BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC.

Patent Trials and Appeals Board

Feb 8, 2022

2021002492 (P.T.A.B. Feb. 8, 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. 15/378,165 12/14/2016 Keith Wilson MER 15-288 1360 33928 7590 02/08/2022 BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC. AH PATENT DEPARTMENT 3239 SATELLITE BLVD. BLDG. 500 DULUTH, GA 30096 EXAMINER SHAHNAN SHAH, KHATOL S ART UNIT PAPER NUMBER 1645 NOTIFICATION DATE DELIVERY MODE 02/08/2022 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): docket.ip@boehringer-ingelheim.com tiki.cantrell@boehringer-ingelheim.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte KEITH WILSON and PAULRAJ LAWRENCE ____________ Appeal 2021-002492 Application 15/378,165 Technology Center 1600 ____________ Before DONALD E. ADAMS, ERIC B. GRIMES, and RICHARD M. LEBOVITZ, 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 21-29 (Appeal Br. 2). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 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 “Boehringer Ingelheim Animal Health USA Inc.,” (Appellant’s July 15, 2020, Appeal Brief (Appeal Br.) 2). Appeal 2021-002492 Application 15/378,165 2 STATEMENT OF THE CASE Appellant’s disclosure relates to compositions or vaccines for combating Mycoplasma hyopneumoniae (M hyo), Porcine Circovirus type 2 (PCV2), and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infections in animals and increasing the ability of pigs to gain weight or improve death loss, methods of vaccination against the infections, and kits for use with such methods and compositions. (Spec. 1:8-12.) Appellant’s independent claims 21 and 26 are reproduced below: 21. A method of vaccinating a swine against a swine disease comprising: administering to the swine a Mycoplasma hyopneumoniae (M hyo) antigen, a killed Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) antigen, and a modified-live PRRSV antigen. (Appeal Br. 16.) 26. A method of vaccinating a swine against a swine disease according to a prime-boost regimen comprising: administering to the swine a M hyo antigen, a PCV2 antigen, and a first PRRSV antigen; and then administering to the swine a second PRRSV antigen. (Id. at 16-17.) Appeal 2021-002492 Application 15/378,165 3 Grounds of rejection before this Panel for review: Claims 21-24, 28, and 29 stand rejected under 35 U.S.C. § 103 as unpatentable over the combination of Kohler2 and Jordan.3 Claims 21 and 25-27 stand rejected under 35 U.S.C. § 103 as unpatentable over the combination of Kohler and Wu.4 ISSUE Does the preponderance of evidence on this record support a conclusion of obviousness? FACTUAL FINDINGS (FF) We adopt Examiner’s findings concerning the scope and content of the prior art, and provide the following for emphasis. FF 1. Kohler discloses: [S]wine infected with PCV-2 exhibit a syndrome commonly referred to as Post-weaning Multisystemic Wasting Syndrome (PMWS). PMWS is clinically characterized by wasting, paleness of the skin, unthriftiness, respiratory distress, diarrhea, icterus, and jaundice. In some affected swine, a combination of all symptoms will be apparent while other swine will only have one or two of these symptoms. During necropsy, microscopic and macroscopic lesions also appear on multiple tissues and organs, with lymphoid organs being the most common site for lesions. A strong correlation has been observed between the amount of PCV-2 nucleic acid or antigen and the severity of microscopic lymphoid lesions. Mortality rates for swine infected with PCV-2 can approach 80%. In addition to PMWS, PCV-2 has been associated with several other infections including pseudorabies, porcine reproductive and respiratory syndrome (PRRS), Glasser’s disease, streptococcal meningitis, 2 Kohler et al., US 2011/0059126 A1, published Mar. 10, 2011. 3 Jordan et al., US 2014/0271698 A1, published Sept. 18, 2014. 4 Wu, US 2009/0162398 A1, published June 25, 2009. Appeal 2021-002492 Application 15/378,165 4 salmonellosis, postweaning colibacillosis, dietetic hepatosis, and suppurative bronchopneumonia. . . . What is needed is a method for reducing the virucidal activity of PCV-2-containing immunogenic compositions[5] and antigens therein such that regulatory requirements can be met and efficacious multivalent compositions can be administered. What is further needed are methods for decreasing or reducing the virucidal activity and effect of PCV-2-containing compositions on Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). What is still further needed are immunogenic compositions that have undergone the methods of the present invention such that their virucidal activity has been reduced to acceptable standards and can be combined with other antigens to form multivalent immunogenic compositions. (Kohler ¶¶ 6, 10; see Ans. 4, 12, 17.) 5 Kohler discloses: The term “immunogenic composition” means, but is not limited to, a composition of matter that comprises at least one antigen which elicits a cellular and/or antibody-mediated immune response in a host against the antigen of interest. Usually, an “immune response” includes but is not limited to one or more of the following effects: the production or activation of antibodies, B cells, helper T cells, suppressor T cells, and/or cytotoxic T cells and/or gamma-delta T cells, directed specifically to an antigen or antigens included in the composition or vaccine of interest. Preferably, the host will display either a therapeutic or protective immune response such that resistance to new infection will be enhanced and/or the clinical severity of the disease reduced. In such a case the immunogenic composition is a “vaccine”. Such protection will be demonstrated by either a reduction or lack of symptoms normally displayed by an infected host, a quicker recovery time and/or a lowered viral titer in the infected host. (Kohler ¶ 68; see Ans. 13.) Appeal 2021-002492 Application 15/378,165 5 FF 2. Kohler discloses: A “PCV-2 antigen” refers to any composition of matter that comprises at least one antigen that can induce, stimulate or enhance the immune response against PCV-2 infection, when administered to an animal, preferably to a pig. Preferably, the PCV-2 antigen is the whole PCV-2 virus, preferably in an inactivated form, a live modified or attenuated PCV-2 virus, a chimeric virus that comprises at least an immunogenic amino acid sequence of PCV-2, or any other polypeptide or component that comprises at least an immunogenic amino acid sequence of PCV-2, preferably ORF2. (Kohler ¶ 17; see also Ans. 4, 11-13, 17.) FF 3. Kohler discloses that a PCV-2 antigenic composition within the scope of its disclosure “can be combined with at least one additional antigen,” wherein “the additional antigens can be of any other disease- causing organisms of swine” and are preferably “selected from the group consisting of: . . . Mycoplasma hyopneumoniae . . . [and] Porcine Reproductive and Respiratory Syndrome Virus” (Kohler ¶ 76; see id. ¶ 81 (Kohler discloses that “the at least one additional antigen includes a viral antigen, preferably a Porcine Reproductive and Respiratory Syndrome Virus antigen . . . and a bacterial antigen, preferably a Mycoplasma hyopneumoniae antigen.”); id. ¶ 102 (Kohler discloses a “PCV-2 antigenic composition comprising the at least one additional antigen from at least one other disease-causing organism in swine” that is “preferably Porcine Reproductive and Respiratory Syndrome Virus and/or Mycoplasma hyopneumoniae antigen”); see also Ans. 4, 12, 17). FF 4. Kohler discloses that “the Porcine Reproductive and Respiratory Syndrome Virus antigen [preferably] comprises a live virus, and still more Appeal 2021-002492 Application 15/378,165 6 preferably a modified live virus, even more preferably a modified live attenuated virus” (Kohler ¶ 79; see also Ans. 4, 12, 17). FF 5. Jordan “relates to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) compositions and associated methods” (Jordan ¶ 3). FF 6. Jordan discloses that its compositions and methods provide, inter alia, immunogenic deletion mutants of PRRSV which are genetically stable, from which vaccines, including attenuated whole virus vaccines and polypeptide subunit vaccines can be made, wherein said vaccines confer immunity from, protective resistance to, reduce transmission of and/or reduce clinical disease caused by infections with PRRSV. (Jordan ¶ 9; see also id. ¶ 66 (Jordan discloses “‘[i]mmunogenic or immunological composition’ or ‘vaccine’ refers to . . . both subunit immunogenic compositions . . ., as well as compositions containing whole killed, or attenuated, and/or inactivated PRRSV.”); see also Ans. 4, 5, 14.) FF 7. Jordan discloses: “Attenuation” means reducing the virulence of a pathogen. In the present invention “attenuation” is synonymous with “avirulent.” In the present invention, an attenuated virus is one in which the virulence has been reduced so that it does not cause clinical signs of a PRRSV infection but is capable of inducing an immune response in the target mammal, but may also mean that the clinical signs are reduced in incidence or severity in animals infected with the attenuated PRRSV in comparison with a “control group” of animals infected with non-attenuated PRRSV and not receiving the attenuated bacterium. (Jordan ¶ 83; cf. id. ¶ 84 (Jordan discloses that “‘[k]illed’ or ‘inactivated’ means treated with a physical or chemical agent which renders the PRRSV virus dead and/or otherwise incapable of reproduction.”); see Ans. 4, 14.) Appeal 2021-002492 Application 15/378,165 7 FF 8. Wu “relates to the field of animal health and provides methods and compositions for protecting pigs against pathogenic type-2B strains of porcine circovirus” (Wu ¶ 2). FF 9. Wu discloses the isolation and identification of two new strains of type 2 porcine circoviruses (PCV2), each of which may be used alone, or in combination, for preparation of a vaccine or immunogenic composition for use in protecting pigs against a pathogenic PCV2 infection or for ameliorating at least one symptom associated with Postweaning Multisystemic Wasting Syndrome (PMWS). (Wu ¶ 11.) FF 10. Wu discloses: The term “immunogenic composition” relates to any pharmaceutical composition containing an antigen, eg. a microorganism, which composition can be used to elicit an immune response in a mammal . . . [and] may contain a live, attenuated, or killed/inactivated vaccine comprising a whole microorganism or an immunogenic portion derived therefrom that induces either a cell-mediated (T cell) immune response or an antibody-mediated (B cell) immune response, or both, and may protect the animal from one or more symptoms associated with infection by the microorganism, or may protect the animal from death due to the infection with the microorganism. (Wu ¶ 79; see also id. ¶ 70 (Wu discloses that “[t]he term ‘attenuated,’ . . . refers to a microorganism, for example, a virus, that is limited in its ability to grow or replicate in vitro or in vivo.”).) FF 11. Wu discloses a method of vaccinating swine with “vaccines or immunogenic compositions comprising the pathogenic PCV2B viruses,” wherein “[t]he vaccine . . . may be administered with a second or third vaccine or immunogenic composition against other porcine pathogens, Appeal 2021-002492 Application 15/378,165 8 including for example, PRRSV, . . . and . . . Mycoplasma hyopneumoniae,” wherein: Particular combinations may include a PCV vaccine or immunogenic composition in combination with a PRRSV vaccine or immunogenic composition; a PCV vaccine or immunogenic composition in combination with a Mycoplasma hyopneumoniae vaccine or immunogenic composition; or a PSV [sic] vaccine or immunogenic in combination with both of the foregoing vaccines or immunogenic compositions. Immune stimulants may be given concurrently to the pig to provide a broad spectrum of protection against other viral or bacterial infections. (Wu ¶ 122; see also id. ¶ 115 (Wu discloses that its “PCV vaccine or immunogenic composition may be combined with a Mycoplasma hyopneumoniae vaccine or immunogenic composition and a porcine reproductive and respiratory syndrome virus (PRRS) vaccine or immunogenic composition”); see Ans. 9, 18). FF 12. Wu discloses that its “vaccines or immunogenic compositions may include . . . live vaccines, modified live vaccines, inactivated vaccines, subunit vaccines, attenuated vaccines, genetically engineered vaccines, etc.” (Wu ¶ 123; id. ¶ 47 (Wu discloses that its immunogenic composition comprises “at least one other microorganism that is pathogenic to pigs, or at least one antigen obtained from said microorganism,” wherein the microorganism may be PRRSV or M. hyo)). FF 13. Examiner finds that Wu discloses a “prime-boost [immunization] regime” (Ans.6 9 (citing Wu ¶ 142); see also Ans. 18). 6 Examiner’s December 11, 2020, Answer. Appeal 2021-002492 Application 15/378,165 9 ANALYSIS The rejection over the combination of Kohler and Jordan: Appellant does not separately argue the rejected claims. Therefore, we select Appellant’s claim 21, reproduced above, as representative. Based on the combination of Kohler and Jordan, Examiner concludes that, before the effective filing date of Appellant’s claimed invention, it would have been prima facie obvious to use Jordan’s killed PRRSV antigen and modified-live PRRSV antigen in Kohler’s immunogenic composition, for immunizing swine against a swine disease, that comprises M. hyo, PCV2, and PRRSV (see Ans. 7-8; see also FF 1-7). Kohler discloses an immunogenic composition, for use in vaccinating swine, which comprises, inter alia, a M. hyo antigen and a modified-live PRRSV antigen (see FF 1-4). Therefore, we are not persuaded by Appellant’s contention that Kohler “does not teach vaccinating a swine by the combined administration of a M. hyo antigen and a modified-live PRRSV antigen” (Appeal Br. 4 (emphasis omitted)). Kohler discloses a PCV-2 antigenic composition comprising Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Mycoplasma hyopneumoniae antigen (FF 3). In addition, the combination of Kohler and Jordan makes obvious an immunogenic composition comprising PCV-2, killed PRRSV antigen, modified-live PRRSV antigen, and M. hyo (see Ans. 7-8; see also FF 1-7). Therefore, we are not persuaded by Appellant’s contention that Kohler alone, or in combination with Jordan, fails to disclose a composition for vaccinating swine that comprises PRRSV and M. hyo (Appeal Br. 5). Appeal 2021-002492 Application 15/378,165 10 Because the combination of Kohler and Jordan expressly directs those of ordinary skill in this art to an immunogenic composition comprising PCV-2, comprising killed PRRSV antigen, modified-live PRRSV antigen, and M. hyo, we are not persuaded by Appellant’s contentions regarding other potential antigens that may be within the scope of Kohler’s disclosure or that a person of ordinary skill in this art would not have “selected and combined the prior art elements in the normal course of research and development to yield the claimed invention” (see FF 1-7; cf. Appeal Br. 9-10). We recognize Appellant’s disclosure of the potential for “interference when multiple vaccines are co-administered in an animal to treat several infectious diseases. In vaccinology and immunology this is the well-known and unpredictable phenomenon called ‘efficacy interference’” (Spec. 3:13- 16). Appellant, however, failed to establish an evidentiary basis on this record to support a finding that such “efficacy interference” would have reasonably been expected to occur in the immunogenic composition disclosed by Kohler that comprises, inter alia, PCV-2, PRRSV, and M. hyo or in an immunogenic composition made obvious by the combination of Kohler and Jordan, which comprises, inter alia, PCV-2, killed PRRSV antigen, modified-live PRRSV antigen, and M. hyo (see FF 1-7; cf. Appeal Br. 5-8 (citing Spec. 3:13-21) (Appellant’s counsel asserts that undue experimentation would have been required to produce an operable vaccine comprising PCV-2, PRRSV, and M. hyo or PCV-2, killed PRRSV antigen, modified-live PRRSV antigen, and M. hyo)). It is well settled that argument by counsel cannot take the place of evidence. See In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take the place of evidence.”). In Appeal 2021-002492 Application 15/378,165 11 addition, we note that prior art is presumed to be enabled. See In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012) (“[A] prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant or patentee.”). Therefore, we are not persuaded by the unsupported assertions of Appellant’s counsel regarding the unpredictability of this art, working examples, amount of direction provided by the combination of Kohler and Jordan, and quantity of experimentation necessary to arrive at an operable vaccine comprising PCV- 2, PRRSV, and M. hyo, or PCV-2, killed PRRSV antigen, modified-live PRRSV antigen, and M. hyo, based on the combined disclosures of Kohler and Jordan (see Appeal Br. 5-8). Jordan discloses that its compositions and methods provide, inter alia, immunogenic deletion mutants of PRRSV which are genetically stable, from which vaccines, including attenuated whole virus vaccines and polypeptide subunit vaccines can be made, wherein said vaccines confer immunity from, protective resistance to, reduce transmission of and/or reduce clinical disease caused by infections with PRRSV. (FF 6; see also id. (Jordan discloses “‘[i]mmunogenic or immunological composition’ or ‘vaccine’ refers to . . . compositions containing whole killed, or attenuated, and/or inactivated PRRSV.”)7.) Thus, not only does Jordan disclose vaccine compositions comprising killed PRRSV antigen and modified-live PRRSV antigen, but Jordan also discloses that its vaccine composition comprising PRRSV antigens is “genetically stable,” “confers 7 Jordan discloses that “[b]oth inactivated and modified (attenuated) live vaccines are commercially available” (Jordan ¶ 6). Appeal 2021-002492 Application 15/378,165 12 immunity from, protective resistance to, reduce[s] transmission of and/or reduce[s] clinical disease caused by infections with PRRSV” (see id.). Thus, we find no error in Examiner’s reasoning that a person of ordinary skill in this art, recognizing the benefits of Jordan’s PRRSV antigens, would have found it prima facie obvious to utilize Jordan’s PRRSV antigens in Kohler’s composition (see Ans. 7-8; see also FF 1-7), because: If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). For the foregoing reasons, we are not persuaded by Appellant’s contention that Examiner failed to establish a reason to combine Kohler with Jordan (see Appeal Br. 9-10). For the foregoing reasons, we are not persuaded by Appellant’s contention that the combination of Kohler and Jordan fails to make obvious a composition comprising “a killed PRRSV antigen, a modified-live PRRSV antigen, a PCV-2 antigen, and a M. Hyo antigen” (see Appeal Br. 10). For the foregoing reasons, we are not persuaded by Appellant’s contention that “Examiner has not shown a reasonable expectation of success in achieving a method of swine vaccination by modifying Kohler’s methods of administration to include administration of a killed PRRSV antigen” (Appeal Br. 11 (emphasis omitted); see also id. at 11-12; id. at 12 (emphasis omitted) (Appellant contends that “[n]o ordinarily skilled artisan Appeal 2021-002492 Application 15/378,165 13 would modify Kohler in the manner needed to derive the claimed invention with a reasonable expectation of success in view of the cited art.”)). For the foregoing reasons, we are not persuaded by Appellant’s contention that “none of the cited art specifically guides the ordinarily skilled artisan towards vaccinating a swine by administering a M. hyo antigen, a killed PRRSV antigen, and a modified-live PRRSV antigen” (Appeal Br. 12). For the foregoing reasons we are not persuaded by Appellant’s contention that “none of the cited art provides guidance on how to successfully implement a vaccination regimen employing two antigens, let alone three or four antigens,” because Kohler “never investigated the safety and/or efficacy of administering a live PRRSV antigen with a specifically manufactured PCV-2 ORF2 antigen” and “Jordan never investigated the safety and/or efficacy of administrating more than a single, modified-live PRRSV antigen” (Appeal Br. 12-13). Appellant fails to direct attention to an evidentiary basis on this record that supports the contention of Appellant’s counsel that “modifying Kohler’s methods of administration to[: ] include administration of a killed PRRSV antigen runs counter to Kohler’s contribution of providing a PCV-2 protein with reduced virucidal activity on live PRRSV” or “utilize two different types of PRRSV antigens [as expressly disclosed by Jordan] would provide unnecessary redundancy in that both antigens would be used to confer protection against the same disease” (Appeal Br. 13). See Pearson, 494 F.2d at 1405 (“Attorney’s argument in a brief cannot take the place of evidence.”). Appeal 2021-002492 Application 15/378,165 14 The rejection over the combination of Kohler and Wu: Appellant’s claims 21 and 26, reproduced above, are representative. Based on the combination of Kohler and Wu, Examiner concludes that, before the effective filing date of Appellant’s claimed invention, it would have been prima facie obvious to provide a method of vaccinating a swine against a swine disease comprising an administration of a PCV-2 antigen, an M. hyo antigen, a killed PRRSV antigen and a modified-live PRRSV antigen and to utilized a prime-boost vaccine regimen as disclosed by Wu “to protect animals against a variety of swine pathogens” (Appeal Br. 10; see also FF 1-4, 8-13). Claim 21: To the extent Appellant relies on its contentions regarding Kohler as set forth above, we refer to our response as discussed above, as well. Kohler and Wu both disclose an antigenic composition comprising PCV-2, PRRSV and M. hyo (FF 3, 11, 12). Kohler discloses that “the Porcine Reproductive and Respiratory Syndrome Virus antigen [preferably] comprises a live virus, and still more preferably a modified live virus, even more preferably a modified live attenuated virus” (FF 4). Wu discloses that an antigen within the scope of its “‘immunogenic composition’ . . . may contain a live, attenuated, or killed/inactivated vaccine comprising a whole microorganism or an immunogenic portion derived therefrom” (FF 10 (emphasis added)). Therefore, we are not persuaded by Appellant’s contention that Examiner failed to establish an evidentiary basis on this record to support a conclusion that the combination of Kohler and Wu makes obvious the use of a “killed PRRSV antigen” (see Appeal Br. 10). Appeal 2021-002492 Application 15/378,165 15 In addition, Wu discloses that its vaccine or immunogenic composition comprises “at least one other microorganism,” such as PRRSV and M. hyo, or “at least one antigen,” i.e. more than one antigen, “obtained from said microorganism” and that the composition may include “live vaccines, modified live vaccines, inactivated vaccines, subunit vaccines, attenuated vaccines, genetically engineered vaccines, etc.” (FF 12). Thus, we find no error in Examiner’s conclusion that Wu “teaches a method of vaccinating a swine comprising an administration of an M. hyo antigen, a killed PRRSV antigen and a modified-live PRRSV antigen and further comprising PCV2 antigen” (Ans. 9). Therefore, we are not persuaded by Appellant’s contention that the combination of Kohler and Wu fails to “guide[] the ordinarily skilled artisan towards vaccinating a swine by administering M. hyo antigen, a killed PRRSV antigen, and a modified-live PRRSV antigen” (Appeal Br. 12). Both of Kohler and Wu disclose vaccines and immunogenic compositions comprising three or more antigens (see FF 1-4, 8-12). Therefore, we are not persuaded by Appellant’s contention that “none of the cited art provides guidance on how to successfully implement a vaccination regimen employing two antigens, let alone three or four antigens,” because Kohler “never investigated the safety and/or efficacy of administering a live PRRSV antigen with a specifically manufactured PCV-2 ORF2 antigen” and “Wu never investigated the safety and/or efficacy of administrating a single antigen” (Appeal Br. 12-13). Appeal 2021-002492 Application 15/378,165 16 Claim 26: Appellant’s claim 26 does not require the PRRSV antigen to be live or killed. Therefore, we are not persuaded by Appellant’s contentions that “Kohler . . . does not teach vaccinating a swine by the combined administration of a M. hyo antigen and a live PRRSV antigen,” that “Examiner has not provided a reasoned rationale for modifying Kohler’s methods of administration to include administration of a killed PRRSV antigen,” or that “Examiner has not shown a reasonable expectation of success in achieving a method of swine vaccination by modifying Kohler’s methods of administration to include administration of a killed PRRSV antigen” (Appeal Br. 14). Appellant fails to identify an evidentiary basis on this record to support the contention of Appellant’s counsel that “[n]o ordinarily skilled artisan would modify Kohler in the manner needed to derive the claimed invention with a reasonable expectation of success in view of the cited art” (Appeal Br. 14). See Pearson, 494 F.2d at 1405 (“Attorney’s argument in a brief cannot take the place of evidence.”). CONCLUSION The preponderance of evidence on this record supports a conclusion of obviousness. The rejection of claim 21 under 35 U.S.C. § 103 as unpatentable over the combination of Kohler and Jordan is affirmed. Claims 22-24, 28, and 29 are not separately argued and fall with claim 21. The rejection of claims 21 and 26 under 35 U.S.C. § 103 as unpatentable over the combination of Kohler and Wu is affirmed. Claims 25 Appeal 2021-002492 Application 15/378,165 17 and 27 are not separately argued and fall with claims 21 and 26, respectively. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 21-24, 28, 29 103 Kohler, Jordan 21-24, 28, 29 21, 25-27 103 Kohler, Wu 21, 25-27 Overall Outcome 21-29 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). See 37 C.F.R. § 1.136(a)(1)(iv) (2019). AFFIRMED