Ex Parte LagaDownload PDFPatent Trials and Appeals BoardApr 17, 201913994173 - (D) (P.T.A.B. Apr. 17, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/994, 173 07/08/2013 Benjamin Laga 4372 7590 04/19/2019 ARENT FOX LLP 1717 K Street, NW WASHINGTON, DC 20006-5344 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. 039621.00412 8121 EXAMINER UYENO, STEPHEN G ART UNIT PAPER NUMBER 1662 NOTIFICATION DATE DELIVERY MODE 04/19/2019 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): patentdocket@arentfox.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte BENJAMIN LAGA 1 Appeal2018-05842 Application 13/994, 173 Technology Center 1600 Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and ROBERT A. POLLOCK, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to Brassica napus comprising two non-naturally occurring full knock-out ale genes. The Examiner rejected the claims under 35 U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134, Appellant appeals the Examiner's determination that the claims are unpatentable. We have jurisdiction for the appeal under 35 U.S.C. § 6(b). The Examiner's decision is reversed. 1 The Appeal Brief ("Appeal Br." entered Nov. 10, 2017) lists Bayer CropScience NV, as the real party in interest. Appeal Br. 1. Appeal2018-05842 Application 13/994, 173 STATEMENT OF THE CASE Claims 5, 7, 8, 15-17, and 20 stand rejected by the Examiner under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Hua et al. (Planta, 2009, 230: 493-505) ("Hua"). Claim 5, the only independent claim on appeal, is reproduced below: 5. A Brassiea napus plant, or a cell, part, seed or progeny thereof, comprising two non[-]naturally occurring full knock- out ale genes, wherein one non-naturally occurring full knock- out ale gene is a mutated version of the native ALC gene comprising at least 98% sequence identity to SEQ ID NO: 3 or encoding an amino acid sequence comprising at least 98% sequence identity to SEQ ID NO: 9; and wherein one non- naturally occurring full knock-out ale gene is a mutated version of the native ALC gene comprising at least 98% sequence identity to SEQ ID NO: 4 or encoding an amino acid sequence comprising at least 98% sequence identity to SEQ ID NO: 10; wherein said full knock-out mutant ale gene comprises a mutated DNA region consisting of one or more inserted, deleted or substituted nucleotides compared to a corresponding wild-type DNA region in the functional ALC gene and wherein said mutant ale allele does not encode a functional ALC protein, wherein the podshatter resistance is increased as compared to the the [sic] podshatter resistance of a corresponding plant not comprising full knock-out ale genes. CLAIM 5 Claim 5 is directed to "Brassiea napus plant, or a cell, part, seed or progeny thereof' which comprises two non-naturally occurring full knock- out ale genes. ALC, or the ALCATRAZ gene, codes for the ale protein that "plays a role in cell separation during fruit dehiscence by promoting the differentiation of a cell layer that is the site of separation ... within the 2 Appeal2018-05842 Application 13/994, 173 dehiscence zone." Spec. 4: 12-17. "Fruit dehiscence" is the process in which the seeds are released from siliques or pods from Brassiea plants. Spec. 1:25. A "knock-out" ALC gene is defined in the Specification as a gene or allele "which does not complement the Brassiea napus double mutant POSH131/ POSH134 as described in this application, or which, when present in a Brassiea napus genetic background comprising no other functional ALC genes or no other functional ALC alleles, gives rise to a podshatter resistant phenotype." Spec. 13:6-10. In other words, the activity of the ALC gene is abolished or silenced when the gene's function is "knocked out" and no functional ale protein is produced. The claim recites that "the podshatter resistance is increased as compared to the ... podshatter resistance of corresponding plant not comprising full knock-out ale genes." "Podshatter" is the shedding of seed by mature pods before or during crop harvest. Spec. 1: 32-33. The Specification explains that premature podshatter results in reduced seed recovery "which represents a problem in crops that are grown primarily for the seeds, such as oil-producing Brassiea plants." Spec. 1 :34--35. The Specification defines the recited increase in "podshatter resistance" to mean "a decreased seed shatter tendency and/or a delay in the timing of seed shattering, in particular until after harvest, of Brassiea plants." Spec. 7:20-23. The Specification discloses that by knocking out the two ALCATRAZ genes from Brassiea napus, BnaC.ALC.a and BnaA.ALC.a, "pod shatter resistance can be increased and seed shattering can be reduced, or seed 3 Appeal2018-05842 Application 13/994, 173 shattering can be delayed until after harvest," resulting in an increase in seed yield. Spec. 5:33---6:7; 8: 12-16. BnaA.ALC.a disclosed in Hua has 98.8% sequence identity with the claimed SEQ ID NO: 3 (ALC-GR3) (corresponding to protein sequence of SEQ ID NO: 10). Appeal Br. 6. BnaC.ALC.a disclosed in Hua has 98.8% sequence identity with the claimed SEQ ID NO: 4 (ALC-GR4) ( corresponding to protein sequence of SEQ ID NO: 10). Appeal Br. 6. REJECTION The Examiner found that Hua describes two Alcatraz (ALC) genes obtained from a Brassica napus plant that have at least 98% identity to the claimed SEQ ID NOs: 3 (BnaA.ALC.a) and 4 (BnaC.ALC.a). Ans. 4. While BnaC.ALC.a is detected in the silique of Brassica, BnaA.ALC.a is not. Hua, Abstract. Hua teaches: We cloned two homologous ALC loci, namely BnaC.ALC.a and BnaA.ALC.a in B. napus. Driven by the 35S promoter, both the loci complemented to the ale mutation of Arabidopsis thaliana, yet only the expression of BnaC.ALC.a was detectable in the siliques of B. napus. Hua, Abstract. The Examiner acknowledges that BnaA.ALC.a is not detected in siliques, but found that Hua teaches that "introduction of the gene into a plant that lacked a functional copy of said gene was sufficient to confer the pod shattering phenotype characterized by silique dehiscence in Arabidopsis siliques." Ans. 4. Based on this evidence, the Examiner concluded: BnaA.ALC.a and BnaC.ALC.a are both independently sufficient for conferring the pod shattering phenotype into a mutant background. Given this restoration of an undesirable pod shattering phenotype, one of ordinary skill in the art would have 4 Appeal2018-05842 Application 13/994, 173 understood that, despite its undetected presence in siliques, expression of BnaA.ALC. a results in a functional protein that leads to pod shattering (silique dehiscence ). Ans. 5. The Examiner further found that because "both copies of an ALCATRAZ gene are capable of complementing a mutant ( as set forth in Figure 4)," the skilled worker would have been "motivated to silence both copies ... because changes in gene expression can lead to other genetic changes, including changes in tissue-specific expression." Ans. 7. The Examiner concluded that "one of ordinary skill in the art would have found it obvious to eliminate both genes of Hua to yield a Brassica napus plant with increased pod shattering resistance." Id. DISCUSSION The rejection is based on the Examiner's determination that it would have been obvious to knock out both BnaA.ALC.a and BnaC.ALC.a in Brassica napus to produce a plant with increased podshatter resistance. Appellant argues that the Examiner erred because only BnaC.ALC. a was found by Hua to have been expressed in siliques of Brassica napus, and not BnaA.ALC.a. Appeal Br. 6. Thus, according to Appellant's argument, BnaA.ALC. a would not have been expected to confer podshatter resistance when knocked out because it is not expressed in the silique ( seed pod) which comprises the dehiscence zone where seed separations occurs (Spec. 4: 12- 17). In contrast to this expectation, Appellant points to the following statement in the Specification, and supportive evidence therein, that knocking out both genes increased podshatter resistance: It was ... found that Brassica napus plants, which are homozygous for a non-naturally occurring knockout ale allele 5 Appeal2018-05842 Application 13/994, 173 in only one of the two ALC genes ALC_GR3 or ALC_ GR4, do not show a significant increase in pod shatter resistance compared to Brassiea napus plants not comprising these non- naturally occurring full knock-out ALC alleles, while in Brassiea napus plants, which are homozygous for a full knockout ale allele in both ALC genes ALC_GR3 and ALC_GR4, pod shatter resistance is significantly increased, and the level of pod shatter resistance is low enough maintain an agronomically relevant threshability. Spec. 19:15-25. The Examiner responded to Appellant's argument in two ways. First, the Examiner cited experiments described Hua in which BnaA.ALC. a, when expressed in an Arabidopsis ale mutant which was indehiscent, restored dehiscence, i.e., release of seeds from siliques or pods. Ans. 4--5. Hua 497, Fig. 4. Second, the Examiner pointed to discussion in Hua about gene expression that led the Examiner to conclude that "the mere fact that BnaA.ALC. a is not detected in siliques does not mean that elimination of BnaC.ALC.a, which is detected in siliques when both BnaA and BnaC are present, will not change the expression pattern of BnaA.ALC. a to be detectable in siliques." Ans. 6. The Examiner stated that "Hua recognizes that the mere fact that it is not detected in siliques by their experiment does not mean that epigenetic changes (i.e. promoter methylation to eliminate gene expression) or other genetic changes including changes to the gene expression pattern ( e.g. tissue location). See page 499, right column." Ans. 6-7. Neither of these arguments establish by a preponderance of the evidence that claim 5 would have been obvious to one of ordinary skill in the art in view of Hua. 6 Appeal2018-05842 Application 13/994, 173 As discussed by Appellant, the experiments in which BnaA.ALC. a restored dehiscence in the Arabidopsis ale mutant used a constitutive 35S promoter which was used to drive expression of the gene in the Arabidopsis mutant. Reply Br. 3; Hua 495 ("Complementation experiments"), 497 (paragraph spanning columns 1-2); 499 ("Driven by the 35S promoter, BnaC.ALC.a and BnaA.ALC.a complemented to the Arabidopsis ale mutation.). The experiment, thus, demonstrated that the proteins expressed by BnaC.ALC.a and BnaA.ALC.a had similar activities. But the BnaC.ALC.a promoter was not used to direct expression of the BnaA.ALC.a gene. Instead, a different promoter was used to drive its expression in a plant part where it is not normally expressed. The experiment therefore does not provide evidence that knocking out the gene would increase podshatter resistance because normally BnaA.ALC.a is not expressed at detectable levels in the silique where dehiscence takes place. The Examiner's second line of reasoning is based on discussion in Hua about gene expression and gene/genome duplication. The Examiner cited the following statement in Hua in support of the rejection: Chen et al. (1989) also reported the expression divergence between the homologous genes from B. eampestris and B. oleraeea in the resynthesized line Sv02372 (B. napus), in which the gene encoding glucosephosphate from B. eampestris was switched off while that of B. oleraeea was expressed. The Examiner interpreted this statement to mean that changes in gene expression of one gene could affect the expression of another gene. Ans. 6. The Examiner did not explain how this result would have lead one of ordinary skill in the art to reasonably expect that knocking out BnaA.ALC.a whose expression in not normally detected in silique would lead to a significant increase in pod shatter resistance when expressed in combination 7 Appeal2018-05842 Application 13/994, 173 with BnaC.ALC.a as compared to knocking out either gene, alone. Spec. 19: 15-25. The Examiner further stated: Hua also acknowledges that owing to the allopolyploid genome of B. napus, drastic modifications such as deletion, translocation, transposition, and epigenetic changes might take place, resulting in novel epistatic interactions, endosperm effects, and many other genetic changes including changes of the gene expression pattern .... See page 499, right column. Ans. 6. The statements referred to by the Examiner on page 499 of Hua are in reference to the evolution of the polyploidy genome: The divergence in expression pattern among homologous loci in allopolyploids provides an inexhaustible reservoir for generating genetic variation and phenotypic diversification, which facilitates polyploid evolution (Lynch and Force 2000). The selective modification of regulatory networks controlling gene expression is thought to enable the colonization of new ecological conditions and respond to developmental programs and environmental cues. Hua 500. The Examiner did not explain how evolutionary changes in the genome as a result of gene and genome duplication would have motivated one of ordinary skill in the art to knock out the BnaA.ALC. a gene in a human directed experiment and to reasonably expect it to result in increased podshatter in combination with the knocked out BnaC.ALC.a gene. The Examiner states that "Hua recognizes that the mere fact that it is not detected in siliques by their experiment does not mean that epigenetic changes (i.e. promoter methylation to eliminate gene expression) or other genetic changes including changes to the gene expression pattern ( e.g. tissue location)," but does not identify where in Hua such "recognition" is made. 8 Appeal2018-05842 Application 13/994, 173 Ans. 6-7. It appears that the Examiner is referring to Hua's discussion of "the formation of the B. napus allopolyploid genome" during evolution (Hua 499). The Examiner did not explain the relevance of this statement to an experiment in which two ALC genes were silenced and how changes in evolution would have made it predictable that silencing both genes would lead to increased pod shatter resistance as required by claim 5. To establish obviousness under 35 U.S.C. § 103, one of ordinary skill in the art must have a reasonable expectation that the prior art, when combined, would succeed in making the claimed invention. "Conclusive proof of efficacy is not necessary to show obviousness." Accorda Therapeutics, Inc. v. Roxane Laboratories, Inc., 903 F.3d 1310, 1333 (Fed. Cir. 2018) (quoting from Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014). "'Obviousness does not require absolute predictability of success ... all that is required is a reasonable expectation of success.' [citing In re O'Farrell, 853 F.2d 894, 903---04 (Fed. Cir. 1988)]." In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009). However, "the evidentiary basis for an inference of reasonable expectation of success may be inadequate." Accorda, 903 F.3d at 1333-34. 9 Appeal2018-05842 Application 13/994, 173 In this case, the Examiner has not provided an adequate evidentiary basis to establish a reason to have knocked out the BnaA.ALC.a gene, whose expression was not detected in the Brassica silique, or a reasonable expectation that knocking out both the BnaA.ALC. a gene and the BnaC.ALC.a gene would result in increased podshatter resistance. Consequently, the obviousness rejection of claim 5, and dependent claims 7, 8, 15-17, and 20, is reversed. REVERSED 10 Copy with citationCopy as parenthetical citation