Ex Parte Souza et alDownload PDFPatent Trial and Appeal BoardAug 17, 201611719508 (P.T.A.B. Aug. 17, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 111719,508 01/26/2010 108197 7590 08/19/2016 Parker Highlander PLLC 1120 South Capital of Texas Highway Bldg. 1, Suite 200 Austin, TX 78746 FIRST NAMED INVENTOR Glauco Souza 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. UTSC:889US 8537 EXAMINER KINSEY WHITE, NICOLE ERIN ART UNIT PAPER NUMBER 1648 NOTIFICATION DATE DELIVERY MODE 08/19/2016 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): docket@phiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GLAUCO SOUZA, WADIH ARAP, RENATA P ASQUALINI, and J. HOUSTON MILLER Appeal2014-003741 Application 11/719,508 Technology Center 1600 Before CHRISTOPHER G. P AULRAJ, JACQUELINE T. HARLOW, and JOHN E. SCHNEIDER, Administrative Patent Judges. HARLOW, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to bacteriophage assemblies. 1 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 According to Appellants, the Real Party in Interest is the Board of Regents of The University of Texas System (App. Br. 3). Appeal2014-003741 Application 11/719,508 STATEMENT OF THE CASE The present invention relates to "making and using phage- nanoparticle assemblies, in particular in the diagnosis and treatment of disease" (Spec. 1:12-13). Claims 2, 3, 6, 7, 10, 11, 13, 14, 17-20, 22, 23, and 60-63 are on appeal. Claim 11, the sole independent claim on appeal, is illustrative and reads as follows: 11. A bacteriophage assembly compnsmg a plurality of filamentous bacteriophage in electrostatic association with a plurality of conductive nanoparticles, wherein said electrostatic association does not rely on genetic manipulation of the bacteriophage, wherein the conductive nanoparticle is a metallic conductive nanoparticle comprising Au, Ag, Pt, Ti, Al, Si, Ge, Cu, Cr, W, Fe, or a corresponding oxide. The claims stand rejected as follows: 2 I. Claims 2, 3, 6, 10, 11, 13, 20, 22, 23, 62 and 63 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over Belcher and Tang. II. Claim 7 stands rejected under 35 U.S.C. § 103(a) as being unpatentable over Belcher,3 Tang,4 Giebel, 5 and Balass. 6 2 The rejection of claim 9 under 35 U.S.C. § 112, fourth paragraph, has been withdrawn, in view of Appellants' cancellation of that claim (Ans. 13). 3 Belcher et al., US 2005/0221083 Al, published Oct. 6, 2005. 4 Tang et al., Counterion Induced Bundle Formation of Rodlike Polyelectrolytes, 100 BER. BUNSENGES. PHYS. CHEM. 796-806 (1996). 5 Giebel et al., Screening of Cyclic Peptide Phage Libraries Identifies Ligands That Bind Streptavidin with High Affinities, 34 AM. CHEM. Soc., BIOCHEM. 15430-15435 (1995). 6 Balass et al., A Cyclic Peptide with High Affinity to a-bungarotoxin Protects Mice from the Lethal Effect of the Toxin, 39 TOXICON 1045-1051 (2001). 2 Appeal2014-003741 Application 11/719,508 Ill. Claims 14 and 17 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, Liou,7 and Sun.8 IV. Claims 18 and 19 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, and Nam. 9 V. Claims 60 and 61 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, and Abbott. 10 I. Issue The Examiner has rejected claims 2, 3, 6, 10, 11, 13, 20, 22, 23, 62 and 63 under 35 U.S.C. § 103(a) as being unpatentable over Belcher and Tang. We focus our discussion on independent claim 11, which is representative. We also address dependent claim 13, as it is separately argued. Because they are not separately argued, claims 2, 3, 6, 10, 20, 22, 23, 62 and 63 rise or fall with claim 11. The Examiner finds that Belcher teaches every aspect of claim 11, except that Belcher "prefers the use of phages genetically engineered to carry metal-binding peptides" (Ans. 5; see also id. at 1-7). The Examiner observes, however, that Belcher "suggests that the nanowires can be formed without genetically engineered bacteriophage and metallic materials" (id. at 7). The Examiner further finds that Tang cures the above described 7 Liou et al., Magnetic Properties of Nanometer-size CoPt Particles, 79 J. APPL. PHYS. 5060-5062 (1996). 8 Sun et al., Monoclisperse FePt Nanoparticles and Ferromagnetic FePt Nanocrystal Superlattices, 287 SCIENCE 1989-1992 (2000). 9 Nam et al., US 2006/0121346 Al, published June 8, 2006. 10 Abbott et al., WO 03/086276 A2, published Oct. 23, 2003. 3 Appeal2014-003741 Application 11/719,508 deficiency of Belcher, as Tang "teaches that filamentous bacteriophage fd, which is negatively charged, can self-assemble in the presence of divalent and trivalent metal ions" (id.). The Examiner concludes that it would have been obvious to incorporate the self-assembly method of Tang into the nanowire production method of Belcher to arrive at the claimed invention (id.). The Examiner finds that an ordinarily skilled artisan would have been motivated to make such a combination because it would be more convenient and less expensive to use the self-assembly method taught by Tang, which does not require genetically modifying the bacteriophages, than the method exemplified in Belcher (id.). The Examiner also determines that an ordinarily skilled artisan would have had a reasonable expectation of success in making the proposed combination because Tang observed the self-assembly of the bacteriophage in the presence of metal containing materials, e.g., divalent or trivalent cations, and given the teachings of Tang et al. that the bacteriophages are charged (one of ordinary skill in the art would expect charged metal or metal oxide nanoparticles of Belcher et al. to also bind the charged bacteriophages just like the metal cations in Tang et al. were able to bind the charged bacteriophage (i.e., electrostatic interaction)). (Id. at 7-8.) The Examiner additionally concludes that [w]ith regard to claims 11and13, given the teaching of Tang et al. that divalent or trivalent forms of metal induce the self- assembly of filamentous bacteriophages, it would be obvious for one of ordinary skill in the art to use charged forms, e.g., divalent or trivalent, of the metal alloys disclosed by Belcher et al. or other known common metals (e.g., Fe, Au, Al, Cu or Cr) in the nanoparticles. (Id. at 8.) 4 Appeal2014-003741 Application 11/719,508 Appellants contend a skilled artisan would not have been motivated to combine Belcher and Tang because "Belcher teaches the requirement for using a genetically engineered phage comprising a metal-binding peptide and Tang is being cited for the proposition that is was known that such peptides are not required! Hence, the secondary reference is being used to 'change the principle of operation' of the Belcher reference" (App. Br. 7-8). Appellants also argue that neither Belcher nor Tang say anything about forming nanoparticles using metals in metallic form. It is evident from Tang that Tang never forms particles and is instead relying upon electrostatic interaction between the charged ionic metal ions and the negative charges present on the bacteriophage (see, for example, Abstract and entire Discussion section of Tang). Thus, nowhere does Tang disclose or suggest the production of a metallic conductive nanoparticle. (Id. at 9.) Lastly, Appellants assert that "it is evident that no prima facie case has been made with respect to claim 13" because neither Belcher nor Tang discloses the use of Au nanoparticles, and Tang teaches that metal ion binding is unpredictable (id. at 10). The issue presented is whether the combination of Belcher and Tang renders obvious claims 11 and 13. Findings of Fact We adopt the Examiner's findings regarding the scope and content of the prior art, and highlight the following for context. FF 1. Belcher discloses the use of "a virus-based scaffold for the synthesis of single crystal ZnS, CdS and free-standing LIO CoPt and FePt 5 Appeal2014-003741 Application 11/719,508 nanowires" (Belcher, Abstract). Belcher further teaches that "substrate specificity" may be modified via "standard biological methods" (id.). FF 2. Belcher discloses that "[i]n one embodiment, scaffolds and virus particles can be used which are not directly genetically engineered" (id. at ii 57). FF 3. Belcher discloses "an inorganic nanowire comprising fused inorganic nanoparticles comprising semiconductor material, metallic material, metal oxide material, or magnetic material, as well as collections of these nanowires" (id. at ii 19). FF 4. Belcher discloses that the present invention relates to the general, universal synthesis of 1-D nano structures, including nano wires, based on, in preferred embodiments, a genetically modified virus scaffold for the directed growth and assembly of crystalline nanoparticles into 1- D arrays, followed by annealing of the virus-particle assemblies into high aspect ratio, crystalline nanowires through oriented, aggregation-based crystal growth (14, 15) (FIG. 2A). The synthesis of analogous nanowire structures from fundamentally different materials, e.g., the II-VI semiconductors ZnS and CdS and the L 10 ferromagnetic alloys Co Pt and F ePt, demonstrates both the generality of the virus scaffold and the ability to precisely control material characteristics through genetic modification. In contrast to other synthetic methods ( 6), this approach allows for the genetic control of crystalline semiconducting, metallic, oxide, and magnetic materials with a universal scaffold template. (Id. at ii 72.) FF 5. Tang discloses that A number of filamentous biopolymers including actin filaments (F-actin), microtubules (MT), tobacco mosaic virus (TMV), and the filamentous bacteriophage f d form bundles under well-defined conditions. All of these macromolecules are negatively charged rodlike assemblies, and lateral association is 6 Appeal2014-003741 Application 11/719,508 induced by a number of cations such as divalent and trivalent metal ions and homopolymers of basic peptides. The general features of bundle formation are largely independent of the specific structure of the biopolymers and the bundling agent used. They are also approximately independent of the concentration of macromolecules. However, a threshold concentration of bundling agent is required in order to form large lateral aggregates, detected by a sharp increase in light scattering and by electron microscopy. The threshold concentration varies strongly with the valence of the cations and increases with the ionic strength of the solution. (Tang, Abstract.) FF 6. The Examiner finds that an ordinarily skilled artisan would have been motivated to combine Belcher and Tang because: i) it is more convenient to use the method of Tang et al. (i.e., no genetic manipulation) to produce the nanowires rather than performing the steps to genetically modify the bacteriophage, and ii) it is less expensive to use the method of Tang et al. (only the bacteriophage and nanoparticles are needed versus the cost of genetically modifying the bacteriophage). There would have been a reasonable expectation of success given the fact that Tang et al. observed the self-assembly of the bacteriophage in the presence of metal containing materials, e.g., divalent or trivalent cations, and given the teachings of Tang et al. that the bacteriophages are charged (one of ordinary skill in the art would expect charged metal or metal oxide nanoparticles of Belcher et al. to also bind the charged bacteriophages just like the metal cations in Tang et al. were able to bind the charged bacteriophage (i.e., electrostatic interaction)). (Ans. 7-8.) FF 7. The Examiner finds that "nanoparticles comprising, for example, gold, aluminum or copper are well-known and well-characterized in the art, and it is well within the purview of one of ordinary skill in the art 7 Appeal2014-003741 Application 11/719,508 to select from among these well-known and well-characterized metals to produce metallic nanoparticles in the method of Belcher" (Ans. 19). Analysis We have considered, but do not find persuasive, Appellants' arguments that the Examiner erred in rejecting claims 11 and 13 as obvious over Belcher and Tang. We address Appellants' arguments below. As an initial matter, we are unpersuaded by Appellants' contention that a skilled artisan would not have been motivated to employee the self- assembly method of Tang in forming nanowires according to Belcher (App. Br. 4--8; Reply Br. 2---6). Rather, we agree with the Examiner that Belcher itself "suggests the use of non-genetically modified scaffolds and virus particles for the disclosed systems" (Ans. 14; FF 2), and that an ordinarily skilled artisan would have been motivated, with a reasonable expectation of success, to combine the methods of Belcher and Tang in order to reduce the expense and complexity of nanowire formation, relative to the methods of Belcher alone (FF 6; see also Ans. 16-17). With particular regard to Appellants' assertion that Belcher requires the use of genetically modified virus to form FePt and CoPt nanowires, and, therefore, is foreclosed from combination with Tang (App. Br. 5-8; Reply Br. 4---6), we agree instead with the Examiner that While Belcher et al. prefers the use of bacteriophages genetically engineered to carry metal-binding peptides (see, for example paragraphs [0048] and [0051 ]), Belcher teaches that "virus particles can be used which are not directly genetically engineered" (see paragraph [0057]). Thus, contrary to appellant's argument, Belcher et al. does not "require" the use of genetically engineered bacteriophage in the nanowires. (Ans. 16.) 8 Appeal2014-003741 Application 11/719,508 Turning to Appellants' argument that "Tang teaches that bacteriophage bundles are formed using specific charged metallic salts," and not a "metallic conductive nanoparticle," as recited in claim 11 (App. Br. 8), we observe that the Examiner does not rely on Tang to satisfy this claim requirement (Ans. 18). Rather, Tang "was cited to demonstrate to one of ordinary skill in the art that a non-modified bacteriophage can self-assemble when mixed with metal containing materials, in this case metal containing salts" (id.). Moreover, we agree with the Examiner that Tang et al. provides motivation to use the same self-assembly method (mixing non-modified bacteriophage with metal containing materials) for the non-modified bacteriophage and metal containing alloys taught by Belcher et al. Belcher et al. already suggested that non-modified bacteriophages can be used with the disclosed nanoparticles, e.g., ZnS, CdS, CoPt and FePt. So, following the method steps of Tang et al., one of ordinary skill in the art is led to mix the non-modified bacteriophage and metal containing alloys. Further, given the findings of Tang et al. (charged metal containing salts and bacteriophages assemble via electrostatic interactions) and given the teachings of Tang et al. that bacteriophages are charged, one of ordinary skill in the art would reasonably expect the non-genetically modified bacteriophages and charged metal- or metal oxide-containing nanoparticles of Belcher et al. to also assemble via electrostatic interactions. (Ans. 18-19.) Accordingly, because Appellants do not present argument or evidence sufficient to rebut the Examiner's prima facie showing of obviousness, we affirm the rejection of claim 11 as obvious over Belcher and Tang. Concerning claim 13, we are unpersuaded by Appellants' contention that "neither Belcher nor Tang teaches Au nanoparticles, and since Tang 9 Appeal2014-003741 Application 11/719,508 teaches the unpredictability of metal ion binding, it is evident that no prima facie case has been made" (App. Br. 10). Belcher teaches the formation of nanowires from fused inorganic nanoparticles including "semiconductor material, metallic material, metal oxide material, or magnetic material" (FF 3; see also Ans. 19), and Tang discloses that "divalent and trivalent metal ions" induce the self-assembly of filamentous bacteriophages (FF 5; see also Ans. 19). Accordingly, we agree with the Examiner that it would be obvious for one of ordinary skill in the art to use charged forms of the metal alloys disclosed by Belcher et al. or other known common metals such as Fe, Au, Al, Cu or Cr in the nanoparticles to associate with the bacteriophage via electrostatic interactions. Further, nanoparticles comprising, for example, gold, aluminum or copper are well-known and well- characterized in the art, and it is well within the purview of one of ordinary skill in the art to select from among these well-known and well-characterized metals to produce metallic nanoparticles in the method of Belcher et al. (Ans. 19; see also FF 7.) Appellants' contention, raised for the first time in the Reply Brief, that Belcher' s disclosure that "an inorganic nanowire comprising fused inorganic nanoparticles comprising semiconductor material, metallic material, metal oxide material, or magnetic material, as well as collections of these nanowires" (FF 3) "in no way teaches 'gold' except by hindsight analysis" (Reply Br. 8) is unavailing. The Examiner does not rely on Belcher alone, but rather relies on Belcher in combination with Tang, to disclose a gold cluster as the claimed conductive nanoparticle (see Ans. 19). We are likewise unpersuaded by Appellants' arguments that Tang's disclosure that magnesium salt did not cause aggregation of bacteriophage 10 Appeal2014-003741 Application 11/719,508 equates to a teaching that "metal ion binding to bacteriophage is unpredictable at best" (App. Br. 10), or that "Tang cannot be said to teach any other metal salt beyond Co(NH3)6, co+2, Mn2+ and Ca2" (Reply Br. 8). Tang explicitly teaches that "[t]he general features of bundle formation are largely independent of the specific structure of the biopolymers and the bundling agent used" (FF 5), and Belcher describes "the general, universal synthesis of 1-D nanostructures" (FF 4 ), which may be formed from a wide variety of "fundamentally different materials, e.g., the II-VI semiconductors ZnS and CdS and the L 10 ferromagnetic alloys CoPt and FePt" (id.). Furthermore, the Examiner explains that Au is a "common metal[,]" "well-known and well-characterized in the art" (FF 7). Accordingly, we agree with the Examiner that an ordinarily skilled artisan in possession of Belcher and Tang would have been motivated to, and had a reasonable expectation of success in, using a gold cluster as the conductive nanocluster, as required by claim 13. See In re O'Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988) ("Obviousness does not require absolute predictability of success .... For obviousness under§ 103, all that is required is a reasonable expectation of success."). We therefore affirm the rejection of claim 13. See In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (concluding that attorney argument is insufficient to rebut a prima facie case of obviousness). Conclusion of Law A preponderance of the evidence of record supports the Examiner's conclusion that the combination of Belcher and Tang renders claims 11 and 13 obvious. Claims 2, 3, 6, 10, 20, 22, 23, 62 and 63 have not been argued separately and therefore fall with claim 11. 11 Appeal2014-003741 Application 11/719,508 IL The Examiner has rejected claim 7 under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, Giebel, and Balass. Appellants present no additional argument based on the teachings of Giebel or Balass, and rely on the same arguments addressed above with regard to Belcher and Tang (see App. Br. 10). For the reasons discussed above, therefore, we affirm the rejection of claim 7. III. The Examiner has rejected claims 14 and 17 under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, Liou, and Sun. Appellants present no additional argument based on the teachings of Liou or Sun, and rely on the same arguments addressed above with regard to Belcher and Tang (see App. Br. 10). 11 For the reasons discussed above, therefore, we affirm the rejection of claims 14 and 1 7. IV. The Examiner has rejected claims 18 and 19 under 35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, and Nam. Appellants present no additional argument based on the teachings of Nam, and rely on the same arguments addressed above with regard to Belcher and Tang (see App. Br. 10). For the reasons discussed above, therefore, we affirm the rejection of claims 18 and 19. 11 We note that Appellants' reference in the Appeal Brief to the rejection of claim 14 and cancelled claim 16 as obvious over Belcher, Tang, Liou, and Sun appears to be an inadvertent typographical error. 12 Appeal2014-003741 Application 11/719,508 V. The Examiner has rejected claims 60 and 61under35 U.S.C. § 103(a) as being unpatentable over Belcher, Tang, and Abbott. Appellants present no additional argument based on the teachings of Abbott, and do not address the rejection of claims 60 and 61 in either the Appeal Brief (see App. Br. 4-- 10), or the Reply Brief (see Reply Br. 2-9). For the reasons discussed above, therefore, we affirm the rejection of claims 60 and 61. 13 Appeal2014-003741 Application 11/719,508 SUMMARY We affirm the rejection of claims 11 and 13 under 35 U.S.C. § 103(a) based on Belcher and Tang. Claims 2, 3, 6, 10, 11, 13, 20, 22, 23, 62 and 63 fall with claim 11. We affirm the rejection of claim 7 under 35 U.S.C. § 103(a) based on Belcher, Tang, Giebel, and Balass. We affirm the rejection of claims 14 and 17 under 35 U.S.C. § 103(a) based on Belcher, Tang, Liou, and Sun. We affirm the rejection of claims 18 and 19 under 35 U.S.C. § 103(a) based on Belcher, Tang, and Nam. We affirm the rejection of claims 60 and 61under35 U.S.C. § 103(a) based on Belcher, Tang, and Abbott. 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)(l )(iv). AFFIRMED 14 Copy with citationCopy as parenthetical citation