12309128 (P.T.A.B. Jul. 18, 2016)

Ex Parte Sunkar et al

Patent Trial and Appeal BoardJul 18, 2016

12309128 (P.T.A.B. Jul. 18, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 12/309, 128 01115/2010 Ramanjulu Sunkar 22798 7590 07118/2016 QUINE INTELLECTUAL PROPERTY LAW GROUP, P,C POBOX458 ALAMEDA, CA 94501 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. 129-002510US 2091 EXAMINER ZHOU,SHUBO ART UNIT PAPER NUMBER 1662 MAILDATE DELIVERY MODE 07/18/2016 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte RAMANJULU SUNKAR, A VNISH KAPOOR, and JIAN-KANG ZHU Appeal2014-004175 Application 12/309, 128 1 Technology Center 1600 Before ULRIKE W JENKS, RICHARD J. SMITH, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. Â§ 134(a) involving claims directed to a recombinant polynucleotide having miR398 resistance and a method of reducing miR398 regulation by mismatching nucleotides in a target gene. Claims 1, 4---6, and 8-13 are on appeal as rejected under 35 U.S.C. Â§ 103(a). We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. 1 The Real Party in Interest is The Regents of the University of California. App. Br. 1. Appeal2014-004175 Application 12/309,128 STATEMENT OF THE CASE The Specification describes enhancing plants' resistance to oxidative stress by increasing the activity of certain superoxide disnmtase (SOD) enzymes, which convert superoxide to hydrogen peroxide and molecular oxygen. Spec. i-fi-1 7, 10. There are three types of SODs, one of which is copper/zinc SOD (Cu/Zn-SOD), which is known to increase ozone tolerance and tolerance against high light I low temperature stresses in tobacco plants. Spec. i1 7. The Specification describes that genes expressing SODs can be repressed from such expression by micro RNAs (miRNAs), which are regulatory RNAs that post-transcriptionally regulate gene expression by directing mRNA cleavage or by translational inhibition. Spec. i13, 7-9, 22. The Specification describes providing mutated genes that encode SOD-mRNAs resistant to miRNA-targeting (for example, CSDl and CSD2 genes for Cu/Zn-SOD, resistant to miR398) and, thus, its regulation. Spec. 10. The miRNA resistance is purportedly accomplished by varying the CSD(l or 2) nucleotide sequences by changing one or more nucleotides so that they continue to encode a peptide retaining SOD enzymatic activity (e.g., maintaining the wild type amino acid sequence), but are changed enough to no longer be an effective miR398 target. Spec. 11-15. In this way, the plants' resistance to oxidative stress is enhanced. Spec. i-fi-133-34. The appealed claims can be found in the Claims Appendix of the Appeal Brief. Claims 1 and 6 are independent claims. Claim 1 is representative and reads as follows: 2 Appeal2014-004175 Application 12/309,128 1. A recombinant polynucleotide comprising: a variant sequence of a first sequence: A AGG GGT TTC CTG AGA TCA CA (SEQ ID NO: 1 ), or of a second sequence: T GCG GGT GAC CTG GGA AAC A (SEQ ID NO: 2); wherein expression of a polypeptide encoded by the polynucleotide is resistant to regulation by miR398; wherein the polynucleotide encodes a Cu/Zn superoxide dismutase I (CSDl) or a Cu/Zn superoxide dismutase 2 (CSD2); wherein the variant encodes a first peptide sequence R G F L R S (SEQ ID NO: 3), encodes a second peptide sequence H A G D LG N (SEQ ID NO: 4) or encodes a conservative variation of the polypeptide of SEQ ID NO: 3 or SEQ ID NO: 4; and, wherein the variant sequence is a recombinant sequence; wherein the sequence of the SEQ ID No: 1 variant is A AGN GGN TTN CTN AGN TCN CA (SEQ ID NO: 26), or the sequence of the SEQ ID NO: 2 variant is N GCN GGN GAN TTN GGN AAN A (SEQ ID NO: 27); and wherein N is any nucleotide, and at least one of the N s represents a[ [ n]] [sic] nucleotide different from a corresponding nucleotide of SEQ ID NO: 1 or SEQ ID NO: 2. Corrected App. Br. 3 (App'x A). 3 Appeal2014-004175 Application 12/309,128 The following rejection is on appeal: Claims 1, 4---6, and 8-13 rejected under 35 U.S.C. Â§ 103(a) over Dugas,2 Abarca,3 and Jones-Rhoades. 4 DISCUSSION We adopt the Examiner's findings of fact, reasoning on scope and content of the prior art, and conclusions set out in the Final Action and Answer. We identify the following only to highlight certain determinations made by the Examiner: FINDINGS OF FACT FPL Dugas disclosed "miRNAs target protein-coding mRNAs (Figure 1 ) .... In plants, miRNAs generally display near-perfect complementarity to a single site within the target message and can direct the cleavage at this site." Dugas 512 (right col.) (internal citations omitted herein except where otherwise indicated); see also Final Action 3--4 (discussing Dugas). 2 Diana V. Dugas & Bonnie Bartel, MicroRNA Regulation of Gene Expression in Plants, 7 CURRENT OPINION IN PLANT BIO. 512-20 (2004) (hereinafter "Dugas"). 3 Dolores Abarca et al., Arabidopsis thaliana Ecotype Cvi Shows an Increased Tolerance to Photo-oxidative Stress and Contains a new Chloroplastic Copper/Zinc Superoxide Dismutase Isoenzyme, 52 J. EXPERIMENTAL BOT ANY 1417-25 (July 2001) (hereinafter "Abarca"). 4 Matthew W. Jones-Rhoades & David P. Bartel, Computational Identification of Plant MicroRNAs and Their Targets, Including a Stress- induced miRNA, 14 MOLECULAR CELL 787-99 (June 16, 2004) (hereinafter "Jones-Rhoades"). 4 Appeal2014-004175 Application 12/309,128 FF2. Dugas disclosed that miR398, found in Arabidopsis, targets CSDl and CSD2 mRNA (CSD indicating copper superoxide dismutase). Dugas 514 (Table 1 ); see also Final Action 3 (discussing Dugas). FF3. Dugas disclosed, "miRNA-mRNA pairs have been validated by expressing miRNA-resistant versions of target genes in transgenic plants." Dugas 515 (right col.); see also Final Action 3--4 (discussing Dugas). FF4. Dugas disclosed genes and mRNA may be "freed from miRNA-directed negative regulation" by mutating the nucleotide sequence thereof. Dugas 515 (right col.); see also Final Action 3--4 and Ans. 9-10 (discussing Dugas). FF5. Dugas disclosed "expressing target genes that have reduced complementarity, which is expected to confer miRNA-resistance upon the target (Table 3). As redundancy in the genetic code allows complementarity to be reduced without altering the protein-coding potential of the target mRNA .... " Dugas 516 (right col.); see also Final Action 3--4 and Ans. 9- 10 (discussing Dugas). FF6. Dugas disclosed several examples where target mRNA was made resistant to miRNA to effect a protein-production phenotype change in plants, for example "[e]xpression of a miR-JAW-resistant version of TCP4 with 6-nt changes in the miRNA complementarity site [was achieved], but [maintained] unaltered coding potential." Dugas 516 (Table 3), 517 (left col.); see also Final Action 4 and Ans. 9-10 (discussing Dugas). FF7. The Examiner determined that the Dugas disclosure, as identified above, would lead one of ordinary skill in the art to have a 5 Appeal2014-004175 Application 12/309,128 reasonable expectation of success in achieving a miRNA-resistant CSD gene allele capable of increasing protein activity. See Ans. 11. FF8. Abarca disclosed "Cu/Zn-superoxide dismutase (SOD) isoenzyme was identified in Arabidopsis thaliana ecotype Cvi. Genetic analyses indicated that the new isoenzyme was encoded by a Cvi-specific allele of Csd2 that was named Csd2-2." Abarca 1417 (Abstract); see also Final Action 4 and Ans. 11, 17 (discussing Abarca). FF9. Abarca disclosed "[h]ybrid plant populations expressing Csd2-2 also exhibited an increased tolerance, suggesting that the Cvi isoenzyme is one of the factors that contribute to a better fitness in photo-oxidative stress [intense light] conditions." Abarca 1417 (Abstract); see also Final Action 4 and Ans. 13 (discussing Abarca). FFlO. The Examiner determined that Abarca's disclosure, as identified above, would have provided motivation for those of ordinary skill in the art to increase CSD2 expression and related Cu/Zn-SOD activity in plants to improve oxidative stress relief in the plants. Ans. 13-14. FFl 1. Jones-Rhoades disclosed "[t]he primary method of identifying miRNA genes has been to isolate, reverse transcribe, clone, and sequence small cellular RNAs." Jones-Rhoades 787 (right col.). 6 Appeal2014-004175 Application 12/309,128 FF12. Jones-Rhoades disclosed Table 2, reproduced below: ~ ~-.,,~,,,,,-......-~~''''~''''''''''''''''''~'~~''' Tnblsls m --~-N~_i_~ __ Â· _______ m_~_R"IA __ ~_.,.,_.~ _______ Ch __ "Â·-------~-~-\~~~-m_.~_N_A_~.....;..."CA,N,Rl ~7 \f>CR,R) ij:\IQ (l>CR,N,il} MIR:JMb :J. MIR~ 1 MIRY.!41> Ml~ MIFl$5b M~5c Mk~>f Mm:l:!fSc MUOOSf "111'1$00~ Mtl'IJOO'I; IWP.S97a M/1'1397J:J MffrÂ¥Je~ M~I> Mf~'l#fu Mi'RJIJ-:)1) MfRJlWI> AW<31lfh; M>'IUW<.1 M/113Wtl ~~fR39$.tt sÂ· sÂ· sÂ· sÂ· 3' 3' 3' 3' aÂ· aÂ· &Â· aÂ· &' &' :I' aÂ· 3Â· :r aÂ· ;r :oÂ· 3Â· 3' UCCAAAGGGAUCGCAUUGJ\UC UCCAAAGGGAUCGCAUU.GAUC uUCIJ!JUOOCAUUCIJGVCCACC uUCUUUGGCAMIJCOO\JCC/\CC ~UOAAGUGUUUO:OQGGAACUO tNQAAGU(lUUOOOGGISMCUC ~VGAAGUGUUUGOGQUN\CUC G'lJGAAQl-"3UUUG(;GQGGAaUC cUG.AA.GVGUUUQCGOOGAOIJC cUl'.'..AAGIKlUIJl..IQGGOG.(l ACIJC IA!CCACAGCU\JUCUUGMCVG. IJ1.ICC>'\Â¢!10CU\JUCIJUGN,CUIJ IJCAUUQAG\.IQCMCOIJ\JGAIJG VQCAUlKlAG\.IGCAU<:GU\.IGAIJJ>.AG.Ql\!3AUWGCCCllG <:Â¢1.itlCCAMOaMlAGllVGCCCUG cctJQCCAAAGaACCAAAGCA.{lAUUUOCCCQQ --------------Â·---------------------------- l'l<:wty id~nti:lled mlBl'IA l1>m3k!~ ar~ llstei:I wilt- $1.imll1;lfY Â¢! e~Âµ~irN:<\t~l V'.slidatkln ~~, PCA >'fliidolli:><><>f m!flNA; N, Nortoom trot m mi.'>i'IA; R. ~Â· RAC~ <>I l."-'\1'1t mRW''}. Tl>Â« <>l'>mntti< k>cw <-) i<1 iI tMS "f rmRtro <:fot!lffiliÂ·n~!l ltoo1 !'CR c! &matt cONA.s. a.i:l dc!net!Xl on N<;; a..su!Md, Fo1 miflNA tamli!~<> lw qffiict> 1i1u1~;1lle 5' Wlds ,.;ere dorocit>t1&e Factors {ARF transcription factors) OICEfM.IKF l NAC !:fiPIIDt: mc:tor FÂ·lxÂ»l prol&i:'l A Tf' su~20(1 ), .<\.t~;<4 '"' i(:-'~~Â·'"L.~ Â·: j", At5g..>;:(),,'i70(1). At5g50071"t.1) . Ai2f]26fJ60JA~'lB10<1{1 5}. Al2g26960/M't'B81(2.5). At2g3246fNMYBW1(1.e), ,i~0/,',1?'f~i~i(Â·1.~:,>'', Al~Q400{'l.5). At4gUl93.IJ!MYBS7(2.5). A<'%/!fiH)>'!:M\B:~~:.i;'j', At5g5W20IMYB 12'.){2} ,.:iÂ·i\.Â·<'.1.Sf, At1g62!'!i01.ATH8Â·Â·16{1.5), AiÂ«:~~:;,i;--;Â·i?i:C~-:'&CJ ~-)Â·, At4g3W81J!ATHS-.$(,1.5!, Â·'1<~~~;Â·fs::>fi{NA.,~:";,i.('.<'>' At1gU!i90{1.S}, A!1g6416f}{2), Af>g72830{_1 .!>}, -'\''.i:;!ii~:<::~;:": ::;, At3gW10f.2). At5gOOS1Q'.l.5i. At5r;l1284D(15l A:~~~i?B&~~~rr(~EÂ·~ ( ~ At~~~i'<~ ~ ~~~~:Â·rcff~\t. . At2g:39251)'.1), AN,)'3:'Â»1?0!.:W?\1l ;;{". . AJ'~>g~~t ~ ~}(~:Â·~ .. ~:~t~Â·:::( ! . ~it A::<'~.2 ~Â· ~Â·~:;:~:~:::Â·:.:.~.~~2. ~ :. ~~) . .. ~ t~::S:.::~:~-=.~:::::J:'<:~~X.3~Â· ~~\ -~~.::~ .. :?Â·~:~~-...:~~~.:iG.~~:~. :.~~ ~:~i At3g5.."910IGRl...4i,3). AN,p,:;,;.;):Ci'\~. :;;" Cytochrome c oxkl- A:':lg; c'-::><â€¢c):'.:l)' 4Wl!w:nitV Ph~tt> transJJ<>rter At3g541Clfl(,2) Fi9tit\> s. CQfW<'lVW Pim!iclCS ot p@ and Ory'<:<> '"<> 11sted. For e,.~c11 targt>l ~im Um seem <>l ttt<.> b<>~l SC'-â€¢tlng 2Qfi1Â»r from any mÂ»m~f of too mlRNA !;imi~/ Is givrÂ«& gre:st!!r tnan 3.0 In elth!>r hab00opliJ..~ <>r o,-y;rn hut that haâ€¢<> bd by 5' -RACE am a!s'ts by pre'1im>s w"'1<:. A<1<111ional mro1malion oo tafgjlt 9<.m~!> can oo found al "'"""~.amt:adei.">.Z ~l al., Z004; b. l'.as'>'dlat1 et at, 200<1; "'- f';;Jatnik ~Â·t ;;J"' 2003; d, Xii> ct a!., 2003; &, Mall"fY Â»! at, 2'.'ltl4; f, Tang n, 20Â°'1. 8 Appeal2014-004175 Application 12/309,128 Jones-Rhoades 795 (Fig. 5). Jones-Rhoades Fig. 5 disclosed copper superoxide dismutases, i.e., CSDl and CSD2, gene sequences validated as miRNA398 targets. Jones-Rhoades 795 (Fig. 5); see also Final Action 4 and Ans. 13 (discussing Jones-Rhoades). FF15. Jones-Rhoades disclosed "miR398 targets two copper superoxide dismutases, CSD 1 and CSD2, enzymes that protect the cell against radicals and whose expression patterns respond to oxidative stress." Jones-Rhoades 797; see also Ans. 13 (discussing Jones-Rhoades). FF16. Jones-Rhoades disclosed "plant miRNAs have a strong propensity to target genes ... of transcription factors and F-box proteins. However, plant miRNAs have conserved regulatory functions extending beyond development, in that they also target superoxide dismutases ... [and] miRNAs can be induced by environmental stress." Jones-Rhoades 787 (Abstract); see also Ans. 13 (discussing Jones-Rhoades and that it was well known that miRNAs suppressed mRNA transcripts and related protein levels). FFl 7. The Examiner determined that Jones-Rhoades disclosure, as indicated above, would have provided motivation to those of ordinary skill in the art to alleviate the miRNA repression of CSD to increase Cu/Zn-SOD protein activity in a plant. Ans. 13. ANALYSIS We agree that the evidence of record supports the Examiner's prima facie case that the claims would have been obvious over the cited prior art combination. We address Appellants' arguments below. 9 Appeal2014-004175 Application 12/309,128 Appellants contend that the claims are not obvious because not all limitations are taught in the cited prior art and there would have been no motivation to combine the cited references. App. Br. 3. We do not find either contention supported by the preponderance of evidence for the reasons discussed below. Moreover, contrary to the focus of Appellants' arguments, one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 426 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellants argue that they first identified the "problem" of protecting plants from oxidative stress in regards to mRNA regulation by miR398. App. Br. 4. This argument is unconvincing. As identified by the Examiner, the prior art combination taught that Cu/Zn-SOD activity increases plant oxidative stress tolerance, that Cu/Zn-SOD is encoded by CSD(l or 2) genes' and respective mRNA, that CSD genes' mRNA are targeted and regulated by miR398, and that miRNA regulation can be controlled by altering the mRNA-encoding genes' sequence in such a way so as to reduce miRNA-targeting potential while retaining wild-type protein encoding properties. FF 1-FF 1 7. Appellants do not proffer convincing evidence as to how the cited prior art combination fails to teach the claimed invention. Appellants argue that the cited references fail to disclose "a peptide sequence of the claims," which Appellants contend "is necessary to engineer functional CSD targets for the miRNA." App. Br. 5. The Examiner determined that Abarca identified several previous studies that identified the sequences of CSD 1 and CSD2 from Arabidopsis thaliana, including both 10 Appeal2014-004175 Application 12/309,128 nucleotide and nucleic acid coding region information, as well as information on primers for amplification of a region of CSD2 genomic DNA. Ans. 11-12. Moreover, Jones-Rhoades identifies the sequences of miR398, the CSD(l and 2) targets thereof, and the CSD(l and 2) gene targets for miR398. FF12-FF14. Thus, the Examiner determined that it would have been within the purview of those of ordinary skill in the art to translate the claimed coding region into an amino acid sequence. Ans. 12. The Examiner also determined that Abarca identified a previous study that taught methods of obtaining an isolated CSD 1 cDNA sequence and, so, one of ordinary skill in the art would have been able to identify the open reading frame and protein sequence encoding the Cu/Zn-SOD. Id. Appellants do not convincingly dispute these determinations. See generally Reply Br. Appellants contend that Abarca did not disclose engineering specific mRNA sequences resistant to miR398. App. Br. 5. This argument is not persuasive. The Examiner has not included the Abarca reference in the prior art combination for a disclosure of engineering miRNA resistant mRNA sequences, but for its disclosure that increased Cu/Zu-SOD protein activity increases plant oxidative stress tolerance (and that the protein is encoded by CSD). Ans. 13. The Examiner indicates this provides motivation to increase such protein activity using the methods of Dugas with the understanding of the nucleotide sequences provided, e.g., by Jones-Rhoades. Appellants argue that they "were the first to discover that mi[R ]398 is down regulated in response to oxidative stress," and, therefore, Jones- Rhoades's disclosure of the relationship between miR398 and CSDl and CSD2 is immaterial. App. Br. 5. This argument is without merit. The 11 Appeal2014-004175 Application 12/309,128 Examiner combines Jones-Rhoades for its identification that miR398 targets (and regulates) the Cu/Zu-SOD encoding genes' mRNA and also its identification of the related genetic sequences. With the understanding from other combined references that Cu/Zu-SOD activity is beneficial and should be promoted to increase plants' oxidative stress tolerance, that the miRNA would act to reduce Cu/Zu-SOD activity, and that this could be controlled by changing the miRNA target sequence(s) so that miRNA could no longer target the encoding mRNA, whether Appellants discovered that miR398 is down-regulated is not relevant (and it is not recited in the claims). Appellants contend that the technical field was highly unpredictable and, so, a person of ordinary skill would have no reasonable expectation of success. App. Br. 6. We do not find this argument persuasive. Appellants cite Chen,5 Park,6 and Reinhart7 as support. Id. However, Appellants do not identify how or where these references support their contention and upon reviewing the publications we cannot agree that they provide such support. In reviewing Chen, for example, we find that rather than support Appellants' contention of non-obviousness, it supports the Examiner's determination that the claims were obvious and their subject matter well known in that the reference disclosed performing the very 5 Xuemei Chen, A MicroRNA as a Translational Repressor of APETALA2 in Arabidopsis Flower Development, 303 SCIENCE 2022-25 (2004) (hereinafter "Chen"). 6 Wonkeun Park et al., CARPEL FACTORY, a Dicer Homolog, and HENJ, a Novel Protein, Act in microRNA Metabolism in Arabidopsis thaliana, 12 CURRENT BIO. 1484--95 (Sept. 3, 2002) (hereinafter "Park"). 7 Brenda J. Reinhart et al., MicroRNAs in Plants, 16 GENES & DEV. 1616-26 (2002) (hereinafter "Reinhart"). 12 Appeal2014-004175 Application 12/309,128 process the Appellants purport to be their invention, that is, varying a sequence of nucleotides encoding a protein so that the encoded mRNA is no longer a target for miRN A, but still encodes for the desired protein-albeit for a different protein and a different miRNA with respect to the claims. See Chen 2023-24 (AP2 protein abundance was elevated in plant with mutated AP2ml gene, which no longer encoded an miRNA-target mRNA because of introduced sequence mismatches, but still encoded the amino acid sequence for the protein); see also Ans. 10, 16 (discussing Chen). Appellants contend that the prior art fails to teach or suggest the sequences of dependent claims 4 and 10. App. Br. 7. The Examiner responds that the sequences of the dependent claims are obvious variants of the sequences of independent claim 1 and would have been at least obvious to try based on the finite number of identified, predictable solutions in the short sequences. Ans. 18. The Examiner indicated that creation of such variant nucleic acid sequences, which still encoded the desired protein, would have been standard procedure for the skilled artisan. Id. (noting an absence of evidence of unexpected results for the recited sequences). The evidence of record, e.g., Dugas (FF1-FF6) and Chen (Fig. 1) successfully achieved such a result, which also supports the Examiner's determination. In the Reply Brief, Appellants attempt to separately argue the patentability of dependent claim 4. 8 We will not consider any new arguments not set forth in the Appeal Brief. 8 In the Reply Brief, Appellants presents new, separate arguments concerning claim 4, which were not presented in the Appeal Brief, separately or otherwise, and which are not responsive to any new 13 Appeal2014-004175 Application 12/309,128 For the above reasons, we find that the evidence of record supports the Examiner's determination that claims 1, 4---6, and 8-13 would have been obvious over Dugas, Abarca, and Jones-Rhoades, therefore, the respective rejection is affirmed. determinations or arguments in the Examiner's Answer. See Reply Br. 4; cf App. Br. 3-7 and Ans. 2-5. Except as provided for in Â§Â§ 41.41, 41.47, and 41.52, any arguments or authorities not included in the appeal brief will be refused consideration by the Board for purposes of the present appeal. ... Notwithstanding any other provision of this paragraph, the failure of appellant to separately argue claims which appellant has grouped together shall constitute a waiver of any argument that the Board must consider the patentability of any grouped claim separately. Under each heading identifying the ground of rejection being contested, any claim(s) argued separately or as a subgroup shall be argued under a separate subheading that identifies the claim( s) by number. 37 C.F.R. Â§ 41.37(c)(l)(iv) (2016); see also MPEP 1205.02 (Rev. 9, Aug. 2012) ("The failure of appellant to separately argue claims which appellant has grouped together constitutes a waiver of any argument that the Board must consider the patentability of any grouped claim separately." citing In re McDaniel, 293 F.3d 1379, 1384 (Fed. Cir. 2002)). Moreover, it is well settled that arguments of counsel cannot take the place of factually supported objective evidence and, here, Appellants present no clear or specific evidence supporting the new arguments made in the Reply Brief. See, e.g., In re Huang, 100 F.3d 135, 139--40 (Fed. Cir. 1996). For these reasons, we will not consider any arguments regarding claim 4 not set forth in the Appeal Brief. 14 Appeal2014-004175 Application 12/309,128 SUMMARY The rejection of claims 1, 4---6, and 8-13 rejected under 35 U.S.C. Â§ 103(a) over Dugas, Abarca, and Jones-Rhoades is affirmed. 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. Â§ 1.136(a). AFFIRMED 15