Ex Parte ReedDownload PDFPatent Trial and Appeal BoardJan 31, 201411841380 (P.T.A.B. Jan. 31, 2014) 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. 11/841,380 08/20/2007 Thomas D. Reed 2584.0260002/RWE/GER 1943 80011 7590 01/31/2014 Sterne, Kessler, Goldstein & Fox P.L.L.C. 1100 New York Avene N.W. Washington, DC 20005 EXAMINER KETTER, JAMES S ART UNIT PAPER NUMBER 1636 MAIL DATE DELIVERY MODE 01/31/2014 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 THOMAS D. REED __________ Appeal 2012-007427 Application 11/841,380 Technology Center 1600 __________ Before DONALD E. ADAMS, LORA M. GREEN, and ERICA A. FRANKLIN, Administrative Patent Judges. FRANKLIN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134(a) involving claims to a method of preparing one or more transgenes. The Patent Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellant identifies the Real Party in Interest as Intrexon Corporation. (See App. Br. 3.) Appeal 2012-007427 Application 11/841,380 2 STATEMENT OF THE CASE The invention “provides a method that incorporates multiple DNA fragments, also known as both ‘inserts’ or ‘modules’, such as one each of a Promoter, Expression, and 3’ Regulatory nucleotide sequence, into a cloning vector plasmid in a single step, rather than having to introduce each insert in a sequential manner.” (Spec. [0029].) Claims 19-33 are on appeal. Claim 19 is representative and reads as follows: 19. A method of preparing one or more transgenes comprising: (a) providing a cloning vector comprising at least a first and a second docking point, wherein said first and said second docking points each comprise a nucleotide sequence that is recognized by at least a first and a second rare restriction enzyme, respectively, and wherein said first and said second rare restriction enzyme are different from each other; (b) digesting said cloning vector using said first and said second rare restriction enzyme to obtain a digested vector having a 5’ end and a 3’ end; (c) providing at least a first and a second polynucleotide insert wherein each of said first and second polynucleotide inserts comprises a 5’ insert end, a nucleotide sequence of interest and a 3’ insert end; (d) placing said first polynucleotide insert and said second polynucleotide inserts and said digested vector together into an appropriate reaction mixture to allow simultaneous annealing and ligating of said inserts and said digested vector, thereby obtaining an insert bearing vector, wherein said first polynucleotide insert and said second polynucleotide insert and said digested vector anneal and ligate with each other in a predetermined order and orientation such that said first docking point of said cloning vector is re-formed between said 5’ end of said first polynucleotide insert and said 3’ end of said digested vector, and said second docking point of said cloning vector is re-formed between said 3’ insert end of said second insert and said 5’ end of said digested vector, wherein at least one additional docking point is formed between the re-formed first and re-formed second docking points, and wherein each additional docking point comprises a nucleotide sequence that is recognized by an additional rare restriction enzyme that is different from said first rare and said second rare restriction enzymes. Appeal 2012-007427 Application 11/841,380 3 The Examiner rejected claims 19-33 under 35 U.S.C. § 103(a) as unpatentable over Sykes,2 in view of Lapize-Gauthey,3 Gage,4 Parrot5 and Botstein.6 7 OBVIOUSNESS The Examiner’s findings and conclusions are set forth in the Answer. (See Ans. 5-8.) Appellant contends that inadequate reasons have been provided why one of ordinary skill in the art would have combined the cited art in an effort to obtain the claimed methods, which provide for simultaneous transfer of at least two nucleotide sequences into a cloning vector plasmid comprising rare restriction endonucleases to form a transgene. (App. Br. 15.) Appellant asserts that Sykes discloses (a) a sequential ligation of separate nucleotide sequences and not a simultaneous ligation, and (b) that the “trimolecular reaction” is an annealing reaction in which a promoter, luciferase sequence, and a terminator are annealed to one another, but are not ligated into a cloning vector plasmid. (Id. at 15-16.) Appellant asserts that “the trimolecular ligations in Botstein do not utilize a cloning vector plasmid having first and second docking points 2 Patent Application Publication No. US 2002/0146733 A1 by Kathryn F. Sykes et al., published Oct. 10, 2002. 3 Patent Application Publication No. US 2004/0253732A1 by Christine Lapize-Gauthey et al., published Dec. 16, 2004. 4 US Patent No. 5,919,667 issued to Fred H. Gage et al., Jul. 6, 1999. 5 US Patent No. 6,096,523 issued to Wayne A. Parrott et al., Aug. 1, 2000. 6 US Patent No. 4,661,454 issued to David Botstein et al., Apr. 28, 1987. 7 The Examiner withdrew the rejection of claims 19-33 on the ground of non-statutory obviousness-type double patenting. (Ans. 4.) Appeal 2012-007427 Application 11/841,380 4 comprising at least one rare endonuclease site (greater than 6 base pairs),” but instead comprise sites having 6 base pairs each. (Id. at 16.) Appellant acknowledges that Lapize-Gauthey discloses that rare restriction sites may be used in a cloning vector. (Id. at 16-17.) Appellants assert, however, that Lapize-Gauthey “fails to disclose that rare endonuclease sites are engineered into the cloning vector plasmid and in the ends of nucleotide sequences to be inserted in the cloning vector plasmid in such a way that when ligation occurs, the inserted nucleotide sequences are simultaneously ligated into the cloning vector plasmid.” (Id. at 17.) Appellant asserts that while Gage relates to modular assembly of retroviral vectors, the reference teaches sequential transfer of sequences into a cloning vector plasmid and further “fails to disclose that rare endonuclease sites are engineered into the cloning vector plasmid and in the ends of nucleotide sequences to be inserted in the cloning vector plasmid in such a way that when ligation occurs, the inserted nucleotide sequences are simultaneously ligated into the cloning vector plasmid.” (Id.) Regarding Parrott, Appellant acknowledges that Parrott discloses the use of shuttle vectors, a docking vector, and rare restriction sites in a cloning vector. (Id.) Appellants asserts, however, that “Parrott fails to disclose that rare endonuclease sites are engineered into the cloning vector plasmid and in the ends of nucleotide sequences to be inserted in the cloning vector plasmid in such a way that when ligation occurs, the inserted nucleotide sequences are simultaneously ligated into the docking vector in a predetermined orientation.” (Id. at 17-18.) Appellants assert that Parrott disclosed that “DNA segments are combined . . . sequentially into a docking vector” and Appeal 2012-007427 Application 11/841,380 5 that “various sequences are inserted one at a time (in separate ligation reactions) into a plasmid.” (Id. at 18.) Further, Appellant assert that even if the cited art was combined, such a combination “would have provided, at best, a vector [wherein] . . . DNA sequences of interest [are added,] one at a time, not more than one sequence simultaneously.” (Id. at 19.) Additionally, Appellant asserts that “the combination of Parrott with the other cited art in an attempt to obtain the claimed methods would have cause Parrot[t] not to have worked for its intended purpose.” (Id.) Appellant also assert that “the Examiner impermissibly relied on Appellant’s disclosure to attempt to establish a prima facie case of obviousness.” (Id. at 22.) After considering all of the evidence and arguments, we conclude that the record supports a conclusion of prima facie obviousness. While we agree with Appellant that differences exist between the claimed invention and each of the cited references individually, these differences do not establish that the claimed invention would not have been obvious to a person of ordinary skill in the art at the time the invention was made over the combined prior art. In particular, as the Examiner found (Ans. 6) and as Appellant has acknowledged (App. Br. 16), Botstein provides evidence that trimolecular ligation reactions, i.e., ligation of DNA fragments into a vector plasmid to obtain an insert bearing vector, were known and used at the time of the invention. Appellants attack Botstein by asserting that the disclosed trimolecular reactions utilized plasmid backbones that had been cut with restriction enzymes “for each of which the cognate recognition site is 6 base Appeal 2012-007427 Application 11/841,380 6 pairs,” and thus, did “not utilize a cloning vector plasmid having first and second docking points comprising at least one rare endonuclease site (greater than 6 base pairs), as recited in independent claim 19.” (App. Br. 16.) As the Examiner explained, however, in the combination, at least Lapize-Gauthey taught the use of rare restriction sites in a cloning vector. (See Ans. 9.) According to the Examiner, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to have simply substituted the restriction sites in Botstein for rare restriction sites, taught by Lapize-Gauthey. (Id.) This modification amounts to “the mere application of a known technique to a piece of prior art ready for the improvement,” see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007), and not improper hindsight, see In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). Thus, we find that the Examiner has established that the combined prior art method of digesting a cloning vector comprising rare restriction sites using rare restriction enzymes and subjecting polynucleotide inserts and the digested vector to a trimolecular ligation reaction allows for the simultaneous annealing and ligating of the inserts and digested vector to obtain an insert- bearing vector, as required by the claimed invention. Based on the evidence relied upon by the Examiner, at the time of Appellant’s claimed invention, a person of ordinary skill in this art would have appreciated that, for example, the 5’ end of one polynucleic acid molecule will predictably ligate to the 3’ end of another polynucleic acid molecule having a complementary overhang, wherein the ligated complementary overhangs result in the creation, or re-creation, of a sequence recognized by a rare restriction endonuclease. At the time of Appellant’s claimed invention, a person of Appeal 2012-007427 Application 11/841,380 7 ordinary skill in this art would have appreciated that a plurality of polynucleic acid molecules will predictably ligate to each other, in a simultaneous reaction, in an arrangement that is dictated by the complementarity between the overhangs at the 5’ and 3’end of each molecule. The ligation of these molecules will predictably re-create the rare endonuclease restriction site defined by the sequences used to ligate the molecules together. Therefore, a person of ordinary skill in this art would have recognized that once a plurality of polynucleic acid molecules were ligated together by complementary overhangs defining a rare restriction site that these molecules could then be separated individually or simultaneously by exposure to the rare endonuclease(s) the recognize(s) the rare endonuclease restriction site. In sum, notwithstanding Appellant’s contentions to the contrary, the subject matter encompassed by Appellant’s claimed invention is both obvious and predictably expected. We remain unpersuaded of nonobviousness by Appellant’s assertion that the docking vector in Figure 2 of Parrott could not have been used to practice the claimed methods and that including Parrott in the combination “would have caused Parrott not to have worked for its intended purpose….” (See App. Br. 19-20.) The Examiner’s combination did not require any modification of Parrott, as the reference was cited merely for its teaching of shuttle vectors in conjunction with docking vectors and use of a plurality of rare-cutting endonuclease sites. (See Ans. 7, 10-11.) Accordingly, we affirm the obviousness rejection of claim 19. Claims 20-33 have not been argued separately and, therefore, fall with claim 19. 37 C.F.R. § 41.37(c)(1)(vii). Appeal 2012-007427 Application 11/841,380 8 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 lp Copy with citationCopy as parenthetical citation