Ex Parte FortDownload PDFPatent Trial and Appeal BoardMay 18, 201814568855 (P.T.A.B. May. 18, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 14/568,855 12/12/2014 Thomas L. Fort 147462 7590 05/22/2018 Botos Churchill IP Law LLP 430 Mountain A venue Suite 401 New Providence, NJ 07974 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 ATTORNEY DOCKET NO. BECTON 3.3-077 CON CON(E CONFIRMATION NO. 3545 EXAMINER HORLICK, KENNETH R ART UNIT PAPER NUMBER 1637 NOTIFICATION DATE DELIVERY MODE 05/22/2018 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): rbotos@bciplaw.com ip.docket@bd.com pto@bciplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Exparte THOMAS L. FORT Appeal2017-005239 Application 14/568,855 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal 1 under 35 U.S.C. § 134 involving claims to kits for an amplification or detection reaction and a method fbr detecting the presence or absence of Cytomegalovin1s (ClVlV) in a sample. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. Statement of the Case Background Cytomegalovirus (CMV) is a member of the herpes virus family, which includes among others herpes simplex virus types 1 and 2, varicella-zoster virus and Epstein-Barr virus. Between 1 Appellant identifies the Real Party in Interest as Becton, Dickinson and Company (see App. Br. 1 ). Appeal2017-005239 Application 14/568,855 50% and 85% of adults in the United States are infected by this virus by 40 years of age .... Once infected, the virus remains alive, but dormant within the infected individual's body for life. . . . CMV remains the most important cause of congenital viral infection in the United States and is an important cause of morbidity and mortality in certain high-risk groups, such as neonates and immunocompromised and immunosuppressed patients. (Spec. ,r 4). The Specification teaches a "need, therefore, exists for a rapid and sensitive means of detecting CMV in clinical samples" (Spec. ,r 6). The Specification teaches "a kit" and a "method for detecting the presence or absence of Cytomegalovirus (CMV) in a sample" (Spec. ,r,r 8-9). The Claims Claims 1-12 are on appeal. Claims 1 and 5 are representative and read as follows: 1. A kit for an amplification or detection reaction comprising: a first amplification primer comprising a target binding sequence selected from the group consisting of the target binding sequences of SEQ ID NOs. 1 and 2; and a second amplification primer comprising a target binding sequence selected from the group consisting of the target binding sequences of SEQ ID NOs. 3, 4 and 5; and a detector probe, wherein the detector probe comprises a sequence that is capable of hybridizing to an amplified target sequence provided by the first amplification primer and the second amplification primer tagged with a moiety that is detectable. 5. A method for detecting the presence or absence of Cytomegalovirus (CMV) in a sample, the method comprising performing polymerase chain reaction (PCR) on sample nucleic acids wherein the PCR comprises: (a) hybridizing (i) a first amplification primer having a sequence selected from the group consisting of the target binding sequences of SEQ ID NOs: 1 and 2 and (ii) a second amplification primer having a sequence selected from the group consisting of the target binding sequences of SEQ ID NOs: 3, 4 and 5, 2 Appeal2017-005239 Application 14/568,855 to a target sequence; (b) amplifying the target sequence; and ( c) detecting the amplified target sequence. The Issue The Examiner rejected claims 1-12 under 35 U.S.C. § 103(a) as obvious over Aquino, 2 Paoletti, 3 and Rychlik4 (Ans. 2-3). The Examiner finds that Aquino teaches "oligonucleotide primers and their use in PCR amplification for detection of CMV, said primers targeting the glycoprotein H gene (gH)" (Ans. 2). The Examiner finds that Paoletti teaches "a CMV glycoprotein H gene nucleotide sequence which contains within it the target binding sequences of instant SEQ ID NO: 1-5. See Paoletti et al. SEQ ID NO: 188, within nucleotides 1381-1450" (Ans. 3). The Examiner finds that Paoletti suggests "the disclosed CMV nucleotide sequence is useful for generating probes or primers for detecting and amplifying CMV nucleic acid in a sample (see column 21, lines 45-49)" (Ans. 3). The Examiner finds that Rychlik teaches that "at the time of the instant invention, the skilled artisan was well aware of the various criteria to use in selecting useful oligonucleotide probes and primers based on known nucleotide sequences (see entire reference on pages 8543-8551 )" (Ans. 3). 2 V.H. Aquino and L.T.M. Figueiredo, Cytomegalovirus infection in renal transplant recipients diagnosed by nested-PCR, 34(1) Brazilian J. Medical Biol. Res. 93-101 (2001) (hereinafter "Aquino"). 3 Paoletti et al., US 5,997,878, issued Dec. 7, 1999 (hereinafter "Paoletti"). 4 Wojciech Rychlik and Robert E. Rhoads, A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA, 17 (21) Nucleic Acids Res. 8543-8551 (1989) (hereinafter "R ychlik"). 3 Appeal2017-005239 Application 14/568,855 The Examiner finds it obvious "to make and use oligonucleotides having the CMV target binding sequences required in the claims" (Ans. 3). The Examiner finds that "the skilled artisan was aware of the CMV glycoprotein H gene sequence by which any number of primers and probes suitable for various amplification procedures like PCR would have been routinely and predictably designed, and used with reasonable expectation of success" (Ans. 3). The issue with respect to this rejection is: Does the evidence of record support the Examiner's conclusion that the combination of Aquino, Paoletti, and Rychlik render the claims obvious? Findings of Fact 1. Aquino teaches "nested-PCRs were carried out using 2 primer sets that recognize part of the glycoprotein B (gB) and H (gH) genes" (Aquino 95, col. 1 ). 2. Aquino teaches "[b ]oth nested-PCRs used for CMV detection were highly sensitive as compared to the observation of cytopathic effects in tissue culture" (Aquino 96, col. 1 ). 3. Paoletti teaches that the DNA from recombinant poxvirus can be used to generate PCR probes and primers, specifically teaching the "recombinant poxvirus DNA is useful for probes for CMV or HCMV or for preparing PCR primers for detecting the presence or absence of CMV or HCMV or antigens thereof' (Paoletti 2:1--4; cf abstract, 10:40--45; 21:45- 50). 4. Paoletti teaches the "sequence of HCMV gH lacking its transmembrane region and cytoplasmic tail is presented in FIG. 67 (SEQ ID 4 Appeal2017-005239 Application 14/568,855 NO: 188)" (Paoletti 94:40-50; cf Sequence listing present from cols. 295- 298). 5. The Examiner identifies nucleotides 13 81-1450 of SEQ ID NO: 188 as the sequences that SEQ ID NO: 1-5 will bind (see Ans. 3). 6. Rychlik teaches: A method is presented for choosing optimal oligodeoxyribonucleotides as probes for filter hybridization, primers for sequencing, or primers for DNA amplification. Three main factors that determine the quality of a probe are considered: stability of the duplex formed between the probe and target nucleic acid, specificity of the probe for the intended target sequence, and self-complementarity. (Rychlik 8543, abstract). 7. Rychlik evidences that at the time of the invention the skilled artisan was well aware of the various criteria to use in selecting useful oligonucleotide probes and primers based on known nucleotide sequences and teaches that a computer program selects primers (see Rychlik 8543; cf 8549). Principles of Law An "obviousness finding was appropriate where the prior art 'contained detailed enabling methodology for practicing the claimed invention, a suggestion to modify the prior art to practice the claimed invention, and evidence suggesting that it would be successful. "' In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853 F.2d 894, 902 (Fed. Cir. 1988). The court commented that "[r]esponding to concerns about uncertainty in the prior art influencing the purported success of the claimed combination, this court [ in O 'Farrell] stated: ' [ o ]bviousness 5 Appeal2017-005239 Application 14/568,855 does not require absolute predictability of success ... all that is required is a reasonable expectation of success."' Kubin, 561 F.3d at 1360 (citing In re O'Farrell, 853 F.2d at 903-904). Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Ans. 2-3; FF 1-7) and agree with the conclusion that the claims are obvious over Aquino, Paoletti, and Rychlik. Aquino teaches nested PCR amplification and sequencing of the gH gene of CMV (FF 1-2). Paoletti teaches that DNA from recombinant poxvirus can be used to generate PCR probes and primers, teaches that one of these recombinant poxviruses is SEQ ID NO: 188, and teaches the sequence of SEQ ID NO: 188. (FF 3-5). Rychlik teaches the routine nature of primer selection for PCR (FF 6-7). We agree with the Examiner's finding that "the skilled artisan was aware of the CMV glycoprotein H gene sequence by which any number of primers and probes suitable for various amplification procedures like PCR would have been routinely and predictably designed, and used with reasonable expectation of success" (Ans. 3). In comparing the obviousness of the instant primers and probes to the NAIL nucleic acid at issue in Kubin, we note that the instant obviousness case is better than that in Kubin. Unlike in Kubin where the NAIL sequence was unknown, the complete region of gH sequence from which the instant primers and probes were selected was disclosed in Paoletti and was suggested as a target for primer and probe selection by Paoletti and Aquino (FF 1-5). The method of using the primers and probes in PCR reactions was 6 Appeal2017-005239 Application 14/568,855 well known in the art (FF 6-7). Thus, we conclude that it is more than reasonable to find that selection of particular PCR primer and probe sequences from a known sequence "would have had a resoundingly 'reasonable expectation of success' in deriving the claimed invention in light of the teachings of the prior art." Kubin, 561 F.3d at 1360. Appellant does not identify any teaching in the Specification suggesting any criticality to the particular primers exemplified, nor does Appellant identify any comparative data or other evidence to show any unexpected results for the particular primers of SEQ ID NO: 1-5 relative to other primers selected from the CMV gH gene. Appellant contends that Paoletti does not disclose "a useful target site for CMV detection" and "cannot be fairly characterized to one skilled in the art as providing any guidance whatsoever on the selection of primers for the amplification and detection of CMV using the portion of the gH gene targeted by the assay" (App. Br. 5; see also Reply Br. 4). We are not persuaded. Paoletti discloses the gene sequence and states that primers and probes can be made from poxviruses such as SEQ ID NO: 188 (FF 3--4). Although Paoletti discloses a long sequence, it is expected that one would be able to select primers and probes from a disclosed sequence given the guidance in Rychlik (FF 6-7). In Merck, the court found that prior art disclosing 1200 "effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). Here, the obvious primers would have been used for PCR of CMV (FF 1). 7 Appeal2017-005239 Application 14/568,855 Appellant contends that Aquino requires two targets: gH and gB, and Appellant discovered that only gH is needed for reliable detection, specifically contending "Aquino et al. requires two target regions. Therefore, Applicant has discovered a target region of the glycoprotein H gene that, alone, provides for the reliable detection of CMV. This is contrary to what is taught in Aquino et al. (i.e., that reliable detection requires two genes targets)" (App. Br. 4--5; Reply Br. 3). We are not persuaded. Aquino provides motivation for developing primers for gH and teaches creating primers which bind to gH in order to detect CMV. While Aquino also teaches creating primers for gB, the claims are not limited to only detecting gH. Moreover, we agree with the Examiner (see Ans. 4) that the use of the open "comprising" language in claims 1 and 5 does not exclude the presence of other primers including gB primers. See Georgia-Pacific Corp. v. US. Gypsum Co., 195 F.3d 1322, 1327 (Fed. Cir. 1999) (The transitional term "comprising" is "inclusive or open-ended and does not exclude additional, unrecited elements or method steps.") Even assuming arguendo that Applicant argues that detecting gH is not the preferred embodiment of Aquino, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including non-preferred embodiments. In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971). See Merck & Co., 874 F.2d at 807 ("That the [prior art] discloses a multitude of effective combinations does not render any particular formulation less obvious.") Here, Aquino also teaches detecting gH using nested PCR and therefore can be relied upon to teach detecting gH with PCR. 8 Appeal2017-005239 Application 14/568,855 Appellant contends that Paoletti 's suggestion that the pox viruses described in Paoletti et al. are useful for generating DNA for probes and primers to detect HCMV ... does not bring the skilled person any closer to the claimed invention, because Paoletti et al. predates Aquino et al. and the specific observation in Aquino et al. of the need for two gene targets (gB and gH) are required for CMV detection. (App. Br. 5---6). We are not persuaded. The length of time and the age of the references are not persuasive of non-obviousness. See In re Wright, 569 F.2d 1124, 1127 (CCP A 1977). In addition, "where a rejection is predicated on two references each containing pertinent disclosure ... we deem it to be of no significance, but merely a matter of exposition, that the rejection is stated to be on A in view of B instead of on B in view of A, or to term one reference primary and the other secondary." In re Bush, 296 F.2d 491, 496 (CCPA 1961). Moreover, as explained above, Aquino teaches that gH can be used for detecting CMV. Appellant contends that Xie5 "reflects the uncertainties with regard to primer/probe design at that time" (App. Br. 7). We find this unpersuasive because Xie at 1 teaches "[ w ]ith help of commercial bio-software such as Oligo or on-line primer design tools such as primer3, experienced researchers can pick out optimized primer pairs under certain parameters to guarantee the efficiency and specificity of the amplification," thereby indicating that one could use software to pick primers with a reasonable expectation of success. While Xie states the 5 Xie et al., Primer-Chaperon: An Accessory to PCR primer design, undated (hereinafter "Xie"). 9 Appeal2017-005239 Application 14/568,855 amplification process is still unpredictable, this refers to the amplification of an extra, undesired product by the primers, not the failure of the primers to amplify the desired target. Specifically, Xie states "[ n ]evertheless, the whole process of primer-template amplification is still unpredictable. The designed pair could, sometimes, amplify some undesired products, yielding multiple products and smears observed in gel-electrophoresis" (Xie at 1, cited on App. Br. 6.). Xie teaches improvements to software to eliminate amplification of undesired products (see id.). We do not agree with Appellant's interpretation that Xie teaches choosing primers based on a known sequence is unpredictable. Moreover, Appellant has not presented evidence that primers for gH will amplify some undesired products or any secondary consideration regarding the claimed primers whatsoever. Appellant contends "Rychlik et al. does not guide the skilled person on the selection of the assay template. Rychlik et al. 's guidance assumes a known target, where the OLIGO tool is used to design primers against that target" (App. Br. 7; cf Reply Br. 4). We find this argument unpersuasive because Aquino suggests the CMV gH gene as a target for PCR (FF 1) and Paoletti discloses the known sequence of the CMV gH gene as well as teaching generating PCR primers and probes to these targets (FF 3--4 ). We agree with the Examiner that selecting primers based on the known and desired target sequence of Aquino and Paoletti based on the parameters and software taught by Rychlik would have been obvious (FF 6-7; cf Ans. 3). Appellant contends "the Examiner's conclusion that Aquino et al. instructs the skilled person to focus an assay on a gH target is only based on impermissible hindsight, not from the reference itself' (Reply Br. 2). 10 Appeal2017-005239 Application 14/568,855 We are not persuaded. While we are fully aware that hindsight bias may plague determinations of obviousness, Graham v. John Deere Co., 383 U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly stated that the "combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). Here, the Examiner has provided specific reasons based on evidence disclosed in the prior art for obtaining the obvious combination, specifically relying on Aquino to suggest a reason to make primers to the gH gene, Paoletti to demonstrate that the gH gene sequence was known, and Rychlik to teach that primer selection parameters were known, thereby rendering the primers of claim 1 and method of claim 5 obvious (FF 1-7). Appellant also contends "Aquino [] teaches that the gB target is better suited to CM[V] detection than the gH target" (Reply Br. 3). We are not persuaded. Aquino does not teach away from creating primers for gH. A teaching away requires a reference to actually criticize, discredit, or otherwise discourage the claimed solution. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) ("The prior art's mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed"). Appellant does not identify, and we do not find, any teaching in any of the cited prior art that criticizes, discredits, or discourages the use of detecting gH using primers. Finally, Appellant contends there are unexpected results (Reply Br. 4-- 5). We are not persuaded. Appellant has not shown nor identified evidence of the unexpected results. "'It is well settled that unexpected results must be 11 Appeal2017-005239 Application 14/568,855 established by factual evidence. Mere argument or conclusory statements ... [do] not suffice."' In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). Conclusion of Law The evidence of record supports the Examiner's conclusion that the combination of Aquino, Paoletti, and Rychlik render the claims obvious. SUMMARY In summary, we affirm the rejection of claims 1 and 5 under 35 U.S.C. § 103(a) as obvious over Aquino, Paoletti, and Rychlik. Pursuant to 37 C.F.R. § 4I.37(c)(l), we also affirm the rejection of claims 2--4 and 6- 12 as these claims were not argued separately. 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 12 Copy with citationCopy as parenthetical citation