Ex Parte Moser et alDownload PDFPatent Trial and Appeal BoardMar 13, 201713403681 (P.T.A.B. Mar. 13, 2017) 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. 13/403,681 02/23/2012 Christian Moser 046549-5030US2(00006) 1348 78905 7590 03/15/2017 Saul Ewing LLP (Philadelphia) Attn: Patent Docket Clerk Centre Square West 1500 Market Street, 38th Floor Philadelphia, PA 19102-2186 EXAMINER POPA, ILEANA ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 03/15/2017 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): patents@saul.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHRISTIAN MOSER, ANDREAS KAMMER, and RINALDO ZURBRIGGEN1 Appeal 2016-000966 Application 13/403,681 Technology Center 1600 Before DONALD E. ADAMS, TAWEN CHANG, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. NEWMAN, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims to a method of treating or preventing a disease involving administration of a lipid vesicle. The Examiner entered final rejections for anticipation and obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellants identify the Real Party in Interest as Helvetic Airways AG. App. Br. 3. Appeal 2016-000966 Application 13/403,681 STATEMENT OF THE CASE Background The Specification discloses: use of a lipid vesicle for the preparation of a medicament for non- specifically stimulating the immune response of an animal to a disease or disorder. The invention further relates to a method of non-specifically stimulating the immune response of an animal, i.e. treating, eliminating and/or preventing a disease or disorder, involving administering a lipid vesicle to an animal in need thereof. The lipid vesicle comprises, in its lipid membrane, at least one viral envelope protein. Spec. 1:3-9. The Claims Claims 37-40, 43, and 47—54 are on appeal. Sole independent claim 37 illustrates the appealed subject matter and reads as follows: 37. A method of non-specifically stimulating the immune response of an animal to effect therapy of a disease or disorder in the animal, comprising administering to the animal an empty lipid vesicle comprising, in its lipid membrane, at least one viral envelope protein, wherein the disease or disorder is not associated with or caused by the virus from which the at least one viral envelope protein is derived, and wherein the disease or disorder is infectious or neoplastic, whereby the immune response of the animal is non- specifically stimulated to effect therapy of the disease or disorder in the animal. App. Br. 44 (Claims Appendix). 2 Appeal 2016-000966 Application 13/403,681 The Issues The following rejections are on appeal: Claims 37-40, 43, 47-49, and 51—53 are rejected under 35 U.S.C. § 102(b) as anticipated by Marchisio2 as evidenced by Eich.3 Ans. 3. Claims 37-40, 43, 47-48, and 51—53 are rejected under 35 U.S.C. § 102(b) as anticipated by Pluschke.4 Ans. 3. Claims 37-40, 43, and 47—54 are rejected under 35 U.S.C. § 103(a) as obvious over Pluschke and Mischler.5 Ans. 5. 2 Paola Marchisio et al., Efficacy of Intranasal Virosomal Influenza Vaccine in the Prevention of Recurrent Acute Otitis Media in Children, 35: Clin. Infect. Dis. 168—174, © 2002 Infectious Diseases Society of America (“Marchisio”). 3 G. Eich, et al., Nasalflu Berna: intranasaler, inaktiviterter Grippeimpfstoff 10: Schweiz Med. Forum 260-262 (2001) (“Eich”). 4 US 2004/0175392, published Sep. 9, 2004 (“Pluschke”). 5 Robert Mischler and Ian C. Metcalfe, Inflexal®Va trivalent virosome subunit influence vaccine: production, 20: Vaccine B17—23, © 2002 Elsevier Science Ltd. (“Mischler”). 3 Appeal 2016-000966 Application 13/403,681 Claims 37-40, 43, and 47—53 are rejected under 35 U.S.C. § 103(a) as obvious over Matsumoto,6 Masihi,7 and Schumacher.8 Ans. 5. Claims 37-40, 43, and 47—54 are rejected under 35 U.S.C. § 103(a) as obvious over Matsumoto, Masihi, Schumacher, and Amacker.9 Ans. 7. Claims 37-40, 43, and 47—54 are rejected under 35 U.S.C. § 103(a) as obvious over Marchisio in view of Mischler. Ans. 8. FINDINGS OF FACT (FF) FF1. The Specification discloses that “the terms ‘non-specific’, ‘unspecific’ and the like refer to a general immunostimulatory activity of the lipid vesicle against at least one disease or disorder which is not associated with or caused by a virus from which the at least one viral envelope protein is derived” and that “‘specific’ immuno stimulatory activity refers to the stimulation of the immune system to prevent, combat and/or eliminate a 6 Kensuke Matsumoto, et al., Stimulation of Nonspecific Resistance to Infection Induced by Muramyl Dipeptide Analogs Substituted in the y- Carobxyl Group and Evaluation of Na-Muramyl Dipeptide- Na- Stearoyllysine, 39: Infect. &Immun. 3, 1029-1040, © 1983, American Society for Microbiology (“Matsumoto”). 7 K.N. Masihi, Immunomodulatory agent for prophylaxis and therapy of infections, 14: Int’l. J. Antimicrob. Agents 181-191 © 2000 Elsevier Science B.V. and International Society of Chemotherapy (“Masihi”). 8 Reto Schumacher, et al., Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation, 22: Vaccine 714—723, © 2003 Elsevier Ltd. (“Schumacher”). 9 Mario Amacker, et al., Peptide-loaded chimeric influenza virosomes for efficient in vivo induction of cytotoxic T cells. 17: Intl. Immun. 695—704 (2005) (“Amacker”). 4 Appeal 2016-000966 Application 13/403,681 particular disease or disorder associated with or caused by the parental virus.” Spec. 11:1—18. FF2. Marchisio teaches “[t]he evidence that viral infections are associated with many, if not most, episodes of AOM [8] has caused immunoprophylaxis against respiratory viruses to receive growing attention.” Marchisio 168. FF3. Marchisio teaches: To evaluate the efficacy of an intranasal, inactivated, virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media (AOM) in children with recurrent AOM, 133 children aged 1-5 years were randomized to receive the vaccine (n = 67) or no vaccination (n = 66). During a 6-month period, 24 (35.8%) vaccine recipients had 32 episodes of AOM; 42 (63.6%) control subjects had 64 episodes. The overall efficacy of vaccination in preventing AOM was 43.7% (95% confidence interval, 18.6-61.1; P = .002). Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season. Marchisio Abstract. FF4. The Examiner cites Pluschke for teaching a method for treating malaria in a mammal comprising two steps: (i) pre-immunization with empty immunopotentiating reconstituted influenza virosomes or IRIVs (i.e., empty lipid vesicles comprising in their membrane HA and NA); and (ii) immunization with IRIVs loaded with malarial antigenic epitopes which occurs at least three weeks after the pre immunization step. Ans. 3. The Examiner finds the “step of pre-immunization with empty IRIVs necessarily stimulates non-specific immune responses to effect therapy for malaria (i.e., a disease not associated with or caused by influenza virus from 5 Appeal 2016-000966 Application 13/403,681 which the envelope proteins are derived; claim 37) because all that is required to achieve such is to administer empty IRIVs.” Id. at 3^4 (citing Pluschke Abstract and H 25, 28, 32, 36, 41, and 59). FF5. Pluschke teaches an example showing the immunogenicity studies of the peptide-loaded virosomes in mice . . . BALB/c mice were pre-immunized intramuscularly with 0.1 ml of the commercial whole virus influenza vaccine Inflexal Bema™ (Bema Biotech, Bern, Switzerland). At least three weeks later they were immunized with peptide-loaded IRIVs in intervals of at least two weeks. Blood was collected before each immunization and two weeks after the final injection. Pluschke 1 59. Monoclonal antibodies were generated from spleen cells of the mice. Id. at 1 64. FF6. Pluschke teaches an example showing “the parasite growth- inhibitory effect of the antibodies elicited by use of the peptides of the invention.” Pluschke 173. Pluschke teaches that when the “two major fine specificities were tested . . . both exhibited substantial inhibitory activity [with] [a] 95.3% reduction of parasite growth was observed” over the control. Id. FF7. Pluschke teaches preimmunization of mice with Inflexal®, a vaccine against influenza, prior to treatment with loaded IRIVs. Pluschke 167. FF8. Mischler teaches that Inflexal comprises three different virosomes, wherein each virosome comprises an HA derived from a different influenza strain. Mischler Table 1, providing composition of virosomal pool production for the three monovalent virosomes. FF9. The Examiner finds that Matsumoto teaches “a method of stimulating non-specific immune responses to generate protection against 6 Appeal 2016-000966 Application 13/403,681 bacterial infections in mice, the method comprising the intravenous administration of the adjuvant MDP-Lys(L18), wherein administering MDP- Lys(L18) confers protection against different subsequent bacterial infections.” Final Act. 6 (citing Matsumoto Abstract, pp. 1032, 1034). FF10. Because Matsumoto teaches stimulating non-specific immune responses using MDP-Lys(L18) and not IRIVs, the Examiner looks to Masihi for the teaching that “MDP-Lys(L18) is a potent inducer of CSFs, TNF, and IFN-y [] wherein IFN- y , TNF, and GM-CSF are immunomodulatory agents suitable to elicit non-specific immune responses suitable to treat infections in general.” (citing Matsumoto Abstract, pp. 181, 185-189). FF11. The Examiner finds Schumacher teaches that “empty IRIVs are adjuvants capable of inducing the Thi cytokines IFN-y, TNF, and GM- CSF and also a CTL response, which are necessary to treat infectious diseases in general and cancer,” meaning that “IRIVs stimulate non-specific immune responses.” (citing Schumacher pp. 714, 718, 722). FF12. The Examiner finds Amacker teaches that “IRIVs comprising influenza HA and NA derived from different influenza strains (i.e., chimeric) were known and used in the prior art as adjuvants.” (citing Amacker Abstract, p. 697). 7 Appeal 2016-000966 Application 13/403,681 ANTICIPATION Rejection over Marchisio as evidenced by Eich The Examiner has rejected claims 37—40, 43, 47 49, and 51—53 under 35 U.S.C. § 102(b) as anticipated by Marchisio as evidenced by Eich. Ans. 3. The Examiner finds that Marchisio, as evidenced by Eich, teach[es] a method of non-specifically stimulating the immune response in children to effect therapy of acute otitis media [AOM] caused by viral or bacterial infections, the method comprising administering to the children Nasaflu Bema spray, i.e., empty virosomes comprising influenza hemagglutinin and neuraminidase. Ans. 3. The Examiner concludes that the limitation “whereby the immune response of the animal is non-specifically stimulated to effect therapy of the disease or disorder in the animal” that is “recited in the instant claim [3]7 is inherent to the method of Marchisio et al. because all that is required to stimulate non-specific immune response to different diseases is to administer empty virosomes.” Id. Based on this finding of inherency, the Examiner concludes Marchisio anticipates the claimed invention. Id. Appellants argue: Marchisio does not teach the administration of IRIVs [empty influenza virosomes] to treat AOM. Rather, Marchisio teaches the administration of influenza virosomes to prevent influenza virus infection. Prevention of influenza can in turn prevent the subsequent development of other secondary diseases, such as AOM. Thus, the immunological properties of the virosome itself as taught in Marchisio are restricted to prevention of influenza virus infection. The use of the influenza virosomes in Marchisio is not “non-specific” as required by the present claims, because in Marchisio the influenza virosomes are used to treat and/or 8 Appeal 2016-000966 Application 13/403,681 prevent a disease (influenza) associated with the vims from which the at least one viral envelope protein is derived (IRIVs). App. Br. 16. Appellants cite several passages in Marchisio that acknowledge ear infection recurrence is mitigated by vaccination against influenza (e.g., “vaccine-induced prevention of influenza also leads to the prevention of AOM and other respiratory infections”). Id. Appellants also argue the recommended timing of the use of IRIVs in Marchisio, ‘“carefully planned to complete the administration of the vaccine doses before the estimated onset of the influenza season,’” demonstrates that the use of influenza virosomes is to induce adaptive immunity (e.g., “specific” immunity) because they treat the disease caused by the same vims from which the virosomal envelope proteins are derived, not non-specific immunity as claimed. Id. at 16—17. The Examiner responds that [although not specifically taught as a mechanism of eliciting non-specific immune responses, stimulating the innate immunity is inherent to the methods of Marchisio et al... . because all that is required to achieve such is to administer empty virosomes. The instant claims do not recite more than this. The instant specification does not teach more than this. Ans. 9—10. Appellants have the better position. Claim 37 requires that the animal have a “disease or disorder” to be treated, meaning that the animal must have previously had the disease, or be suspected of contracting the disease in the future, to receive the treatment. Further, the disease to be treated must be “not associated with or caused by the virus from which the at least one viral envelope protein is derived” in order to cause a non-specific immune 9 Appeal 2016-000966 Application 13/403,681 response. See FF1, defining “non-specific” as “general immunostimulatory activity of the lipid vesicle against at least one disease or disorder which is not associated with or caused by a vims from which the at least one viral envelope protein is derived.” Marchisio teaches “viral infections are associated with many, if not most, episodes of AOM.” FF2. With this understanding, Marchisio evaluated the effect of IRIVs in preventing new episodes of AOM in children with recurrent AOM, and found increased success when the treatment was given prior to influenza season. FF3. We agree with Appellants that the increased resistance to new episodes of AOM observed by Marchisio suggests a correlation with causation of AOM by the influenza vims, rather than the viral independence required for the claimed non specific immunity. The Examiner has not identified any teaching in Marchisio from which we may confirm that the therapy of AOM was solely for those episodes caused by bacterial infections, and not by the viral infections established by Marchisio to cause “many, if not most, episodes of AOM.” FF2. Accordingly, the Examiner has not established that the episodes of AOM that are treated by delivery of the IRIVs in Marchisio were not caused by influenza such that the observed treatment can be attributed to non specific immunity as required by claim 37. “The keystone of the inherency doctrine is inevitability. For anticipation by inherency, a later-claimed invention must have necessarily resulted from the practice of a prior art reference. Our precedent has been steadfast in this strict requirement of inevitability.” In re Montgomery, 677 F.3d 1375, 1384 (Fed. Cir. 2012). 10 Appeal 2016-000966 Application 13/403,681 Because the Examiner has not provided evidence sufficient to support a prima facie case of anticipation, we reverse the rejection of claims 37—40, 43, 47-49, and 51—53. See In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993) (“In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial burden of presenting a prima facie case of obviousness. Only if that burden is met, does the burden of coming forward with evidence or argument shift to the applicant.”). Rejection over Pluschke We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions with regard to anticipation of the invention by Pluschke, as set out in the Final Action and Answer. Final Act. 3-A; Ans. 3^4. The Examiner has set forth a prima facie case that claims 37-40, 43, 47-48, and 51—53 are anticipated by Pluschke. FF4. We address Appellants’ arguments below. Appellants argue “[t]he pre-immunization taught in Pluschke is performed not to provide the desired immunization against malaria, but to allow for the generation of anti-influenza antibodies in naive animals, so that these mice better model influenza infection in human patients.” App. Br. 11. Appellants argue this pre-immunization is “directed to the elicitation of anti influenza antibodies in naive animals as part of the animal’s adaptive immunity and is specific in nature [and therefore] bear[s] no relation to the non-specific stimulation of the present invention, which relates to the animal’s innate immunity.” Id. at 12. We are not persuaded. 11 Appeal 2016-000966 Application 13/403,681 In some cases, [an] inherent property corresponds to a claimed new benefit or characteristic of an invention otherwise in the prior art. In those cases, the new realization alone does not render the old invention patentable. Thus, when considering a prior art method, the anticipation doctrine examines the natural and inherent results in that method without regard to the full recognition of those benefits or characteristics within the art field at the time of the prior art disclosure. Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1377—1378 (Fed. Cir. 2005). Although Pluschke may have pre-immunized the mice for the sole purpose of generating anti-influenza antibodies, Pluschke nonetheless treated an animal with an empty IRIV and ultimately looked for and observed an immune response generated against malaria. FF5, FF6. While it is true that after treating with the empty IRIV, Pluschke subsequently immunized mice with a peptide-loaded virosome before measuring the immune response generated against malaria (FF5), Appellants have not persuasively shown that the immune response identified by Pluschke is exclusively specific and that the claimed non-specific immune response did not also occur. We agree with the Examiner that the steps taken by Pluschke would inherently have generated the claimed non-specific immune response. Although Appellants attempt to distinguish in time between the “transient, short-lived effect” of the non-specific response generated by the invention as compared to the “long-lasting immune response” of Pluschke as a means to distinguish any observed effect, the cited support in the Specification (9:1— 12 Appeal 2016-000966 Application 13/403,681 32) does not clarity the time frame or meaningfully distinguish it from Pluschke’s observed immune response.10 App. Br. 12—13. We do not address Appellants’ second argument directed to the second step of Pluschke, as we agree with the Examiner that step one is the anticipating disclosure, not step two. Ans. 3^4. Appellants rely on their arguments regarding the rejection of claim 37 for all dependent claims. App. Br. 13—15. Where “claims are not separately argued, they all stand or fall together.” In re Kaslow, 707 F.2d 1366, 1376 (Fed. Cir. 1983); 37 C.F.R. § 41.37(c)(l)(iv). Separately arguing a claim requires “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.” In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011). Accordingly, claims 38-40, 43, 47-48, and 51—53 fall with claim 37. 10 The Specification states the effect is “transient” and the “onset of this effect is quite rapid, and is certainly more rapid than any immunostimulatory effect arising from a specific, i.e. adaptive immune response would be expected to be.” Spec. 9:24—26. However, this does not foreclose that the response could indeed be adaptive, nor does it demonstrate that any non specific immune effects would not have continued through the time period in which the effects were measured in Pluschke. In addition, Appellants cite paragraph 38 of Pluschke as evidence that the alleged “specific” immune response is “long-lasting” (App. Br. 12), but paragraph 38 does not address the time frame of the immune response. 13 Appeal 2016-000966 Application 13/403,681 OBVIOUSNESS Rejection over Pluschke and Mischler We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions with regard to obviousness of the invention over Pluschke and Mischler, as set out in the Final Action and Answer. Final Act. 5—6; Ans. 5. For the reasons discussed above (FF4—6), we find Pluschke anticipates and also renders claims 37—40, 43, 47-48, and 51—53 obvious because Pluschke teaches every limitation of claim 37. “[A] determination of anticipation, as well as obviousness, involves two steps. First is construing the claim,. . . followed by, in the case of anticipation or obviousness, a comparison of the construed claim to the prior art.” Key Pharms. v. Hereon Labs. Corp., 161 F.3d 709, 714 (Fed. Cir. 1998). See also In re McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002) (citations omitted) (“It is well settled that ‘anticipation is the epitome of obviousness’”). Accordingly we determine only whether claims 49, 50, and 54 are obvious over Pluschke and Mischler. The Examiner has set forth a prima facie case that claims 49, 50, and 54 are obvious over Pluschke and Mischler. Ans. 5; FF4—8. We address Appellants’ arguments below. In making the rejection, the Examiner finds that although “Pluschke et al. teach a mammal, they do not specifically teach a human or a ruminant” as recited in claims 49 and 50. Ans. 5. The Examiner concludes “one of skill in the art would have found it obvious to use the method of Pluschke et al. to treat malaria in any mammal, including humans and ruminants such as cows.” Id. We agree, as both humans and ruminants are mammals regularly targeted for treatment with pharmaceutical compositions. 14 Appeal 2016-000966 Application 13/403,681 With regard to claim 54, which recites a chimeric IRIV, the Examiner finds that Pluschke teaches preimmunization of mice prior to treatment with an IRIV with Inflexal®. FF7. The Examiner finds Mischler discloses that Inflexal is composed of three monovalent virosomes, each comprising “an HA derived from a different influenza strain.” Ans. 5; FF8. The Examiner concludes a skilled artisan “would have found it obvious to modify the composition of Pluschke et al. by incorporating all three HAs into the same virosome to achieve the predictable result of obtaining an IRIV adjuvant.” Ans. 5. Appellants argue “Mischler does not cure the deficiencies in Pluschke [because it] teaches the use of an influenza virus-related virosome (IRIV) to treat an influenza infection, and thus the therapy taught in Mischler is “specific.” App. Br. 22. For this reason, Appellants argue the skilled artisan “would not have identified Pluschke and/or Mischler as a way to solve the scientific problem addressed by the present invention: a method of non- specifically stimulating the immune response of an animal to effect therapy of an infectious or neoplastic disease or disorder.” Id. at 23. Instead, Appellants argue the Examiner used “impermissible hindsight” in constructing the rejection. Id. Appellants also argue the skilled artisan “would not have modified the teachings of Pluschke and Mischler as to arrive at the present invention with reasonable expectation of success” because Mischler “teaches ‘specific’ methods of treating an influenza infection with an IRV” while Pluschke is targeted at eliciting innate immunity in an animal. Id. at 24. We are not persuaded. While we are fully aware that hindsight bias may plague determinations of obviousness, Graham v. John Deere Co., 383 15 Appeal 2016-000966 Application 13/403,681 U.S. 1,36 (1966), we are also mindful that the Supreme Court has clearly stated that the “combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int 7 Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). In this case, Pluschke alone teaches the use of a chimeric IRIV because it teaches administration of Inflexal®. FF7. The Examiner looks to Mischler merely to confirm that the vaccine is chimeric. Ans. 5. As discussed above, Pluschke anticipates the central invention, and claim 54 recites a natural enhancement of that invention, a chimeric vaccine, which one of skill in the art would recognize would stimulate and/or broaden the immune response, precisely as it is used by Pluschke. Ans. 5; FF7. Without evidence, which Appellants do not provide, these attorney arguments are unpersuasive. See In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take the place of evidence.”). We affirm the rejection. Rejection over Matsumoto, Masihi, and Schumacher We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions with regard to obviousness of the invention over Matsumoto, Masihi, and Schumacher, as set out in the Final Action and Answer. Final Act. 6—7; Ans. 5—7. The Examiner has set forth a prima facie case that claims 37-40, 43, and 47—53 are obvious over Matsumoto, Masihi, and Schumacher. FF9-11. We address Appellants’ arguments below. Appellants argue the Matsumoto teaches “the use of a bacterial cell wall fragment analog to stimulate non-specific resistance to bacterial infection” and that a bacterial cell wall fragment analog is “wholly unrelated 16 Appeal 2016-000966 Application 13/403,681 and distinct” from a lipid vesicle or IRIV. App. Br. 27. Applicants argue the Examiner applied “impermissible hindsight” to reconstruct the invention. Appellants further argue Masihi and Schumacher do not cure the deficiencies in Matsumoto because both are “wholly unrelated to the present invention” and use distinct methods. Id. at 27—28. We are not persuaded. In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. . . . [A]ny need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed. KSR, 550 U.S. at 419-20. We agree with the Examiner that “[t]he problem addressed by the instant invention is [achieving] non-specific stimulation of immune responses to stimulate resistance to infections. Matsumoto et al. teach eliciting non-specific immune responses to stimulate resistance to infections and thus their teachings are material to the problem addressed by the appellants]” and, further, that Matsumoto “teach[es] all method steps required by the claims.” Ans. 15—16; FF9—11. Appellants next argue a skilled artisan would not have had a reasonable expectation of success combining the teachings of the cited references because the methods taught are different and cannot be combined. App. Br. 28. According to Appellants, “Matsumoto teaches a method of stimulating non-specific resistance to bacterial infection. Contrary to Matsumoto, Schumacher teaches a method of stimulating specific resistance to bacterial infection.” Id. at 29. Appellants argue “the Office has failed to present any actual argument or evidence that Matsumoto and Schumacher 17 Appeal 2016-000966 Application 13/403,681 are indeed combinable in an obviousness rejection” and that the Examiner has used impermissible hindsight to recreate the invention. Id. at 30. This argument is unpersuasive. “Obviousness does not require absolute predictability of success. . . . For obviousness under § 103, all that is required is a reasonable expectation of success.” In re O’Farrell, 853 F.2d 894, 903—04 (Fed. Cir. 1988). Both Matsumoto and Schumacher induced immune responses in mammalian cells. FF9, FI 1. The Examiner presented a prima facie case of obviousness, shifting the burden to Appellants. See In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992) (“the examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant.”) Absent evidence, which Appellants do not provide, we are not persuaded by Appellants that the skilled artisan would not have replaced MDP-Fys(F18) as used by Matsumoto with IRIVs to stimulate non-specific immune responses, given that Masihi and Schumacher teach the substitution would accomplish the same type(s) of immune stimulation. FF9—11. See KSR, 550, U.S. at 420 (“. . . in many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.”). We affirm the rejection of claim 37. Because Appellants rely on their arguments regarding the rejection of claim 37 for all dependent claims (App. Br. 31—32), we similarly affirm the rejection of claims 38—40, 43, and 47-53. Rejection over Matsumoto, Masihi, Schumacher, and Amacker 18 Appeal 2016-000966 Application 13/403,681 We adopt the Examiner’s findings of fact, reasoning on scope and content of the prior art, and conclusions with regard to obviousness of the invention over Matsumoto, Masihi, Schumacher, and Amacker, as set out in the Final Action and Answer. Final Act. 7—8; Ans. 7—8. In responding to this rejection, Appellants rely on their arguments regarding the alleged the alleged deficiencies of Matsumoto, Masihi, and Schumacher. App. Br. 33. We have addressed those arguments above. Appellants argue Amacker does not cure the deficiencies of the other cited references as “Amacker teaches only the use of chimeric IRIVs.” Id. This argument is not persuasive because the Examiner’s reference is based on the combined teachings of Matsumoto, Masihi, Schumacher, and Amacker. Ans. 7—8. Nonobviousness cannot be established by attacking the references individually when the rejection is predicated upon a combination of prior art disclosures. In re Merck & Co. Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986); see also In re Keller, 642 F.2d 413, 426 (CCPA 1981) (finding “one cannot show non-obviousness by attacking references individually where, as here, the rejections are based on combinations of references” (citations omitted)). Thus, whether Amacker fails to individually teach induction of a non-specific immune response is not dispositive. The Examiner cites Amacker as teaching use of chimeric IRIVs. Ans. 7; FF12. The Examiner sufficiently establishes that an ordinary artisan reading Matsumoto, Masihi, Schumacher, and Amacker would have reasonably expected that the chimeric IRIVs of Amacker could be substituted for the IRIV of Schumacher. Ans. 7—8. Appellants next argue that Amacker teaches away from the claimed invention because “the IRIVs taught by Amacker are not empty because they 19 Appeal 2016-000966 Application 13/403,681 are loaded with bioactive peptides” rather than the empty virosomes claimed, which would not motivate the skilled artisan to use empty virosomes. App. Br. 33—34. The Examiner responds: Amacker et al. was cited as evidence that chimeric IRIVs were known and used in the prior art, thus rendering obvious using chimeric IRIVs in the method of Matsumoto et al., Masihi, and Schumacher et al. There is no teaching or suggestion in the entire reference or the entire art pointing against using empty chimeric IRIVs instead of empty IRIVs in the method of Matsumoto et al., Masihi, and Schumacher et al. Ans. 19. The Examiner has the better position. Under the proper legal standard, a reference will teach away when it suggests that the developments flowing from its disclosures are unlikely to produce the objective of the applicant’s invention. A statement that a particular combination is not a preferred embodiment does not teach away absent clear discouragement of that combination. Syntex (U.S.A.) LLCv. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005) (citations omitted). We agree with the Examiner that, absent evidence to the contrary, Amacker informs a person of ordinary skill that chimeric IRIVs may be used to induce an immune response, rather than teaching away from the instant claims. The rejection is affirmed. Rejection over Marchisio and Mischler The Examiner has rejected claims 37—40, 43, and 47—54 under 35 U.S.C. § 103(a) as obvious over Marchisio and Mischler. Ans. 8. As discussed above, we find that the Examiner has not established that the 20 Appeal 2016-000966 Application 13/403,681 episodes of AOM that are treated by delivery of the IRIVs in Marchisio were not caused by influenza such that the observed treatment can be attributed to non-specific immunity as required by claim 37. Because the Examiner relies on the anticipation rejection in making the obviousness rejection, and does not cite any additional bases for the rejection relevant to establishing the required non-specific immunity, we also reverse this rejection. SUMMARY We reverse the rejection of claims 37-40, 43, 47 49, and 51—53 under 35 U.S.C. § 102(b) as anticipated by Marchisio as evidenced by Eich. We affirm the rejection of claims 37-40, 43, 47-48, and 51—53 under 35 U.S.C. § 102(b) as anticipated by Pluschke. We affirm the rejection of claims 37-40, 43, and 47—54 under 35 U.S.C. § 103(a) as obvious over Pluschke and Mischler. We affirm the rejection of claims 37-40, 43, and 47—53 under 35 U.S.C. § 103(a) as obvious over Matsumoto, Masihi, and Schumacher. We affirm the rejection of claims 37-40, 43, and 47—54 under 35 U.S.C. § 103(a) as obvious over Matsumoto, Masihi, Schumacher, and Amacker. We reverse the rejection of claims 37-40, 43, and 47—54 under 35 U.S.C. § 103(a) as obvious over Marchisio in view of Mischler. 21 Appeal 2016-000966 Application 13/403,681 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 22 Copy with citationCopy as parenthetical citation