Ex Parte SeitzDownload PDFPatent Trial and Appeal BoardJan 28, 201612095485 (P.T.A.B. Jan. 28, 2016) 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. 12/095,485 09/19/2008 Alexander Seitz SONN:1007 2259 34725 7590 01/28/2016 CHALKER FLORES, LLP 14951 North Dallas Parkway, Suite 400 DALLAS, TX 75254 EXAMINER CHUNDURU, SURYAPRABHA ART UNIT PAPER NUMBER 1637 MAIL DATE DELIVERY MODE 01/28/2016 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ALEXANDER SEITZ1 __________ Appeal 2013-008548 Application 12/095,485 Technology Center 1600 __________ Before ERIC B. GRIMES, ULRIKE W. JENKS, and RICHARD J. SMITH, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method for amplifying polynucleotides, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 Appellant identifies the Real Party in Interest as Lexogen GmbH. (Appeal Br. 2.) Appeal 2013-008548 Application 12/095,485 2 STATEMENT OF THE CASE “Studying the genome (DNA), transcriptome (RNA), and proteome (protein)” has led to various techniques to assess differential expression of RNA in cells. (Spec. 1.) Several “differential display (DD)” techniques are known (id. at 2) but the Specification states that all of them suffer from the drawback of “giv[ing] the investigator only part of the mRNA sequence that is differentially expressed” (id. at 3). The Specification states that “[a] goal of the present invention is to provide a method that can amplify (enrich for) defined subpopulations of transcripts in their entire length with full coverage of all mRNA molecules present in the sample.” (Id.) Claims 1, 3–7, 11, 13, 14, 16–18, 22, 25, 26, 33, and 35–39 are on appeal. Claim 1 is illustrative and reads as follows (emphasis added): 1. A method for amplifying a pool of polynucleotide molecules comprising the steps of: obtaining a RNA; reverse transcribing the RNA using one or more reverse transcription primers, thereby creating a full length cDNA or obtaining a full length cDNA; adding a polynucleotide tail at a 3' end of the full length cDNA; amplifying the full length cDNA using a pair of amplification primers, wherein the amplification primers comprise a first 3' amplification primer that hybridizes to a 5' end of the full length cDNA, and a second 5' amplification primer that hybridizes to both at least a part of the polynucleotide tail and a part of the cDNA, wherein the second 5' primer hybridizes to one to ten nucleotides upstream of the 3' polynucleotide tail of the cDNA. Appeal 2013-008548 Application 12/095,485 3 The claims stand rejected under 35 U.S.C. § 103(a) as follows: Claims 1, 3–5, 7, 13, 14, 16, 18, 22, 26, 33, and 35–38 as obvious based on Fry2 and Weinstein3 (Ans. 5); Claims 6 and 25 as obvious based on Fry, Weinstein, and Brennan4 (Ans. 6); and Claims 11, 17, and 39 as obvious based on Fry, Weinstein, and Slepnev5 (Ans. 7). DISCUSSION The Examiner has rejected all of the claims on appeal as obvious based on Fry and Weinstein, by themselves or combined with either Brennan or Slepnev. The same issue is dispositive for all of the rejections. The Examiner finds that Fry discloses all of the limitations of claim 1 except that it “does not expressly teach a second amplification primer that hybridizes to both the added polynucleotide tail and specific section of the cDNA.” (Ans. 5.) The Examiner finds that Weinstein “teaches the concept of adding specific nucleotides complementary to the original target nucleic acid sequence to the 3' end of a 5' ‘universal’ primer in order to amplify specific sequences within an mRNA/cDNA pool.” (Id. at 5–6.) The Examiner concludes that it would have been obvious “to incorporate specific nucleotides to the 3' end of a 5' ‘universal’ amplification primer in Fry since 2 Fry et al., US 6,114,149 issued September 5, 2000. 3 Weinstein et al., US 6,270,966 B1 issued August 7, 2001. 4 Brennan et al., US 6,632,461 B1 issued October 14, 2003. 5 Slepnev, WO 03/035841 A2 published May 1, 2003. Appeal 2013-008548 Application 12/095,485 4 Weinstein suggests such a modification to allow for amplification of specific sequences in a mRNA/cDNA pool.” (Id. at 6.) The Examiner elaborates on this rationale, explaining that it would have been obvious “to incorporate one aspect of the Weinstein method (i.e. the use of specific primer nucleotides at the 3' end of a primer) into the Fry method in order to obtain a desirable, predictable result (i.e. the production of specific full-length cDNAs).” (Id. at 9.) The Examiner also reasons that [t]he prior art makes clear study of both pools of transcripts and specific transcripts were of interest at the time of invention. Thus, clearly a skilled practitioner would have seen the benefit of adjusting the Fry method to focus on specific full-length transcripts in contrast to proceeding with amplification of the entire full-length library only to have to isolate specific transcripts from the pool when needed for study with additional downstream method(s). (Id. at 10.) Appellant argues that “there is no motivation to combine the references as suggested.” (Appeal Br. 13.) Appellant points out that “Fry teaches a method for ‘non-specifically amplifying’ RNA or DNA (col. 2, line 17)” and teaches use of primers that amplify full-length products. (Id.) Appellant argues that Weinstein, by contrast, digests cDNA with restriction enzymes and amplifies subsets of the fragments using primers specific for the ends of the fragments, including nucleotides adjacent to added adapters. (Id. at 14.) Thus, Appellant argues, “the proposed modification would render Weinstein unsatisfactory for its intended purpose.” (Id.) Appellant also argues that “[t]he Examiner’s Answer suggests that the supposed motivation to combine the elements comes from the supposed desire of the skilled practitioner to have the elements combined. This Appeal 2013-008548 Application 12/095,485 5 reasoning is circular reasoning.” (Reply Br. 8.) Appellant also argues that “[t]he supposition that a skilled practitioner would ‘have seen the benefit’ of the combination of elements that are set forth in the present invention is not a fact. It is merely an assumption. . . . Such a test also fails to meet the Supreme Court’s ‘rational underpinning’ requirement to support the legal conclusion of obviousness.” (Id. at 8–9.) We agree with Appellant that the Examiner has not established that the cited references would have led a person of ordinary skill in the art to combine their respective teachings. “In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial burden of presenting a prima facie case of obviousness.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993). “Obviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination.” Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011). “Rather, obviousness requires the additional showing that a person of ordinary skill at the time of the invention would have selected and combined those prior art elements in the normal course of research and development to yield the claimed invention.” Id. In this case, Fry discloses a “method for non-specifically amplifying RNA or DNA fragments non-specifically, i.e., without regard to fragment sequence.” (Fry 2:17–19.) Fry states that “a more specific object of the invention [is] to provide such a method which allows successful library clone formation from small quantities of RNA.” (Id. at 2:20–22.) Fry’s method includes the “obtaining,” “reverse transcribing,” and “adding” steps of claim 1 on appeal. (See id. at 4:33–62.) Appeal 2013-008548 Application 12/095,485 6 Fry’s method also includes amplifying the full-length cDNA using two amplification primers, one of which hybridizes to a 5' end of the full- length cDNA (“Primer 2” in Fry’s Fig. 1), and one of which hybridizes to at least a part of the polynucleotide tail (“Primer 1” in Fry’s Fig. 1). However, Fry’s primer that hybridizes to the polynucleotide tail does not “hybridize[] to one to ten nucleotides upstream of the 3' polynucleotide tail of the cDNA,” as required by claim 1 on appeal. Weinstein states that “there is a need to increase the specificity of detection of mRNA species in a sample to allow more accurate detection of mRNA content that is characteristic of the cell, tissue or other samples” and that a “method that produces a more specific differential display is generally useful for medical or forensic applications that require characterization of a cell or tissue sample.” (Weinstein 4:5–8, 13–16.) Weinstein discloses that its method (“restriction display-polymerase chain reaction (RD-PCR)”) “us[es] adaptor sequences that anneal to restriction enzyme recognition sites in the amplified cDNA” (id. at 4:18–21) and “primer DNA sequences [that] have at least one nucleotide at the 3' end that specifically hybridizes to a subset of cDNA molecules” (id. at 4:38–40). More specifically, Weinstein’s method involves PCR amplification of the cDNA fragments using sets of primers based on the adaptor sequences and adjacent bases. In this way, the cellular mRNA is divided into multiple portions (e.g., 196 portions) for identification of different subsets of the mRNA that are transcribed into cDNA, amplified and detected by any of a variety of well known methods. (Id. at 6:47–53.) In the embodiment shown in Weinstein’s Figure 2, “PCR is performed with primers. . . including one, two, or three specific ‘nesting’ Appeal 2013-008548 Application 12/095,485 7 bases . . . at the 3' end. These nesting bases add specificity to the differential display produced because they hybridize to a selected subset of the cDNA produced.” (Id. at 12:26–32.) Thus, Fry describes its method as one that non-specifically amplifies RNA or DNA fragments in order to allow formation of a library of clones from small quantities of RNA, while Weinstein describes its method as one that produces a display of the mRNA content that is characteristic of a particular cell or tissue for medical or forensic applications that require characterization of a cell or tissue sample. Weinstein states that its method provides more specificity by amplifying different subsets of the expressed mRNAs, those subsets being determined by one or more “nesting” bases on the PCR primers. Given the different purposes of Fry and Weinstein, the Examiner has not adequately explained why Weinstein’s suggestion of adding nesting bases to its PCR primers “to allow for amplification of specific sequences in a mRNA/cDNA pool” (Ans. 6) would have been an obvious modification of Fry’s method of non-specifically amplifying nucleic acid fragments to form a library of clones. The Examiner reasons that incorporating Weinstein’s use of specific nucleotides at the 3' end of a primer into Fry’s method would provide the “desirable, predictable result” of producing specific full-length cDNAs. (Id. at 9.) However, the Examiner does not explain why such a result would have been considered desirable by a skilled artisan in light of the full teachings of the references. Appeal 2013-008548 Application 12/095,485 8 Finally, the Examiner states that “[t]he prior art makes clear study of both pools of transcripts and specific transcripts were of interest at the time of invention.” (Id. at 10.) While this is true, the context is important to the conclusion of obviousness: Fry is interested in pools of transcripts for the purpose of constructing clone libraries, while Weinstein is interested in specific subsets of transcripts for the purpose of identifying cells or tissues based on their characteristic expression patterns. The Examiner reasons that “a skilled practitioner would have seen the benefit of adjusting the Fry method to focus on specific full-length transcripts in contrast to proceeding with amplification of the entire full- length library only to have to isolate specific transcripts from the pool when needed for study.” (Id.) This reasoning also does not persuade us that a conclusion of obviousness is supported by the evidence. The modification of Fry’s method that the Examiner proposes would not, in fact, result in amplification and cloning of “specific full-length transcripts” (id.) but would result in amplification of randomly determined subsets of the non-specific library described by Fry. That is, adding a particular nucleotide (A, for example) to the 3' end of Fry’s Primer 1 would result in amplification of transcripts that contained a complementary nucleotide (T), rather than one of the three other possible nucleotides, in that position. The result would be a library containing a randomly determined subset of Fry’s desired full library. The Examiner has not explained how such a subset library would avoid any additional cloning steps that would otherwise be required in order to further study the clones in Fry’s library. Appeal 2013-008548 Application 12/095,485 9 The Examiner has also rejected claims 6, 11, 17, 25, and 39 as obvious based on Fry and Weinstein, further combined with either Brennan or Slepnev. These rejections rely on the combination of Fry and Weinstein. (See Ans. 6–7.) We therefore reverse these rejections as well, for the reasons discussed above. SUMMARY We reverse all of the rejections on appeal. REVERSED sl Copy with citationCopy as parenthetical citation