Ex Parte Jiang et alDownload PDFPatent Trial and Appeal BoardAug 23, 201612897997 (P.T.A.B. Aug. 23, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/897,997 10/05/2010 Shibo Jiang 45200 7590 08/25/2016 K&L Gates LLP-Orange County 1 Park Plaza Twelfth Floor IRVINE, CA 92614 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. 1958427.00161 2988 EXAMINER BLUMEL, BENJAMIN P ART UNIT PAPER NUMBER 1648 NOTIFICATION DATE DELIVERY MODE 08/25/2016 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address( es): uspatentmail@klgates.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte SHIBO JIANG and LANYING DU Appeal 2015-001614 Application 12/897 ,997 Technology Center 1600 Before DONALD E. ADAMS, DEMETRA J. MILLS, and JOHN E. SCHNEIDER, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL 1 This appeal under 35 U.S.C. § 134(a) involves claims 1, 3, 8-10, 12, 13, and 15 (Final Rej. 2). 2 Examiner entered rejections under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM-IN-PART. 1 Appellants identify the Real Party in Interest as the "New York Blood Center, Inc." (App. Br. 3). 2 Pending claims 4, 5, 16, and 17 stand "withdrawn from further consideration ... as being drawn to nonelected species and invention" (Final Rej. 3). Claim 11 stands cancelled on this record (see Appellants' January 7, 2014 Response 4). Appeal 2015-001614 Application 12/897 ,997 STATEMENT OF THE CASE Appellants disclose immunogenic compositions comprising trimeric proteins that comprise: "1) an immunogen, such as an influenza hemagluttinin sequence; 2) a trimerization or stabilization sequence; and 3) an immunopotentiator sequence" (Spec. i-f4). Claims 1 and 15 are representative and reproduced in the Claims Appendix of Appellants' Brief. Claims 1, 3, 8-10, 12, and 13 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, 3 Ma, 4 and Strongin. 5 Claim 1 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, Xiao, 6 and He. 7 Claim 1 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Ando. 8 3 Song et al., Efficacious Recombinant !r.fluenza Vaccines Produced by 1-ligh Yield Bacterial Expression: A Solution to Global Pandemic and Seasonal Needs, 3 PLos ONE 1-8 (2008). 4 Ma et al., Carcinoembryonic antigen-immunoglobulin Fe fusion protein (CEA-Fe) for identification and activation of anti-CEA immunoglobulin-T- cell receptor-modified T cells, representative of a new class of Jg fusion proteins, 11 Cancer Gene Therapy 297-306 (2004). 5 Strongin et al., US 8,053,553 B2, issued Nov. 8, 2011. 6 Xiao et al., Evaluation of recombinant Onchocerca volvulus activation associated protein-I (ASP-I) as a potent Thi-biased adjuvant with a panel of protein or peptide-based antigens and commercial inactivated vaccines, 26 Vaccine 5022-5029 (2008). 7 He et al., Recombinant ov-ASP-1, a Thi-Biased Protein Adjuvant Derived from the Helminth Onchocerca volvulus. Can Directly Bind and Activate Antigen-Presenting Cells, 182 J. Immunol. 4005--4016 (2009). 8 Ando et al., Preparation of influenza virosome vaccine with muramyldipeptide derivative B30-MDP, 14 J. Microencapsulation 79-90 (1997). 2 Appeal 2015-001614 Application 12/897 ,997 Claim 1 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Watanabe. 9 Claim 15 stands rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Jiang. 10 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Song discloses that "[i]t is known that physical linkage of [Toll-like receptor (TLR)] ligands and vaccine antigens significantly enhances the immunopotency of the linked antigens" (Song, Abstract; see generally Ans. 3). FF 2. Song discloses that "TLRs are expressed on various cell types, including professional antigen presenting cells (APC[s]), where they act as primary sensors of microbial infection and then activate signaling pathways that lead to the induction of immune and inflammatory genes" (Song e2257; see generally Ans. 3). FF 3. Song discloses that "[ e ]ngagement of TLRs by their cognate agonists and the subsequent signaling within APC leads to enhanced processing and presentation of antigens that are co-delivered to those APC" (Song e2258; see generally Ans. 3). FF 4. Song discloses "that the physical linkage of vaccine antigens to the Toll-like receptor 5 (TLR5) ligand, flagellin, generates a significantly more 9 Watanabe et al., Protection against influenza virus infection by intranasal administration of C3d-fused hemagglutinin, 21 Vaccine 4532--453 8 (2003). 10 Jiang et al., US 2010/0098724 Al, published Apr. 22, 2010. 3 Appeal 2015-001614 Application 12/897 ,997 potent vaccine than simple mixing of antigen and tlagellin" (Song e2257- e2258; see generally Ans. 3; see Song e2258 ("The sequence SGSGSGS was incorporated at the junction of STF2 [(Salmonella typhimurium type 2 flagellin)] and [influenza] HA as a flexible linker")). FF 5. Song discloses the production of "influenza vaccines that fuse the globular head domain of the protective [influenza] hemagglutinin (HA) antigen with the potent TLR5 ligand, flagellin," wherein "the vaccines elicit robust antibody responses" (Song, Abstract (emphasis added); see generally Ans. 3). FF 6. Examiner finds that Song fails to suggest "the use of an Fe from human IgG, which would result in the fusion protein HAl-hFC" (Ans. 3). FF 7. Examiner finds that while Song discloses the use of TLR ligands, such as flagellin, "which target antigen presenting cells [to] improve immune responses towards vaccine antigens that are stably linked" to flagellin; the "Fe fragment of a human IgG fused via a stable linker to an antigen can also function in the capacity to improve immune functions as the Fe targets mononuclear immune cells in the blood, as taught by Ma" (Ans. 3--4; see id. at 3 ("human IgG Fe ... is a functional equivalent of the TLR5 ligand flagellin"); id. at 12). FF 8. Ma discloses the creation of anti-carcinoembryonic antigen (CEA) designer T cells by fusing the antigen-binding portion of an anti-CEA antibody [] to the zeta chain of TCR[ 11LCD3 complex[]. These designer T cells combine the specificity of the anti-CEA antibody with the cytotoxic potency of T cells to specifically kill the CEA- 11 The acronym "TCR" refers to the T cell receptor (see generally Ma 297). 4 Appeal 2015-001614 Application 12/897 ,997 expressing tumor cells in vitro[] and inhibit the CEA- expressing tumor growth in animal models. (Ma 297 (endnotes omitted).) FF 9. Ma discloses the use of "[a] CEA-immunoglobulin Fe (CEA-Fe) fusion protein ... for the purposes of activation and detection of anti-CEA designer T cells" (Ma Abstract; see id at 298 ("Fe receptor present on monocytes can bind to and crosslink Ag-Fe bound to IgTCR+ T cells in vivo leading to their activation and selective proliferation"); id. at 298 ("By selectively activating [the anti-CEA designer T] cells with immobilized Ag- Fc, the modified cell fraction can be induced to expand to large numbers of designer T cells")). FF 10. Ma discloses that "[s]everal advantages derive from the creation of[] an Ag-Fe molecule," including the advantage that "Ag-Fe protein is simple and economical to produce in large scale, whereas obtaining purified natural antigen may often be problematic or expensive" (Ma 298; see Ans. 13). FF 11. Ma discloses that "[t]he fact that the [CEA-Fe] product is entirely human in sequence (human CEA, human F c) means that it can safely be used in humans with a low likelihood of immunogenicity" (Ma 305 ( emphasis added)). FF 12. Examiner relies on Strongin to disclose "influenza HA fusion proteins [that contain a] peptide linker" that "is a T4 foldon" having "the same amino acid sequence of [the] foldon used by [Appellants]" (Ans. 3, citing Strongin 43: 57-64 and Spec. 11: SEQ ID NO. 6; see also Spec. i-f 44 ("The expressed recombinant protein was fused with a foldon (Fd) sequence (SEQ ID NO. 6) and the Fe fragment (SEQ ID NO. 7) of human IgGl (hFc)"; see Strongin 43: 57---60 ("To facilitate the yield of the stable [influenza] H5 [hemagglutinin] precursor, the C-terminal region of the 5 Appeal 2015-001614 Application I2/897 ,997 [construct] contained the bacteriophage T4 fibritin 'foldon' trimerizing sequence, a thrombin cleavage site and a Hisx6 tag")). FF I 3. Examiner finds that the combination of Song, Ma, and Strongin fails to suggest "the use of an ASP-I[, C3d, cholera toxin, or muramyl peptide,] as [an] immunopotentiator" (Ans. 4---6). FF I 4. Examiner finds that "recombinant ASP- I from Onchocerca volvulus [] provide[ s] adjuvanting properties to different vaccine compositions" when mixed with antigen (Ans. 4, citing Xiao§§ 2. I-2.2 and Figure 6; see Xiao § 2.3 (mice were immunized with antigen "mixed with ASP-I")). FF I5. He discloses that recombinant ASP-I from Onchocerca volvulus "rOv-ASP-I" binds "to the APCs among human PBMCs and trigger[s] ThI- biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-I is a novel potent innate adjuvant" (He, Abstract; see Ans. 4). FF I 6. He discloses that TLR signaling stimulates the activation and maturation of APCs including the regulated presentation of Ags, up- regulation of costimulatory molecules, and secretion of proinflammatory chemokines and cytokines. These events mediate not only innate but ultimately also adaptive immunity[]. Vaccinations with adjuvants that mimic TLR ligands are advantageous as they are capable of eliciting positive effects across the entire spectrum of innate and adaptive immunity. (He 40I4.) FF I 7. Examiner finds that Ando discloses "the use of muramyldipeptide [(MDP)] derivative B30-MDP as an adjuvant with [] influenza vaccine compositions[, wherein] [t]he B30-MDP is conjugated with a virosome that 6 Appeal 2015-001614 Application 12/897 ,997 contains the HA and NA proteins of influenza" (Ans. 5, citing Ando 81 and 80: Figure 1; see Ando 80 ("B30-MDP [is] a MDP analog which has less toxicity and more potent immunoadjuvant activity than MDP")). FF 18. Watanabe discloses the induction of "protective mucosal immune responses in the nasal area against influenza virus infection" through the use of a "recombinant protein composed of ... C3 d ... fused to the secreted form of [influenza virus] hemagglutinin" (Watanabe Abstract; Ans. 6 (Watanabe's "fusion protein contains an influenza HA fused to a polyGS linker, which is fused to C3d")). FF 19. Watanabe discloses that "[ fJor the induction of mucosal immune response by intranasal vaccination, cholera toxin B subunits (CTB) and Escherichia coli heat-labile toxin (LT) are often administered as mucosal adjuvants in order to enhance immune responses to mucosally co- administered bystander antigens" (Wantabe Abstract; Ans. 6 ("Watanabe [] teach the use of cholera toxins in conjunction with influenza HA fragments")). FF 20. Examiner finds that the combination of Song, Ma, and Strongin "while ... [suggesting] the fusion of immunogenic TLR ligands with influenza HA proteins through a flexible linker, [fails to suggest] the use of an adjuvant" and relies on Jiang to disclose "immunogenic compositions [that] comprise[] an adjuvant" and a "2,2-bipyridine-5-carboxylic acid" (BCA) linker (Ans. 7; see Jiang i-fi-f 13 and 39). ANALYSIS The combination of Song, Ma, and Strongin: Based on the combination of Song, Ma, and Strongin, Examiner concludes that, at the time Appellants' invention was made, it would have 7 Appeal 2015-001614 Application 12/897 ,997 been prima facie obvious "to modify [Song's] compositions ... in order to use the foldon stabilizing sequence to generate a [] fusion protein, such as HAl-Fd-hFc" (Ans. 3). In this regard, Examiner reasons that "the TLR5 [ligand, flagellin,] and Fe molecules are [both] immunopotentiators and are effective at activating a specific immune response [in] a host," wherein an antigen-Fe conjugate has the advantage of being "simple and economical to produce in large scale, whereas obtaining purified natural antigen may often be problematic or expensive" (Ans. 12-13; id. at 3 ("human IgG Fe ... is a functional equivalent of the TLR5 ligand flagellin"); see FF 7 and 10). We are not persuaded. As Appellants explain, "the immune responses generated in Song and Ma are not the same, either in mechanism or in effect" and, therefore, "the Fe of Ma is[] not the functional or mechanical equivalent of [Song's] flagellin" (App. Br. 8; see Reply 3--4; FF 1-5; cf FF 7-11). In this regard, Appellants contend that "the goal in Song is to fuse an antigen from a pathogen with a specific ligand (flagellin) capable of inducing specific receptor (TLR)-mediated signaling in APCs, resulting in enhanced processing and presentation of the antigen and production of neutralizing antibodies" (App. Br. 9; see Reply Br. 2-3; FF 1-5). In contrast, Appellants contend, inter alia, that Ma's "fusion protein 'is entirely human in sequence' and can therefore 'safely be used in humans with a low likelihood of immunogenicity"' (App. Br. 9; see FF 11 ). In addition, Appellants contend that while Ma suggests that the "CEA-Fe fusion protein activates [Ma's] anti-CEA designer T cells via monocyte Fe receptors ... there is no teaching or suggestion that the immune responses induced by [Ma's] CEA-Fe are 8 Appeal 2015-001614 Application 12/897 ,997 achieved via processing and antigen presentation by APCs" (App. Br. 10; cf FF 3). In sum, Examiner failed to establish an evidentiary basis on this record to support a conclusion that replacing Song's TLR ligand, flagellin, with Ma's Fe fragment would result in "enhanced processing and presentation of antigens" by APCs and, thereby, result in the production of "vaccines [that] elicit robust antibody responses" (see FF 3--4). Substituting an Fe of Ma for the flagellin of Song ... would render the protein of Song unsuitable for its intended purpose, because the success of the Song vaccine proteins depends on the engagement of TLR, a specific receptor on the surface of APCs, and on the subsequent signaling induced by activation of that receptor. (App. Br. 10.) "[R]ejections on obviousness grounds cannot be sustained by mere conclusory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." Irz re Kahn; 441F.3d977; 988 (Fed. Cir. 2006). In the alternative, Examiner failed to establish an evidentiary basis on this record to support a conclusion that a person of ordinary skill in this art would have had a reason to substitute Song's influenza HA protein for the CEA portion of Ma's fusion protein, which was designed to detect and activate designer T cells that "specifically kill [] CEA-expressing tumor cells in vitro[] and inhibit the CEA-expressing tumor growth in animal models" (FF 8; see App. Br. 10 ("substituting the HA antigen of Song for the CEA antigen of Ma ... would render the fusion protein of Ma unsuitable for its intended purpose")). See Kahn, 441 F.3d at 988. 9 Appeal 2015-001614 Application I2/897 ,997 The combination of Song, Ma, Strongin, Xiao, and He: Based on the combination of Song, Ma, Strongin, Xiao, and He, Examiner concludes that, at the time Appellants' invention was made, it would have been prima facie obvious "to modify [Song's] compositions ... in order to use [] Onchocerca volvulus ASP- I[, as suggested by the combination of Xiao and He,] as the immunopotentiator" instead of flagellin (Ans. 5). The combination of Xiao and He suggests that ASP- I, like flagellin, is a TLR ligand that binds APCs (FF I4-I6). Therefore, we recognize, but are not persuaded by Appellants' contention "that the ASP-I of Xiao is not the functional or mechanical equivalent of the flagellin of Song" (App. Br. I 6; see generally Reply Br. 5). For the same reason, we are not persuaded by Appellants' contention that the combination of "Xiao [and He] does not ... suggest that ASP-I is capable of binding to TLR, inducing TLR-mediated signaling in APCs, or inducing enhanced processing and presentation of a linked foreign antigen by APCs" (App. Br. I 6). Song discloses that "[i]t is known that physical linkage of [TLR] ligands and vaccine antigens significantly enhances the immunopotency of the linked antigens" and "that the physical linkage of vaccine antigens to the Toll-like receptor 5 (TLR5) ligand, flagellin, generates a significantly more potent vaccine than simple mixing of antigen and flagellin" (FF I and 4 ). Thus, absent evidence to the contrary, a person of ordinary skill in this art would reasonably conclude that the physical linkage of the TLR ligand, ASP- I, would exhibit similar results as those obtained for flagellin (see FF I-5 and I4-I6). For the foregoing reasons, we recognize, but are not persuaded by, Appellants' contention that Xiao and He both relate "to the IO Appeal 2015-001614 Application 12/897 ,997 use of ASP- I as a conventional vaccine adjuvant [], wherein the ASP- I protein is mixed with the antigen and injected" (App. Br. 16; see id. at 16- 17; id. at 17 ("Although ASP-1 may be used to induce antibody production, the cited prior art does not disclose fusing a conventional adjuvant directly to an antigen to produce the same effects or substituting a conventional adjuvant for a specific sequence that acts via a specific receptor"); see generally App. Br. 17-18). Strongin discloses "influenza HA fusion proteins" that contain "a T 4 foldon" linker (FF 12). Stated differently, Strongin suggests the use of a linker as part of an influenza HA fusion protein (id.). Similarly, Song suggests the use of a linker as part of an influenza HA fusion protein (FF 4 (a flexible linker was incorporated at the junction of flagellin and influenza HA)). Therefore, absent evidence to the contrary, we find no error in Examiner's conclusion that, at the time of Appellants' claimed invention, a person of ordinary skill in this art would have reasonably used either Strongin's foldon linker or Song's flexible linker to create a fusion protein that comprises a linker and influenza HA (see FF 4 and 12). For the foregoing reasons, we recognize, but are not persuaded by, Appellants' contention that "the foldon of Strongin is not the functional or mechanical equivalent of the linker of Song" (App. Br. 17). To the contrary, the linkers of Strongin and Song serve the purpose of linking two pieces of a fusion protein to each other. Therefore, notwithstanding Appellants' contention to the contrary, the two linkers serve the same function and mechanical purpose. We recognize, but are not persuaded by, Appellants' contentions that Song's linker is characterized as "flexible," while Strongin's linker is characterized as a "trimerizing sequence" and that Strongin discloses other 11 Appeal 2015-001614 Application 12/897 ,997 linkers, thereby making "a distinction between ... linkers and the foldon sequence used for its trimerization properties" (App. Br. 11 ). Appellants fail to provide persuasive evidence or argument to support a conclusion that a person of ordinary skill in this art would not appreciate that Strongin's foldon linker would link components of a fusion protein together as disclosed by Strongin and, similarly, disclosed by Song (FF 4 and 12). In addition, Appellants fail to provide persuasive evidence or argument to support a conclusion that replacing Song's linker with Strongin's foldon linker would render Song's construct inoperable (see generally App. Br. 11- 12 and 18-19). In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974) ("Attorney's argument in a brief cannot take the place of evidence."). The combination of Song, Ma, Strongin, and Ando: Based on the combination of Song, Ma, Strongin, and Ando, Examiner concludes that, at the time Appellants' invention was made, it would have been prima facie obvious "to modify [Song's] compositions ... in order to use [Ando' s] muramyl peptide as the immunopotentiator" instead of flagellin (Ans. 5-6). Ando discloses "the use of muramyldipeptide [(MDP)] derivative B30-MDP as an adjuvant with [] influenza vaccine compositions[, wherein] [t]he B30-MDP is conjugated with a virosome that contains the HA and NA proteins of influenza" (FF 17). As Appellants explain, Examiner failed to establish an evidentiary basis on this record to support a conclusion that Ando's "B30-MDP could be fused to an antigen in a single polypeptide in order to produce the same [adjuvant] effect with a reasonable expectation of success" (App. Br. 22; see Ans. 15 (Ando "do not teach that 12 Appeal 2015-001614 Application 12/897 ,997 muramyldipeptide derivative B30-MDP is part of a fusion protein")). Therefore, notwithstanding Examiner's assertion that Ando's B30-MDP is an adjuvant/immunopotentiator, Examiner failed to establish an evidentiary basis on this record to support a conclusion that a person of ordinary skill in this art would have found it prima facie obvious to fuse Ando's B30-MDP to influenza HA or that B30-MDP, in such a fusion construct, would reasonably have been expected to retain its "function[] as an adjuvant/immunopotentiator" (see Ans. 15). See Kahn, 441 F .3d at 988. The combination of Song, Ma, Strongin, and Watanabe: Based on the combination of Song, Ma, Strongin, and Watanabe, Examiner concludes that, at the time Appellants' invention was made, it would have been prima facie obvious "to modify [Song's] compositions ... in order to use [Watanabe's] C3d as the immunopotentiator" instead of flagellin (Ans. 7). We recognize Appellants' contention that "Ma ha[s] no relevance to the instant rejection based on C3d" (App. Br. 24). We note, however, that in affirming an obviousness rejection, the Board may rely upon less than all the references cited by the Examiner. See In re Kronig, 539 F.2d 1300, 1302 (CCPA 1976). Watanabe discloses the induction of "protective mucosal immune responses in the nasal area against influenza virus infection" through the use of a "recombinant protein composed of ... C3d ... fused to the secreted form of [influenza virus] hemagglutinin" (FF 18). The difference between Watanabe and Appellants' claim 1, lies in the choice of linker to link C3d to influenza HA, e.g., a foldon linker as suggested by Strongin (see FF 12). 13 Appeal 2015-001614 Application 12/897 ,997 Therefore, we recognize, but are not persuaded by Appellants' contention "that the C3d of Watanabe is not the functional or mechanical equivalent of the flagellin of Song" (App. Br. 24; see generally id. at 24--25; see generally Reply Br. 5). Strongin suggests the use of a foldon linker in a fusion protein comprising influenza HA (see FF 12). Therefore, for the foregoing reasons, we are not persuaded by Appellants' contention that "[t]he foldon of Strongin is ... not the functional or mechanical equivalent of the linker of Watanabe [because] []the linker of Watanabe is a short, glycine-containing linker, similar to the linker described above for Song" (App. Br. 25; see also id. at 26). Appellants fail to provide persuasive evidence or argument to support a conclusion that a person of ordinary skill in this art would not have found it prima facie obvious to use an art recognized linker, i.e. a foldon linker such as that of Strongin, that is known in the art to be useful to link influenza HA to another protein, to link influenza HA to C3d (see FF 12). See Pearson, 494 F.2d at 1405. The combination of Song, Ma, Strongin, and Jiang: Based on the combination of Song, Ma, Strongin, and Jiang, Examiner concludes that, at the time Appellants' invention was made, it would have been prima facie obvious "to modify [Song's] compositions ... in order to link [influenza] HA protein with an immunopotentiator with [a] BCA [linker] and include an adjuvant" as suggested by Jiang (Ans. 8). Examiner failed to establish that Jiang's disclosure of the use of an adjuvant with immunogenic compositions and a BCA linker makes up for 14 Appeal 2015-001614 Application 12/897 ,997 the deficiencies in the combination of Song, Ma, and Strongin discussed above (see FF 20; App. Br. 27). CONCLUSION OF LAW The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness with respect to the combination of Song, Ma, Strongin in view of: (a) the combination of Xiao and He or (b) Watanabe. The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, Xiao, and He is affirmed. The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Watanabe is affirmed. The preponderance of evidence relied upon by Examiner fails to support a conclusion of obviousness with respect to the combination of Song, Ma, and Strongin with or without Ando or Jiang. The rejection of claims 1, 3, 8-10, 12, and 13 under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, and Strongin is reversed. The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Ando is reversed. The rejection of claim 15 under 35 U.S.C. § 103(a) as unpatentable over the combination of Song, Ma, Strongin, and Jiang is reversed. 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-IN-PART 15 Copy with citationCopy as parenthetical citation