Etubics Corporation

Patent Trials and Appeals Board

Jan 18, 2022

2022000215 (P.T.A.B. Jan. 18, 2022)

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. 16/859,490 04/27/2020 Joseph P. Balint 8774ETU-1- PCT-C1-CON-D1 7603 157773 7590 01/18/2022 Sheridan Ross PC 1560 Broadway Suite 1200 Denver, CO 80202 EXAMINER ZEMAN, ROBERT A ART UNIT PAPER NUMBER 1645 NOTIFICATION DATE DELIVERY MODE 01/18/2022 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): e-docket@sheridanross.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JOSEPH P. BALINT, FRANK R. JONES, and RICHARD B. GAYLE III1 Appeal 2022-000215 Application 16/859,490 Technology Center 1600 Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and TAWEN CHANG, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims related to a replication defective adenovirus vector, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. STATEMENT OF THE CASE One aspect of the invention provides a method of generating an immune response against one or more target antigens in an 1 Appellant identifies the real party in interest as Etubics Corporation. Appeal Br. 3. “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42(a). Appeal 2022-000215 Application 16/859,490 2 individual comprising administering to the individual an adenovirus vector comprising: a) a replication defective adenovirus vector, wherein the adenovirus vector has a deletion in the E2b region, and b) a nucleic acid encoding the one or more target antigens; and readministering the adenovirus vector at least once to the individual; thereby generating an immune response against the one or more target antigens. Spec. 4:8-14. “[O]ne advantage of the present invention is the capability to administer multiple vaccinations with the same or different adenovirus vectors.” Id. at 61:9-10. “[T]he adenoviral vaccines of this invention may also be administered as part of a prime and boost regimen. A mixed modality priming and booster inoculation scheme may result in an enhanced immune response.” Id. at 61:11-14. Claims 37-44 and 47-56 are on appeal. Claim 37, reproduced below, is illustrative: 37. A composition comprising: a replication defective adenovirus vector comprising: (a) a deletion in the E2b region; and (b) a nucleic acid sequence encoding an antigen, wherein the antigen is a viral protein, and wherein the virus is a human severe acute respiratory syndrome (SARS) coronavirus. Appeal 2022-000215 Application 16/859,490 3 The claims stand rejected as follows: Claims 37-44 and 47-56 under 35 U.S.C. § 103(a) as obvious based on Zakhartchouk2 and Chamberlain3 (Ans. 3); Claims 37-44, 47-54, and 56 under 35 U.S.C. § 103(a) as obvious based on Kobinger4 and Chamberlain (Ans. 5); Claims 37-44 and 47-56 under 35 U.S.C. § 103(a) as obvious based on Zakhartchouk and Amalfitano5 (Ans. 6-7); and Claims 37-44, 47-54, and 56 under 35 U.S.C. § 103(a) as obvious based on Kobinger and Amalfitano (Ans. 8). OPINION Claims 37-44 and 47-56 stand rejected as obvious based on Zakhartchouk combined with either Chamberlain or Amalfitano. Claims 37- 44, 47-54, and 56 stand rejected as obvious based on Kobinger combined with either Chamberlain or Amalfitano. The Examiner’s reasoning is the same with respect to all of the rejections, and Appellant presents the same arguments with respect to all of the rejections. Therefore, we will address them together. 2 Zakhartchouk et al., Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice, Journal of General Virology 86:211-215 (2005). 3 US 6,083,750, issued July 4, 2000. 4 Kobinger et al., Adenovirus-based vaccine prevents pneumonia in ferrets challenged with the SARS coronavirus and stimulates robust immune responses in macaques, Vaccine 25:5220-5231 (2007). 5 Amalfitano et al., Production and Characterization of Improved Adenovirus Vectors with the E1, E2b, and E3 Genes Deleted, Journal of Virology 72(2):926-933 (1998). Appeal 2022-000215 Application 16/859,490 4 The Examiner finds that Zakhartchouk discloses “compositions comprising the nucleocapsid protein (N protein) of the SARS-CoV . . . expressed in an E1/E3 deleted replication defective Ad5 human adenovirus vector.” Ans. 3, 7. Similarly, the Examiner finds that Kobinger discloses “compositions comprising adenovirus vectors expressing SARS-CoV spike proteins,” where “said adenovirus vectors can be the Ad5 and Ad7 vectors with the E1 and E3 regions deleted.” Id. at 5, 9. The Examiner acknowledges that Zakhartchouk and Kobinger do not “disclose the use of a replication defective adenovirus vector comprising a deletion in the E2b.” Id. at 4, 5, 7, 9. The Examiner finds, however, that Chamberlain “disclose[s] the effective use of E2b deletion adenovirus mutants as viral vectors.” Id. at 4, 5. The Examiner finds that Chamberlain also discloses “that their deletion vectors are superior to standard adenovirus vectors since they can’t express all viral proteins nor can they generate replication competent adenoviruses.” Id. at 4, 6. Similarly, the Examiner finds that Amalfitano discloses “adenovirus vectors wherein the E1, E2b and E3 genes have been replaced with a transgene.” Id. at 7, 9. The Examiner finds that Amalfitano also discloses that its “vectors [do] not require helper virus for high titer propagation . . . and that their deletion vectors are superior to standard adenovirus vectors.” Id. at 7-8, 9. The Examiner concludes that it would have been obvious “to utilize the E2b deletion adenovirus vector to express SARS-CoV N protein in order to take advantage of the increased safety . . . and efficacy.” Id. at 4, 8. The Appeal 2022-000215 Application 16/859,490 5 Examiner also concludes that it would have been obvious “to utilize the E2b deletion adenovirus vector to express SARS-CoV spike protein in order to take advantage of the increased safety . . . and efficacy.” Id. at 6, 9. Appellant does not dispute that the cited references support a prima facie case of obviousness. Rather, Appellant argues that the Amalfitano Declaration6 “establishes that at the time of the effective filing date of the instant application the claimed composition can successfully elicit specific immunity by homologous re-administration, and that this result was surprising and unexpected to skilled persons.” Appeal Br. 7. Dr. Amalfitano declares that the Amalfitano reference cited by the Examiner “disclosed new replication defective adenovirus vectors deleted for the E1, E2b, and E3 gene functions.” Amalfitano Decl. ¶ 4. Declarant states that, [b]ased on [his] experience in virology and immunology, [he] did not believe-until the findings disclosed by the present inventors in the instant application-that these replication defective adenovirus vectors with deletions in the E1 and E2b gene regions could be useful to generate immune responses to target antigens when re-administered to a subject multiple times. Id. Dr. Amalfitano also declares that, as of July 2, 2007 (the effective filing date), it was his opinion that the effectiveness of “replication defective adenoviruses with deletions in the E1 and E2b gene regions . . . would have been limited to heterologous immunization methods.” Amalfitano Decl. ¶ 5. Dr. Amalfitano declares that “[i]t was surprising to [him] at the time of the 6 Declaration under 37 C.F.R. § 1.132 of Andrea Amalfitano, filed Dec. 9, 2020. Appeal 2022-000215 Application 16/859,490 6 claimed invention that an even more replication defective vector (i.e., a vector having the presence of an E2b deletion in addition to the E1 deletion) could be successfully used in homologous prime-boost protocols.” Id. ¶ 6. See also Spec. 65-69 (Examples 2, 3). Finally, Dr. Amalfitano declares that, as of July 2007, “it was [his] opinion that researchers would not use homologous prime-boost protocols . . . due to the large amount of data showing that i) homologous immunization protocols do not generate an effective immune response to target antigens and ii) heterologous immunization protocols . . . were superior to homologous immunization protocols.” Amalfitano Decl. ¶ 7. Dr. Amalfitano cites Liu7 as evidence supporting this statement. Liu states that “[r]eplication-incompetent, recombinant adenovirus serotype 5 (rAd5) vectors have been explored as candidate vaccines . . . but may be substantially limited by preexisting anti-Ad5 immunity.” Liu 4844, left col. Liu carried out experiments using “[r]eplication-incompetent, E1/E3-deleted” adenovirus vectors. Id. at 4844, right col. Liu discloses that “monkeys primed with rAd5-Gag were not efficiently boosted by a second injection of rAd5-Gag, presumably due to anti-Ad5 immunity generated by the priming immunization. In contrast, monkeys primed with rAd26-Gag were boosted remarkably well by rAd5-Gag.” Id. at 4847, right col. (references omitted). 7 Jinyan Liu et al., Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys, Journal of Virology 82(10):4844-4852 (2008). Appeal 2022-000215 Application 16/859,490 7 In summary, in his Declaration, Dr. Amalfitano establishes that he is skilled in the relevant art by education, training, and experience. See Amalfitano Declaration, App. A. Dr. Amalfitano also states unequivocally that, as of the effective filing date of the claimed invention, he did not expect replication-defective adenovirus vectors with a deletion in the E2b region, as recited in the claims, to generate an immune response to a target antigen when administered to a subject multiple times or when used in a homologous prime-boost protocol. In our view, the Amalfitano Declaration presents persuasive evidence of unexpected results for the claimed invention. Weighing against the Amalfitano Declaration are Chamberlain’s statement that deletion of the adenovirus E2b genes “decreases immune recognition of virally infected cells, and allows for extended durations of foreign gene expression.” Chamberlain 13:61-66. In addition, the Amalfitano reference states that adenoviral vectors with a deletion in the polymerase (E2b) gene “have a significantly decreased potential to express viral late genes such as the Ad fiber protein” and that “an Ad vector with a decreased potential to express viral epitopes may improve gene transfer in vivo.” Amalfitano 932, left col. We conclude that the probative value of the Amalfitano Declaration outweighs that of the Chamberlain and Amalfitano references, because Dr. Amalfitano directly addresses what effect would have been expected for an E2b-deleted adenoviral vector when administered to the same host multiple times, whereas the relevant statements in the references only indirectly relate to homologous re-administration. Thus, the preponderance of the evidence of record favors a conclusion of nonobviousness. Appeal 2022-000215 Application 16/859,490 8 The Examiner reasons that, “[e]ven if, in arguendo, the ability of the claimed replication defective adenovirus vectors to successfully elicit specific immunity by homologous re-administration was unexpected, said ability was not the basis of the . . . rejection.” Ans. 13. “[T]he skilled artisan would have been motivated [to] utilize the E2b deletion adenovirus vectors of Chamberlain et al. to express an SARS viral protein in order to take advantage of the increased safety . . . and efficacy.” Id. The issue presented in this appeal, however, is not whether a skilled artisan would have considered it obvious to combine the cited references, but whether the result of doing so was superior to what would have been expected before the combination was made. “When prima facie obviousness is established and evidence is submitted in rebuttal, the decision-maker must start over.” In re Rinehart, 531 F.2d 1048, 1052 (CCPA 1976). “There is always at least a possibility of unexpected results, that would then provide an objective basis for showing that the invention, although apparently obvious, was in law nonobvious.” In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). The Examiner also reasons that “it is well settled within the immunological arts that the reduction of available antigens (e.g. surfaces proteins) would necessarily make the adenovirus vector less immunogenic.” Ans. 13-14. Thus, the reasoning goes, the ability of to induce an immune response when re- administered to a subject multiple times is an inherent characteristic of the adenovirus vector and hence the adenovirus vectors resulting from the combination of the teachings of Zakhartchouk et al. and Chamberlain et al. would have all the immunological characteristics of the instant invention. The mere recognition of inherent properties in the prior art does not Appeal 2022-000215 Application 16/859,490 9 render nonobvious an otherwise known invention. In re Wiseman, [596 F.2d 1019] (CCPA 1979). Id. at 15-16. It is true that a chemical compound, even a complex one like an adenoviral vector, will have the properties that result from its chemical composition and structure. However, the issue is not whether combining the cited references would produce a vector having the same structure, and therefore the same properties, as the vector recited in Appellant’s claims. The issue is whether a person of ordinary skill in the art would have expected those properties, based on the teachings of the cited references. The Wiseman court did not address unexpected results. In that case, “[t]he board found that the Ruppe brake, when provided with Benini’s grooves, would inherently overcome the steam or vapor cause of the problem, relied on for patentability by appellants, as well as the cause recognized by Benini, namely, dust and overheating.” Wiseman, 596 F.2d at 1023. Thus, the issue presented in Wiseman was whether the prior art supported a prima facie case when it provided a reason to combine the prior art teachings that was different from the inventors’ reason. Wiseman does not support the rejection here. Appeal 2022-000215 Application 16/859,490 10 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 37-44, 47- 56 103(a) Zakhartchouk, Chamberlain 37-44, 47- 56 37-44, 47- 54, 56 103(a) Kobinger, Chamberlain 37-44, 47- 54, 56 37-44, 47- 56 103(a) Zakhartchouk, Amalfitano 37-44, 47- 56 37-44, 47- 54, 56 103(a) Kobinger, Amalfitano 37-44, 47- 54, 56 Overall Outcome 37-44, 47- 56 REVERSED