Luis Rafael. Herrera-Estrella et al.Download PDFPatent Trials and Appeals BoardAug 14, 201913560680 - (D) (P.T.A.B. Aug. 14, 2019) 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. 13/560,680 07/27/2012 Luis Rafael Herrera-Estrella LIP 301USCON2 8986 23581 7590 08/14/2019 KOLISCH HARTWELL, P.C. 520 SW YAMHILL STREET, SUITE 300 PORTLAND, OR 97204 EXAMINER BURAN, ASHLEY KATE ART UNIT PAPER NUMBER 1662 NOTIFICATION DATE DELIVERY MODE 08/14/2019 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): docketing@khpatent.com veronica@khpatent.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte LUIS RAFAEL HERRERA-ESTRELLA, DAMAR LIZBETH LÓPEZ-ARREDONDO, and ALFREDO HERIBERTO HERRERA- ESTRELLA1 ____________ Appeal 2019-002835 Application 13/560,680 Technology Center 1600 ____________ Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and MICHAEL A. VALEK, Administrative Patent Judges. VALEK, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellants submit this appeal under 35 U.S.C. § 134(a) involving claims to a method of propagating a transgenic fungus. Examiner rejected claims 18, 20, and 26–37 as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellants identify the real party in interest as Centro de lnvestigación y de Estudios Avanzados del lnstituto Politécnico Nacional (CINVESTAV). App. Br. 4. Appeal 2019-002835 Application 13/560,680 2 STATEMENT OF THE CASE Claims 18, 20, and 26–37 are on appeal and can be found in the Claims Appendix of the Appeal Brief. App. Br. 35–37. Claim 18 is the only independent claim and representative of the claims on appeal. It reads as follows: 18. A method of propagating a fungus, comprising: obtaining a fungus transgenically adapted to express a phosphite dehydrogenase enzyme that catalyzes oxidation of phosphite to phosphate; and growing the fungus in a medium containing phosphite as a source of phosphorus. App. Br. 35 (Claims Appendix). Appellants seek review of Examiner’s rejection of claims 18, 20, and 26–37 under 35 U.S.C. § 103 as unpatentable over Metcalf,2 in view of Herrera-Estrella,3 Wong,4 Metcalf 98,5 and McDonald.6 App. Br. 9. Because Appellants do not argue the dependent claims 20 and 26–37 2 William W. Metcalf et al., US 2004/0091985 A1; published May 13, 2004 (“Metcalf”). 3 Alfredo H. Herrera-Estrella et al., US 5,922,603; issued July 13, 1999 (“Herrera-Estrella”). 4 Mee-Hua Wong, Phosphite Induces Morphological and Molecular Changes in Phytophthora Species (2006) (Masters thesis, Murdoch University) (“Wong”). 5 William W. Metcalf et al., Molecular Genetic Analysis of Phosphite and Hypophosphite Oxidation by Pseudomanas Stutzeri WM88, J. Bacteriology, Vol. 180, 5547–5558 (1998) (“Metcalf 98”). 6 Allison E. McDonald et al., Phosphite (Phosphorous Acid): Its Relevance in the Environment and Agriculutre and Influence on Plant Phosphate Starvation Response, J. Plant Nutrition, Vol. 24, 1505-1519 (2001) (“McDonald”). Appeal 2019-002835 Application 13/560,680 3 separately, we focus our analysis on independent claim 18 and Appellants’ other claims stand or fall with claim 18. 37 C.F.R. § 41.37 (c)(1)(iv). The issue is: Has Examiner established a prima facie case of obviousness, and if so have Appellants provided evidence of secondary considerations that, upon reweighing the entire merits of the case, demonstrates Examiner’s determination of obviousness is not supported by the preponderance of the evidence of record? Findings of Fact FF1. Metcalf teaches the amino acid sequence for a phosphite dehydrogenase enzyme designated PtxD, which “was cloned from Pseudomonas and also found in other bacteria.”7 Metcalf Abst. According to Metcalf, PtxD catalyzes the oxidation of phosphite to phosphate. Id. Abst., ¶ 65. Metcalf further teaches E. coli can be transformed “by use of a recombinant system” to overproduce PtxD and then grown on a media with phosphite as the sole source of phosphorus. Metcalf ¶¶ 65, 68, ¶¶ 135–136. FF2. Herrera-Estrella teaches methods for transforming a fungus, Trichoderma spp., to express the proteinase PrB1 in order to improve its “capacity as biological control agents for phytopathogenic fungi and nematodes.” Herrera-Estrella Abst. In particular, Herrera-Estrella teaches the cotransformation of Trichoderma cells with a first vector comprising the PrB1 gene and a second vector comprising a selectable maker that codes for resistance to antibiotics, an herbicide, or a fungicide. Id. at col. 4, l. 61– col. 5, l. 10; col. 11, ll. 21–52. The selectable marker allows for the selection of 7 Examiner determines that the SEQ IDs taught in Metcalf share “100% identity” with SEQ ID NO:1 of Appellants’ Specification. Non-Final Act. 4. Appellants do not challenge that finding on appeal. Appeal 2019-002835 Application 13/560,680 4 transformed cells by means of the trait, e.g., resistance to a particular antibiotic or fungicide, conferred by the selectable marker. See id.; see also id. at col. 6, ll. 51–60 (describing transformation of a Trichoderma strain with a plasmid that “contains all of the information that is necessary for the expression of the gene prb1” and a second plasmid that “contains the elements that are necessary for selecting the transgenic strains by means of their resistance to the antibiotic hygromycin B”). FF3. Wong teaches that “[p]hosphite is currently an effective chemical to control Phytophthora species.” Wong 20. While acknowledging that Phytophthora “are not true fungi,” Wong teaches that “they share many characteristics with the true fungi such as an absorptive mode of nutrition, growth by polarized hyphal extension and reproduction involving the formation of spores.” Id. at 2. Wong describes experiments in which five species of Phytophthora were grown in “a low phosphate defined medium” and exposed to various concentrations of phosphite. Id. at Abst. Wong reports that these Phytophthora showed decreased mycelial growth and “[s]welling of hyphae with stunted side-branches and shrinking of cytoplasm from hyphal tips and hyphal walls.” Id. According to Wong, “[p]hosphite also retarded the development and caused distortion and lysis of chlamydospores, sporangia and zoospores.” Id. FF4. Metcalf 98 teaches that because “[a]ll organisms require P [i.e., phosphorus] in its most-oxidized form, phosphate, for growth . . . it is possible to select for organisms capable of oxidizing reduced P compounds to phosphate.” Metcalf 98 5550. According to Metcalf 98, “in media containing reduced P compounds,” such as phosphite, “as the sole P source, Appeal 2019-002835 Application 13/560,680 5 only those organisms capable of oxidizing these reduced compounds to phosphate are able to grow.” Id. FF5. McDonald teaches that phosphite is “widely marketed . . . as an agricultural fungicide” and that it is “an effective control agent for a number of crop diseases caused by various species of pathogenic pseudo fungi belonging to the genus Phytophthora.” McDonald Abst.; see also id. at 1516 (teaching phosphite is “an effective fungicide”). McDonald further teaches that Saccharomyces cerevisiae, i.e., a yeast, “[l]ike plants . . . is clearly unable to substitute the P in [phosphite] for the P in [phosphate]” and that phosphate deprived “plants and yeast that have been treated with [phosphite] suffer far greater deleterious consequences of [phosphate] starvation as compared to those that had not been treated with [phosphite].” Id. at 1514. Analysis Examiner determines that Herrera-Estrella “teaches transforming Trichoderma species with a selectable marker that provides fungicide tolerance” and the other cited references teach that fungi “do not naturally metabolize phosphite . . . and thus . . . phosphite is an effective selectable marker for transgenic fungi.” Non-Final Act. 6. Accordingly, Examiner finds that it would be obvious to use the PtxD gene taught in Metcalf “as a selectable marker gene” to transform Trichoderma, according to the methods taught in Herrera-Estrella, in order to “obtain successfully transformed fungal species.” Id. at 6–7. Appellants contend Examiner has not made out a prima facie case of obviousness because none of the cited prior art teaches “that fungi cannot grow on phosphite as a phosphorous source.” App. Br. 12. According to Appellants, Wong and McDonald relate only “to Phytophthora species, Appeal 2019-002835 Application 13/560,680 6 which are water molds (Oomycetes), not true fungi.” Id. at 18. Thus, Appellants urge, “there would have been no motivation for a skilled person to obtain ‘a fungus transgenically adapted to express a phosphite dehydrogenase enzyme that catalyzes oxidation of phosphite to phosphate,’ as recited in claim 18.” Id. at 18–19. Appellants additionally argue that secondary considerations, including that the claimed invention unexpectedly allows the use of phosphite as both a “fertilizer and contaminant suppressant” and has garnered significant “professional and commercial interest,” demonstrate that claim 18 is non-obvious. See id. at 29–33 (relying on Declaration of Luis Rafael Herrera-Estrella dated July 25, 2017 (“Herrera-Estrella Decl.”)). We are not persuaded by Appellants’ arguments and agree with Examiner’s statement of the rejection and responses to Appellants’ arguments in both the Answer and Non-Final Action, which we adopt and incorporate by reference. In addition, we address Appellants’ arguments in turn below. We agree that Examiner has met the burden to establish a prima facie showing of obviousness. The prior art teaches that PtxD can be used as a selectable marker by transforming organisms and then growing them in an environment where phosphite is the sole phosphorus source. See FF1; FF4. McDonald teaches that both “pseudo fungi” like Phytophthora and yeast (i.e., fungi) cannot effectively use phosphite as their sole phosphorus source and that phosphite is a known fungicide. FF5. Thus, the record supports Examiner’s finding that a skilled artisan would be motivated to use the PtxD gene as a selectable marker (i.e., one that codes for resistance to a fungicide) Appeal 2019-002835 Application 13/560,680 7 in Herrera-Estrella’s method for transforming and selecting transgenic Trichoderma fungi. FF2; Id. at 6–7. We are not persuaded by Appellants’ argument that the cited prior art fails to teach that fungi cannot utilize phosphite as a phosphorus source. See App. Br. 12–19. Both Wong and McDonald teach that Phytophthora cannot utilize phosphite and describe Phytophthora as “pseudo fungi” that share many characteristics with fungi. FF3; FF5. In addition, we agree with Examiner that McDonald also teaches that “true-fungi (exemplified by Saccharomyces cerevisiae) have a similar response[] to phosphite as plants, and it was known (and also explicitly taught by McDonald) that plants cannot metabolize phosphite.” Ans. 15; see also FF5. Accordingly, the record supports Examiner’s finding that a skilled artisan would reasonably expect that the PtxD gene could be successfully used as a selectable marker for transgenic fungi because only fungi with that gene would exhibit sufficient resistance to phosphite to be grown in an environment where phosphite is the sole source of phosphorus. See Par Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1198 (Fed. Cir. 2014) (citation omitted) (“[T]he reasonable expectation of success requirement for obviousness does not necessitate an absolute certainty for success.”). We are also unpersuaded by Appellants’ objective indicia evidence, which Appellants contend demonstrates that the claimed subject matter is nonobvious. Appellants contend that the “use of phosphite as fertilizer and contaminant suppressant is an unexpected product of modifying a fungus to allow it to use phosphite instead of phosphate as a phosphorus source” as recited in claim 18. See App. Br. 29–32. We, however, agree with Examiner’s determination that a skilled artisan would expect such results Appeal 2019-002835 Application 13/560,680 8 from the prior art. See Non-Final Act. 10–13. Metcalf teaches that an organism can be transformed with the PtxD gene, thereby allowing it to be grown in a medium containing phosphite as the sole phosphorus source. FF1. Thus, it would be expected that phosphite could be used as a fertilizer on fungi transformed to express PtxD. In addition, McDonald teaches that both plants and fungi cannot effectively metabolize phosphite and that phosphite exacerbates the deleterious effects of phosphate starvation. FF5. Thus, a skilled artisan would likewise expect phosphite to suppress contaminants, e.g., other untransformed fungi and weeds, in fungi transformed to express PtxD, particularly in a low-phosphate environment. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.”); In re Skoner, 517 F.2d 947, 950 (CCPA 1975) (“Expected beneficial results are evidence of obviousness of a claimed invention.”). We are also unpersuaded by Appellants’ arguments pertaining to commercial success and industry praise. See App. Br. 33. As we understand the evidence in and attached to the Herrera-Estrella Declaration,8 the alleged commercial interest and industry praise relates to engineering crops so that such crops (not fungi) can be fertilized by phosphite as opposed phosphate. Appellants have not clearly established a nexus between that evidence and the “method of propagating a fungus” in claim 18. See In re GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995) (citation omitted) (“For objective evidence 8 Our review is limited by the fact that some of the exhibits attached to the Herrera-Estrella Declaration are not in English. See Herrera-Estrella Decl. Exs. B and D. Appellants have not provided translations of those exhibits. Appeal 2019-002835 Application 13/560,680 9 to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.”). Even if Appellants had established a sufficient nexus between their objective indicia evidence and claim 18, that claim9 is broadly directed to the propagation of any fungus species and does not require the use of the transformed fungi to support phosphite metabolism in crops. Indeed, claim 18 encompasses the use of the PtxD gene purely as a selectable marker in laboratory research to select for fungi transformed to express another protein of interest (as taught in Herrera-Estrella). Thus, Appellants’ evidence pertaining to a need for alternatives to phosphate fertilizers as well as the alleged “professional and commercial interest” that Appellants’ research has garnered is not reasonably commensurate with the broader scope of claim 18. See In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (Evidence of unexpected results must also be “commensurate in scope with the degree of protection sought by the claim[s]” on appeal to demonstrate non-obviousness). Given these deficiencies and reweighing “the entire merits of the matter” in light of Appellants’ unexpected results evidence, we determine that Appellants’ evidence is insufficient to overcome Examiner’s prima facie showing of obviousness. See In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir. 1986). Accordingly, Examiner’s rejection of claim 18 is supported by the preponderance of the evidence. As noted above, Appellants do not argue 9 As explained above, Appellants have not argued any of their other claims separately on appeal. Thus, all of the claims presently before us stand or fall with the validity of the broadest claim, independent claim 18. See 37 C.F.R. § 41.37 (c)(1)(iv). Appeal 2019-002835 Application 13/560,680 10 any of the other claims separately from claim 18. Thus, we affirm Examiner’s rejection in full. SUMMARY We affirm the rejection of claims 18, 20, and 26–37 under 35 U.S.C. § 103 over Metcalf, Herrera-Estrella, Wong, Metcalf 98, and McDonald. 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 Copy with citationCopy as parenthetical citation