DANIEL ADER et al.Download PDFPatent Trials and Appeals BoardFeb 3, 20212020002277 (P.T.A.B. Feb. 3, 2021) 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. 13/612,929 09/13/2012 DANIEL ADER P34110US01/0024021.00175 6489 66056 7590 02/03/2021 Arnold & Porter Kaye Scholer LLP 601 Massachusetts Ave., NW Washington, DC 20001-3743 EXAMINER KOVALENKO, MYKOLA V ART UNIT PAPER NUMBER 1662 NOTIFICATION DATE DELIVERY MODE 02/03/2021 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): IPDocketing@apks.com apks-ipdocketing@apks.com ipdocketing@aporter.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte DANIEL ADER, JOHN J. FINNESSY, ZHAOLONG LI, CHRISTINA MARIE TAYLOR, JENNIFER CHOU TAYLOR, RONAK HASMUKH SHAH, NENGBING TAO, DAFU WANG, and LISA MARIE WEAVER ____________ Appeal 2020-002277 Application 13/612,9291 Technology Center 1600 ____________ Before JEFFREY N. FREDMAN, DEBORAH KATZ, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of plant control. The Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. According to Appellant, Bayer AG is the real party in interest. Appeal Br. 3. Appeal 2020-002277 Application 13/612,929 2 STATEMENT OF THE CASE The Specification discloses that “[t]he ALS (acetolactate synthase, also known as acetohydroxyacid synthase, AHAS) enzyme catalyzes the first step in the synthesis of the branched-chain amino acids (valine, leucine, and isoleucine).” Spec. 3. According to the Specification, the ALS enzyme “is the target of many ALS inhibiting herbicides that include members of the chemical families of Sulfonylureas, Imidazolinones, Triazolopyrimidines, Pyrimidinyl(thio)benzoates, and Sulfonylaminocarbonyl-triazolinones.” Id. at 3. The Specification discloses, “a method of weedy plant control comprising an external application to a weedy plant of a composition comprising a polynucleotide and a transfer agent, wherein the polynucleotide is essentially identical or essentially complementary to an ALS gene sequence, or to the RNA transcript of said ALS gene sequence.” Id. at 3. Claims 1, 2, 5–10, 14–18, 32, 33, 36, and 37 are on appeal. Claim 1 is representative and reads as follows: 1. A method of plant control comprising: topically applying a composition to a surface of a plant to modulate acetolactate synthase (ALS) gene expression in said plant, wherein said composition comprises a double stranded RNA (dsRNA) and a transfer agent, wherein said dsRNA comprises a sequence that is from 18 to about 700 nucleotides in length and is identical or complementary to at least 18 contiguous nucleotides of an RNA sequence of an ALS gene sequence, wherein said ALS gene sequence is selected from the group consisting of SEQ ID NOs: 15, 25-27, 30-33, 35, 36, 39-45, 1692-1697, 1699, 1705, 1707, 1709-1712, 1714-1721, 1727-1742, 1744-1774, and 1776-1788, wherein said transfer agent conditions the surface of said plant for permeation by said dsRNA, whereby said plant’s growth, Appeal 2020-002277 Application 13/612,929 3 development, or reproductive ability is reduced or said plant is more sensitive to an ALS inhibitor herbicide, relative to an untreated plant. Appeal Br. 63. The claims stand rejected as follows: Claims 1, 5, 8, 9, 17, 36, and 37 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Hou,2 Yao,3 Riggins,4 Prado,5 Hofgen,6 and Pratt.7 2 Hou, CN 101914540 A; published Dec. 15, 2010 (hereinafter “Hou”). Hou is a Chinese language document. All citations herein are to the Google translation of Hou that is of record in this proceeding. 3 Yao et al., US 2005/0044591 A1; published Feb. 24, 2005 (hereinafter “Yao”). 4 Riggins et al., Characterization of de novo transcriptome for waterhemp (Amaranthus tuberculatus) using GS-FLX 454 pyrosequencing and its application for studies of herbicide target-site genes, Society of Chemical Industry, Pest Management Science, Vol. 66, 1042–1052 (2010), www.soci.org, last visited Dec. 2020 (hereinafter “Riggins”). 5 Prado et al., Design and optimization of degenerated universal primers for the cloning of the plant acetolactate synthase conserved domains, 52 Weed Science 487–491 (2004) (hereinafter “Prado”). 6 Hofgen et al., Repression of Acetolactate Synthase Activity through Antisense Inhibition, 107 Plant Physiol. 469–477 (1995) (“hereinafter “Hofgen”). 7 Pratt et al., Amaranthus rudis and A. tuberculatus, One Species of Two? 128(3) Journal of the Torrey Botanical Society 282–296 (2001) (“hereinafter “Pratt”). Appeal 2020-002277 Application 13/612,929 4 Claims 2, 6, 7, 10, 14–16, 18, 32, and 33 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Hou, Yao, Riggins, Prado, Hofgen, Pratt, Nettleton-Hammond,8 and Sun.9 The Examiner also objected to claims 1, 9, and 17 due to an “informality.” Ans. 30 (explaining that these claims “were not rejected as indefinite, but objected to for an informality”). Objections or other requirements imposed by an Examiner are reviewed by way of a petition to the Director under Rule 181. 37 C.F.R. §§ 1.113, 1.181. As such, we do not address this objection herein. OBVIOUSNESS OVER HOU, YAO, RIGGINS, PRADO, HOFGEN, AND PRATT Claims 1, 9, 17, and 37 Appellant argues claim 1, 9, 17, and 37 together. Appeal Br. 21–54. We designate claim 1 as representative. In finding claim 1 obvious, the Examiner found that Hou disclosed a “method for introducing siRNA into a plant, comprising synthesizing the siRNA according to a target gene sequence, preparing a solution of said siRNA in water, and spraying that solution directly onto the surface of plant leaves.” Ans. 5. The Examiner noted that Hou taught using “a 21- nucleotide long RNA” and that the “stomatal and epidermal cell of the plants can absorb the siRNA,” which can be confirmed by flow cytometry. Id. at 8 Nettleton-Hammond et al., US Patent Publication No. 2011/0166023, (PCT Application published as WO2008/142391 on Nov. 27, 2008) (hereinafter “Nettleton-Hammond”). 9 Sun, CHARACTERIZATION OF ORGANOSILICONE SURFACTANTS AND THEIR EFFECTS ON SULFONYLUREA HERBICIDE ACTIVITY, PhD Thesis, Virginia Polytechnic Inst. and State University (1996) (hereinafter “Sun”). Appeal 2020-002277 Application 13/612,929 5 5–6. The Examiner acknowledged, however, that Hou does not disclose applying its method to target an ALS gene, as recited in claim 1. Id. at 6. The Examiner relied on Yao, Riggins, Prado, and Hofgen, as providing teachings that would have suggested targeting an ALS gene. Id. at 6–10. The Examiner found that Yao taught “using siRNAs targeting an essential plant gene . . . as herbicides.” Id. at 6. The Examiner further found that Yao taught that “siRNA may be sprayed onto plants” and that it was “well-known that siRNAs comprising 21 to 23 nucleotides can trigger silencing of genes in plants.” Id. Finally, the Examiner found that Yao teaches that “methods for designing siRNA based on an mRNA target are known in the art.” Id. at 6. The Examiner found that Prado taught “universal degenerate primers that allow cloning conserved domains of the ALS genes from weeds, and . . . using said primers to clone the nucleic acid encoding said domains from Amaranthus quitensis, and other dicot and monocot weeds, such as Lolium rigidum.” Id. The Examiner also found that Prado taught the GenBank Accession Number for an ALS gene from Amaranthus sp. having “94% sequence identity to the instant SEQ ID NO: 15 over 53% of the length of the latter, with a number of regions of at least 21 contiguous nucleotides with 100% identity.” Id. at 7. The Examiner found that Riggins taught “cloning ALS genes (along with other herbicide target genes) from Amaranthus species, including A. palmeri and A. tuberculatus.” Id. The Examiner also found that Riggins taught that “primers to amplify ALS genes were known in the art and routinely used” and that “the Amaranthus species are aggressive and agriculturally important weeds.” Id. Appeal 2020-002277 Application 13/612,929 6 The Examiner found that Hofgen taught “transforming potato plants with an expression construct comprising the potato ALS gene in antisense orientation” and that the “phenotypical changes induced” by this method were “comparable to the effects of ALS-inhibiting herbicides.” Id. at 7–8. More specifically, the Examiner found that “the growth and biomass production of the ALS antisense plants were severely impaired.” Id. at 8. Based on the combined teachings of cited art, the Examiner concluded: At the time the invention was made, it would have been prima facie obvious to one having ordinary skill in the art to modify the method of Hou in view of the teaching of You et al, Riggins et al, and Hofgen et al and use the siRNA, which is double-stranded RNA, to target the ALS of weeds, including that of Amaranthus sp. in order to reduce the expression of the endogenous ALS and to mimic the phenotype of the ALS inhibiting herbicides. It would have been prima facie obvious to use the universal primers of Prado et al to isolate the coding and the genomic sequences of the ALS gene from any weed species, including Amaranthus palmeri or Amaranthus tuberculatus taught by Riggins et al, and use said sequences to design the siRNAs targeting said gene. In addition, given the conserved nature of the ALS gene (as taught by Prado et al) including among the Amaranthus sp. (as taught by Riggins et al), it would have been obvious and predictable to use the ALS of one species, for example, that of GenBank Accession U55852, to design siRNAs targeting the ALS of another species, such as, for example the Amaranthus quitensis gene, that comprises regions of sufficient identity to the instant SEQ ID NO: 15. Id. at 8. We adopt the Examiner’s findings of fact and reasoning regarding the scope and content of the prior art and agree that claims 1, 9, 17, and 37 Appeal 2020-002277 Application 13/612,929 7 would have been obvious over the cited art. We address Appellant’s arguments below. Appellant argues that the Examiner “relies on an improper interpretation of the term transfer agent to allege that the water of Hou is a transfer agent.” Appeal Br. 28. According to Appellant, “[w]ater is not one of the seven categories of transfer agent described in the Specification.” Id. at 23. Citing the Declaration of Dr. Gregory R. Heck as support, Appellant contends that the ordinary artisan would “understand that water serves as a carrier or solvent of a transfer agent” rather than as the transfer agent itself.10 Id. (citing Heck Decl. ¶ 26). Accordingly, Appellant argues that the term “transfer agent” should be construed to exclude water. Id. We are not persuaded. Appellant relies heavily on the fact that water is not listed among the seven categories of transfer agents identified in the Specification. Appeal Br. 23. However, the portion of the Specification cited by Appellant is exemplary only, and does not limit transfer agents to the categories listed. Spec 14–15 (“Chemical agents for conditioning or transfer include (a) surfactants, (b) an organic solvent or an aqueous solution or aqueous mixtures of organic solvents, (c) oxidizing agents, (d) acids, (e) bases, (f) oils, (g) enzymes, or combinations thereof.”) (emphasis added). We do not find in this statement, or elsewhere in the record, a basis for limiting the term “transfer agent” to the seven categories of “chemical agents for . . . transfer” identified in the Specification. Id. 10 Declaration of Gregory R. Heck under 37 C.F.R. § 1.132, signed, August 30, 2018 (hereinafter “Heck Decl.”). Appeal 2020-002277 Application 13/612,929 8 Moreover, the Specification expressly defines the term “transfer agent.” It states: “As used herein, a transfer agent is an agent that, when combined with a polynucleotide in a composition that is topically applied to a target plant surface, enables the polynucleotide to enter a plant cell.” Spec. 14. This broad definition does not exclude water, so long as water “enables the polynucleotide to enter a plant cell” when “topically applied to a target plant surface.” Id. As the term “transfer agent” is expressly defined in the Specification, we are not persuaded by Dr. Heck’s testimony that “[a] person of ordinary skill in the art would not identify water as a transfer agent.” Heck Dr. ¶ 26. Accordingly, we do not construe the term “transfer agent” to exclude water. Rather, in accord with the express definition provided in the Specification, we construe “transfer agent” to mean: an agent that, when combined with a polynucleotide in a composition that is topically applied to a target plant surface, enables the polynucleotide to enter a plant cell. We note that, “during patent prosecution when claims can be amended, ambiguities should be recognized, scope and breadth of language explored, and clarification imposed.” In re Zletz, 893 F.2d 319, 321 (Fed. Cir. 1989). Having construed the term “transfer agent” not to exclude water, we agree with the Examiner that the water disclosed in Hou meets the definition of a transfer agent. More specifically, Hou teaches that water is combined with a polynucleotide and topically applied to a target plant surface. Hou Abstract (disclosing a method comprising “preparing a 1 to 10 percent solution of siRNA by using double distilled water” and “spraying the solution of siRNA on the surface of plant leaves”). Hou further teaches that “[a]ccording to the method, the RNA interference is introduced into the plants from the surface of the leaves, and stomatal cells and epidermic cells Appeal 2020-002277 Application 13/612,929 9 of the plants can absorb the siRNA.” Id. Hou thus discloses that water enables the polynucleotide to enter the plant cell. Id. Accordingly, we agree with the Examiner that the water in Hou corresponds to the claimed transfer agent. Appellant argues that Hou does not enable its teaching that a topically applied solution of water and siRNA introduces the siRNA into the plant and, more specially, that the solution is absorbed into stomatal and epidermic cells. According to Appellant, “Hou does not spray an siRNA water solution on an intact, non-viral infected plant, let alone show credible evidence that the siRNA water solution can enter such a plant via ‘stomatal cells and epidermal cells’ thereof..” Appeal Br. 30. Appellant points out that the only data in Hou “lacks any control whatsoever” and that Hou never “materialized into a granted patent.” Id. at 29. Appellant also presents the testimony of Dr. Heck, who provides reasons why the ordinary artisan: 1) would doubt Hou’s teaching that Hou was able to confirm the presence of siRNA in plan cells using flow cytometry (Heck Decl. ¶¶ 10–15); 2), would doubt the reliability of Hou’s Figure 1, which Hou describes as showing the effect of various concentrations of siRNA on plants that have Apple chlorotic leaf spot virus (“ACLSV”) (id. ¶¶ 16–19); 3) would understand that Hou’s teachings were limited to plants having ACLSV (which damages leaves allowing siRNA to penetrate) and would not extend to healthy plants (Heck Decl. ¶ 20–23); and 4) would not have a reasonable expectation of success that a solution of water and siRNA (which is a large, highly charged molecule) would be able to permeate the surface of a plant (id. ¶¶ 24–32). Appeal 2020-002277 Application 13/612,929 10 Appellant’s arguments do not persuaded us that the Examiner erred in crediting Hou’s teaching of introducing siRNA into plants by topically applying a solution of siRNA in water. As an initial matter, regardless of whether it ever “materialized into a granted patent,” prior art is presumed to be enabled. In re Sasse, 629 F.2d 675, 681 (CCPA 1980); see also In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012). Once such a prior art reference is found, the burden is on the Appellants to provide evidence rebutting the presumption. Id. Here, Hou discloses a method in which a solution of water and siRNA is topically applied to plants. Hou, Abstract. Hou broadly teaches that when this method is used, siRNA is absorbed into the plants. Id. Hou states: The method comprises the following steps of: 1, designing and synthesizing siRNA according to a target gene sequence; 2, preparing 1 to 10 percent solution of siRNA by using double distilled water; and 3, spraying the solution of siRNA on the surface of plant leaves. According to the method, the RNA interference is introduced into the plants from the surface of the leaves, and stomatal cells and epidermic cells of the plants can absorb the siRNA. Hou, Abstract. Hou exemplifies this broad teaching by applying 1%, 5%, and 10% siRNA solutions to peach tree leaves “once every 3 days” and Appeal 2020-002277 Application 13/612,929 11 conducting a “reverse transcription — PCR analysis” “detect treatment effect on ACLSV.” Id. ¶¶ 24, 27. The results are provided in Figure 1 (reproduced below). In Figure 1, “[lane] 1 represents 10% siRNA solution results; [lanes] 2, 3 represent[] 5% siRNA solution results; [lane] 4 shows the effect of 1% siRNA solution; [and lane] 5 represents a DNA marker.” Id. ¶ 28. According to Hou, the 1% solution was “the worst among the three” concentrations, the 5% solution provided a “better treatment,” and the 10% solution provided the “best treatment.” Id. These teachings are presumed to enabled. We acknowledge that some of Dr. Heck criticisms of Hou’s disclosure may have merit. Heck Decl. ¶¶ 10–19. In particular, we agree that Hou’s disclosure would have been improved by the use of a control. We also acknowledge Dr. Heck’s testimony that an ordinary artisan would not have expected Hou’s method to work. Id. ¶¶ 24–32. However, we are not persuaded that this testimony is sufficient to overcome the presumption that Hou’s teachings are enabled. In this regard, we note that Dr. Heck’s criticisms are not supported by experimental evidence showing that Hou’s method does not work. Instead Dr. Heck’s testimony relies principally on his informed opinion. In contrast, Hou purports to have conducted an experiment confirming its teachings. Hou ¶¶ 20–28. Considering the totality of the evidence, we give greater weight to Hou’s experimentally confirmed, presumed-enabled teaching that its method works as described, than to Dr. Heck’s opinion-based testimony that it would not work. See In re Am. Acad, of Sci. Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) (“[T]he Board is entitled to weigh the declarations and conclude that the lack of Appeal 2020-002277 Application 13/612,929 12 factual corroborations warrants discounting the opinions expressed in the declarations.”) In addition to criticizing of Hou’s methods and testifying that the ordinary artisan would not have expected Hou’s methods to work, Dr. Heck also testifies that the ordinary artisan would understand that Hou’s teachings were limited to plants having ACLSV (which, according to Appellant, damages leaves allowing siRNA to penetrate) and would not extend to healthy plants. Heck Decl. ¶ 21–23. We do not find this testimony persuasive because Hou’s teachings are not limited to plants having ACLSV. See Hou, Abstract (teaching broadly that using its method, siRNA is introduced into plants). Moreover, it is not clear that claim 1 is limited to application to healthy plants.11 Appellant argues that “Hou does not even mention ALS gene, let alone a dsRNA targeting ALS gene sequences selected from the recited SEQ ID NOs.” Appeal Br. 28. We are not persuaded because the Examiner does not rely on Hou alone for that teaching. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Here, Hofgen teaches that ALS is “the first enzyme in the biosynthetic pathway of leucine, valine, and isoleucine” and is “the biochemical target of 11 At oral argument, when the Board observed that the claims did not appear to be limited to healthy plants, Appellant responded that the claim language requires that the transfer agent condition the surface of said plant for permeation by said dsRNA. Tr. 8. It is not clear to us how this claim language limits the plant surfaces conditioned by the transfer agent to healthy plants. Appeal 2020-002277 Application 13/612,929 13 different herbicides.” Hofgen, Abstract. Hofgen further teaches that inhibition of ALS using antisense gene expression generated “herbicide action” and that plants in which ALS was so inhibited “revealed severe growth retardation” and “strong phenotypical effects resembling those caused by ALS-inhibiting herbicides.” Id. Yao teaches that it is “well known that small interfering RNA (siRNA) with 21 to 23 nucleotides can trigger silencing of genes containing the same nucleotide sequences in plants.” Yao ¶ 163. Yao further teaches that siRNA from the Pin1 gene of a weed species can be used as an herbicide and “should only silence the weed Pin1 gene and cause weed death but not affect crop plants. Id. ¶ 164. Finally, Yao teaches that “[t]he siRNA agent may be generated using in vitro transcription techniques and sprayed onto plants.” Id. ¶ 166. Prado discloses that “[a] set of universal and degenerate primers has been designed to clone (by polymerase chain reaction [PCR]) the conserved domains of the acetolactate synthase (ALS) gene where mutations confer resistance to ALS herbicides in plants.” Prado, Abstract. Prado further discloses that these primers were “successful in cloning conserved domains of ALS in all monocotyledonous and dicotyledonous plants tested to date, as well as bacteria.” Id. In view of the disclosures of Hofgen, Yao and Prado, and Riggins, we agree with the Examiner that it would have been obvious to modify the method of Hou to target “the ALS gene given that its product is a well- characterized herbicide target, whose inhibition mimics the effects of the ALS inhibiting herbicides, as taught by Hofgen, and because the gene is Appeal 2020-002277 Application 13/612,929 14 known to be conserved in plants, including weeds, as taught by Prado et al and Riggins et al.” Ans. 9. We further agree with the Examiner that: Given the conserved nature of the ALS gene (as taught by Prado et al) including among the Amaranthus sp. (as taught by Riggins et al), it would have been obvious and predictable to use the ALS of one species, for example, that of GenBank Accession U55852, to design siRNAs targeting the ALS of another species, such as, for example the Amaranthus quitensis gene, that comprises regions of sufficient identity to the instant SEQ ID NO: 15.. Ans. 8. Accordingly, we are not persuaded by Appellant’s argument that Hou fails to disclose targeting the ALS gene sequences selected from the recited SEQ ID NOs. Appellant argues that Hou “does not teach or suggest an effect on treated plants.” Appeal Br. 28. Again, we are not persuaded because the Examiner does not rely on Hou alone for that teaching. In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). As discussed above, we agree with the Examiner that it would have been obvious to use a siRNA sequence comprising at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 15 in Hou’s method. Given Hou’s teaching that siRNA applied using its method is absorbed into plants (Hou, Abstract), Yao’s teaching that siRNA can be used as an herbicide because it triggers silencing of genes in plants (Yao ¶¶ 162–166), and Hofgen’s teaching that inhibition of ALS had herbicidal effects (Hofgen, Abstract), the ordinary artisan would reasonably have expected that treating plants with siRNA comprising 18 contiguous nucleotides of the gene comprising SEQ ID NO: 15 would reduce a plant’s growth, development or reproductive ability relative to untreated plants. As the Examiner explains: Given the express teachings of Hofgen et al, one would reasonably expect that suppressing the expression of an ALS Appeal 2020-002277 Application 13/612,929 15 gene in a plant would result in suppression of the plant’s growth, development or reproductive ability, or that said plant would be more sensitive to ALS inhibitors. Ans. 10. Appellant argues that “Yao at most creates transgenic plants with stably incorporated non-ALS gene sequences (sense or antisense) via Agrobacterium-mediated transformation.” Appeal Br. 36. According to Appellant, “Yao does not spray any plants with anything, let alone dsRNA with a transfer agent.” Id. at 39. We are not persuaded. Yao discloses that its herbicidal siRNA “may be generated using in vitro transcription techniques and sprayed onto plants.” Yao ¶ 166. We recognize that Yao also discloses other methods of incorporating siRNA into plants, including via Agrobacterium-mediated transformation. However, Yao’s disclosure is not limited to these other methods. Merck & Co. Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976) (“But in a section 103 inquiry, ‘the fact that a specific [embodiment] is taught to be preferred is not controlling, since all disclosures of the prior art, including unpreferred embodiments, must be considered.’”)). Appellant argues that Yao’s disclosure of spraying actually refers to a “biolistic” method in which “RNAs or DNAs are loaded on gold particles and delivered to plant leaves using a particle gun.” Appeal Br. 38. We are not persuaded. As an initial matter, it is not clear to us that Yao uses the terms “biolistics” and “spraying” synonymously. Indeed, the choice of different words suggests different meanings. Appellant points to Yao’s statement that “siRNA can be delivered into plant cells using a range of techniques, such as biolistics,[] Agrobacterium infiltration[,] and viral Appeal 2020-002277 Application 13/612,929 16 infection” (Yao ¶ 163), and argues that Yao’s subsequent reference to applying siRNA by spraying must refer back to one of these three techniques (Appeal Br. 40). But, Yao nowhere limits the techniques by which siRNA can be delivered to the three techniques identified in this statement. Indeed the words “such as” make clear that the three techniques are exemplary, as does Yao’s statement that “[o]ther means to generate and deliver siRNA may also be used.” Yao ¶ 166. Moreover, even if, contrary to the evidence, Yao did not teach topically applying its herbicide, Hou does. See Hou, Abstract (disclosing that its method includes “spraying the solution of siRNA on the surface of plant leaves”). While Yao’s disclosure facially provides further support for spraying siRNA onto plant leaves, it is not necessary to the rejection. Appellant argues that “Riggins does not teach or suggest a dsRNA, let alone a dsRNA of certain length and sequence identity to the recited SEQ ID NOs for topical application to a plant surface in a method of plant control.” Appeal Br. 42. We are not persuaded because, as discussed above, we agree with the Examiner that based on the disclosure of cited art it would have been “obvious and predictable to . . . to design siRNAs targeting . . . ALS . . . that comprises regions of sufficient identity to the instant SEQ ID NO: 15.” Ans. 8. And the teachings of siRNA necessarily disclose dsRNA because siRNAs are double stranded RNAs. Ans. 10 (Examiner’s undisputed finding that siRNA “is double-stranded RNA”). Appellant argues that the Examiner failed to examine claim 1 as a whole and does not provide a reason to combine. Appeal Br. 44–50. We do not agree. The Examiner did not simply find each of the limitations recited in claim 1 to be present in the cited art. Rather, the Examiner identified Appeal 2020-002277 Application 13/612,929 17 reasons, grounded in the prior art, why the ordinary artisan would have modified Hou’s method to target the ALS gene with a reasonable expectation of success. Ans. 3–10. In so doing, the Examiner explained how the resulting method would include all of the limitations of claim 1. Appellant argues that cost and convenience are not reasons to combine. Appeal Br. 47–50. But Appellant relies exclusively on attorney argument, which cannot take the place of evidence. See Id.; see also In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997); and In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984). Moreover, as the Examiner explains, “low cost of the siRNA approach would not have been the only reason why one would have been motivated to arrive at the instant invention.” Ans. 24. More specifically “convenience of topical application and the advantages over conventional herbicides, as taught by Hou and Yao . . . would have also motivated one to use siRNA to inhibit an endogenous ALS in a commercially important weed.” Id. The additional benefits taught by Hou include simplicity, “high speed,” “quick response, high timeliness, stability, high efficiency,” “easy popularization and the like.” Hou, Abstract. The benefits taught by Yao with respect to its Pin1 gene based siRNA herbicide include that it “can be highly species specific.” Yao ¶ 164. Yao also asserts, more generally, that its method “has advantages over herbicides currently available in the market.” Id. Appellant argues that an ordinary artisan “would not have had a reasonable expectation of success that a large, highly charged molecule such as dsRNA would be able to permeate a surface of a plant.” Appeal Br. 50. Similarly, Appellant argues that Dr. Heck expressed contemporaneous skepticism that applying siRNA topically to plants would work. Appeal Br. Appeal 2020-002277 Application 13/612,929 18 52–53. We are not persuaded because, as discussed above, Hou teaches that siRNA topically applied to plants is introduced into the plant. Yao further supports that siRNA applied to plants can act as an herbicide. Yao ¶¶ 162– 166. Appellant argues that “Yao and Hofgen lead away from the claimed invention by requiring Agrobacterium-mediated transformation to make transgenic plants, features not described in the Specification or recited in the claims.” Appeal Br. 54. As discussed above, we are not persuaded that Yao is limited to applying siRNA using Agrobacterium-mediated transformation, biolistics methods, or viral infection. See e.g., Yao ¶ 166 (“Other means to generate and deliver the siRNA may also be used.”). But even if it were so limited, Appellant does not identify, and we do not find, any disclosure in the art that discourages topical application of a composition comprising siRNA. Accordingly, the record does not support that the prior art taught away from the claimed method. See, DyStar Textilfarben GmbH & Co. Deutschland Kg v. C.H. Patrick Co., 464 F.3d 1356, 1364 (Fed. Cir. 2006) (“We will not read into a reference a teaching away from a process where no such language exists.”). Appellant argues that the Examiner incorrectly treats the “wherein” clause reciting “wherein said transfer agent conditions the surface of said plant for permeation by said dsRNA,” as an intended use, giving it no patentable weight. Appeal Br. 24–25. According to Appellant this “wherein” clause “defines a transfer agent by its function, i.e., its ability to condition the surface of a plant for permeation by a dsRNA, and is thus a claim limitation.” Id. at 25. We are not persuaded. Appeal 2020-002277 Application 13/612,929 19 We have already construed the term “transfer agent” to mean: “an agent that, when combined with a polynucleotide in a composition that is topically applied to a target plant surface, enables the polynucleotide to enter a plant cell.” The “wherein” claim language does not further limit the claim beyond this construction. As discussed above, the water in Hou’s method enables the polynucleotide to enter the plant cell and thus, even if we were to give weight to the “wherein” claim language, the cited art teaches this limitation. Appellant argues that the Examiner incorrectly treats the “whereby” clause reciting “whereby said plant’s growth, development, or reproductive ability is reduced or said plant is more sensitive to an ALS inhibitor herbicide” relative to an untreated plants as an intended use. Id. at 26. According to Appellant, this clause “effectively limit[s] the recited dsRNA[s] to only those that are capable of achieving the desired results as recited in the claims.” Id. at 26. We are not persuaded because, even if claim 1 is construed to require that the treated plant’s growth, development, or reproductive ability is reduced or said plant is more sensitive to an ALS inhibitor herbicide relative to an untreated plants, the prior art fairly suggests this feature. As discussed above, we agree with the Examiner that it would have been obvious to use a siRNA sequence comprising at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 15 in Hou’s method. Given Hou’s teaching that siRNA applied using its method is absorbed into plants (Hou, Abstract), Yao’s teaching that siRNA can be used as an herbicide because it triggers silencing of genes in plants (Yao ¶¶ 162–166), and Hofgen’s teaching that inhibition of ALS has herbicidal effects (Hofgen, Abstract), the ordinary Appeal 2020-002277 Application 13/612,929 20 artisan would reasonably have expected that treating plants with siRNA comprising 18 contiguous nucleotides of the gene comprising SEQ ID NO: 11 would reduce a plant’s growth, development or reproductive ability relative to untreated plants. Accordingly, we affirm the Examiner’s rejection of claim 1. Because they were not argued separately, claims 9, 17, and 37 fall with claim 1. Claim 5, 36, and 37 Claim 5 depends from claim 1 and further requires that the recited plant is selected from a group of specifically identified plants. Claim 36 depends from claim 1 and further requires that the plant is Amaranthus palmeri. Claim 37 depends from claim 9 and likewise further requires that the plant is Amaranthus palmeri. Appellant argues that “[n]one of the cited references, alone or in combination, teach or suggest treating any of the recited plant species in a method of plant control as recited” in claim 5 and, more specifically, Amaranthus palmeri, as recited in claims 36 and 37. Appeal Br. 54, and 56–57. We do not find this argument persuasive because, as the Examiner explains, “Amaranthus sp. including A. palmeria are known and important weeds” and thus “it would have been obvious to use the teachings of Prado et al and Riggins et al to isolate the coding and the genomic sequences of the ALS gene from A. palmeri or A. tuberculatus, and use said sequences to design the siRNAs targeting said gene, with reasonable expectation of success.” Ans. 27. Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 54–57. We do not find the repeated arguments persuasive for the reasons already discussed. Appeal 2020-002277 Application 13/612,929 21 Accordingly, we affirm the Examiner’s rejection of claims 5 and 42. Claim 8 Claim 10 depends from claim 1 and further recites that the composition comprises two or more of said dsRNAs. Appellant argues that “[n]one of the cited references, alone or in combination, teach or suggest a dsRNA targeting ALS gene sequences for use in a method of plant control as claimed, let alone two or more of such dsRNAs.” Appeal Br. 55. We are not persuaded because, for the reasons discussed above, it would have been obvious to employ a composition comprising siRNA targeting the ALS gene. As the Examiner explains, “combining, in a composition two or more of said RNAs, both of them targeting the same endogenous ALS gene, as recited in claim 8, would have been obvious because, ‘[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art.’” Ans. 28 (quoting In re Kerkhoven, 626 F.2d 846, 850, 205 USPG 1069, 1072 (CCPA 1980)). Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 55–56. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claim 8. OBVIOUSNESS OVER HOU, YAO, RIGGINS, HOFGEN, PRADO, PRATT, NETTLETON-HAMMOND, AND SUN Appeal 2020-002277 Application 13/612,929 22 In rejecting claims 2, 6, 7, 10, 14–16, 18, 32, and 33 as obvious over the combination of Hou, Yao, Riggins, Prado, Hofgen, Pratt, Nettleton- Hammond, and Sun, the Examiner applied Hou, Yao, Riggins, Hofgen, Prado, and Pratt as discussed in connection with claim 1. The Examiner acknowledge, however, that this combination of art did not “expressly teach using an ALS inhibitor or a co-herbicide in said composition; and do not teach the use of an organosilicone surfactant.” Ans. 10. The Examiner found, however, that Nettleton-Hammond taught “herbicidal composition[s] comprising at least one ALS-inhibitor herbicide, such as nicosulfuron, and at least on HPPD-inhibitor herbicide, such as mesotrione, including wherein the composition comprises a surfactant.” Id. at 11. The Examiner also found that Sun disclosed that “organosilicone surfactants . . . improve the uptake of ALS inhibitors from the leaf surface, including wherein the ALS inhibitor was nicosulfuron, and wherein the target weeds included Amaranthus sp.” Id. 11. Based on these disclosures, the Examiner concluded that it would have been obvious to include in the composition used in Hou’s method, modified as discussed above, “an ALS inhibitor, including nicosulfuron, either alone or in combination with another herbicide, including an HPPD inhibitor herbicide, such as mesotrione” as well as “an organosilicon surfactant, such as those taught by Sun.” Id. at 11. Claims 6, 7, and 14–16 Appellant argues claims 6, 7 and 14–16 together. Appeal Br. 58–59. We designate claim 6 as representative. Appeal 2020-002277 Application 13/612,929 23 Claim 6 depends from claim 1 and further requires that the composition comprises an ALS inhibitor herbicide. Appellant argues that “Nettleton-Hammond at most discusses an herbicidal composition comprising at least one ALS inhibitor herbicide and at least one p- hydroxyphenyl pyruvate dioxygenase (HPPD) inhibitor herbicide.” Appeal Br. 58. Appellant thus argues that Nettleton-Hammond “does not provide any teaching, suggestion, or motivation that any ALS inhibitor herbicide and/or other herbicides can be used in a composition with a transfer agent and a dsRNA targeting ALS gene sequences in a method of plant control as recited.” Id. We are not persuaded. Nettleton-Hammond teaches an herbicidal composition comprising at least one ALS-inhibitor and at least on HPPD inhibitor. Nettleton- Hammond, Abstract. We agree with the Examiner that this would have motivated the ordinary artisan to combine the siRNA herbicidal composition suggested by the cited art with another ALS herbicide (or with both an ALS herbicide and an HPPD herbicide). Ans. 29; In re Kerkhoven, 626 F.2d 846, 850, 205 USPG 1069, 1072 (CCPA 1980). Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 58–59. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly we affirm the Examiner’s rejection of claim 6. Because they were not argued separately, claim 7 and 14–16 fall with claim 6. Claims 2, 10, 18, 32, and 33 Appellant argues claims 2, 10, 18, 32, and 33 together. We designate claim 2 as representative. Appeal 2020-002277 Application 13/612,929 24 Claim 2 depends from claim 1 and further requires that the transfer agent is “an organosilicon surfactant composition or an organosilicone compound contained therein.” Appellant argues that “Sun at best discusses the physico-chemical properties of organosilicone surfactants and their effects on herbicide activity on weedy plants.” Appeal Br. 59. Appellant argues that Sun does not support that an organosilicone surfactant would inherently function as a transfer agent. Id. at 60–61. We agree with the Examiner that the disclosure of Sun would have suggested the use of an organosilicone surfactant in Hou’s method. As the Examiner explains: “Sun . . . teaches that organosilicone surfactants improve the uptake of ALS inhibitors from the leaf surface and wherein the target weeds included Amaranthus sp.” Ans. 29. We agree with the Examiner that these teachings would have motivated the ordinary artisan to use an ornanosilicone surfactant in a composition comprising a siRNA targeting the endogenous ALS gene. Id. We are not persuaded by Appellant’s inherency argument because the Examiner relies not on inherency, but on the teaching in the art that organosilicone surfactants improve the uptake of ALS inhibitors from the leaf surface. Sun 2–3, 4–6, 9–10. Moreover, the Examiner does not propose to eliminate water, which Hou teaches has the properties of a transfer agent. See supra. Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 61. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claim 2. Because they were not argued separately, claims 12, 22, 38, 48, and 49 fall with claim 2. Appeal 2020-002277 Application 13/612,929 25 CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 5, 8, 9, 17, 36, 37 103(a) Hou, Yao, Riggins, Hofgen, Prado, Pratt 1, 5, 8, 9, 17, 36, 37 2, 6, 7, 10, 14– 16, 18, 32, 33 103(a) Hou, Yao, Riggins, Hofgen, Prado, Pratt, Nettleton-Hammond, Sun 2, 6, 7, 10, 14–16, 18, 32, 33 Overall Outcome 1, 2, 5–10, 14–18, 32, 33, 36, 37 No time period for taking any subsequent action in connection with this appeal may be extended under 3 7 C.F .R. § 1.136(a)(1). AFFIRMED Copy with citationCopy as parenthetical citation