Ex Parte Herzog et alDownload PDFPatent Trial and Appeal BoardDec 19, 201613688468 (P.T.A.B. Dec. 19, 2016) 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. 13/688,468 11/29/2012 Christian HERZOG 2578-8401.3US 8615 24247 7590 12/21/2016 TRASKBRITT, P.C. P.O. BOX 2550 SALT LAKE CITY, UT 84110 EXAMINER HUMPHREY, LOUISE WANG ZHIYING ART UNIT PAPER NUMBER 1657 NOTIFICATION DATE DELIVERY MODE 12/21/2016 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): U S PTOMail @ traskbritt .com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHRISTIAN HERZOG and HEDVIKA LAZAR1 Appeal 2015-004916 Application 13/688,468 Technology Center 1600 Before JEFFREY N. FREDMAN, RICHARD J. SMITH, and RACHEL H. TOWNSEND, Administrative Patent Judges. SMITH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of vaccinating a human subject against influenza. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 According to Appellants, the real party in interest is Crucell Switzerland A.G. (Appeal Br. 2.) Appeal 2015-004916 Application 13/688,468 STATEMENT OF THE CASE Claims on Appeal Claims 19-30 are on appeal. (Claims Appendix, Appeal Br. 13—14.) Claim 19 is illustrative and reads as follows: 19. A method of vaccinating a human subject against influenza, wherein the improvement comprises: intradermally administering to the human subject a virosomal preparation comprising influenza hemagglutinin (HA) antigen wherein the preparation does not contain an additional adjuvant. Examiner’s Rejections 1. Claims 19-26, 29, and 30 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Mischler2 and Kenney.3 (Ans. 2-4.) Claims 19-26, 29, and 30 were not argued separately, and we therefore limit our consideration of those claims to claim 19. 2. Claims 27 and 28 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Mischler, Alarcon,4 and Rosenberg.5 (Id. at 4—6.)6 2 Mischler et al., Inflexal®V a trivalent virosome subunit influenza vaccine: production, Vaccine 20, B17—B23 (2002) (“Mischler”). 3 Kenney et al., Dose Sparing with Intradermal Injection of Influenza Vaccine, N. Engl. J. Med. 351, 2295-301 (2004) (“Kenney”). 4 Alarcon et al., Preclinical Evaluation of Microneedle Technology for Intradermal Delivery of Influenza Vaccines, 14 Clinical and Vaccine Immunology 4, 375-81 (2007) (“Alarcon”). 5 Rosenberg, US 6,623,457 Bl, issued Sept. 23, 2003 (“Rosenberg”). 6 The Examiner inadvertently identifies Rejection No. 2 as a rejection of claims 19-26, 29, and 30. (See Ans. 4; Final Act. dated July 8, 2014, at 6; Office Action dated Feb. 21, 2014, at 4.) Appellants correctly address the rejection as directed to claims 27 and 28. (Appeal Br. 9.) 2 Appeal 2015-004916 Application 13/688,468 FINDINGS OF FACT We adopt as our own the Examiner’s findings and analysis concerning the scope and content of the cited prior art. The following findings are included for emphasis and reference convenience. FF 1. The Specification states that “[t]he art has disclosed that virosomal preparations comprising influenza HA antigen did not provide sufficient seroconversion-, seroprotection- and GMT-fold increase levels in animals (pigs). The inventors . . . now show that the international standards were met when these vaccines were administered to humans.” (Spec. 111.) FF 2. The Specification states that Influenza virosomes have been used for intradermal administration and such methods were disclosed in WO 2004/016281.[7] The examples and drawings in [Garcon] disclose that a virosomal-based influenza vaccine ... in combination with different concentrations of an [adjuvant] fulfills one of the criteria set by the [European Medicines Agency] (at least 40% seroconversion rate . . .) for each vaccine strain, see FIGS. 1 through 3 therein. However, no positive results were obtained when the adjuvant . . . was omitted . . . Seroconversion rates did not reach 40% in any of the cases that the virosomes without [adjuvant] were administered intradermally. The ordinary way of administration, intramuscularly, did result in sufficient seroconversion. Hence, the conclusion from [Garcon] would be that intradermal administration of virosome-based influenza vaccines should not be used to obtain sufficient protection. {Id. at U 19.) 7 Garcon, W0 2004/016281 Al, published Feb. 26, 2004 (“Garcon”). Appellants refer to Garcon in the Specification and briefing by its publication number, W0 2004/016281. 3 Appeal 2015-004916 Application 13/688,468 FF 3. Mischler teaches “parenterally administered trivalent virosome influenza vaccine” comprising haemagglutinin (HA) antigen without an additional adjuvant, and that the use of virosomes “stimulate a strong immune response.” (Mischler B20; Ans. 2—3.) FF 4. Kenney teaches intradermal administration of influenza vaccines. (Kenney Abstract.) Kenney teaches a comparison of intradermal administration to intramuscular administration, finding that “[sjeroconversion and seroprotection rates were similar in the two groups,” and that “intradermal administration of one fifth the standard intramuscular dose of an influenza vaccine elicited immunogenicity that was similar to or better than that elicited by intramuscular injection.” (Id.) Kenney teaches that dose-sparing strategies that use intradermal delivery may be an approach to address the critical shortage of influenza vaccine. (Id.) ISSUE Whether a preponderance of evidence of record supports the Examiner’s conclusion of obviousness under 35 U.S.C. § 103(a). ANALYSIS We adopt the Examiner’s findings and analysis regarding the cited prior art, and agree with the Examiner’s conclusion that claims 19—30 would have been obvious to a person of ordinary skill in the art at the time of the invention. (Ans. 2—8; Final Act. 2—8.) Rejection No. 1—Claim 19 Appellants argue that Mischler and Kenney, taken alone or together, do not teach or suggest all of the elements of claim 19, that there is no motivation or reason to combine the teachings of Mischler and Kenney, and that “there was not a reasonable expectation of success that intradermal 4 Appeal 2015-004916 Application 13/688,468 injection of a virosomal preparation without an added adjuvant would elicit a satisfactory immune response.” (Appeal Br. 6—9; Reply Br. 2-4.) As an initial matter, we find that Mischler and Kenney teach all of the elements of claim 19. (FF 3 and 4.) We further find that claim 19 does not recite a seroconversion rate or standard, or any other measure of vaccination efficacy or sufficiency. (Appeal Br. 13.) See In re Self, 671 F.2d 1344, 1348 (CCPA 1982). Appellants’ remaining arguments are addressed below. Motivation to Combine Appellants point to the Specification and Garcon to argue that there was no reason to combine the parenteral administration of virosome influenza vaccine of Mischler with the intradermal administration of influenza vaccines of Kenney. (Appeal Br. 7—9.) In particular, Appellants argue that, at the time of the claimed invention, the art taught “that virosomal preparations comprising influenza HA antigen did not provide sufficient seroconversion-, seroprotection-, and GMT-fold increase levels in animals” (see FF 1), and “that intradermally administered influenza virosomes demonstrated poor seroconversion rates without co administration of (potentially problematic) adjuvants” (see FF 2). (Id. at 8.) We are not persuaded. Mischler teaches the use and advantage of parenterally administered virosome preparations comprising influenza HA antigen without an adjuvant, and Kenny teaches the advantage of intradermal administration of influenza vaccine. (FF 3 and 4.) We thus find a motivation to combine the teachings of Mischler and Kenney in the cited art, including to obtain the advantages of intradermal administration of virosome influenza preparations without an adjuvant. See SIBIA Neurosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1356—59 (Fed. 5 Appeal 2015-004916 Application 13/688,468 Cir. 2000) (concluding that patent would have been obvious in light of teachings in prior art which provided motivation and suggestion to modify existing techniques to arrive at method in question). We address Appellants arguments regarding Garcon below.8 Appellants essentially argue that there would be no motivation to combine the teachings of Mischler and Kenney because Garcon taught that to do so would produce insufficient or poor seroconversion rates compared to intradermal administration of virosomes with an adjuvant. (Appeal Br. 7— 9.) However, we find that argument unpersuasive for at least the following reasons. First, Garcon discloses a test of various vaccine combinations on pigs, including the intradermal administration of flu virosomes, both with and without a particular adjuvant, and illustrates the results of those tests at Figures 1—3.9 (Garcon 15,1. 19-16,1. 21; Fig. 1—3.) Even if we assume that Garcon describes the intradermal administration of flu virosomes without an adjuvant as somewhat inferior to administration with an adjuvant, we do not find that such a description constitutes a persuasive reason that one skilled in 8 We acknowledge the issue addressed by the Examiner and Appellants regarding the needles or syringes disclosed in Kenney and Garcon, but do not find that relevant to the rejections or Appellants’ arguments regarding Garcon. (See Ans. 7—8; Reply Br. 2—5.) 9 The Y axis in Figures 1—3 of Garcon is identified as “HI titers (GMT)” and reflects a range of numerical values, with some tested vaccines exceeding a numerical value of 100. (Garcon Fig. 1—3.) Furthermore, Garcon defines seroconversion rate as “the percentage of vaccinees who have at least a 4- fold increase in serum haemagglutinin (HI) titres after vaccination, for each vaccine strain.” (Garcon 4,11. 4—6.) 6 Appeal 2015-004916 Application 13/688,468 the art would not combine the teachings of Mischler and Kenney, particularly in light of the fact that claim 19 is not limited to a particular vaccine efficacy or seroconversion rate. See, e.g., In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994) (“A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.”). Second, Garcon identifies a formulation (Bema ID) described as “flu virosomes 3pg” (apparently without the adjuvant) delivered intradermally to pigs. (Garcon 15,1. 25.) Appellants argue that “no positive results” were obtained with that formulation, apparently because seroconversion rates “did not reach 40%.” (Appeal Br. 8; see FF 2.) However, that formulation (Bema ID) is shown in Figure 1 of Garcon as having an increase in HI titers, which may, for example, approximate or meet the desired seroconversion rate for individuals over 60 years old; namely, >30%. (See Garcon 4,11. 1—7 and Fig. 1.) Moreover, Figures 1 and 3 of Garcon indicate that Bema ID had a greater level of HI titers (post-vaccination) than a nonvirosome vaccine (Plain ID) delivered intradermally, thus suggesting that a person of skill in the art desiring to use the intradermal administration method, for the advantage taught by Kenney, would use a virosome vaccine rather than a nonvirosome vaccine. {Id. at Fig. 1 and Fig. 3.) Furthermore, a direct comparison between the intramuscular and intradermal administrations in Garcon is inapt, at least because the vaccine delivered intramuscularly (Plain IM) is not a virosome vaccine and the quantity of Plain IM administered (15 pg) is greater than the quantity of the virosome vaccines (3 pg). (Garcon 15,1. 19-16,1. 21.) 7 Appeal 2015-004916 Application 13/688,468 Finally, Appellants’ arguments regarding Garcon are not commensurate in scope with claim 19. Appellants’ arguments regarding Garcon focus on “international standards” and criteria set by the European Medicines Agency (“40% seroconversion rate”). (See FF 1 and 2.) But claim 19 does not recite a seroconversion rate or standard, or any other measure of vaccination efficacy or sufficiency. Reasonable Expectation of Success Appellants argue that “given the teachings of [Garcon] there was no reasonable expectation of success that intradermal injection of a virosomal preparation without an added adjuvant would elicit a satisfactory immune response.” (Appeal Br. 8.) In particular, Appellants argue that “there was no reasonable expectation of success that the intradermal injection teachings of Kenney would be successful with a virosomal preparation lacking an adjuvant.” (Id.) We are not persuaded. The reasonable expectation of success requirement “refers to the likelihood of success in combining references to meet the limitations of the claimed invention.” Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir. 2016). Here, claim 19 is not limited to a particular “satisfactory immune response” and, in fact, Garcon shows an increase in HI titers for intradermal administration of virosome vaccines without an adjuvant (Bema ID). (See, e.g., Garcon Fig. 1.) Accordingly, given the teachings of Mischler and Kenney, we find a reasonable expectation of success in combining the teachings of those references to meet the limitations of claim 19 (that does not recite a particular immune response). 8 Appeal 2015-004916 Application 13/688,468 Rejection No. 2—Claims 27 and 28 Appellants argue that dependent claims 27 and 28 are nonobvious because Mischler, Alarcon, and Rosenberg do not teach or suggest all of the elements of claims 27 and 28, and because “no motivation exists to modify the teachings of Mischler to include the intradermal delivery devices of Alarcon or Rosenberg.” (Appeal Br. 9-11; see also Reply Br. 4—5.) However, the cited references do teach and suggest all of the elements of claims 27 and 28. (Ans. 4—6.) Moreover, Appellants’ arguments are based on the same arguments advanced in connection with Rejection No. 1, including their arguments regarding the teachings of Mischler and Garcon. (Id.) Accordingly, for the reasons set forth above, and because we discern no error in the Examiner’s reliance on, and combination of, Mischler, Alarcon, and Rosenberg, we affirm the rejection of claims 27 and 28. CONCLUSION OF LAW A preponderance of evidence of record supports the Examiner’s conclusion that claims 19-30 are obvious under 35 U.S.C. § 103(a). SUMMARY We affirm the rejections of all claims on appeal. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 9 Copy with citationCopy as parenthetical citation