Biotecon Diagnostics GmbH

Patent Trials and Appeals Board

Mar 17, 2022

2021002527 (P.T.A.B. Mar. 17, 2022)

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. 14/549,467 11/20/2014 Cordt Grönewald 719176 5156 23460 7590 03/17/2022 LEYDIG VOIT & MAYER, LTD TWO PRUDENTIAL PLAZA, SUITE 4900 180 NORTH STETSON AVENUE CHICAGO, IL 60601-6731 EXAMINER HAMMELL, NEIL P ART UNIT PAPER NUMBER 1636 NOTIFICATION DATE DELIVERY MODE 03/17/2022 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): Chgpatent@leydig.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte CORDT GRÖNEWALD and KORNELIA BERGHOF-JÄGER ____________ Appeal 2021-002527 Application 14/549,467 Technology Center 1600 ____________ Before DONALD E. ADAMS, ERIC B. GRIMES, and JOHN E. SCHNEIDER, 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 32-38 (Appeal Br. 3).2 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM-IN-PART. 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 “Biotecon Diagnostics GmbH” (Appellant’s September 11, 2020, Appeal Brief (Appeal Br.) 2). 2 Pending claims 17-19, 21, 23, 24, 27, and 28 stand withdrawn from consideration (Appeal Br. 3). Appeal 2021-002527 Application 14/549,467 2 STATEMENT OF THE CASE Appellant’s disclosure relates to a “detection means and method specific for the genus Cronobacter (E. sakazakii) which are sensitive by using a target molecule which is multiple existent in Cronobacter cells” (Abstr.3). Appellant’s only independent claim, claim 32, is reproduced below: 32. A method of amplifying DNA, comprising, providing a sample comprising bacteria, amplifying DNA from the bacteria with primers in an amplification step, wherein the primers used in the amplification step comprise a first primer comprising SEQ ID NO:2 or a variant thereof, together with a second primer comprising the complement of SEQ ID NO:3 or a variant thereof, wherein the variant of the first primer is a sequence which is identical to SEQ ID NO:2 other than the substitution of one nucleotide base within SEQ ID NO:2 with a different base and the variant of the second primer is a sequence which is identical to the complement of SEQ ID NO:3 other than the substitution of one nucleotide base within the complement of SEQ ID NO:3 with a different nucleotide base. (Appeal Br. 22-23.) 3 Appellant’s November 20, 2014, Abstract. Appeal 2021-002527 Application 14/549,467 3 Grounds of rejection before this Panel for review: I. Claims 32-34 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski,4 GenBank,5 Buck,6 and Rozen.7 II. Claims 34-35 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski, GenBank, Buck, Rozen, and Seo.8 III. Claims 36-38 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski, GenBank, Buck, Rozen, Stephan 2008,9 and Stephan 2007.10 4 Grabowski et al., US 7,202,027 B1, issued Apr. 10, 2007 (hereinafter “Grabowski”). 5 Enterobacter sakazakii ATCC BAA-894, complete genome, GenBank: CP000783.1, http://www.ncbi.nlm.nih.gov/nuccore/156530483?sat= 13&satkey=6255603, last accessed Jan. 7, 2022 (hereinafter “GenBank”). 6 Buck et al., Design Strategies and Performance of Custom DNA Sequencing Primers, BioTechniques Vol. 27, No. 3, 528-536 (1999) (hereinafter “Buck”). 7 Rozen et al., Primer3 on the WWW for General Users and for Biologist Programmers, Methods in Molecular Biology Vol. 132, Bioinformatics Methods and Protocols, 365-386 (2000) (hereinafter “Rozen”). 8 Seo et al., Rapid, Specific Detection of Enterobacter sakazakii in Infant Formula Using a Real-Time PCR Assay, Journal of Food Protection, Vol. 68, No. 1, 59-63 (2005) (hereinafter “Seo”). 9 Stephan et al., Enterobacter pulveris sp. nov., isolated from fruit powder, infant formula and an infant formula production environment, International Journal of Systematic and Evolutionary Microbiology Vol. 58, 237-241 (2008) (hereinafter “Stephan 2008”). 10 Stephan et al., Enterobacter turicensis sp. nov., and Enterobacter helveticus sp. nov., isolated from fruit powder, International Journal of Systematic and Evolutionary Microbiology, Vol. 57, 820-826 (2007) (hereinafter “Stephan 2007”). Appeal 2021-002527 Application 14/549,467 4 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? ANALYSIS Rejection I: Appellant’s claim 32 is reproduced above. The method of Appellant’s claim 32 comprises the amplification of bacterial DNA from a sample comprising bacteria using primers comprising, inter alia, a first primer comprising Appellant’s SEQ ID NO: 2 and a second primer comprising the complement of SEQ ID NO: 3. Grabowski “relates to nucleic acid molecules which allow the identification of bacteria or groups of bacteria. For detection, the region of the bacterial genome containing the 23 S/5 S rRNA is used as the target sequence for the bacterial detection” (Grabowski, Abstr.; see also id. at 3:36-37 (Grabowski discloses that “[t]he transcribed spacer between the 23 S and 5 S rDNA is . . . [a] target sequence for identification of bacteria.”); see Ans.11 3-4). Grabowski further discloses that the “selection of the primer combinations and/or probe combinations can establish the conditions of the detection reactions so that they either demonstrate generally the presence of bacteria in a sample, or specifically indicate the presence of a certain bacterial species” (Grabowski 4:37-41; see Ans. 4). Examiner finds that “[a]lthough Grabowski teaches a variety of oligonucleotide primer sequences . . ., Grabowski does not teach nucleic acid molecules according to SEQ ID NO 2 or a nucleic acid molecule 11 Examiner’s December 31, 2020, Answer. Appeal 2021-002527 Application 14/549,467 5 complementary to SEQ ID NO 3” (Ans. 4 (citing Grabowski 27-28: Table 5)). Examiner relies on the combination of GenBank, Buck, and Rozen to make up for this deficiency in Grabowski (see Ans. 4-5). In particular, Examiner finds that “the complete genome sequence of E. sakazakii ATCC strain BAA 894 was known,” at the time of Appellant’s invention (see Ans. 4 (citing GenBank)). Examiner further relies on Buck and Rozen to establish that “the art was replete with guidance regarding the design and synthesis of oligonucleotide PCR primers” (Ans. 5 (citing Buck 529: Table 1; Rozen 365)). Based on the combination of Grabowski, GenBank, Buck, and Rozen, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious to have made and used oligonucleotide primer pairs to target and amplify the 23S-5S region of E. sakazakii whose nucleotide sequence is given by . . . [GenBank] because it would have merely amounted to applying a known method for discriminating between closely related bacterial species or groups of bacterial species based on 23S-5S as taught by Grabowski to a known bacterial 23S-5S transcribed spacer sequence to yield predictable results. (Ans. 5.) In support of this conclusion, Examiner reasons that GenBank discloses that the “23S-5S transcribed spacer region is only 91 nucleotides in length, indicating that there was a finite number of possible oligonucleotide primer pairs that could be designed to target this specific region” (Ans. 6). We find no error in Examiner’s conclusion of obviousness. Because Appellant’s claim 32 does not require the specific detection of any particular bacteria, we are not persuaded by Grönewald’s statement that “it was not obvious at the earliest priority date of this application that the 23S-5S spacer region would be suitable for the specific detection of E. Appeal 2021-002527 Application 14/549,467 6 sakazakii” (Grönewald Decl. ¶ 6; see also id. (Grönewald states that “[t]he clear takeaway was that this region was not likely to be suitable for the specific detection of E. sakazakii”); id. ¶ 8 (Grönewald addresses the selection of primer sets that may “cause off-target amplification of non- Cronobacter DNA.”)).12 For the foregoing reasons, we are not persuaded by Grönewald’s statement that Buck and Rozen are “only negligibly helpful, because these documents do not describe how to select suitable primers for amplification of a group of related sequences which do not also amplify another group of related sequences” (Grönewald Decl. ¶ 7). Because Appellant’s claim 32 does not require the specific detection of any particular bacteria, we are not persuaded by Grönewald’s statement that there is a large number of possible primer combinations in the 23S-5S transcribed spacer region (id.). To the contrary, although a large number of possible primer combinations may exist in the target region made obvious by the combination of Grabowski, GenBank, Buck, and Rozen, we find that the preponderance of evidence on this record supports a finding that the selection of suitable primer combinations would have been no more than routine to those of ordinary skill in this art. For the foregoing reasons, we are not persuaded by Appellant’s contention that “Examiner has provided no evidence that a person of ordinary skill, in view of Buck and Rozen, would have identified [the] specific primer combination [required by Appellant’s claim 32] among the 12 Declaration of Dr. Cordt Grönewald, signed August 30, 2018 (hereinafter “Grönewald Decl.”). Appeal 2021-002527 Application 14/549,467 7 thousands of possible primer combinations in the [GenBank] genome sequence,” because a person of ordinary skill in the art would recognize that Buck and Rozen provide no guidance as to which of the thousands of possible primer combinations would allow for the specific detection of all known species of the Cronobacter genus, to the exclusion of other closely-related species such as E. helveticus and E. pulveris. (Appeal Br. 6-7 (citing Grönewald Decl. ¶ 7)). For the foregoing reasons, we are not persuaded by Appellant’s contention that Examiner’s conclusion of obviousness is based on improper hindsight (Appeal Br. 7). For the foregoing reasons, we are not persuaded by Appellant’s contention that “Examiner has not established that there is a small and finite number of identified potential solutions to the recognized need or problem” (Appeal Br. 8 (citing Grönewald Decl. ¶¶ 7-8)). For the same reasons, we are not persuaded by Appellant’s contention that “the testing required to identify . . . candidate amplification targets is far beyond routine and certainly not easily traversed,” because in order to distinguish Cronobacter species from other closely- related non-Cronobacter species, a person of ordinary skill in the art would have needed to know the relevant sequences of both the Cronobacter and non-Cronobacter species or have undertaken testing to empirically determine whether those species contained one or more copies of the DNA sequence that could serve as a template for the candidate primer sequences. (Appeal Br. 9, 10 (citing Grönewald Decl. ¶¶ 7-8); see also Reply Br. 3-4.) For the foregoing reasons, we are not persuaded by Appellant’s contention that Grabowski “provides evidence of the laboriousness of sifting Appeal 2021-002527 Application 14/549,467 8 through the potential primer combinations . . . including running each primer set in a PCR reaction with the genomic DNA of each species that the experimenter wished to differentiate” (Appeal Br. 11 (citing Grabowski 6:25-7:6)). For the same reasons, we are not persuaded by Appellant’s contention that “neither Buck nor Rozen provides any guidance as to whether a primer combination would distinguish Cronobacter species from other closely related taxa” (Appeal Br. 12). For the foregoing reasons, Appellant’s contention that “[t]he presently claimed primer set unexpectedly distinguishes Cronobacter species from other closely related taxa, even though the primer set sequences are present seven times within the genome of Cronobacter species” (Appeal Br. 12; see also Reply Br. 5), is not commensurate in scope with Appellant’s claimed invention, and is, therefore, not persuasive. See In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (In order to be persuasive of non- obviousness, “[e]vidence of secondary considerations must be reasonably commensurate with the scope of the claims.”). Rejection II: Appellant’s representative claim 34 depends from and further limits the sample of Appellant’s claim 32 to comprise foodstuffs (see Appeal Br. 23). Examiner relies upon the combination of Grabowski, GenBank, Buck, and Rozen discussed above (see Ans. 8). Examiner finds that the combination of Grabowski, GenBank, Buck, and Rozen fails to disclose foodstuffs that are “dried infant formulae” and relies on Seo to make up for this deficiency (id.). Appeal 2021-002527 Application 14/549,467 9 Based on the combination of Grabowski, GenBank, Buck, Rozen, and Seo, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious “to have applied the method [made obvious by the combination of Grabowski, GenBank, Buck, and Rozen] to infant formulae because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results” (Ans. 9). In support of this conclusion, Examiner reasons that “[o]ne would have been motivated to have done so for the advantage of screening for the presence of microbial contamination by E. sakazakii in the infant formulae. This would have been advantageous because it would help to identify batches of infant formula that are contaminated” (id.). Initially, we note that Appellant’s representative claim 34 was included in Rejection I and falls with claim 32, therein. Further, having found no deficiency in the combination of Grabowski, GenBank, Buck, and Rozen, as discussed above, we are not persuaded by Appellant’s contention that Seo does not make up for Appellant’s asserted deficiencies in the combination of Grabowski, GenBank, Buck, and Rozen (Appeal Br. 13). Rejection III: Appellant’s claim 36 depends from and further limits the sample of Appellant’s claim 32 to comprise Cronobacter sakazakii strain DSM 4485 and Enterobacter turicensis strain DSM 18397, and wherein the primers amplify DNA from Cronobacter sakazakii strain DSM 4485, but do not amplify DNA from Enterobacter turicensis strain DSM 18397 (see Appeal Appeal 2021-002527 Application 14/549,467 10 Br. 23). Appellant’s claims 37-38 depend directly or indirectly from Appellant’s claim 36 (id.). Examiner relies on the combination of Grabowski, GenBank, Buck, and Rozen as discussed above (Ans. 9). Examiner further finds that Grabowski discloses “primers . . . selected so that only the DNA of certain bacteria are amplified” (id. (citing Grabowski 21:15-23)). Examiner recognizes, however, that the combination of Grabowski, GenBank, Buck, and Rozen does “not teach the nucleotide sequence of the 23S-5S transcribed spacer region of Enterobacter turicensis, Enterobacter helveticus, or Enterobacter pulveris” (Ans. 9-10 (emphasis added)). To make up for the foregoing deficiency in the combination of Grabowski, GenBank, Buck, and Rozen, Examiner relies on Stephan 2008 to disclose that “closely related species can be distinguished from E. sakazakii on the basis of nucleotide sequence differences in the 16S rRNA and rpoB genes” (Ans. 10 (emphasis added) (citing Stephan 2008, 238-239)). Examiner further relies on Stephan 2007 to disclose “using comparative 16S rRNA gene sequence analysis allocated to the isolates of the family of Enterobacteriaceae to distinguish these different species” (Ans. 10 (emphasis added) (citing Stephan 2007, Fig. 1)). Based on the combination of Grabowski, GenBank, Buck, Rozen, Stephan 2008 and Stephan 2007, Examiner concludes that, at the time Appellant’s invention was made, it would have been prima facie obvious “to have applied known genome sequencing techniques to these recently identified bacterial species to determine the nucleotide sequence of their 23S-5S transcribed spacer region” (Ans. 11). In support of this conclusion, Examiner reasons that those of ordinary skill in this art “would have been Appeal 2021-002527 Application 14/549,467 11 motivated to have done so because there was a need for discriminating Enterobacter Sakazakii from these related bacterial strains as discussed by [Stephan 2008 and Stephan 2007]” (id.). We are not persuaded. On this record, Examiner failed to establish that those of ordinary skill in this art would have reasonably extrapolated Stephan’s13 disclosure of the use of 16S rRNA and rpoB gene sequence analysis to distinguish different bacterial species to analysis of the 23S-5S transcribed spacer region as suggested by the combination of Grabowski, GenBank, Buck, and Rozen (see generally Appeal Br. 14-15 (Appellant contends that “Examiner seems to contend that [based on Stephan’s disclosure] the 23S-5S region could be similarly sequenced to determine which sequence(s) could be used to differentiate Cronobacter species from the closely related E. turicensis, E. helveticus, and E. pulveris species.”)). CONCLUSION The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness with respect to Rejections I-II. Rejection I: The rejection of claims 32-34 under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski, GenBank, Buck, and Rozen is affirmed. Claims 33-34 are not separately argued and fall with claim 32. Rejection II: The rejection of claims 34 and 35 under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski, GenBank, 13 The combined Stephan 2007 and Stephan 2008 disclosures. Appeal 2021-002527 Application 14/549,467 12 Buck, Rozen, and Seo is affirmed. Claim 35 is not separately argued and fall with claim 34. The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness with respect to Rejection III. Rejection III: The rejection of claims 36-38 under 35 U.S.C. § 103(a) as unpatentable over the combination of Grabowski, GenBank, Buck, Rozen, Stephan 2008 and Stephan 2007 is reversed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 32-34 103(a) Grabowski, GenBank, and Buck, Rozen 32-34 34-35 103(a) Grabowski, GenBank, Buck, Rozen, and Seo 34-35 36-38 103(a) Grabowski, GenBank, Buck, Rozen, Stephan 2008 and Stephan 2007 36-38 Overall Outcome 32-35 36-38 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-IN-PART