Aviagen et al.Download PDFPatent Trials and Appeals BoardDec 2, 20212021001517 (P.T.A.B. Dec. 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. 16/384,782 04/15/2019 Scott Geoffrey Tyack 90598-A/GJG/DH 7370 23432 7590 12/02/2021 c/o COOPER & DUNHAM LLP 90 PARK AVENUE, 21st Fl NEW YORK, NY 10016 EXAMINER WILSON, MICHAEL C ART UNIT PAPER NUMBER 1632 NOTIFICATION DATE DELIVERY MODE 12/02/2021 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): DUSPTO@cooperdunham.com patcomm-in-grp@cooperdunham.com pdocketing@cooperdunham.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte SCOTT GEOFFREY TYACK ____________ Appeal 2021-001517 Application 16/384,782 Technology Center 1600 ____________ Before DONALD E. ADAMS, TAWEN CHANG, and RYAN H. FLAX, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 2–7 and 10–15 (Appeal Br. 1). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as: (1) Aviagen, having a place of business at 920 Explorer Boulevard NW, Huntsville, Alabama 35806, USA; and (2) Commonwealth Scientific and Industrial Research Organisation (“CSIRO”), having a place of business at CSIRO Black Mountain Science and Innovation Park, Clunies Ross Street, Acton ACT 2601, Australia. (Appellant’s August 10, 2020, Appeal Brief (Appeal Br.) 6). Appeal 2021-001517 Application 16/384,782 2 STATEMENT OF THE CASE Appellant’s disclosure “relates to methods for transfecting cells. In particular, the present invention relates to methods of transfecting primordial germ cells in avians, and to methods of breeding avians with modified traits” (Spec.2 ¶ 1). Appellant’s independent claims 2 and 10 are reproduced below: 2. A process for using CRISPR to incorporate a polynucleotide into the genome of a chicken primordial germ cell (PGC), comprising: (i) injecting, into a blood vessel of a chicken embryo at stage 13-17 that is contained in an egg, a transfection mixture comprising: (a) a DNA polynucleotide encoding the components of a Type II CRISPR locus comprising a pre-crRNA array, tracrRNA, and a Cas9 nuclease; (b) a DNA polynucleotide for integration into the genome of one or more germ cells in the chicken embryo; and (c) a cationic lipid, whereby the DNA polynucleotides enter one or more PGCs in the chicken embryo, and (1) the pre-crRNA array and the tracrRNA of the Type II CRISPR locus are transcribed; (2) tracrRNA hybridizes to repeat regions of the precrRNA and mediates processing of pre-crRNA into mature crRNAs containing guide spacer sequences, thereby producing a mature crRNA:tracrRNA complex; (3) the Cas9 nuclease is expressed and the mature crRNA:tracrRNA complex directs the Cas9 nuclease to a target DNA via Watson-Crick base-pairing between the guide spacer sequences on the crRNA and a 2 Appellant’s April 15, 2019, Specification. Appeal 2021-001517 Application 16/384,782 3 protospacer on the target DNA next to a protospacer adjacent motif (PAM) having the sequence NGG; (4) the Cas9 nuclease mediates cleavage of the target DNA to create a double-stranded break within the protospacer on the target DNA; and (5) the DNA polynucleotide of (b) is incorporated into the genome of the one or more PGCs in the chicken embryo. (App.3 A.1.) 10. A process for using CRISPR to incorporate a polynucleotide into the genome of a chicken primordial germ cell (PGC), comprising: (i) injecting, into a blood vessel of a chicken embryo at stage 13-17 that is contained in an egg, a transfection mixture comprising: (a) a DNA polynucleotide encoding a chimeric crRNAtracrRNA hybrid and a Cas9 nuclease; (b) a DNA polynucleotide for integration into the genome of one or more germ cells in the chicken embryo; and (c) a cationic lipid, whereby the DNA polynucleotides enter one or more PGCs in the chicken embryo, and (1) the chimeric crRNA-tracrRNA hybrid is transcribed; (2) the Cas9 nuclease is expressed and the chimeric crRNAtracrRNA hybrid directs the Cas9 nuclease to a target DNA via Watson-Crick base-pairing between a guide spacer on the chimeric crRNA-tracrRNA hybrid and a protospacer on the target DNA next to a protospacer adjacent motif (PAM) having the sequence NGG; 3 Appendix A of Appellant’s August 10, 2020, Appeal Brief. Appeal 2021-001517 Application 16/384,782 4 (3) the Cas9 nuclease mediates cleavage of the target DNA to create a double-stranded break within the protospacer on the target DNA; and (4) the DNA polynucleotide of (b) is incorporated into the genome of the one or more PGCs in the chicken embryo. (App. 3.) Grounds of rejection before this Panel for review: Claims 2–7 and 10–15 stand rejected under the written description provision of 35 U.S.C. § 112, first paragraph. Claims 2–7 and 10–15 stand rejected under the enablement provision of 35 U.S.C. § 112, first paragraph. Priority: We recognize Examiner’s assertions relating to Appellant’s claimed benefit to U.S. Provisional Application 61/363,331, filed April 20, 2012 (see Final Act.4 2–4). We do not find, however, an analysis relating to priority in Examiner’s November 3, 2020, Answer (Ans.). Thus, it appears that Examiner’s Answer withdrew the assertions, made in the Final Office Action, regarding priority. To the extent that Examiner’s concerns regarding priority remain, we find that Examiner does not dispute Appellant’s contention that “Examiner acknowledged that U.S. Provisional Application No. 61/783,823, filed March 14, 2013[,] contemplated using CRISPR” and directs attention to, 4 Examiner’s January 9, 2020, Final Office Action. Appeal 2021-001517 Application 16/384,782 5 inter alia, Cong5 for a description of CRISPR technology (see generally App. Br. 10–11; Provisional Application 61/783,823 ¶¶ 101–102). As our reviewing Court made clear: As we stated in Capon, “[t]he ‘written description’ requirement states that the patentee must describe the invention; it does not state that every invention must be described in the same way. As each field evolves, the balance also evolves between what is known and what is added by each inventive contribution.” . . . Indeed, the forced recitation of known sequences in patent disclosures would only add unnecessary bulk to the specification. Accordingly we hold that where, as in this case, accessible literature sources clearly provided, as of the relevant date, genes and their nucleotide sequences (here “essential genes”), satisfaction of the written description requirement does not require either the recitation or incorporation by reference (where permitted) of such genes and sequences. Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1368 (Fed. Cir. 2006) (citing Capon v. Eshhar, 418 F.3d 1349, 1358 (Fed. Cir. 2005) (endnote omitted)). Examiner, nonetheless, contends: While Cong (2013) was available at the time of filing and can be used to help establish what was enabled, its disclosures cannot be incorporated by reference into the specification of the instant application if applicants believe they contain “essential material” regarding specific species of cells and specific protocols and reagents required to target avian genes using CRISPR technology that were not disclosed by applicants. Item e) of 37 CFR 1.57 allows incorporation by reference of non-patent literature for “non-essential material”; however, applicants appear to be attempting to “incorporate” a vast amount of information of Cong (2013) beyond what is “nonessential” because the references describe structures, method steps, and reagents required to use a Type II CRISPR system comprising crRNA, tracrRNA and a precrRNA array 5 Cong et al., Multiplex Genome Engineering Using CRISPR/CAS Systems, 339 SCIENCE 819–23 (2013). Appeal 2021-001517 Application 16/384,782 6 containing guide sequences (spacers) to target specific sequences within specific genes. (Final Act. 3.) According to Examiner: The information newly incorporated is essential to the invention . . . and those essential elements, i.e.[,] the specific structures or the gRNA, the specific target sequences within specific genes, the specific genetic modification obtained by inserting a donor sequence, the specific non-wild-type phenotype obtained, and how to use for the genetically modified embryo obtained, described by Cong are not readily apparent from the original disclosure. (Id. at 3–4.) We are not persuaded. Examiner’s concerns, at best, relate to the incorporation of subject matter relating to CRISPR technology that is readily accessible in the literature and, thus, does not require either a recitation or incorporation by reference. See id.; cf. Falkner, 448 F.3d at 1368. Thus, we are not persuaded by Examiner’s finding that “the effective filing date of claims 2 and 10 is 4-15-19, the filing date of the instant application because they require the specific reagents required to use the Type II CRISPR system described by Cong (2013) newly provided with the instant application” (Final Act. 4). Appeal 2021-001517 Application 16/384,782 7 Written Description: ISSUE Does the preponderance of evidence on this record support Examiner’s finding that Appellant’s Specification fails to provide written descriptive support for the claimed invention? ANALYSIS Appellant’s claimed method comprises, inter alia, injecting, into a blood vessel of a stage 13–17 chicken embryo that is contained in an egg, a transfection mixture comprising: (a)(i) a DNA polynucleotide encoding the components of a Type II CRISPR locus comprising a pre-crRNA array, tracrRNA, and a Cas9 nuclease or (ii) a DNA polynucleotide encoding a chimeric crRNA-tracrRNA hybrid and a Cas9 nuclease; (b) a DNA polynucleotide for integration into the genome of one or more germ cells in the chicken embryo; and (c) a cationic lipid. As Appellant explains: [T]he inventive contribution, and therefore the claims, relate to the “direct injection technique” described in the specification. The “direct injection technique” is the process of delivering the components for genome editing to chicken primordial germ cells (PGCs) in vivo, which is calibrated as recited in the claims to result in the PGCs being genetically modified. It is the technique of direct injection that is the inventor’s contribution, and the specifics of the technique are detailed in the claims. (Appeal Br. 22–23.) In this regard, Appellant contends that “[i]n the context of the claimed invention of a delivery method and the state of the knowledge in the art, Appellants submit that a description of specific structures to be delivered, such as the structure of a CRISPR target sequence within the PANK1 gene or any other avian gene, is not required for the claims to be adequately described (id. at 38–39; see also Reply Br. 12–13). See Falkner, Appeal 2021-001517 Application 16/384,782 8 448 F.3d at 1365 (A specification need not disclose what is well known in the art.). Therefore, we are not persuaded by Examiner’s finding that Appellant’s Specification fails to disclose the reagents necessary to perform Appellant’s claimed method, which are known in the art (see Ans. 19–21 (Examiner finds that Appellant does not describe the reagents required to perform a method involving CRISPR technology)). As Appellant explains, “Examiner alleged without basis that ‘the starting reagents for genetically modifying chicken genes using gRNA, Cas9, and exogenous DNA were not conventional or well-known’” at the time of Appellant’s claimed invention (Reply Br. 13). Although Appellant’s claimed invention requires the incorporation of a DNA polynucleotide into the genome of one or more PGCs of a chicken embryo, Appellant’s claimed method does not require that the incorporation of a specific DNA polynucleotide or that the incorporated DNA polynucleotide results in a chicken with an altered phenotype (see generally Appeal Br. 41; Reply Br. 14). Therefore, we are not persuaded by Examiner’s findings regarding “trait modification,” the “repair[] [of] an endogenous gene,” or “the unpredictability of obtaining the desired phenotype using CRISPR” (see Ans. 20–23). As Appellant explains, its claimed method was sufficiently predictable once it was experimentally shown to stably transform PGCS in chickens (see Appeal Br. 40). Thus, we are not persuaded by Examiner’s statements concerning “the unpredictability of CRISPR technology . . . and the lack of expectation that ‘the claimed method could be used to stably transform[] primordial germ cells (PGCs) in avians’” (Ans. 21). For the Appeal 2021-001517 Application 16/384,782 9 same reason, we are not persuaded by Examiner’s finding that “Ono taught such methods were unpredictable” and Appellant has “provided no greater teachings than Ono” (Ans. 22). As Appellant explains, Ono is concerned with a delivery method, like Appellants’ invention. Appellants’ invention is an improvement over Ono. Notably, however, Appellants have noted previously that lack of an expectation in the art, a priori, regarding whether the claimed method could be used to stably transform avian germ cells does not equate to a lack of expectation once Appellants successfully demonstrated their method of stable transformation. (Reply Br. 9.) Appellant’s Specification discloses that “[t]he term [avian] includes the various known strains of Gallus gallus (chickens), for example, White Leghorn, Brown Leghorn, Barred-Rock, Sussex, New Hampshire, Rhode Island, Australorp, Comish, Minorca, Amrox, California Gray, Italian Partidge-coloured” (Spec. ¶ 75). Therefore, we are not persuaded by Examiner’s finding that Appellant’s Specification fails to provide written descriptive support for the scope of the term chicken set forth in Appellant’s claimed invention (see Ans. 23–24). As Appellant explains, its Specification “describes using the claimed method for chickens and the Examiner has not presented any evidence that Appellants were not in possession of the claimed method of modifying any breed of chicken” (Appeal Br. 42; see also Reply Br. 11 (Appellant contends that “[t]he record is completely devoid of any evidence that undue experimentation would be required to practice the claimed method, or indeed any type of genetic manipulation that has been shown to work on one breed, with any particular breed of chicken” (footnote omitted)). Appeal 2021-001517 Application 16/384,782 10 In addition, we agree with Appellant’s contention that Examiner’s rejection presupposes that the reagents for genetically modifying chicken genes using CRISPR are different from reagents that were known in the art for modifying other eukaryotic species. The Examiner has presented no evidence to suggest that specific reagents, different from those known in the art or recited in the claims, are required to modify chicken genes using CRISPR. (Reply Br. 13.) CONCLUSION The preponderance of evidence on this record fails to support Examiner’s finding that Appellant’s Specification fails to provide written descriptive support for the claimed invention. The rejection of claims 2–7 and 10–15 under the written description provision of 35 U.S.C. § 112, first paragraph is reversed. Enablement: ISSUE Does the evidence of record support Examiner’s conclusion that undue experimentation would be required to practice the claimed invention? ANALYSIS Examiner finds that although Appellant’s Specification provides an enabling disclosure of “injecting a vector encoding a protein into a blood vessel of an avian embryo, and obtaining expression of the protein in an avian obtained from the embryo,” Appellant’s Specification “does not reasonably provide enablement for using a polynucleotide encoding CRISPR, any exogenous DNA polynucleotide for insertion, and a cationic lipid injected into a blood vessel of an avian embryo to obtain any avian with germ cells comprising any genetic modification as broadly Appeal 2021-001517 Application 16/384,782 11 encompassed by claims 2, 10” (Ans. 3). Thus, Examiner concludes that Appellant’s Specification “does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims” (Ans. 3–4). We are not persuaded. As Appellant explains, “[b]y April 19, 2013, the Type II CRISPR- Cas9 system had been characterized in detail and demonstrated to work in eukaryotic cells, as reported by, . . . Cong” (Appeal Br. 16; see also id. at 24 (Appellant explains that “Jinek . . . experimentally demonstrated that Cas9 proteins do, in fact, function in eukaryotic cells”)). We find no persuasive evidence on this record to support a finding that a DNA polynucleotide encoding: (a) the components of a Type II CRISPR locus comprising a pre- crRNA array, tracrRNA, and a Cas9 nuclease, or (b) a chimeric crRNA- tracrRNA hybrid and a Cas9 nuclease, would not be functionally expressed when injected into a blood vessel of a chicken embryo at stage 13–17, as set forth in Appellant’s claimed invention. Therefore, we are not persuaded by Examiner’s assertion that Appellant’s [S]pecification fails to provide adequate guidance for those of skill to determine specific target sequences within specific chicken genes for incorporating an exogenous polynucleotide using CRISPR technology, the specific structures of gRNA that target those sequences, the specific structure of the “DNA polynucleotide for integration into the genome” that would integrate into those target sequences, or the final desired genetic modification in the PGC’s genome made by the method of [Appellant’s] claims 2 or 10. (Ans. 13–14; see also id. at 14–16). We recognize Examiner’s assertion that Appellant’s “[S]pecification does not teach the human codon-optimized Cas9 of Cong (2013) would Appeal 2021-001517 Application 16/384,782 12 function in chicken PGCs” (id. at 14). Examiner, however, failed to establish an evidentiary basis on this record to support a finding that Appellant’s presumptively accurate disclosure does not adequately enable the claimed invention. See In re Wright, 999 F.2d 1557, 1561–62 (Fed. Cir. 1993); In re Marzocchi, 439 F.2d 220, 224, 169 USPQ 367, 370 (CCPA 1971). As Appellant explains, “[c]odon optimization was routine in the art well before the filing date” of Appellant’s claimed invention (Appeal Br. 32). “[A] patent need not teach, and preferably omits, what is well known in the art.” Hybritech Incorporated v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384 (Fed. Cir. 1986). For the foregoing reasons, we are not persuaded by Examiner’s assertions regarding codon-optimization (see Ans. 14 and 33). Appellant’s claimed invention does not require the production of a chicken with a modified phenotype. Therefore, we are not persuaded by Examiner’s intimation that Appellant’s Specification fails to enable the production of a chicken with a particular phenotype (see Ans. 13; see also id. at 17–18). For the same reasons, we are not persuaded by Examiner’s assertions regarding “unexpected phenotypes,” gene knockouts, or mutation correction at a specific location, or off target insertions that may cause unexpected phenotypes (see id. at 5–6; see also id. at 10–11). For the same reasons, we are not persuaded by Examiner’s assertion that “Cong does not teach specific target sequences within specific chicken genes for incorporating an exogenous polynucleotide using CRISPR technology” (id. at 14). Claims 27 and 35 are not before this Panel for review and Appellant’s claim 1 requires injection into a blood vessel of a chicken embryo at stage Appeal 2021-001517 Application 16/384,782 13 13–17, therefore, we are not persuaded by Examiner’s assertion that a mixture “injected into a window in the [egg] shell . . . is equivalent to ‘wherein the transfection mixture is injected in the eggshell in which the embryo developed’ as required in [Appellant’s] . . . claims 1, 27, [and] 35’” (Ans. 6). Examiner failed to establish that Ono suggested injecting a transfection mixture comprising, inter alia, a DNA polynucleotide encoding: (a) the components of a Type II CRISPR locus comprising a pre-crRNA array, tracrRNA, and a Cas9 nuclease, or (b) a chimeric crRNA-tracrRNA hybrid and a Cas9 nuclease. Therefore, we are not persuaded by Examiner’s finding that Ono supports conclusion that “the art of injecting polynucleotides into a blood vessel of the embryo for the purpose of integrating an exogenous sequence into the genome of a cell was unpredictable” (Ans. 7; see also id. at 16–17). Examiner failed to establish an evidentiary basis on this record to support a finding that Appellant’s “[S]pecification does not enable genetically modifying any species of chicken gene as broadly encompassed by [Appellant’s] claims 2 and 10” (Ans. 18–19; cf. Appeal Br. 35 (Appellant contends that “Examiner has not presented any evidence that particular breeds of chicken could not be used in the claimed invention”); Reply Br. 11 (Appellant contends that “[t]he record is completely devoid of any evidence that undue experimentation would be required to practice the claimed method, or indeed any type of genetic manipulation that has been shown to work on one breed, with any particular breed of chicken” (footnote omitted)).). Appeal 2021-001517 Application 16/384,782 14 Examiner finds that Tyack’s testimony supports a finding that “it was unpredictable in the art at the time of filing whether direct injection of a transfection mixture into a blood vessel of an avian embryo would result in stable transfection of PGCs in the avian embryo” (Ans. 11–12 (citing Tyack Decl.6 ¶¶ 11 and 15). We are not persuaded. As Appellant explains, the evidence of record establishes that the portions of the Tyack Declaration relied upon by Examiner relate to prior art methods of “directly injecting a transfection mixture into the vein of an avian embryo[, which] only provided a very low level of efficiency of transfections” (Appeal Br. 26 (citing Third Doran Decl. ¶ 8 (Doran declares that “the prior art taught that directly injecting a transfection mixture into the vein of an avian embryo only provided a very low level of efficiency of transfection.”))). As Doran explains: [O]nce Scott Tyack had shown that a transfection mixture comprising a cationic lipid and a polynucleotide construct encoding a zinc finger nuclease can be directly injected into the vein of an avian embryo to achieve stable transformation of avian germ cells, a person of skill in the art would be able to follow Scott’s procedure to deliver other types of targeting nucleases to avian germ cells. (Third Doran Decl. ¶ 7; see also Appeal Br. 36 (Appellant contends that “[c]onsistent with the Third Doran Declaration, once the claimed process was shown to work, the claimed invention could be practiced very predictably.”).) 6 Declaration of Scott Tyack, Ph.D., signed November 2, 2018, which is Exhibit 6 of the Timothy Doran, Ph.D., Declaration, signed October 11, 2019 (Third Doran Decl.) (see Third Doran Decl. ¶ 7; see also Appeal Br. 5). Appeal 2021-001517 Application 16/384,782 15 In sum, we find that Examiner failed to establish an evidentiary basis on this record to support a conclusion that undue experimentation would be required to practice Appellant’s claimed invention. CONCLUSION The evidence of record fails to support Examiner’s conclusion that undue experimentation would be required to practice the claimed invention. The rejection of claims 2–7 and 10–15 under the enablement provision of 35 U.S.C. § 112, first paragraph is reversed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 2–7, 10–15 112(a) Written Description 2–7, 10–15 2–7, 10–15 112(a) Enablement 2–7, 10–15 Overall Outcome 2–7, 10–15 REVERSED Copy with citationCopy as parenthetical citation