Daniel Ader et al.Download PDFPatent Trials and Appeals BoardFeb 2, 20212020002276 (P.T.A.B. Feb. 2, 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. 13/612,925 09/13/2012 Daniel Ader P34109US01/0024021.00170 9715 66056 7590 02/02/2021 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 02/02/2021 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, ZHAOLONG LI, RONAK HASMUKH SHAH, MENGBING TAO, DAFU WANG, and HEPING YANG ____________ Appeal 2020-002276 Application 13/612,9251 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-IN-PART. 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 2020-002276 Application 13/612,925 2 STATEMENT OF THE CASE The Specification discloses that “[t]he EPSPS (5- enolpyruvylshikimate-3-phosphate synthase) enzyme catalyzes the conversion of shikimate-3-phosphate into 5-enolpyruvyl-shikimate-3- phosphate, an intermediate in the biochemical pathway for creating three essential aromatic amino acids (tyrosine, phenylalanine, and tryptophan).” Spec. 1–2. According to the Specification, “[t]he EPSPS enzyme is the target for the herbicide N-phosphonomethyl glycine also known as glyphosate.” Id. at 3. The Specification discloses, “a method of plant control comprising an external application to a plant or plant part a composition comprising a polynucleotide and a transfer agent, wherein the polynucleotide is essentially identical or essentially complementary to an EPSPS gene sequence or fragment thereof, or to the RNA transcript of said EPSPS gene sequence or fragment thereof.” Id. at 3. Claims 1, 2, 5–12, 16–22, 27–34, 38, 39, and 42–49 are on appeal. Claim 1 is representative and reads as follows: 1. A method of plant control comprising: topically applying a composition to a plant surface to modulate 5- enolpyruvylshikimate-3-phosphate synthase (EPSPS) 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 EPSPS gene sequence, wherein said EPSPS gene sequence is selected from the group consisting of SEQ ID NOs: 11, 18, 19, 21, 22, 53-55, 61, 72, 74, 75, 84, 88, 99, 101, 110, 115, and 119, wherein said transfer agent conditions the surface of said plant for permeation by said dsRNA, whereby said plant’s growth, development, or reproductive ability is reduced or said plant is more sensitive to an EPSPS inhibitor herbicide relative to an Appeal 2020-002276 Application 13/612,925 3 untreated plant. Appeal Br. 68. The claims stand rejected as follows: Claims 1, 5, 10, 11, 21, and 42–47 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Hou,2 Yao,3 and Riggins.4 Claims 2, 6–9, 12, 16–20, 22, 38, 39, 48, and 49 were rejected under 35 U.S.C. § 103(a) as obvious over the combination of Hou, Yao, Riggins, Shaner,5 Singh,6 and Sun.7 The Examiner also objected to claims 1, 11, 21, and 44 due to an “informality.” Ans. 32 (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 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 Shaner, The impact of glyphosate-tolerant crops on the use of herbicides and on resistance management, Society of Chemical Industry, Pest Management Science, Vol. 56, 320–326 (2000) (hereinafter “Shaner”). 6 Singh, et al., Absorption and translocation of glyphosate with conventional and organosilicone adjuvants, Weed Science Society of Japan, Weed Biology and Management, Vol. 8, 104–111 (2008) (hereinafter “Singh”). 7 Sun, CHARACTERIZATION OF ORGANOSILICONE SURFACTANTS AND THEIR EFFECTS ON SULFONYLUREA HERBICIDE ACTIVITY, PhD Thesis, Virginia Polytechnic Inst. and State University (1996) (hereinafter “Sun”). Appeal 2020-002276 Application 13/612,925 4 the Director under Rule 181. 37 C.F.R. §§ 1.113, 1.181. As such, we do not address this objection herein.8 OBVIOUSNESS OVER HOU, YAO, AND RIGGINS Claims 1, 11, 21, and 44 Appellant argues claim 1, 11, 21, and 44 together. Appeal Br. 22–52. 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. 6. 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. The Examiner acknowledged, however, that Hou does not disclose applying its method to target an EPSPS gene, as recited in claim 1. The Examiner relied on Yao and Riggins as providing teachings that would have suggested targeting an EPSPS gene. Id. at 6–12. With respect to Yao, 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 8 The Examiner withdrew the rejection of claims 44 and 45 on the basis that they contained an improper Markush grouping. Ans. 33. Accordingly, this rejection is no longer part of this appeal. Appeal 2020-002276 Application 13/612,925 5 teaches that “methods for designing siRNA based on an mRNA target are known in the art.” Id. at 6. With respect to Riggins, the Examiner found that Riggins taught that “EPSPS is the target for glyphosate, one of the world’s most widely used herbicides,” and that “the inhibition of EPSPS interrupts the production of essential aromatic amino acids.” Id. at 7. The Examiner also found that Riggins disclosed a “method and primers for identifying ESPS genes . . . from seven Amaranthus species, including A. palmeri and A. hybridus” and provided “GenBank Accession numbers for complete coding cDNAs of EPSPS from A. palmeri and A. tuberculatus.” Id. According to the Examiner, “[t]he primers of Riggins et al show a 95% and 100% sequence identity to the instant SEQ ID NO: 10” and “GenBank Accession number FJ861243, which is taught by Riggins et al as an EPSPS cDNA from A palmeri, shows 99% identity with the instant SEQ ID NO: 12 over the majority of the length of the latter.” Id. at 7–8. Based on the combined teachings of Hou, Yao, and Riggins, the Examiner concluded: 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 Yao et al and Riggins et al and use the siRNA, which is double-stranded RNA, to target the EPSPS of weeds, including that of Amaranthus sp. in order to reduce the expression of the endogenous EPSPS. It would have been obvious to use the primers of Riggins et al to isolate the coding and the genomic sequences of the endogenous EPSPS gene from A. tuberculatus (syn. A. rudis) and Amaranthus palmeri, and to design siRNA targeting said gene. It would have been also obvious to design said siRNA using the EPSPS coding sequences of the GenBank Accession Numbers taught by Riggins et al. The siRNA thus obtained would be a functional Appeal 2020-002276 Application 13/612,925 6 equivalent of the claimed dsRNA sequences derived from SEQ ID NO: 11, for example. Moreover, given that SEQ ID NO: 11 is a fragment of genomic DNA from A. palmeri, and in view of the fact that the primers of Riggins et al could be used to isolate genomic EPSPS sequences, one would have predictably arrived at the sequence that would comprise at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 11. Id. at 10. We adopt the Examiner’s findings of fact and reasoning regarding the scope and content of the prior art and agree that claims 1, 11, 21, and 44 would have been obvious over Hou, Yao, and Riggins. 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. 30. According to Appellant, “[w]ater is not one of the seven categories of transfer agent described in the Specification.” Id. at 24. 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.9 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. 24. However, the portion of the Specification cited by Appellant is exemplary only, and does not limit transfer agents to the categories listed. 9 Declaration of Gregory R. Heck under 37 C.F.R. § 1.132, signed, August 30, 2018 (hereinafter “Heck Decl.”). Appeal 2020-002276 Application 13/612,925 7 Spec 16 (“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. 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. 16. 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 Appeal 2020-002276 Application 13/612,925 8 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 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, “there is no credible evidence that any siRNA entered the leaves of Hou.” Appeal Br. 31. Appellant points out that the only data in Hou “lacks any control whatsoever” and that Hou never “materialized into a granted patent.” Id. 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. ¶¶ 16–20); Appeal 2020-002276 Application 13/612,925 9 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. ¶ 21–23); 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). 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 conducting a “reverse transcription — PCR analysis” “detect treatment Appeal 2020-002276 Application 13/612,925 10 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. ¶¶ 10–20. 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 Appeal 2020-002276 Application 13/612,925 11 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 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.10 Appellant argues that “Hou does not even mention EPSPS gene, let alone a dsRNA targeting EPSPS gene sequences selected from the recited 10 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 2020-002276 Application 13/612,925 12 SEQ ID NOs.” Appeal Br. 29. 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, 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. Riggins teaches that EPSPS is “the target for glyphosate, which is one of the most widely used herbicides in the world.” Riggins, 1050. Riggins also discloses primers for EPSPS. (id. at 1045 (Table 2)) as well as the Gen Bank Accession number for an EPSPS cDNA from A. palmeri ((id. at 1050); see also Ans. 8). In view of the disclosures of Yao and Riggins, we agree with the Examiner that it would have been obvious to modify the method of Hou to “target the EPSPS of weeds . . . in order to reduce the expression of the endogenous EPSPS.” Ans. 10. As the Examiner explains: One would have been motivated to combine said teachings for the following reasons. First, one would have selected the EPSPS gene given that its product is a well-known herbicide target, whose inhibition disrupts essential biochemical pathways, as taught by Riggins et al. Second, one would have been motivated to topically apply the siRNA directly to the Appeal 2020-002276 Application 13/612,925 13 leaves of an Amaranthus sp. weed because of the convenience and low cost of that approach, as taught by Hou,11 and in view of the express suggestion of Yao et al that siRNA be used as an herbicide. One would have been motivated to target amaranth weeds, including A. palmeri, given that they constitute agriculturally important and aggressive weeds, as taught by Riggins et al. Ans. 11. We further agree with the Examiner that: [G]iven that SEQ ID NO: 11 is a fragment of genomic DNA from A. palmeri, and in view of the fact that the primers of Riggins et al. could be used to isolate genomic EPSPS sequences, one would have predictably arrived at the sequence that would comprise at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 11. Ans. 10. Accordingly, we are not persuaded by Appellant’s argument that Hou fails to disclose targeting the EPSPS gene. Appellant argues that Hou “does not teach or suggest an effect on treated plants.” Appeal Br. 30. 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: 11 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 11 Hou teaches that its method “has the advantages of simple and convenient operation, high speed, low cost, quick response, high timeliness, stability, high efficiency, low using cost, easy popularization and the like.” Hou, Abstract. Appeal 2020-002276 Application 13/612,925 14 Riggins’ teaching that “inhibition of EPSPS interrupts the production of essential amino acids” (Riggins, 1050), the ordinary 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. As the Examiner explains, because “EPSPS is an enzyme that is essential for aromatic amino acid synthesis and is a target for glyphosate, one would have reasonably expected that inhibiting it would result in suppression of the plant’s growth, development or reproductive ability, or that said plant would be more sensitive to glyphosate.” Ans. 11– 12 Appellant argues that “Yao at most generates transgenic plants by using the conventional Agrobacterium-mediated transformation in which a gene of interest is stably incorporated into the genome of the transformed plant.” Appeal Br. 38. Appellant thus contends that “Yao does not spray any plants with anything, let alone dsRNA with a transfer agent.” Id. 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 Appeal 2020-002276 Application 13/612,925 15 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. 40. 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 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 a recited SEQ ID NO 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 Appeal 2020-002276 Application 13/612,925 16 disclosure of Riggins “one would have predictably arrived at the sequence that would comprise at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 11.” Ans. 24. 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. 42–48. 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 reasons, grounded in the prior art, why the ordinary artisan would have modified Hou’s method to target the EPSPS gene with a reasonable expectation of success. Ans. 3–12. 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. 45–48. 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. 27. More specifically “the advantages over conventional herbicides, as taught by Hou and Yao . . . would have also motivated one to use siRNA to inhibit an endogenous EPSPS 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 Appeal 2020-002276 Application 13/612,925 17 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. 48. Similarly, Appellant argues that Dr. Heck expressed contemporaneous skepticism that applying siRNA topically to plants would work. Appeal Br. 50–51. 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 leads away from the claimed invention by requiring Agrobacterium-mediated transformation, biolistics methods, or viral infection, to make transgenic plants, features not described in the Specification or recited in the claims.” Appeal Br. 51–52. 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. Appeal 2020-002276 Application 13/612,925 18 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. 25–26. According to Appellant this “wherein” clause “further defines [the] 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. 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 EPSPS 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. Appellant’s argument that the whereby clause limits claim 1 to only a subset of the specifically recited SEQ ID’s is in tension with an argument it Appeal 2020-002276 Application 13/612,925 19 made with respect to the Examiner’s rejection of claims 44 and 45 as reciting an improper Markush group of EPSPS gene sequences. More specifically, Appellant argued that the EPSPS sequences recited in these claims, which encompass all of the sequences recited in claim 1, share a common function, and thus do not present an improper Markush group because “all of SEQ ID NOs 1–120, which encompass all sequences recited in claims 44 and 45, ‘suppress, repress or otherwise delay the expression of the target EPSPS gene.’” Appeal Br. 64 (omitted citation). This is consistent with the Specification, which suggests that the disclosed method encompasses application of any of the recited SEQ IDs. For example, it states: [T]he invention provides a method of plant control comprising an external application to a plant or plant part a composition comprising a polynucleotide and a transfer agent . . . wherein said EPSPS gene sequence is selected from the group consisting of SEQ ID NO: 1–120 or a polynucleotide fragment thereof. As a result of such application, the plant growth or development or reproductive ability is reduced or the plant is made more sensitive to an EPSPS inhibitor herbicide relative to a plant not treated with said composition. Spec. 3; see also, id. 24 (identifying SEQ ID NO:1–120 as “target gene RNA and DNA polynucleotide molecules”). Appellant does not identify, and we do not find, anything in the Specification to support that only a subset of the specifically recited SEQ IDs would be expected to achieve the results recited in the claims. In any event, 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 EPSPS inhibitor herbicide relative to an untreated plants, the prior art fairly suggests this feature. As discussed above, we Appeal 2020-002276 Application 13/612,925 20 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: 11 in Hou’s method. Given Hou’s teaching that siRNA applied using its method is absorbed into plants, Yao’s teaching that siRNA can be used as an herbicide because it triggers silencing of genes in plants (Yao ¶¶ 162–166), and Riggins’ teaching that “inhibition of EPSPS interrupts the production of essential amino acids” (Riggins, 1050), the ordinary 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 11, 21, and 44 fall with claim 1. Claim 5, 42, and 43 Claim 5 depends from claim 1 and further requires that the recited plant is selected from a group of specifically identified plants. Claim 42 depends from claim 1 and further requires that the plant is Amaranthus palmeri. Claim 43 depends from claim 11 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 42 and 43. Appeal Br. 52, and 54–55. We do not find this argument persuasive because, as discussed above, Riggins discloses the Gen Bank Accession number for an EPSPS cDNA from A. palmeri, one of the species recited in Appeal 2020-002276 Application 13/612,925 21 claim 5, and the Examiner provides persuasive reasoning why it would have been obvious to target the EPSPS gene of A. palmeri. Riggins, 1050; see also Ans. 11 (“One would have been motivated to target amaranth weeds, including A. palmeri, given that they constitute agriculturally important and aggressive weeds, as taught by Riggins et al.”). Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 52–53. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claims 5 and 42. Claim 10 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 EPSPS gene sequences for use in a method of plant control as claimed, let alone two or more of such dsRNAs.” Appeal Br. 53. We are not persuaded because, for the reasons discussed above, it would have been obvious to employ a composition comprising siRNA targeting the EPSPS gene. As the Examiner explains, “a composition [comprising] two or more of said RNAs, both of them targeting the same endogenous EPSPS gene 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. 30 (quoting In re Kerkhoven, 626 F.2d 846, 850, 205 USPG 1069, 1072 (CCPA 1980)). Appeal 2020-002276 Application 13/612,925 22 Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 53. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claim 10. Claim 45 Claim 45 depends from claim 44 and further limits the SEQ ID NOs recited in the Markush group. Notably, the narrowed Markush group of claim 45 does not recite SEQ ID NO: 11. Appellant argues that “[n]one of the cited references, alone or in combination, teach or suggest any of the SEQ ID NOs as recited in the claims.” Appeal Br. 54. The Examiner’s Answer does not address this argument. See generally, Ans. Moreover, the Examiner’s obviousness rationale posits that the ordinary artisan “would have predictably arrived at the sequence that would comprise at least 18 contiguous nucleotides of the gene comprising SEQ ID NO: 11.” Ans. 10. As noted above, SEQ ID NO. 11 is not recited in claim 45. As the Examiner does not explain why any of the sequences recited in claim 45 would have been obvious, we reverse the Examiner’s rejection of claim 45. Claim 46 Claim 46 depends from claim 44 and further recites that the plant is selected from a specifically recited group of plants. Notably, the recited plants do not include 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 composition for plant control as recited.” Appeal 2020-002276 Application 13/612,925 23 Appeal Br. 56. The Examiner’s Answer does not address this argument. See generally, Ans. Moreover, while the Examiner explains why it would have been obvious to target A. plameri, the Examiner does not explain why it would have been obvious to target any of the plant species recited in claim 46. Accordingly, we reverse the Examiner’s rejection of claim 46. Claim 47 Claim 47 depends from claim 44 and further recites that the transfer agent is a chemical agent. 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 composition for plant control as recited.” Appeal Br. 57. We are not persuaded because claim 47 does not recite any particular plant species. Appellant also repeats several of the arguments it makes with respect to claim 1. Appeal Br. 57. We do not find the repeated arguments persuasive for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claim 47. OBVIOUSNESS OVER HOU, YAO, RIGGINS, SHANER, SINGH, AND SUN In rejecting claims 2, 6–9, 12, 16–20, 22, 38, 39, 48, and 49 as obvious over the combination of Hou, Yao, Riggins, Shaner, Singh, and Sun, the Examiner applied Hou, Yao, and Riggins as discussed in connection with claim 1. The Examiner acknowledge, however, that Hou, Yao, and Riggins do not “expressly teach using an EPSPS inhibitor or a co- Appeal 2020-002276 Application 13/612,925 24 herbicide in said composition; and do not teach the use of an organosilicone surfactant.” Ans. 12. The Examiner found, however, that Shaner taught that “‘combinations of glyphosate with 2, 4-D or dicamba are needed to give adequate control’ to the populations of weeds, including Amaranthus sp. that are developing glyphosate resistance.” Id. The Examiner further found that Singh taught that “organosilicone-based adjuvants increase glyphosate translocation in Amaranthus retroflexus . . . and that ‘[o]rganosilicone adjuvants have the potential to provide greater rainfastness to glyphosate on redroot pigweed and, to a lesser extent, on guineagrass.’” Id. at 13. Finally, the Examiner found that Sun disclosed that “organosilicone surfactants generally increase the efficacy and uptake of herbicides, including that of glyphosate.” Id. 12. 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 EPSPS inhibitor, such as glyphosate, either alone or in combination with another herbicide directed to a different target, such as dicamba or 2, 4-D, taught by Shaner” as well as “an organosilicon surfactant, such as those taught by Sun and Singh.” Id. at 13. Claims 6–9 and 16–20 Appellant argues claims 6–9 and 16–20 together. Appeal Br. 58–59. We designate claim 6 as representative. Claim 6 depends from claim 1 and further requires that the composition comprises an EPSPS inhibitor herbicide. Appellant argues that “Shaner at most discusses ‘the effect of glyphosate-tolerant crops may have on the use and availability of other herbicides and the impact that the Appeal 2020-002276 Application 13/612,925 25 widespread adoption of this technology will have on herbicide resistance management.’” Appeal Br. 58. Appellant thus argues that Shaner “does not provide any teaching, suggestion, or motivation that any EPSPS inhibitor herbicide and/or other herbicides can be used in a composition with a transfer agent and a dsRNA targeting EPSPS gene sequences in a method of plant control as recited.” Id. We are not persuaded. Shaner teaches that “combinations of glyphosate and 2, 4-D or dicamba are needed to give adequate control” of weed populations that are developing glyphosate resistance, including Amaranthus sp. Shaner, 324. We find that this would have motivated the ordinary artisan to combine the siRNA herbicidal composition suggested by the cited art with another herbicide. 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 7–9 and 16–20 fall with claim 6. Claims 2, 12, 22, 38, 39, 48, and 49 Appellant argues claims 2, 12, 22, 38, 48, and 49 together. We designate claim 2 as representative. 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 Appeal 2020-002276 Application 13/612,925 26 effects on herbicide activity on weedy plants” and “Singh at most ‘measure[s] the effects of adjuvants on the absorption and translocation of glyphosate using selected conventional and organosilicone adjuvants.’” Appeal Br. 59. Appellant argues that Sun and Singh do not support that an organosilicone surfactant would inherently function as a transfer agent. Id. at 60–61. We agree with the Examiner that the disclosures of Sun and Singh would have suggested the use of an organosilicone surfactant in Hou’s method. As the Examiner explains: Sun and Singh et al teach the advantages of using organosilicone surfactants when an agricultural composition is applied to the surface of a plant. Sun teaches that organosilicone surfactants generally increase the efficacy and uptake of herbicides, including that of glyphosate (except in a few grass species). Importantly, Sun also teaches that organosilicone surfactants increase the spreading area of aqueous solutions on a plant leaf, and have been used as adjuvants to enhance penetration not only of herbicides but also growth regulators and foliar nutrients. Singh et al teach that organosilicone-based adjuvants increase glyphosate translocation in Amaranthus retroflexus. Ans. 31. 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 EPSPS 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 enhance penetration of herbicides, growth regulators and foliar nutrients, and increase the efficacy and uptake of herbicides. Sun 2–3, 4–6, 9–10; see also Singh, Abstract, 110. Moreover, Appeal 2020-002276 Application 13/612,925 27 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. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 5, 10, 11, 21, 42–47 103(a) Hou, Yao, Riggins 1, 5, 10, 11, 21, 42–44, 47 45, 46 2, 6–9, 12, 16– 20, 22, 38, 39, 48, 49 103(a) Hou, Yao, Riggins, Shaner, Singh, and Sun 2, 6–9, 12, 16–20, 22, 38, 39, 48, 49 Overall Outcome 1, 2, 5–12, 16–22, 38, 39, 42–44, 47–49 45, 46 No time period for taking any subsequent action in connection with this appeal may be extended under 3 7 C.F .R. § 1.13 6( a )(1 ). AFFIRMED IN PART Copy with citationCopy as parenthetical citation