the need for a preliminary or further growth step in selective media”) (emphasis added)). Thus, Atrache, like Burns, discloses the detection of microorganisms that have either been precultured or not cultured. Examiner relies on Manafi and Hansen to disclose techniques for detecting a microorganism by either agglutination or the detection of specific enzymes produced by the microorganism (see FF 14–18). Examiner does not, however, identify a teaching in either reference to support a conclusion that the detection of the microorganism would be contemporaneous with the culturing of the microorganism as required by Appellant’s claimed invention. Thus, the combination of Burns, Manafi, Atrache, and Hansen suggests, at best, a method of preculturing a microorganism obtained from a sample prior to identifying the microorganism (see FF 1–18). This is, however, not what Appellant claimed. To the contrary, Appellant’s claimed invention requires, inter alia, “subjecting a mixture including the sample, a sensitized solid support, and a culture medium in a container to culturing conditions for 4 to 96 hours so as to culture the microorganism when present in the sample such that the microorganism is multiplied,” wherein “the binding of the microorganism to the sensitized solid support takes place simultaneously with the multiplication of the microorganism when present in the sample” and “binding of the microorganism to the sensitized solid support indicates that the microorganism is present in the sample,” wherein binding of the microorganism to the sensitized solid support is measured in Appeal 2020-004646 Application 12/918,159 13 real time during culturing (see Claim 59: Appeal Br. A-1; see also Claim 77: Appeal Br. A-3–A-4; Claim 82: Appeal Br. A-4–A-5). We acknowledge Examiner’s assertion that a microorganism may grow in the sample itself (i.e. blood, plasma, serum, environmental sources such as sewage, streams, rivers, lakes, ground water, irrigation water, municipal water supplies, etc.) (Ans. 28). According to Examiner, because “bacteria can grow in stored blood products, such blood products are representative of a culture media where bacteria are . . . cultured at any time prior to testing” and, thus, “Burns teaches methods for testing samples that are precultured or cultured prior to testing” (id.). Examiner’s assertion, however, conflates the sample with the culture medium and, thus, fails to account for the requirement of Appellant’s claimed invention that the sample is mixed with, inter alia, culture medium (see, e.g., Claim 59: Appeal Br. A-1; see also Claim 77: Appeal Br. A-3–A-4; Claim 82: Appeal Br. A-4– A-5). See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) (citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)) (“[O]bviousness requires a suggestion of all limitations in a claim.”). Therefore, we agree with Appellant’s contention that the combination of “Burns, Atrache, Hansen, and Manafi do not teach or suggest subjecting a mixture containing a sample . . . and a culture medium to culturing conditions for 4 to 96 hours so as to multiple the microorganism, or measuring binding of the microorganism to the solid support during culturing, as recited by claims 59, 77, and 82” (Appeal Br. 18; see also Reply Br.10 2 (“Burns does not teach or suggest measuring an amount of 10 Appellant’s June 2, 2020 Reply Brief. Appeal 2020-004646 Application 12/918,159 14 binding of the microorganism to a sensitized solid support during culturing of a mixture including a sample, a culture medium, and the solid support.”); see generally Reply Br. 2–14). II Based on the combination of Burns, Manafi, Atrache, Hansen, and Sun, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious “to substitute the microspheres of Burns, Manafi, Atrache and Hansen for the microspheres in Sun since Sun provides an alternative capturing ligand that would improve and expand the testing techniques discussed in Burns, Manafi, Atrache and Hansen” (Ans. 23; see FF 1–19). As Appellant explains, however, “Sun, which is only applied as allegedly teaching magnetic beads coated with a biotinylated bacteriophage . . . do[es] not cure the above-deficiencies of Burns, Manafi, Atrache, and Hansen with respect to independent claims 59, 77, and 82” (Appeal Br. 31). We agree. III Based on the combination of Burns, Manafi, Atrache, Hansen, and McCoy, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious “to add the McCoy MPN technique to Burns, Manafi, Atrache and Hansen since McCoy provides an alternative analytical method that would improve and to provide accurate results of the testing techniques discussed in the Burns, Manafi, Atrache and Hansen references” (Ans. 26; see also FF 1–18 and 20). As Appellant explains, however, “McCoy, which is only applied as allegedly teaching the additional feature recited by dependent claim 61, Appeal 2020-004646 Application 12/918,159 15 do[es] not cure the above-deficiencies of Burns, Manafi, Atrache, and Hansen with respect to independent claims 59, 77, and 82” (Appeal Br. 31). We agree. CONCLUSION The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness. Rejection I: The rejection of claims 59, 60, and 62–87 under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi, Atrache, and Hansen is reversed. Rejection II: The rejection of claims 59, 71, and 77 under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi, Atrache, Hansen, and Sun is reversed. Rejection III: The rejection of claim 61 under 35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi, Atrache, Hansen, and McCoy is reversed. DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 59, 60, 62–87 103 Burns, Manafi, Atrache, Hansen 59, 60, 62–87 59, 71, 77 103 Burns, Manafi, Atrache, Hansen, Sun 59, 71, 77 61 103 Burns, Manafi, Atrache, Hansen, McCoy 61 Overall Outcome 59–87 REVERSED Copy with citationCopy as parenthetical citation