Ex Parte Petrovykh et alDownload PDFPatent Trial and Appeal BoardFeb 8, 201711457713 (P.T.A.B. Feb. 8, 2017) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/457,713 07/14/2006 Dmitri Y. Petrovykh 97607-US2 7597 26384 7590 02/09/2017 NAVAL RESEARCH LABORATORY ASSOCIATE COUNSEL (PATENTS) CODE 1008.2 4555 OVERLOOK AVENUE, S.W. WASHINGTON, DC 20375-5320 EXAMINER PRIEST, AARON A ART UNIT PAPER NUMBER 1637 MAIL DATE DELIVERY MODE 02/09/2017 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 DMITRI Y. PETROVYKH, LLOYD J. WHITMAN, MICHAEL J. TARLOV, ARIC M. OPDAHL, and HIROMI KIMURA-SUDA1 __________ Appeal 2016-002966 Application 11/457,713 Technology Center 1600 __________ Before ROBERT A. POLLOCK, TAWEN CHANG, and RACHEL H. TOWNSEND, Administrative Patent Judges. POLLOCK, Administrative Patent Judge. DECISION ON APPEAL Appellants appeal under 35 U.S.C. § 134(a) from the final rejection of claims 1–8, 10–23, 25, 27–39, 41–51, 53–65, and 67–69. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE Appellants’ invention relates to methods for immobilizing nucleic acids to a metal surface. 1 Appellants identify the real party-in-interest as The Government of the United States of America, as represented by the Secretary of the Navy. App. Br. 2. Appeal 2016-002966 Application 11/457,713 2 Claims 1, 16, 33, 45, and 57 are independent. For the purpose of this appeal, claim 1 is representative (emphasis added): 1. A method for attaching nucleic acids or nucleic acid analogs to a metal surface in a controlled conformation comprising: providing a metal surface; providing an immobilization solution comprising at least one nucleic acid or nucleic acid analog, said nucleic acid or nucleic acid analog comprising a functional sequence and at least one block of adenine nucleotides or adenine nucleotide analogs having a length of about 5 to about 25; identifying solute and temperature conditions tending to cause a configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal surface; and contacting said immobilization solution with said metal surface under the solute and temperature conditions. Claims 1–5, 8, 10–20, 23, 25, 27–32, 57–62, and 67–69 stand rejected under 35 U.S.C. § 103(a) as obvious over the combination of Demers,2 Kimura-Suda,3 and Petrovykh.4 2 Demers et al., A Fluorescence-Based Method for Determining the Surface Coverage and Hybridization Efficiency of Thiol-Capped Oligonucleotides Bound to Gold Thin Films and Nanoparticles, 72 Anal. Chem. 5535–41 (2000) (“Demers”). 3 Kimura-Suda et al., Base-Dependent Competitive Adsorption of Single- Stranded DNA on Gold, 125 J. Am. Chem. Soc. 9014–15 (2003) (“Kimura- Suda”). 4 Petrovykh et al., Quantitative Analysis and Characterization of DNA Immobilized on Gold, 125 J. Am. Chem. Soc. 5219–26 (2003) (“Petrovykh”). Appeal 2016-002966 Application 11/457,713 3 Claims 6, 7, 21, 22, 33–39, 41–44, 63, and 64 stand rejected under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura- Suda, Petrovykh, and Zhao.5 Claims 45–51 and 54–56 stand rejected under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, and Kumar.6 Claim 53 stands rejected under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, Kumar, and Lizardi.7 Claim 65 stands rejected under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, and Mergny.8 ANALYSIS We have reviewed Appellants’ contentions that the Examiner erred in rejecting claims 1–8, 10–23, 25, 27–39, 41–51, 53–65, and 67–69 as unpatentable over the cited art. App. Br. 1–9; Reply Br. 2–5.9 We disagree with Appellants’ contentions and, to the extent not otherwise clarified below, adopt the findings regarding the scope and content of the prior art set forth in the Examiner’s Answer, as well as the Examiner’s reasoned analysis 5 Zhao et al., Immobilization of oligodeoxyribonucleotides with multiple anchors to microchips, 29(4) Nucl. Acids Res. 955–59 (2001) (“Zhao”). 6 Kumar, US 5,912,124, issued June 15, 1999. 7 Lizardi, US 5,854,033, issued Dec. 29, 1998. 8 Mergny et al., Fluorescence energy transfer as a probe for nucleic acid structures and sequences, 22(6) Nucl. Acids Res. 920–28 (1994) (“Mergny”). 9 Appellants did not argue the rejections separately. Rather, they focused on an alleged lack of teaching or suggestion of the configuration recited by the independent claims. Appeal 2016-002966 Application 11/457,713 4 with respect to secondary considerations. For emphasis, we highlight and address the following: Findings of Fact FF1. In discussing the solute and temperature conditions for the immobilization of nucleic acids or nucleic acid analogs to a metal surface, the Specification provides that “[t]he immobilization solution temperature ranges from about 20 °C to about 35 °C. The salt added to immobilization solution can be NaCl, KCl, K2HPO4, KH2PO4, CaCl2, or MgCl2. The salt concentration ranges from about 1 to about 3 M.” Spec. ¶ 70; see Ans. 20–21. FF2. Demers explores conditions for binding single-strand oligonucleotides to gold nanoparticle and films. Demers, Abstract. Demers discloses thio-derivatized oligonucleotides SA20N12f and S3’X20N12f (where X may be A or T), comprising a functional sequence of 12 DNA monomer units and a block of 20 adenine nucleotides. Id. at 5539 & Table 2, 5540 & Table 4. Demers teaches that a “salt aging step was crucial in obtaining stable oligonucleotides-modified nanoparticles. . . . [which] resisted aggregation when centrifuged, even in high ionic strength solutions (up to 1 M NaCl).” Id. at 5539. According to Demers, Using the SA20N12f modified particles, we examined the effect of electrolyte conditions on oligonucleotide surface loading. As shown in Table 3, final surface coverages for Au nanoparticles that were exposed to oligonucleotides in water for 48 h are much lower ( 7.9 ± 0.2 pmoV cm2) as compared with those that were “aged” in salt or prepared by increasing the salt concentration gradually over the course of the final 24 h of the deposition experiment. Id. at 5539–5540, Table 3 (employing buffer containing 1.0 M NaCl). Appeal 2016-002966 Application 11/457,713 5 FF3. Kimura-Suda “examine[d] room-temperature adsorption of homo- oligonucleotides onto polycrystalline [gold] films . . . by soaking clean Au substrates in 1 μM solutions of unmodified homo-oligonucleotides (1 M NaCL–TE buffer) for 20 h.” Kimura-Suda 9014. Kimura-Suda disclose that “the homo-oligonucleotides adsorb on Au with relative affinity A > C ≥ G > T.” Id. at 9014. Kimura-Suda further state: To examine the relevance of our results to applications that use thiol-modified ssDNA on Au, unmodified (dA)25 was mixed with thiolated (dT)25. Thiolated (dT)25 probes adsorb on Au as randomly coiled molecules each anchored via the thiol group. Thus, one would expect this mixture to result in (dA)25·(dT)25 duplexes adsorbed via the thiolated 5’ end of the (dT)25. However, the extraordinary affinity of oligo(dA) for Au again produces a film composed largely of adsorbed (dA)25 (Figure 2, bottom). Id. at 9015. FF4. Petrovykh “describe[s] the complementary use of X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy to quantitatively characterize the immobilization of thiolated (dT)25 single-stranded DNA (ssDNA) on gold.” Petrovykh, Abstract. These studies show “that at lower coverages much of the DNA lies flat on the surface, with a substantial fraction of the thymine bases chemisorbed. At higher immobilization densities, the (dT)25 film consists of randomly coiled ssDNA molecules each anchored via the thiol group and at possibly one or two other bases.” Id.; see id. at 5224. Petrovykh reports “strong effects of different buffer salts on the immobilization efficiency” and that “cation valence has a larger effect on immobilization than its concentration.” Id. at 5224–25. In particular, “[b]uffers with divalent salts dramatically increase the efficiency of immobilization and result in Appeal 2016-002966 Application 11/457,713 6 very high surface densities (>5 x 1013/ cm2), densities that may only be possible if the divalent counterions induce strong attractive intermolecular interactions.” Id. at Abstract; see also id. at 5220 (studies conducted at room temperature). In Figure 7, Petrovykh states that maximum coverage is “obtained with 2 M CaCl2 and 0.1 M MgCl2.” Analysis During prosecution, an application’s claims are given their broadest reasonable scope consistent with the specification. In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004). “[T]he specification ‘is always highly relevant to the claim construction analysis. Usually it is dispositive; it is the single best guide to the meaning of a disputed term.’” In re Abbott Diabetes Care Inc., 696 F.3d 1142, 1149 (Fed. Cir. 2012) (quoting Phillips v. AWH Corp., 415 F.3d 1303, 1315 (Fed. Cir. 2005) (en banc)). Our reviewing court cautions, however, that “[t]here is a fine line between construing the claims in light of the specification and improperly importing a limitation from the specification into the claims.” Retractable Techs., Inc. v. Becton, Dickinson, and Co., 653 F.3d 1296, 1305 (Fed. Cir. 2011), reh’g and reh’g en banc denied, 659 F.3d 1369 (Fed. Cir. 2011), cert. denied, 133 S. Ct. 833 (2013). Any special definition for a claim term must be set forth in the specification with reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Our analysis focuses on whether the prior art teaches or suggests the claim term, “identifying solute and temperature conditions tending to cause a configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal Appeal 2016-002966 Application 11/457,713 7 surface” as set forth in each of the independent claims. As an initial matter, the Examiner interprets the words “tending to cause . . .” in this phrase to mean “leaning toward but not necessarily causing.” Ans. 21. As Appellants do not object to this definition, we adopt the Examiner’s definition as within the common and ordinary meaning consistent with the Specification. See Reply 1–5. The Examiner and Appellants generally refer to the “configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal surface,” set forth in claim 1 as an “L-shaped” configuration. See Ans. 21; Reply 2–3. However, the Examiner interprets the referenced claim language as not limited to a strict L-shape configuration, whereas Appellants contend that the claim language should be read to exclude configurations in which the functional sequence exhibits a random coil configuration. Id. Appellants do not convince us that the claim is so limited. Figure 2 of the Specification is reproduced below. Figure 2 “is an idealized schematic of d(Tm-An) oligonucleotides adsorbed on gold” (Spec. ¶ 10) and illustrates “an absorption model (L-shape model) Appeal 2016-002966 Application 11/457,713 8 where d(A) blocks preferentially adsorb on the gold substrate and the d(T) blocks extend away from the substrate” (id. ¶ 58). With reference to Figure 2, the Specification states: Films obtained using oligos with long d(T) blocks, such as d(T25-A5) and d(T25-A10) display the same trend of decreasing grafting density with increasing length of the d(A) block, but overall have lower grafting densities than short block oligos—an effect attributed to steric and electrostatic repulsion between the longer d(T25) brush strands, which can no longer be approximated as [] extended chains, but instead behave as anchored random coils. Id. ¶ 59. Accordingly, the Specification draws a distinction between “extended chains” in the first two rows of Figure 2, and “anchored random coils” in the third row of the figure. Notably, the claim phrase at issue does not use the terms “L-shaped,” “extended chains,” or “anchored random coils.” Nevertheless, because “the longer d(T25) brush strands,” of Figure 2, that “behave as anchored random coils,” generally extend away from the substrate, they comprise “functional sequence [that] extends away from the metal surface,” as set forth in claim 1. Accordingly, we do not read the instant claims as excluding random coils. Our opinion as to the meaning of this claim phrase is further informed by Figure 12, reproduced below. Appeal 2016-002966 Application 11/457,713 9 “FIG. 12 shows FTIR spectra and XPS oligonucleotide coverages before and after denaturing.” Id. ¶ 21. With reference to the inset in the lower right hand portion of Figure 12, the Specification further states: Because of the complementary nature of the d(Tm-An) oligos, films of oligos with both long d(T) and long d(A) blocks, such as d(T25-A15) and d(T25-A20), contain stable hybrids. Exposing these films to denaturing conditions recovers the d(T25) brush structure, i.e, the structure with d(T) blocks extending away from the surface, as shown in FIG. 12. Id. ¶ 59 (italics added). The inset of Figure 12 depicts a d(T25-A15) oligonucleotide hybridized to a gold film via its poly-A block, before and after urea treatment. See id. ¶ 90. Although paragraph 59 of the Specification state that, after the urea treatment, “d(T) blocks extend[s] away from the surface,” Figure 12 does not show the d(T25-A15) oligonucleotide as forming the strict L-configuration depicted in the top two rows of Figure 2. To the contrary, the “brush structure” of “d(T) blocks extending away from the surface,” in the inset of Figure 12, is not substantially different from the “random coils” shown in the bottom row of Figure 2. See also Appeal 2016-002966 Application 11/457,713 10 Whitman Declaration ¶ 6 (implying that Fig. 4B of the Specification represents the “L-shaped configuration”).10 This underscores our determination that the claimed “configuration wherein . . . the functional sequence extends away from the metal surface,” may encompass random coils. In setting forth the rejection, the Examiner relies on Demers as teaching a method for attaching nucleic acids to a surface at a controlled surface density comprising: (a) providing a gold surface . . . (b) providing a solution comprising at least one chemical functional unit attached at one of its ends to at least one block of 20 adenine nucleotides . . . (c) providing at least one separate lateral spacer block of 20 adenine nucleotides . . . (d) contacting the immobilization solution and the lateral spacer block with the surface for a period of time sufficient to directly attach the adenine nucleotide block and the lateral spacer block to the gold surface. Ans. 5–6 (citations omitted). The Examiner relies on Kimura-Suda as teaching the high affinity of poly-adenine for gold surfaces in 1 M NaCl at room temperature. See id. at 6–7. The Examiner further relies on Petrovykh as describing the immobilization of thiolated poly-T oligonucleotides on a gold surface, where the salt concentration of the immobilization solution in both Petrovykh and Demers is a results-effective variable influencing immobilization density and orientation. Id. at 7. In short, the Examiner further finds that both Petrovykh and Demers explicitly teach L-shaped poly-A anchors and their benefits; and all of Petrovykh, Demers and Kimura-Suda teach the same conditions as described in the 10 See App. Br. 5 (incorporating by reference the Declaration under 37 C.F.R. § 1.132 of Lloyd J. Whitman. Appeal 2016-002966 Application 11/457,713 11 instant Specification which cause L-shaped anchors. Thus, both Petrovykh and Demers teach the claimed limitations of “solute and temperature conditions tending to cause a configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal surface.” Id. at 22. Accordingly, the Examiner concludes that in view of Demers and Petrovykh, the ordinary artisan would have been motivated to conduct routine experimentation to determine the optimal immobilization conditions for achieving the desired result of immobilization of the oligonucleotides at the desired density and with the desired orientation, i.e., with direct (horizontal) attachment of the lateral spacer block as taught by Demers and also with direct (horizontal) attachment of the adenine block in the oligonucleotide of Demers additionally containing the functional sequence as suggested by the teachings of Kimura-Suda describing the very strong affinity of adenine nucleotides for gold surfaces. Id. at 7–8. Appellants respond that the Examiner has failed to establish that the cited references teach or suggest the claimed “configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal surface,” and, thus, the desirability of identifying solute and temperature conditions tending to cause that configuration. See Ans. 5–9; Reply Br. 2–9. With respect to Petrovykh, Appellants argue that “Petrovykh describes a structure going from nearly flat to randomly coiled. At no point is an L shape expected.” Reply Br. 3–4. As noted above, however, we do not read the claim as excluding a random coil configuration. Petrovykh Appeal 2016-002966 Application 11/457,713 12 teaches that immobilization efficiency and, thus, density, is a results- effective variable dependent on cation valence and salt concentration. See FF 4. “At higher immobilization densities, the (dT)25 film consists of randomly coiled ssDNA molecules each anchored via the thiol group and at possibly one or two other bases.” Appellants point to the following Figure from Petrovykh as evidencing a random coil configuration. See Reply Br. 3. The above figure depicts the absorption of (dT)25 to gold film at high and low density. As depicted here, under high-density conditions (upper panel) a substantial portion of the poly-T tails extend away from the gold substrate. Petrovykh further teaches that maximum density is obtained at room temperature in 2 M CaCl2—conditions with the scope of those disclosed in Appellants’ Specification. See FF 1, 4. Accordingly, and contrary to the Whitman Declaration upon which Appellants rely, we agree with the Examiner that Petrovykh teaches “identifying solute and temperature conditions tending to cause a configuration wherein the at least one block of adenine nucleotides or adenine nucleotide analogs attaches directly to and substantially flat along said metal surface and the functional sequence extends away from the metal surface,” as required by the rejected claims. Moreover, even if one or more of the cited references do not Appeal 2016-002966 Application 11/457,713 13 expressly disclose the recited conformation, because they identify the same solute and temperature conditions set forth in the Specification, we agree with the Examiner that the disclosed conditions would at least “tend to cause” the configuration as claimed. See Ans. 22, 24–27, 31, 40 (concluding that “the combination of the prior art of record clearly teaches to use the same ‘solute and temperature conditions’ of the claimed invention which tend to yield L-shaped poly-A anchors, if not explicitly teaches the L-shape poly-A anchors”). Appellants argue that Demers “fails to even hint at the L-shaped configuration” because rather than employing a block of poly-A nucleotides to attach the oligonucleotide to the substrate, Demers Scheme 3 relies on chemical modification at the end of the oligonucleotide to achieve a vertical orientation and, thus, “teaches away from having any part of the nucleotides in flat contact with a surface.” App. Br. 6–9. Demers, however, is not limited to the experiments set forth in Scheme 3. “It is well settled that a prior art reference is relevant for all that it teaches to those of ordinary skill in the art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992). Demers teaches the adsorption of SA20N12f oligonucleotides to gold particles and “aging” the adsorbed complex under solute and temperature conditions taught by Appellants’ Specification. See Ans. 26–28; FF 2. The Examiner has the burden of providing reasonable proof that a claim limitation is an inherent characteristic of the prior art. In re Best, 562 F.2d 1252, 1254–55 (CCPA 1977); see also Crown Operations Int’l, Ltd. v. Solutia Inc., 289 F.3d 1367, 1377 (Fed. Cir. 2002). The Examiner meets this “burden of production by ‘adequately explain[ing] the shortcomings it perceives so that the applicant is properly notified and able to respond.’” In Appeal 2016-002966 Application 11/457,713 14 re Jung, 637 F.3d 1356, 1362 (Fed. Cir. 2011) (quoting Hyatt v. Dudas, 492 F.3d 1365, 1370 (Fed. Cir. 2007)). The burden of proof then shifts to the applicant “to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on.” In re Best, 562 F.2d at 1254–55; In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir. 1997) (holding that once the Examiner established a prima facie case of anticipation, the burden of proof was properly shifted to the inventor to rebut the finding of inherency). In re Mousa, 479 F. App’x 348, 352 (Fed. Cir. 2012). In the present case, Appellants rely on the Whitman declaration, which asserts that “under condition analogous to those of Demers et al., the claimed L-shaped configuration was not achieved (see the present Specification, FIG. 4A as compared to FIG. 4 B, explained in ¶[0064].” Whitman Decl. ¶ 6. Appellants do not explain, however, why the cited portions of the Specification represent “analogous” conditions, nor address the relevance of any differences—such as the significance of the length of the poly-A blocks (20 in Demers vs. 5 in Figure 4) and differences in adsorption conditions (e.g., oligonucleotide concentration of 1 μM used in Figure 4A as compared to the 3 μM used in Figure 4B and Demers). See Demers, at e.g., 5536. Accordingly, we do not find Appellants’ argument persuasive. In sum, we agree with the Examiner that Petrovykh, Demers and Kimura-Suda explain the benefits of poly-A anchors/attachments (optimized high-density and L- oriented nucleic acid attachments in the presence of high-salt solutions to allow higher throughput and sensitivity of detection and analysis . . . [such that] a skilled artisan would have been motivated to apply the poly-A anchors/attachments of Appeal 2016-002966 Application 11/457,713 15 Petrovykh, Demers and Kimura-Suda in order to take advantages of such benefits. Ans. 21–22. Moreover, “[t]he teachings of Petrovykh, Demers, and Kimura- Suda concerning immobilization conditions and the factors influencing the interaction with the surface would have provided the ordinary artisan with the required reasonable expectation of success.” Id. at 13. SUMMARY I. We affirm the rejection of claims 1–5, 8, 10–20, 23, 25, 27–32, 57– 62, and 67–69 under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, and Petrovykh. II. We affirm the rejection of claims 6, 7, 21, 22, 33–39, 41–44, 63, and 64 under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, and Zhao. III. We affirm the rejection of claims 45–51 and 54–56 under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, and Kumar. IV. We affirm the rejection of claim 53 under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, Kumar, and Lizardi. V. We affirm the rejection of claim 65 under 35 U.S.C. § 103(a) as obvious over the combination of Demers, Kimura-Suda, Petrovykh, and Mergny. Appeal 2016-002966 Application 11/457,713 16 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 Copy with citationCopy as parenthetical citation