Ex Parte Grunkemeyer et alDownload PDFPatent Trial and Appeal BoardMay 31, 201612940112 (P.T.A.B. May. 31, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/940,112 11/05/2010 7590 05/31/2016 Norman L Sims DOBRUSIN & THENNISCH PC Suite 210 29 W. Lawrence Street Pontiac, MI 48342 FIRST NAMED INVENTOR James A. Grunkemeyer 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 1251-025 6787 EXAMINER CHEN, STACY BROWN ART UNIT PAPER NUMBER 1648 MAILDATE DELIVERY MODE 05/31/2016 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAMES A. GRUNKEMEYER and WAYNE L. RYAN 1 Appeal2014-003627 Application 12/940, 112 Technology Center 1600 Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 Appellants state the real party-in-interest is Streck Inc. App. Br. 2. Appeal2014-003627 Application 12/940, 112 SUMMARY Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner's Non-Final Rejection of claims 1-2, 4, and 8-14.2 Specifically, claims 1, 2, 4, 8, 10, 11, and 14 are rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Oxford et al. (US 5,162,112, November 10, 1992) ("Oxford"), Ryan (US 5,811,099, September 22, 1998) ("Ryan '099"), Ryan (US 5,849,517, December 15, 1998) ("Ryan '517''), and Barrett et al. (US 6, 136,321, October 24, 2000) ("Barrett"). Claim 9 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Oxford, Ryan '099, Ryan '517, Barrett, and DePablo et al. (US 6,653,062 Bl, November 25, 2003) ("DePablo"). Claim 12 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Oxford, Ryan '099, Ryan '517, Barrett, and Webster et al. (US 6,344,354 Bl, February 5, 2002) ("Webster"). Claim 13 stands rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Oxford, Ryan '099, Ryan '517, Barrett, and Renoux et al. (US 3,885,011, May 20, 1975) ("Renoux"). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 2 Claims 3 and 5-7 are canceled. App. Br. 21-22. Claims 15-20 are currently withdrawn. App. Br. 4. 2 Appeal2014-003627 Application 12/940, 112 NATURE OF THE CLAIMED INVENTION Appellants' invention is directed to a composition comprising a live virus having an infectious component with a plurality of surface antigens in contact with a formaldehyde donor agent having a molecular weight that is less than about 400 g/mol. The present invention further provides a method for deactivating a live virus having an infectious component and a plurality of surface antigens. Abstract. REPRESENTATIVE CLAIM Appellants group their claims as follows, corresponding to the Examiner's rejections: Group I, claims 1, 2, 4, 8, 10, 11, and 14; Group II, claim 9, Group III, claim 12, and Group IV, claim 13. App. Br. 13. Claim 1 is representative of the claims on appeal and recites: Claim 1: A method comprising the steps of a) providing a live virus having an infectious component and a plurality of surface antigens; b) contacting the virus with a non-crosslinking chemical fixative that contains urea having a molecular weight that is greater than about 50 g/mol and less than about 400 g/mol at a concentration of about 5 w /v grams per 100 ml total volume or less for a period of time of about 24 to about 72 hours, at a temperature of about 23 °C to about 3 7°C, the conditions being sufficient for de- activating the infectious component, and for preserving at least a portion of the surface antigens to form a deactivated virus. App. Br. 21. 3 Appeal2014-003627 Application 12/940, 112 ISSUES AND ANALYSES We agree with, and adopt, the Examiner's findings and conclusion that the appealed claims are prima facie obvious over the cited prior art references. We address the arguments raised by Appellants below. A. Group I: Claims 1, 2, 4, 8, 10, 11, and 14 Issue Appellants argue the Examiner erred by failing to properly establish that the cited references can be combined and, further, failing to establish that the combined cited prior art teaches or suggests several features of the claimed process. App. Br. 8. Analysis Appellants argue Oxford teaches the use of formaldehyde in inactivating live viruses. 1A .. pp. Br. 16. According to Appellants, Oxford teaches formaldehyde performs two functions: (1) deactivating flu viruses; and (2) stabilizing antigenic cites by crosslinking proteins. Id. Appellants assert Oxford also teaches that its disclosed process is used only with certain viral strains grown in a certain way, and possessing a certain morphology. Id. Appellants maintain these teachings indicate the sensitivity of the process and, therefore, the unpredictability of the processes. Appellants argue Ryan '099 discloses that diazolidinyl urea ("DU") or imidazolidinyl urea ("IDU") can be used as a fixative for antigens in place of formaldehyde. App. Br. 16. Appellants assert Ryan '099 neither teaches nor suggests that DU or IDU will function to deactivate a virus in addition to stabilizing the antigenic sites and state that this is admitted by the Examiner. 4 Appeal2014-003627 Application 12/940, 112 Id. (citing Final Act. 4) ("Though Ryan does not specify that the viruses used in the vaccines are those that are live prior to treatment with [DU] or [IDU], one would still have had a reasonable expectation of success that Ryan's method would have inactivated the live viruses of Oxford"). Appellants dispute the Examiner's subsequent conclusion that a person of ordinary skill in the art would have a reasonable expectation that DU or IDU would inactivate the viruses, claiming the Examiner has not the articulated sufficient reasoning required by KSR Int'!. Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) ("[T]here must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness"). Id. at 16-17. Appellants contend Ryan '099 teaches that formaldehyde is toxic and that DU does not exhibit the same toxicity; and that formaldehyde functions differently than DU as a fixative. App. Br. 17. Appellants therefore argue that, based on these teachings, a person of ordinary skill in the art would not expect DU to deactivate a virus in the same manner as formaldehyde and there is consequently no factual support for the conclusion that there would be a reasonable expectation of success in using DU as a non-crosslinking chemical fixative that contains urea and is able to deactivate the viruses taught by Oxford. Id. at 17-18. Appellants also point to the Examiner's admission that neither Oxford nor Ryan '099 teaches the contact interval of about 24 to about 72 hours as required by claim 1. App. Br. 18 (citing Final Act. 4). Appellants admit Ryan '51 7 teaches that HIV was inactivated after treatment with diazo lidiny 1 urea (5%) after 4 days. Id. (citing Ryan '517, Ex. XIII). According to Appellants, Ryan '51 7 relates to a process for killing HIV while preserving the antigens of white blood cells. Id. (citing Ryan '517 col. 3 11. 42-51). 5 Appeal2014-003627 Application 12/940, 112 However, Appellants contend, Ryan '517 provides no guidance as to the conditions, including time of contact, which could result in inactivating a virus and preserving antigens in the virus to establish an immunological response. Id. Appellants therefore dispute the Examiner's conclusion that a person of ordinary skill in the art would have a reasonable expectation of success based upon the teachings of Ryan '517. Id. Similarly, Appellants argue the Examiner, in admitting that the combined prior art references do not teach the claimed temperature range of about 23°C to about 37°C, incorrectly combined the references with the teachings of Barrett, which teaches inactivation of viruses at temperatures between 20°C and 40°C. App. Br. 18. Appellants maintain this combination is improper because Barret teaches a method of virus inactivation in which a lipid-enveloped intact virus is incubated with a non-ionic detergent from a group of polysorbates for a period of time sufficient to completely inactivate the virus particle, yet without affecting its structural integrity and, particularly, the biological activity of its surface and enveloping proteins. Id. at 19. Appellants argue there is no logical reason why the methods of Barrett would be utilized in processes using DU and IDU, as taught by Ryan '099, or formaldehyde, as taught by Oxford. Id. Finally, Appellants argue none of the cited prior art teaches the limitation of claim 8 reciting: "wherein the method is free of any step of contacting the virus with binary ethylene-imine, formaldehyde, formalin, phenol, 2-phenoxyethanol, thimerosal, bromo-ethylene-imine, ethyl methane sulfonate, Nitrosoguanidine, fluorouracil, 5-azacytadine, or any combination thereof." App. Br. 19. Similarly, Appellants contend none of the cited prior art teaches the limitation of claim 10 reciting: "a step of performing an assay 6 Appeal2014-003627 Application 12/940, 112 of the deactivated virus to confirm that the infectious component has been de-activated." Id. The Examiner responds that a person of ordinary skill would be motivated to use DU and IDU, as taught by Ryan '099, to inactivate the live viruses taught by Oxford, based upon Ryan '099's teaching that viruses inactivated by formaldehyde may be inactivated with DU or IDU. Ans. 7 (citing Ryan '099 col. 7, 11. 28-32). The Examiner finds a person of ordinary skill in the art would recognize that treating viruses with formaldehyde deactivates them, as taught by Oxford. Id. The Examiner finds Ryan '099 teaches that viruses that can be inactivated by formaldehyde may similarly be inactivated with DI or IDU. Id. The Examiner finds that, even if the mechanisms of inactivation are different between Oxford's formaldehyde and Ryan '099's DU and IDU, both mechanisms result in deactivation. Id. Therefore, the Examiner finds, a person of ordinary skill would have had a reasonable expectation of success that Ryan '099's DU and IDU would inactivate the viruses taught by Oxford. Id. We are not persuaded by Appellants' argument that the combined cited references fail to teach claim 1 's required contact interval of "about 24 to about 72 hours." App. Br. 18. The Examiner finds Ryan '517's Example XIII demonstrates a process of inactivating HIV while preserving antigens in white blood cells. Ans. 7-8. The Examiner finds the claim term the term "about 24 to about 72 hours" is "relative" and therefore finds it reasonable to broadly interpret the term. Id. at 8. Moreover, the Examiner finds that, given Ryan '517' s teachings with respect to the characteristics of the treated viruses, it would be within the skill of an ordinary artisan to optimize the length of contact time to achieve inactivation, or any other parameter, such 7 Appeal2014-003627 Application 12/940, 112 as temperature, recited in claim 1, to arrive at inactivated, immunogenic viruses. Id. We are not persuaded by Appellants' arguments that "there is no factual support for the conclusion that there is a reasonable expectation of success." App. Br. 17. Oxford teaches a method of inactivating viruses using formaldehyde: "The invention further provides a process of preparing a 'killed (inactivated) vaccine, which comprises selecting a viral strain by the invented method and then inactivating the viral particles, for example with the aid of formaldehyde."' Oxford col. 5, 11. 16-20. However Ryan '099 teaches, with respect to the use of formaldehyde as a fixative: The usual formulations for stabilization of cells contain one or more agents which react vigorously with the proteins of the cells to denature and insolubilize the components of the cell. Typical of this type of agent is picric acid, mercuric ions, formaldehyde and glutaraldehyde. In addition, some less toxic compounds can also be utilized which denature and stabilize the proteins such as acetic and formic acid. Unfortunately, the toxicity associated with such compounds renders their use less than satisfactory. For example, a 37% solution of formaldehyde, the most common of these fixatives, is a noxious gas which is also toxic, flammable, and carcinogenic. Ryan '099 col. 2, 11. 6-17. Ryan '099, therefore, is directed to the use of, inter alia, DU and IDU, which: "provide a fixative which in addition to being low in toxicity gives off no noxious fumes, [are] not flammable or carcinogenic, and which can be disposed of safely and conveniently." Ryan '099 col. 3, 11. 19-22. 8 Appeal2014-003627 Application 12/940, 112 Furthermore, Ryan '099 teaches: The mechanism by which the active agents of the invention provide the desired tissue and cell membrane stabilization is not known for certain. It is believed that the active agent binds in some fashion to the cell membrane or tissue. This hypothesis is drawn because many of the active agents of the invention are known disinfectant which kill bacteria by binding to cell structures. The ability of the active agents of the invention to preserve antigens is also not understood but it is probably due to a difference in the reaction between proteins and the active agents of the invention compared to prior art fixatives such as formaldehyde. Formaldehyde cross-links with itself and proteins to obscure the antigen. To determine if this is true, diazolidinyl urea was added to the protein, albumin. After incubation of the diazolidinyl urea and protein mixture for 24 hours, disc-gel electrophoresis indicated no change in the rate of migration of the protein. When this experiment is conducted with formaldehyde, a large number of multimers and insoluble proteins result. Ryan '099 col. 4, 11. 24--45. Ryan '099 thus teaches that it is well-known in the art that formaldehyde fixes tissue by cross-linking proteins, which may obscure cell-surface antigens. Ryan '099 also suggests DU does not cross- link proteins in the manner of formaldehyde and other prior art fixatives because treatment of proteins (albumin) with DU does not result in the generation of cross-linked multimers and insoluble proteins. We therefore agree with the Examiner that a person of ordinary skill in the art, seeking to inactivate viruses without obscuring antigenic proteins, would have been motivated to substitute DU or IDU, as taught by Ryan '099, into the methods of viral inactivation taught by Oxford, with a 9 Appeal2014-003627 Application 12/940, 112 reasonable expectation of success. See KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results"); see also In re Langi, 795 F.2d 887, 897 (Fed. Cir. 1985) ("Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness."); Nor are we persuaded by Appellants' arguments with respect to the ranges of intervals and temperatures recited in claim 1. Claim 1 recites a range of contact intervals of "about 24 to about 72 hours" and a range of temperature intervals "of about 23°C to about 37°C." We agree with the Examiner that the usage of the term "about" in both ranges would suggest to a person of ordinary skill that these are not absolute or precise limits but suggest ranges that are to be broadly interpreted. Moreover, because these are result-effective variables, i.e., ranges of contact duration and temperature suggested as necessary to achieve viral inactivation, we agree it would have been within the skill of an ordinary artisan to optimize contact duration and temperature to achieve the desired inactivation. See Application of Aller, 220 F.2d 454, 456 (C.C.P.A. 1955); see also In re Boesch, 617 F.2d 272, 276 (C.C.P.A. 1980) ("[D]iscovery of an optimum value of a result effective variable ... is ordinarily within the skill of the art"). Finally, with respect to Appellants' arguments with respect to claims 8 and 10, Appellants adduce no evidence in support of their bare assertion that the combined cited prior art fails to teach the recited limitations. See App. Br. 19. As such, Appellants' arguments constitute only attorney argument, to which we assign little probative weight. See, e.g., In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011): ("[W]e hold that the Board 10 Appeal2014-003627 Application 12/940, 112 reasonably interpreted Rule 41.37 to require more substantive arguments in an appeal brief than a mere recitation of the claim elements and a naked assertion that the corresponding elements were not found in the prior art."); see also In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (Attorney arguments and conclusory statements that are unsupported by factual evidence are entitled to little probative value). We consequently affirm the Examiner's rejection of claims 1, 2, 4, 8, 10, 11, and 14. B. Group II: Claim 9 Claim 9 recites: "The method of Claim[] 1 wherein the method includes a step of freeze-drying and re-hydrating the deactivated virus." App. Br. 22. Appellants argue that DePablo fails to cure the alleged deficiencies of the combined cited prior art with respect to the claims of Group I and provide a person of ordinary skill with a reasonable expectation of success in combining the teachings of the references to arrive at Appellants' claimed invention. Id. at 19. We have related supra our reasons for finding Appellants' arguments are without merit, and we incorporate that reasoning here with respect to claim 9. We consequently affirm the Examiner's rejection of claim 9. C. Group III: Claim 12 Claim 12 recites: "The method of Claim 11 wherein the virus is an avian virus provided in a titer amount of about 106 to about 1011 EIDso per milliliter of the resulting vaccine composition." App. Br. 22. Appellants argue the Examiner has failed to establish a prima facie case of obviousness by failing to address the limitations of claim 12. Id. at 20. Appellants 11 Appeal2014-003627 Application 12/940, 112 further contend there is no evidence presented that any of the prior art references cited by the Examiner teaches or suggests appropriate titer levels for deactivated and fixed avian viruses in a vaccine. Id. As an initial matter, it is incorrect of Appellants to assert that the Examiner has failed to address the limitations of the claim. See Final Act. 7. The Examiner finds Oxford discloses that the method is applicable to human and avian influenza viruses, among others. Ans. 6 (citing Oxford col. 4, 11. 56-60.) The Examiner finds Webster discloses virus vaccine compositions comprising from about 102 to 109 pfu/ml when describing attenuated (live) viruses, such as influenza. Id. (citing Webster col. 10, 11. 38--44). The Examiner notes that, typically, inactivated viruses are described in terms of HA content, since "pfu" (plaque forming units) indicates that the virus is still "living" (i.e., attenuated). Id. Nevertheless, the Examiner finds, a person of ordinary skill would have been motivated to use the concentrations taught by Webster because Webster also teaches an influenza viral vaccine, as does Oxford, with a reasonable expectation of success. Id. We agree with the Examiner's finding that the combined cited prior art teaches the limitations of claim 12, i.e., the range of titer amounts of attenuated virus taught by Webster substantially overlaps that recited in claim 12 and Oxford teaches avian viruses. Moreover, we also agree with the Examiner that a person of ordinary skill in the art could have combined these teachings with a reasonable expectation of success. We consequently affirm the Examiner's rejection of claim 12. 12 Appeal2014-003627 Application 12/940, 112 D. Group l V: Claim 13 Appellants argue Renoux fails to cure the deficiencies in the teachings of the combined cited prior art, as argued with respect to Group I and that the Examiner has therefore failed to establish a prima facie case of obviousness. App. Br. 20. For the reasons already related supra, we disagree and we consequently affirm the Examiner's rejection of claim 13. DECISION The Examiner's rejection of claims 1-2, 4, and 8-14 as unpatentable under 35 U.S.C. § 103(a) is reversed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 13 Copy with citationCopy as parenthetical citation