Ex Parte Rovinski et alDownload PDFPatent Trial and Appeal BoardSep 23, 201412233021 (P.T.A.B. Sep. 23, 2014) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte BENJAMIN ROVINSKI, JAMES TARTAGLIA, SHI-XIAN CAO, ROY PERSSON, and MICHEL H. KLEIN __________ Appeal 2012-005779 Application 12/233,021 Technology Center 1600 __________ Before DEMETRA J. MILLS, ULRIKE W. JENKS, and CHRISTOPHER G. PAULRAJ Administrative Patent Judges. Opinion for the Board filed by Administrative Patent Judge MILLS. Opinion Dissenting-in-part filed by Administrative Patent Judge JENKS. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134. The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). STATEMENT OF CASE The following claims are representative: 1. A method for generating neutralizing antibodies to an envelope glycoprotein of a primary isolate of HIV-1 in a host, comprising: at least one administration of a priming antigen to the host, wherein the Appeal 2012-005779 Application 12/233,021 2 priming antigen comprises a DNA molecule encoding an envelope glycoprotein of a primary isolate of HIV-1, resting the host for at least one specific resting period to provide for clonal expansion of an HIV antigen specific population of precursor B-cells therein to provide a primed host, and at least one administration of a boosting antigen to the primed host to provide said neutralizing antibodies, wherein the boosting antigen is a non- infectious, non-replicating, immunogenic HIV-like particle having at least the envelope glycoprotein of a primary isolate of HIV-1, wherein said non- infectious, non-replicating, immunogenic HIV-like particle comprises an assembly of: (i) an env gene product, (ii) a pol gene product, and (iii) a gag gene product, said particle being encoded by a modified HIV genome deficient in long terminal repeats (LTRs) and containing gag, pol and env in their natural genomic arrangement. 5. The method of claim 4 wherein the vector is pCMV3Bx08 shown in Figure 2. Cited References Haynes et al. US 5,439,809 Aug. 8, 1995 Sia et al. US 5,639,854 June 17, 1997 Berzofsky et al. US 5,932,218 Aug. 3, 1999 Clements-Mann et al., Immune Responses to Human Immunodeficiency Virus (HIV) Type 1 Induced by Canarypox Expressing HIV-1MN gp120, HIV- 1SF2 Recombinant gp120, or Both Vaccines in Seronegative Adults, 177 J. INFECTIOUS DISEASES 1230–1246 (1998). Caver et al., A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations for HIV-1 envelope presentation, 17 VACCINE 1567– 1572 (1999). Appeal 2012-005779 Application 12/233,021 3 Grounds of Rejection 1. Claims 1, 6–8, and 17 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Clements-Mann and Haynes. 2. Claims 1, 2, and 10 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Clements-Mann in view of Haynes and Sia. 3. Claims 1, 3, and 4 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Clements-Mann in view of Haynes and Caver. 4. Claims 1 and 5 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Clements-Mann in view of Haynes, Sia, and Caver. 5. Claims 1, 11, and 12 are rejected under 35 U.S.C. § 103(a) as being unpatentable over Clements-Mann in view of Haynes and Berzofsky. FINDINGS OF FACT The Examiner’s findings of fact are set forth in the Answer at pages 5–18. The following facts are highlighted. 1. Figure 2 of Appellants’ Specification is reproduced below. Appeal 2012-005779 Application 12/233,021 4 Figure 2 shows, “[a] DNA construct was prepared incorporating the env gene from the primary isolate Bx08 under the control of the cytomegalovirus promoter and the construct, pCMV3Bx08, is shown in Figure 2.” (Spec. 6.) Discussion Rejection 1 ISSUE The Examiner finds with respect to claim 1 that With regard to the limitations “at least one administration of a priming antigen to the host”, “resting the host for at least one specific resting period” and “at least one administration of a boosting antigen to the primed host”, Clements-Mann et al. teaches various prime-boost vaccination schedules for a safety and immunogenicity trial were conducted in human immunodeficiency virus (HIV)-uninfected adults who were randomized to receive canarypox (ALVAC) vector expressing HIV-IMN gp160 at 0 and 1 or 2 months followed by ALVAC- gpI60 or HIV-1SF2 recombinant (r) gp120 at 9 and 12 months (See abstract, and Figure 1 shown below, Clements-Mann et al., 1998). . . . Appeal 2012-005779 Application 12/233,021 5 Clements-Mann et al. teaches neutralizing antibody responses of HIV-1 following serial immunization with ALVAC-HIV-l gp160 MN or HIV-lSF2 (r) gp120 (See Table 4, page 1238, Clements-Mann et al., 1998). The frequency and duration of priming and boosting taught by Clements-Mann et al. in Figure 1 (included below) reads on the limitations of claims 6-8 and 17 as the priming antigen is administered twice (claim 6), at 0 and at either 1 or 2 months with the period between administrations being the resting period (claims 7 and 8). The boosting antigen was administered at 9 and 12 months, which is at least 2 administrations as required by claim 17. With regard to the limitation “DNA molecule encoding an envelope glycoprotein of a primary isolate of HIV -1”, the HIV -1 primary isolate taught by Clements-Mann et al. are MN isolate and SF2 isolate. Clements-Mann et al. does not explicitly teach a boosting antigen being a non-infectious, non-replicating, immunogenic HIV-like particle, which comprises an env gene product, a pol gene product, and a gag gene product, as recited in claim 1, for vaccination against HIV -1 infection. However, at the time of filing of instant application, using non-infectious, non-replicating, immunogenic HIV-like particle as a booster for HIV vaccination is known in the art. For instance, Haynes et al. teaches an immunogenic HIV retrovirus-like particle which is non-infectious and non- replicating and which is useful as a candidate vaccine component against HIV infection, is produced by genetic engineering, a DNA molecule comprising the HIV genome devoid of long terminal repeats is incorporated into an expression vector, which is introduced into mammalian cells for expression of the HIV retrovirus-like particle, and the HIV-like particle encoding env, pol, and gag proteins (See abstract, Figure 1, Haynes et al., 1995). Haynes further teaches primary and boosting immunization using HIV-1 virus-like particles in mouse (See Example 8, columns 13-14, Haynes et al., 1995). (Ans. 6–8.) Appeal 2012-005779 Application 12/233,021 6 Appellants contend that It is not seen how combining the teaching of a prime- boost procedure from Clements-Mann et al using a priming administration of a DNA molecule encoding an envelope glycoprotein gp 120 with a boosting administration of a recombinant gp120 fragment of HIV with a priming administration of a non-infectious, non-replicating, immunogenic HIV-like particle followed by a boosting administration with non-infectious, non-replicating immunogenic HIV-like particles, as described in Haynes et al, can lead to the prime-boost administration effected in the present invention. There is nothing in the references to suggest that the use of non-infectious, non-replicating, immunogenic HIV-like particles as a boosting antigen is effective other than with a priming using of the HIV-like particles. There is certainly no suggestion provided by the combination of Clements-Mann et al and Haynes et al that neutralizing antibodies to an envelope glycoprotein of a primary isolate of HIV-1 can be attained by administration of a priming antigen which comprises a DNA molecule encoding an envelope glycoprotein of a primary isolate of HIV-1 and by administering a boosting antigen which is a non-infectious, non-replicating immunogenic HIV-like particle as claimed. (Br. 10–11.) Appellants further argue that, “[g]iven the unpredictability of the prior art, it is submitted that there is no reasonable expectation of success in making the modifications suggested by the Examiner” and that the Examiner has engaged in hindsight analysis. (Br. 11 and 12.) The issue is: Does the cited prior art support the Examiner’s conclusion that the claimed subject matter is prima facie obvious? Appeal 2012-005779 Application 12/233,021 7 PRINCIPLES OF LAW “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.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993) (citations omitted). In order to determine whether a prima facie case of obviousness has been established, we consider the factors set forth in Graham v. John Deere Co., 383 U.S. 1, 17 (1966): (1) the scope and content of the prior art; (2) the differences between the prior art and the claims at issue; (3) the level of ordinary skill in the relevant art; and (4) objective evidence of nonobviousness, if present. “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’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “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). After a prima facie case of obviousness has been established, the burden of going forward shifts to the applicant. Rebuttal is merely “a showing of facts supporting the opposite conclusion,” and may relate to any of the Graham factors including so-called secondary considerations. If rebuttal evidence of adequate weight is produced, the holding of prima facie obviousness, being but a legal inference from previously uncontradicted evidence, is dissipated.” In re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir. 1984) (citations omitted). When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable Appeal 2012-005779 Application 12/233,021 8 solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated technical success, it is likely the product not of innovation but of ordinary skill and common sense. KSR, 550 U.S. at 421. ANALYSIS We agree with the Examiner’s fact finding, statement of the rejection and responses to Appellants’ arguments as set forth in the Answer. We find that the Examiner has provided evidence to support a prima facie case of obviousness. We provide the following additional comment to arguments set forth by Appellants. Appellants argue that it would have been unpredictable whether the combination of Clements-Mann and Haynes would result in neutralizing antibodies to HIV-1. (Br. 10–11.) However, both Clements Mann (abstract) and Haynes (Col. 14) teach that the administration of the gp160 and/or gp120 immunogen results in the production of neutralizing antibodies to HIV-1. Given the common immunogenic response, we find that one skilled in the art would have found it obvious to use the HIV-like particle taught by Haynes as the boosting agent in the prime-boost regimen taught by Clements-Mann. Appellants have provided no rebuttal evidence supporting their position that one of ordinary skill in the art would have found the production of neutralizing antibodies unpredictable in view of the disclosure of Clements-Mann and Haynes, or any other available evidence at the time of filing of the present application. Therefore, we are not persuaded by Appellants’ unpredictability argument. Appeal 2012-005779 Application 12/233,021 9 Appellants argue that the Examiner has engaged in hindsight reconstruction of Appellants’ invention. (Br. 11.) The Examiner’s rationale for combining Clements-Mann with Haynes is set forth on pages 9–10 of the Answer. The Examiner’s suggested rationale for combining Haynes with Clement-Mann is found in Haynes’ statement that “[t]hese preparations [Haynes] will serve as candidates for whole-virus-like vaccines for human retrovirus diseases and should not be subject to the ethical concerns regarding the production of classical whole-virus vaccines from infectious virus preparations (See Field of Invention, lines 5-14, column 1, Haynes et al.).” (Ans. 9.) We are not persuaded by the Appellants’ contention that the Examiner has engaged in hindsight reconstruction of Appellants’ invention. Both of the constructs of Clements-Mann and Haynes resulted in the production of neutralizing antibodies to HIV-1. When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. See KSR, 550 U.S. at 421. In view of the rationale provided by the Examiner, we find that one of ordinary skill in the art would have had a reason provided in the cited art to select the non-infectious and non-replicating HIV-like particle of Haynes and use it in the priming protocol of Clements-Mann. Rejection 1 is affirmed for the reasons of record. Rejections 2, 3, and 5 Appellants do not argue Rejections 2, 3, and 5 on the merits, but instead rely on their arguments for patentability based on the combination of Appeal 2012-005779 Application 12/233,021 10 Clements-Mann and Haynes. (Br. 14, 15, 16.) For the reasons of record and given the comments above (Rejection 1) regarding the lack of patentability of the claimed invention in view of Clements-Mann and Haynes, Rejections 2, 3 and 5 are also affirmed. Rejection 4 We reverse the rejection of claim 5, as we do not find that the Examiner has set forth a prima facie case of obviousness. Appellants argue that combined teachings do not lead to the plasmid pCMV3Bx08 as shown in Figure 2. (Br. 17–18.) The Examiner responds to Appellants’ argument noting that [I]n the absence of disclosure of specified sequences and/or specified deposit number of pCMV3Bx08, the limitation “pCMV3Bx08” recited in claim 5 encompasses any plasmid comprising any coding sequence of any HIV-1 envelope glycoprotein of Bx08 isolate. It is further noted the ordinarily skilled artisan would be well-versed and knowledgeable in various molecular cloning techniques for constructing a plasmid of interest, including the pCMV3Bx08 plasmid disclosed in Figure 2 and Example 1 of instant application, because these molecular techniques would be well within the skills of the ordinary artisan by the teachings of Caver et al. and Sia et al. (Ans. 23.) Although the Examiner asserts that it would have been obvious to use any pCMV3Bx08 vector, claim 5 requires the specific vector of Fig. 2 (FF1). The Examiner does not provide any rationale or evidence in the prior art to use a pCMV3Bx08 vector such as that of Fig. 2, that includes, for example, the KanR gene or the restriction enzyme sites included in Fig. 2. “[R]ejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning Appeal 2012-005779 Application 12/233,021 11 with some rational underpinning to support the legal conclusion of obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). In this case, however obvious to one of ordinary skill in the art the Examiner may believe it may be, the Examiner needs to provide some supporting evidence to show that the cloning techniques and resistance genes shown in the claimed vector of Fig. 2 of the Specification was known in the art at the time of the invention and obvious. Here, we do not find that the Examiner has supported the rejection of claim 5 with sufficient evidence, and we are constrained to reverse that rejection. CONCLUSION OF LAW The cited references support the Examiner’s obviousness rejections 1– 3 and 5, which are affirmed. Rejection 4 (claim 5) 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). AFFIRMED-IN-PART cdc UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte BENJAMIN ROVINSKI, JAMES TARTAGLIA, SHI-XIAN CAO, ROY PERSSON, and MICHEL H. KLEIN __________ Appeal 2012-005779 Application 12/233,021 Technology Center 1600 __________ Before DEMETRA J. MILLS, ULRIKE W. JENKS, and CHRISTOPHER G. PAULRAJ Administrative Patent Judges. JENKS, Administrative Patent Judge, dissenting-in-part. I respectfully dissent from the Majority’s analysis with respect to the obviousness rejection of claim 5 (Rejection 4). The Majority does not find that the Examiner has provided sufficient “supporting evidence to show that the cloning techniques and resistance genes shown in the claimed vector of Fig. 2 of the Specification was known in the art at the time of the invention and obvious.” (Majority opinion 11.) Here, claim 5 recites a vector as shown in Figure 2 (see FF1 of Majority opinion). The disclosed vector shows the CMV promoter (pCMV), Kan resistance sequence, the BX08 sequence, as well as some restriction enzyme sites. Appeal 2012-005779 Application 12/233,021 2 In setting out the prima facie case, the Examiner finds, and Appellants concede (App. Br. 17), that Sia et al. teaches the HIV-1 isolate sequences, including BX08 (Ans. 15; see also Sia, col. 4, ll. 45–53), and Caver teaches expression of HIV envelope protein using an expression plasmid that contains a CMV promoter (Ans. 15; see also Caver Abstract, and p. 1568, 2.2.1 DNA). Thus, these two references in combination provide the critical information needed for the expression of the particular HIV sequence, BX08, using a CMV promoter. The issue with respect to this obviousness rejection is whether basic undergraduate knowledge in molecular biology can be ascribed to the ordinary artisan. As noted by the Majority, the Examiner did not supply a reference for disclosing the KanR gene or the restriction enzyme sites included in Fig. 2. Instead, the Examiner’s position on this point is that “the ordinarily skilled artisan would be well-versed and knowledgeable in various molecular cloning techniques for constructing a plasmid of interest, including the pCMV3Bx08 plasmid disclosed in Figure 2 and Example 1 of instant application, because these molecular techniques would be well within the skills of the ordinary artisan” (Ans. 23). In my view, I agree with the Examiner’s position that one of ordinary skill in the art versed in molecular cloning techniques would know to add an antibiotic resistance gene to a plasmid in order to propagate the resultant plasmid construct in a bacterial system. Indeed, the Specification provides that the commercially available plasmid, that serves as the backbone for the plasmid disclosed in Fig. 2, contained an antibiotic resistance gene, AmpR gene (Spec. 8: ¶ 36). It is routine practice in molecular biology to change Appeal 2012-005779 Application 12/233,021 3 the antibiotic resistance gene from one cloning round to the next in order to identify the plasmid containing the gene of interest. I find no evidence in the record that the KanR gene serves any other function other than to help propagate the plasmid of interest in a bacterial system. Accordingly, I agree with the Examiner’s conclusion that the ordinary artisan equipped with the knowledge of the particular gene sequence (BX08) with the suggested use of a particular promoter (CMV) for the expression of the gene would arrive at a plasmid construct containing an antibiotic resistance gene, that would reasonably include KanR gene. “[I]nterrelated teachings of multiple patents; the effects of demands known to the design community or present in the marketplace; and the background knowledge possessed by a person having ordinary skill in the art, all [should be considered] in order to determine whether there was an apparent reason to combine the known elements in the fashion claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007) (italicized emphasis added). In this case, the background knowledge possessed by a person having ordinary skill in the art has been relied upon by the Examiner (Ans. 23), and this form of prior art has been sanctioned under KSR. As recognized by the Court in KSR, “[a] person of ordinary skill is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421. Therefore, I find that the Examiner has supported the rejection of claim 5 with appropriate prior art evidence. In conclusion, I would affirm the Examiner’s obviousness rejection of claim 5. Copy with citationCopy as parenthetical citation