11581800 (P.T.A.B. Aug. 8, 2016)

Ex Parte Koob et al

Patent Trial and Appeal BoardAug 8, 2016

11581800 (P.T.A.B. Aug. 8, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 111581,800 10/16/2006 Michael D. Koob 27829 7590 08/09/2016 Eugenia S. Hansen Hemingway & Hansen, LLP 1700 Pacific A venue Suite 4800 Dallas, TX 75201 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. CONFIRMATION NO. KOOB 00200 PTUS 8135 EXAMINER WILSON, MICHAEL C ART UNIT PAPER NUMBER 1632 MAILDATE DELIVERY MODE 08/09/2016 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 MICHAEL D. KOOB and YOUNG G. YOON 1 Appeal2013-005475 Application 11/581,800 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and JACQUELINE T. HARLOW, Administrative Patent Judges. HARLOW, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. Â§ 134(a) involving claims to methods for making transmitochondrial cells. We have jurisdiction under 35 U.S.C. Â§ 6(b). We AFFIRM-IN-PART. 1 According to Appellants, the real parties in interest are the named inventors, Michael D. Koob and Young G. Yoon (App. Br. 1). Appeal2013-005475 Application 11/581,800 STATEMENT OF THE CASE The present invention "discloses methods of transferring isolated mitochondrial genomes ... into mitochondria within a cell" (Spec. ,-i 4). Claims 1, 2, 4, 6, 27, 28, and 30-32 are on appeal. 2 Claim 1, the sole independent claim on appeal, is illustrative and reads as follows: 1. A method for introducing an isolated exogenous complete mitochondrial genome into a mitochondrion of a eukaryotic cell, said method comprising: introducing said isolated, exogenous complete mitochondrial genome into said eukaryotic cell using particle bombardment, wherein said cell comprises a mitochondrion having two mitochondrial membranes and no mitochondrial DNA, and wherein said introducing allows said isolated exogenous complete animal mitochondrial genome to pass through the two mitochondrial membranes, to incorporate into said eukaryotic cell mitochondrion, and to form viable mitochondrial genomes capable of replicating and being maintained through multiple rounds of cell division. 2 We observe that although the Appeal Brief variously identifies claims 1, 2, 4-6, and 27-31 or 1, 2, 4-6, and 27-32 as being rejected and on appeal (App. Br. 3), the Answer and Final Rejection identify claims 1, 2, 4, 6, 27, 28, and 30-32 as being subject to the instantly appealed rejections (Ans. 2; Final Act. 4). 2 Appeal2013-005475 Application 11/581,800 The claims stand rejected as follows: Claims 1, 2, 4, 6, 27, 28, and 30-32 stand rejected under 35 U.S.C. Â§ 103(a) as being unpatentable over Yoon,3 Fox,4 Klein 1992,5 Klein 1993,6 and Johnston. 7 Claim 6 stands rejected under 35 U.S.C. Â§ 112, second paragraph as being indefinite. I. Issue The Examiner has rejected claims 1, 2, 4, 6, 27, 28, and 30-32 under 35 U.S.C. Â§ 103(a) as being unpatentable over Yoon, Fox, Klein, and Johnston. We focus our discussion on independent claim 1. Of particular relevance to this appeal, the Examiner finds that "Yoon introduced a complete isolated genetically modified mouse mitochondrial genome into a mouse cell using electroporation" (Ans. 2). The Examiner acknowledges that ""Yoon did not teach introducing the exogenous mitochondrial genome using particle bombardment," but 3 Yoon et al., Efficient cloning and engineering of entire mitochondrial genomes in Escherichia coli and transfer into transcriptionally active mitochondria, 31 NUCLEIC ACIDS RESEARCH 1407-1415 (2003). 4 Fox et al., Plasmids can stably transform yeast mitochondria lacking endogenous mtDNA, 85 PROC. NAT'LACADEMY OF SCI. 7288-7292 (1988). 5 Klein et al., Transformation of Microbes, Plants and Animals by Particle Bombardment, 10 BIO/TECHNOLOGY 286-291 (1992) (hereinafter "Klein 1992 "). 6 Klein, et al., Particle bombardment: a universal approach for gene transfer to cells and tissues' 4 CURRENT OPINION IN BIOTECHNOLOGY 5 83- 590 (1993) (hereinafter "Klein 1993"). 7 Johnston et al., Mitochondrial Transformation in Yeast by Bombardment with Microprojectiles, 240 SCIENCE 1538-1541 (1998). 3 Appeal2013-005475 Application 11/581,800 contends that the disclosures of Fox, Klein 1992, Klein 1993, and Johnston remedy this deficiency (id. at 3--4). In particular, the Examiner finds that "Fox introduced an isolated exogenous mitochondrial gene into mitochondria of yeast cells lacking mtDNA using particle bombardment" (id. at 3), "Klein (1992 and 1993) taught particle bombardment was a universal approach to gene transfer," including "for introducing genetic material into mitochondria inside cells" (id.), and "Johnston introduced isolated exogenous mitochondrial DNA into mitochondria of yeast cells using particle bombardment (abstract) and crossed them with yeast lacking mtDNA" (id. at 4). (Id.) Based on these teachings, the Examiner concludes that it would have been obvious to those of ordinary skill in the art at the time the invention was made to introduce an isolated exogenous mitochondrial genome into a mouse cell as described by Yoon using particle bombardment described by Fox, Klein (1992 or 1993) or Johnston. Those of ordinary skill would have been motivated to replace electroporation taught by Yoon with particle bombardment because particle bombardment was known as being a technique universally applicable to microbes, plant and animal cells and was known to transform mitochondrial genomes. The issue presented is whether the combination of Yoon, Fox, Klein 1992, Klein 1993, and Johnston renders obvious claim 1. Findings of Fact FF 1. Yoon discloses an experimental approach in which we transfer circular mitochondrial genomes into E.coli, where they can be readily manipulated and modified using standard molecular techniques. Once the mtDNA genome has been engineered, we use 4 Appeal2013-005475 Application 11/581,800 electroporation to transfer it back into isolated mitochondria devoid of their own DNA and assay transcriptional activity using in organello RNA synthesis followed by R T-PCR analysis. (Yoon 1413.) FF 2. Yoon discloses that an mtDNA-less p0 LL/2 cell line was isolated (id. at 1408), and the cells were grown, harvested, and subsequently broken (id. at 1409). Yoon further discloses that the mtDNA-less mitochondria were isolated from the mtDNA-less p0 LL/2 cells, and then electroporated with cloned mouse mtDNA (id.). Yoon teaches that in organello RNA synthesis was performed (id.). FF 3. Yoon discloses that "[ n Jo practical means have yet been found to directly modify the mitochondrial genomes of vertebrate organisms" (id. at 1413). Yoon further explains that "[u]ltimately, we hope to transfer engineered mitochondrial genomes back into the mitochondria of intact, living cells in order to make both tissue culture and animal mitochondrial models, but an effective method for delivering DNA into the mitochondria inside cells is not yet available" (id.). FF 4. Fox discloses that "yeast mitochondria lacking mtDNA can be transformed by bombardment of a rho0 strain with microprojectiles carrying a mitochondrial gene, axil (8-10), on a plasmid" (Fox 7288). FF 5. Klein 1992 discloses that mitochondria "were transformed by delivering a gene that complements a specific mutation" via microprojectiles (Klein 1992, 288). FF 6. Klein 1992 discloses that "the quantity of DNA that each particle can carry into the cell" is an "[i]mportant factor[]" affecting transformation efficiency (id. at 287). 5 Appeal2013-005475 Application 11/581,800 FF 7. Klein 1993 discloses the use of particle bombardment for "the transfer of genes into organelles," including "the mitochondria of yeast" (Klein 1993, 583). FF 8. Johnston discloses that The newly developed "biolistic" (biological ballistic) process was used to deliver DNA into yeast cells to stably transform their mitochondria. A nonreverting strain, which is respiratory deficient because of a deletion in the mitochondrial oxi3 gene, was bombarded with tungsten microprojectiles coated with DNA bearing sequences that could correct the oxi3 deletion. Respiratory-competent transformants were obtained in which the introduced oxi3 DNA is integrated at the homologous site in the mitochondrial genome. (Johnston, Abstract.) Analysis We agree with Appellants that the Examiner erred in concluding that the combination of Yoon, Fox, Klein 1992, Klein 1993, and Johnston renders obvious claim 1. Central to the Examiner's obviousness rejection is the finding that Yoon discloses the introduction of a complete exogenous mouse mitochondrial genome "into a mouse cell using electroporation" (Ans. 2). But Yoon does not support such finding. Rather, Yoon discloses the introduction of a complete exogenous mouse mitochondrial genome into an isolated mitochondrion, which has been removed from the cell (FF 1-2). Moreover, Yoon explains that "an effective method for delivering DNA into the mitochondria inside cells is not yet available" (FF 3). Yoon' s observations regarding the absence of available techniques for introducing a complete mitochondrial genome into the mitochondria of intact cells is 6 Appeal2013-005475 Application 11/581,800 particularly noteworthy because Yoon, which was published in 2003, postdates each of the remaining references relied on by the Examiner. It is, therefore, unsurprising that the Examiner does not identify any disclosure by Fox, Klein 1992, Klein 1993, or Johnston to remedy this deficiency (see Ans. 2-8). Indeed, the portions of these references relied on by the Examiner teach the use of particle bombardment to introduce individual genes, not complete exogenous genomes, into eukaryotic cells (FF 4-8). Stated plainly, the Examiner has not identified any disclosure of the introduction of a complete mitochondrial genome into a mitochondrion of a eukaryotic cell, as required by claim 1. To the contrary, the cited references indicate that transformation of a complete mitochondrial genome into a eukaryotic cell was not feasible at the time of invention (FF 3, 6). We, therefore, agree with Appellants that the Examiner has not presented evidence or reasoning sufficient to support the conclusion that the combination of Yoon, Fox, Klein 1992, Klein 1993, and Johnston renders obvious claim 1. Because they depend from claim 1, the rejection of claims 2, 4, 6, 27, 28, and 30-32 is also reversed. II. Issue The Examiner has rejected claim 6 under 35 U.S.C. Â§ 112, second paragraph as being indefinite for failing to particularly point out and distinctly claim the subject matter which Appellants regard as the invention (Ans. 5). Appellants respond that claim 6 was amended "to specify that the modification does not alter 20% of the naturally occurring genome (e.g. 80% 7 Appeal2013-005475 Application 11/581,800 is still the naturally occurring genome)," and that it "adds a step to [ c ]laim l" (Reply Br. 9). The issue presented is whether claim 6 is indefinite. Findings of Fact FF 9. The Specification states that "[a] mitochondrial genome refers to the circular nucleic acid present in a mitochondrion. . . . As used herein, mitochondrial 'genome' refers to the complete mitochondrial genome (i.e., 100%) or at least 80% (e.g., at least 85%, 90%, 95%, or 99%) of a naturally occurring mitochondrial genome" (Spec. iJ 25). Analysis We agree with the Examiner that claim 6 is indefinite. In particular, we observe that neither claim 6, nor claim 1, from which it depends, provides an antecedent basis for the terms "said mitochondrial genomes" and "said isolated exogenous naturally occurring genome," as recited in claim 6. As the Specification makes clear, the term "isolated exogenous complete mitochondrial genome," recited in claim 1, refers to a genome that is "l 00%" of a naturally occurring mitochondrial genome (FF 9; see also Ans. 8). This stands in contrast to the "said mitochondrial genomes" of claim 6, which are explicitly recited as constituting "at least 80% of said isolated exogenous naturally occurring genome." The term "isolated exogenous complete mitochondrial genome" likewise does not provide an antecedent basis for the term "said isolated exogenous naturally occurring genome." 8 Appeal2013-005475 Application 11/581,800 Accordingly, because the claim 6 phrases "said mitochondrial genomes" and "said isolated exogenous naturally occurring genome" lack an antecedent basis, we affirm the indefiniteness rejection. SUMMARY We reverse the rejection of claims 1, 2, 4, 6, 27, 28, and 30-32 under 35 U.S.C. Â§ 103(a) based on Yoon, Fox, Klein 1992, Klein 1993, and Johnston. We affirm the rejection of claim 6 under 35 U.S.C. Â§ 112, second paragraph. 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. Â§ l .136(a)(l )(iv). AFFIRMED-IN-PART 9