Ex Parte Bosnyak et alDownload PDFPatent Trial and Appeal BoardMay 14, 201814628248 (P.T.A.B. May. 14, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/628,248 02/21/2015 130577 7590 05/16/2018 ANDREWS KURTH KENYON LLP 600 Travis Street Suite 4200 Houston, TX 77002 FIRST NAMED INVENTOR Clive P. Bosnyak 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. MORE-0019 (223865) 5087 EXAMINER VU, JAKE MINH ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 05/16/2018 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): patenttrademarks@andrewskurth.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CLIVE P. BOSNYAK, KURT W. SWOGGER, NANCY HENDERSON, and PAUL EVERILL Appeal2017-000874 1 Application 14/628,248 Technology Center 1600 Before FRANCISCO C. PRATS, RICHARD J. SMITH, and JOHN E. SCHNEIDER, Administrative Patent Judges. PRATS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134(a) involves claims to carbon nanotubes that contain a payload molecule, such as a drug, within their inner cavities. The Examiner rejected the claims as anticipated, and for obviousness. We have jurisdiction under 35 U.S.C. § 6(b)(l). We reverse. STATEMENT OF THE CASE The following rejections are before us for review: 1 Appellants state that the "real party in interest is Molecular Rebar Design LLC, the assignee of record." App. Br. 2. Appeal2017-000874 Application 14/628,248 (1) Claims 1--4, 8-14, 16, and 18-22, under 35 U.S.C. § 102(a)(l) as anticipated by Mashat, 2 as evidenced by Shen, 3 and Rosca4 (Ans. 2-5); (2) Claims 1-5, 8-14, 16, 18-22, and 25-34, under 35 U.S.C. § 103 as unpatentable over Mashat, Shen, Rosca, and Appellants' Specification5 (Ans. 5-7); and (3) Claims 1-5, 8-14, 16, 18-22, and 25-34, under 35 U.S.C. § 103 as unpatentable over Wu, 6 Shen, Rosca, Lowman, 7 and Appellants' Specification (Ans. 8-11). Claims 1 and 16 are the independent claims on appeal, and read as follows: 1. A composition comprising: a plurality of functionalized discrete multi-wall carbon nanotubes having an innermost wall and an outermost wall, the innermost wall defining an interior cavity, and at least one type of payload molecule; wherein the functionalized discrete carbon nanotubes are open on at least one end; and wherein greater than 30 weight percent of the at least one type of payload molecule is within the interior cavity of the discrete multi-wall carbon nanotubes. 2 Afnan Mashat et al., Zippered release from polymer-gated carbon nanotubes, 22 J. Mater. Chem. 11503---08 (2012) (hereinafter "Mashat"). 3 Mingwu Shen et al., Polyethyleneimine-Mediated Functionalization of Multiwalled Carbon Nanotubes: Synthesis, Characterization, and In Vitro Toxicity Assay, 113 J. Phys. Chem. 3150-56 (2009) (hereinafter "Shen"). 4 Iosif Daniel Rosca et al., Oxidation of multiwalled carbon nanotubes by nitric acid, 43 Carbon 3124--31 (2005) (hereinafter "Rosca"). 5 We understand the Examiner's citation to Appellants' Specification as a citation to admitted prior art. 6 Chia-Hsuan Wu et al., Trojan-Horse Nanotube On-Command Intracellular Drug Delivery, 12 Nano Lett. 5475-80 (2012) (hereinafter "Wu"). 7 Lowman et al., US 7,708,979 B2 (issued May 4, 2010) (hereinafter "Lowman"). 2 Appeal2017-000874 Application 14/628,248 16. In a payload molecule delivery system composition comprising carbon nanotubes and at least one payload molecule, the improvement comprising using functionalized discrete carbon nanotubes, wherein the functionalized discrete carbon nanotubes are aqueous dispersible, having an innermost wall and an outermost wall, the inner-most wall defining an interior cavity; wherein the functionalized discrete carbon nanotubes have an apparent aspect ratio and an average actual aspect ratio and are open on at least one end; and wherein greater than 30 weight percent of the at least one type of payload molecule is within the interior cavity of the discrete multi-wall carbon nanotubes; wherein at least about 5% (volume) of the functionalized discrete carbon nanotubes have an apparent aspect ratio from about 50% to about 99% of the average actual aspect ratio of the discrete carbon nanotubes. Appeal Br. 15, 16 (emphasis added to show certain limitations at issue). ANTICIPATION As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden ... of presenting a primafacie case ofunpatentability .... After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. In the present case, Appellants persuade us that the preponderance of the evidence does not support the Examiner's prima facie case of anticipation as to independent claims 1 and 16. In particular, Appellants persuade us that the Examiner has not shown sufficiently that Mashat describes nanotube-containing compositions in which greater than 30 weight percent of the payload molecule is within the interior cavity of discrete multi-wall carbon nanotubes, as required by both claims 1 and 16. 3 Appeal2017-000874 Application 14/628,248 As the Examiner found, Mashat describes the preparation of drug-carrying carbon nanotubes which are functionalized, that is "coated with polyethylenimine (PEI) and polyvinyl alcohol (PV A) via the 'zipper effect' that provides both support and control over drug release. PEI/PVA provides excellent support to increase DOX [ doxorubicin] loading on the nanocarrier." Mashat 11503 (abstract). Mashat explains that its drug delivery system is "controlled by changes in temperature due to the complexation (low temperature) and decomplexation (high temperature) of PEI and PV A via hydrogen bonding." Id. Thus, "[ w ]hen the bonds between PEI and PV A are decomplexed at high temperature (2:40 °C), drug release was observed as verified by fluorescence microscopy. There was no drug release at room temperature (25 °C) and a slow release at normal body temperature (37 °C)." Id. The Examiner relied on Shen and Rosca as evidence that the acid treatment used to prepare Mashat' s nanotubes yields discrete nanotubes, as recited in Appellants' claims. Ans. 4--5. As to the requirement in Appellants' claims 1 and 16, that at least 30% by weight of the drug in the composition must be loaded into the nanotubes' interior cavities, the Examiner stated as follows: [T]he sample was washed 5 times (see pg. 11504, under DOX loading), which is the similar to the wash filtration disclosed by Applicant (see pg. 17, [0056]), thus removing the payload molecule, such as anticancer drug doxorubicin (DOX; see abstract; pg. 11504, under DOX loading), which is sparingly soluble in water, from the outside and resulting in 100% of payload molecule within the interior cavity. Id. at 3. 4 Appeal2017-000874 Application 14/628,248 Appellants contend, for several reasons, that certain disclosures in Mashat do not support the Examiner's finding that at least 30% of the doxorubicin in Mashat's compositions was loaded into the nanotubes' interior cavities. App. Br. 7-9 (citing Mashat Figs. 1, 4); Reply Br. 3-7. The Examiner responds that one "possib[le ]" interpretation of Mashat's Figure 1 is that the drug diffuses into the "opening on the top and bottom of the nanotubes and the PV A zipper prevents the drug from escaping." Ans. 12; see also id. at 13 ("Appellant's composition could be this exact diagram" of Mashat's Figure 1 annotated to show drug entering through an open end of a nanotube.) (emphasis added). In particular, the Examiner contends that Mashat "is theorized to be inherently having at least 30% drugs inside the nanotube, because MASHA T's carbon nano tubes have every ingredients as claimed by Applicant, unless proven otherwise." Ans. 15; see id. ("MASHAT is inherently having at least 30% drugs inside the nanotube, because MASHA T's carbon nano tubes have every ingredients as claimed by Applicant."). Having carefully considered the arguments and supporting evidence advanced by Appellants and the Examiner, we find that Appellants have the better position. As seen above, the Examiner's position, at best, is that it is possible that at least 30% of Mashat's drug was loaded into the interior cavity of its nanotubes. It is well settled, however, that the "very essence of inherency is that one of ordinary skill in the art would recognize that a reference unavoidably teaches the property in question." Agilent Technologies, Inc. v. Afjj;metrix, Inc., 567 F.3d 1366, 1383 (Fed. Cir. 2009) (emphasis added); see also In re 5 Appeal2017-000874 Application 14/628,248 Oelrich, 666 F.2d 578, 581 (CCP A 1981) ("Inherency, however, may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient."). Thus, even if we were to agree that Mashat possibly, or even probably, discloses that at least 30% its drug was loaded into the interior cavity of its nanotubes, that fact is insufficient to demonstrate that the reference unavoidably, that is, inherently, describes nanotubes having that property. Agilent, 567 F.3d at 1383; Oelrich, 666 F.2d at 581. We agree with Appellants, moreover, that the disclosures cited by the Examiner in support of the inherency finding do not actually support the Examiner's position. As to the Examiner's reliance on Mashat's washing step as removing exteriorly-bound drug, leaving behind only drug contained in the nanotubes' interior cavities (Ans. 3), we note that, consistent with Figure 1 of Mashat cited by Appellants, Mashat's electron microscope studies show the PEI/PV A polymer combination as being on the exterior of the carbon nanotubes. Mashat 11505 (discussing Fig. 3). We note, moreover, Mashat's disclosure, cited by Appellants, that doxorubicin becomes bound to the nanotubes only when the PEI/PV A polymer combination is applied to the tubes. See id. (disclosing that control nanotube samples having no bound polymer, or only bound PEI but no PV A, "show little DOX load efficiencies ... after washing"). And as noted above, Mashat discloses that its drug is only released upon heating the nanotubes to a temperature at which the PEI/PV A combination "decomplex[ es]." Id. at 11503 (abstract) (disclosing effective drug release at temperatures 2:40 °C), but "slow release" at 37 °C"). 6 Appeal2017-000874 Application 14/628,248 Rather than performing its washing step at a temperature that allows drug release from the exterior of the nanotubes, the washing step cited by the Examiner involves washing drug-loaded PEI/PVA coated nanotubes after the tubes were "cooled down in an ice bath for 2 h[ours]." Id. at 11504. Thus, Mashat' s washing step was not performed under conditions that would allow removal of the drug from the exterior of the nanotubes. The Examiner does not persuade us, therefore, that Mashat's washing step would remove the exteriorly-bound drug from the nanotubes, leaving only drug bound to the nanotubes' interior cavities, such that Mashat's compositions inherently meet the requirement in claims 1 and 16, that at least 30% by weight of the drug in the compositions is present in the nanotubes' inner cavities. Accordingly, because we are not persuaded that a preponderance of the evidence supports the Examiner's finding that Mashat describes compositions having all of the features required by independent claims 1 and 16, we reverse the Examiner's rejection of those claims, and their dependents, as anticipated by Mashat. OBVIOUSNESS- MASHAT, SHEN, ROSCA, AND APPELLANTS' SPECIFICATION In rejecting claims 1-5, 8-14, 16, 18-22, and 25-34 for obviousness over Mashat, Shen, Rosca, and Appellants' Specification, the Examiner relied on the teachings in Mashat, Shen, and Rosca, discussed above, and cited Appellants' Specification as evidence that it was "well known in the art to provide directed delivery of a drug to a particular tissue in vivo, such as a tumor tissue by antibodies." Ans. 6. The Examiner reasoned, therefore, that 7 Appeal2017-000874 Application 14/628,248 it would have been obvious to bind tissue-targeting antibodies to Mashat's cancer-treating compositions. Id. The Examiner also conceded that the cited references "do not specifically teach the length, size, ratios, carboxylates and amount as claimed by Applicant." Id. The Examiner found, however, that the "length, size, ratios, and amount of CNTs [carbon nanotubes] are clearly result effective parameters that a person of ordinary skill in the art would routinely optimize." Id. The Examiner concluded, therefore, that claims reciting specific values for those parameters would have been obvious to an ordinary artisan. Id. at 7. As is evident, the Examiner does not identify, nor do we discern, any specific teachings in any of the cited prior art that remedy the deficiencies, discussed above, of Mashat with respect to claims 1 and 16. Accordingly, we reverse this rejection as well. OBVIOUSNESS- WU, SHEN, ROSCA, LOWMAN, AND APPELLANTS' SPECIFICATION In rejecting claims 1-5, 8-14, 16, 18-22, and 25-34 for obviousness over Wu, Shen, Rosca, Lowman, and Appellants' Specification, the Examiner cited Wu as describing functionalized nanotubes containing a drug loaded into the nanotubes' interior cavities, but conceded that Wu's compositions differed from the claimed compositions in that "WU does not teach the carbon nanotubes are mul[t]i-walled." Ans. 9. To address that deficiency, the Examiner cited Shen as evidence that multi-walled carbon nanotubes were known in the art. Id. The Examiner concluded, therefore, that it "would have been obvious to the person of ordinary skill in the art at the time the invention was made to use multi- 8 Appeal2017-000874 Application 14/628,248 walled CNTs." Id. at 10. The Examiner reasoned that an ordinary artisan "would have been motivated to make those modifications, because it would [sic, provide?] drug loading in other types of carbon nanotubes and reasonably would have expected success because CNTs only come in single- walled or multi-walled." Id. In KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), although the Supreme Court emphasized "an expansive and flexible approach" to the obviousness question, id. at 415, the Court also reaffirmed the importance of determining "whether there was an apparent reason to combine the known elements in the fashion claimed by the patent at issue." Id. at 418 (emphasis added). Ultimately, therefore, "[i]n determining whether obviousness is established by combining the teachings of the prior art, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art." In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted). In the present case, having carefully considered the arguments and evidence advanced by Appellants and the Examiner, Appellants persuade us that the Examiner has not shown by a preponderance of the evidence that the cited references would have rendered obvious the subject matter recited in Appellants' independent claims 1 and 16. In particular, Appellants persuade us that the cited references would not have suggested using multi-wall carbon nanotubes in Wu's compositions. Claims 1 and 16 both recite compositions that contain multi-wall carbon nanotubes. Appeal Br. 15 (claim 1 reciting "functionalized discrete multi-wall carbon nanotubes" (emphasis added)); see also id. at 16 (claim 16 9 Appeal2017-000874 Application 14/628,248 reciting discrete carbon nanotubes having at least two walls, "an innermost wall and an outermost wall," and also reciting that greater than 30 weight percent of the claimed composition's payload molecule is within the interior cavity "of the discrete multi-wall carbon nanotubes" (emphasis added)). In contrast, as the Examiner concedes, Wu describes compositions that contain single-wall carbon nanotubes. See, e.g., Wu 5476 (Fig. lb showing an electron micrograph of an array of Wu's synthesized nanotubes, each having a single tubular wall). The Examiner contends that substituting a multi-wall nanotube, such as disclosed in Shen, for the single wall nanotubes used in Wu's compositions, would have been obvious because there are only two types of walls for carbon nanotubes, such as single-walled and multi-walled. There is no such thing as a "no-walled" nanotube. One skilled in the art would have to pick one or both. Thus, it would have been obvious for one skilled in the art to pick one or both. Ans. 17. As Appellants point out, however, Wu contrasts its carbon nanotubes from conventional ones, and describes a specialized process for preparing its carbon nanotubes and loading them with a drug: In contrast to conventional CNTs, the CNTs used here have a relatively large diameter ( ~40 nm inner diameter). The CNTs are fabricated in an array with a perfectly aligned vertical orientation by growing them in a highly ordered and uniform anodic aluminum oxide (AAO) nanopore array template by chemical vapor deposition (CVD). After fabrication the CNTs undergo either a mechanical or chemical treatment to open both ends while embedded in the template, which provides access to the interior space for en-masse loading of molecules. Drug loading was accomplished by depositing droplets of the drug 10 Appeal2017-000874 Application 14/628,248 solution on top of the vertically aligned nanotube array membrane while applying vacuum suction at the bottom. The template-synthesized carbon nanotubes are intrinsically conductive but possess higher electrical resistivity than those synthesized by arc-discharging. This property is beneficial for our purpose .... Wu 5476. Thus, contrary to the Examiner's contention that multi-wall and single-wall nanotubes may be arbitrarily substituted for each other in Wu's compositions, Wu expressly contrasts conventional nanotubes from the single-walled nanotubes produced by its specialized process, and further discloses that the single-walled nanotubes produced by its specialized process are particularly suited to its drug delivery techniques. Given the specialized nature of the single-wall nanotubes used in Wu's compositions, the Examiner does not persuade us that an ordinary artisan would have been motivated to arbitrarily replace Wu's nanotubes with multi-wall nanotubes. The Examiner, moreover, does not identify in the record any specific evidence suggesting that the multi-wall nanotubes described in Shen, or any other multi-wall nanotubes, would be suitable, or even useful, for the particular applications described in Wu. In that regard, we note that Rosca, Lowman, and Appellants' Specification were cited as evidence of the obviousness of features not relating to the requirement in claims 1 and 16 for the composition to contain multi-wall nanotubes. See Ans. 9. In sum, the Examiner does not provide a specific evidentiary basis to support a finding that an ordinary artisan would have considered multi-wall nanotubes equivalently useful to the single-wall nanotubes used in Wu's compositions. The Examiner does not persuade us, therefore, that an ordinary artisan would have considered it obvious to substitute multi-wall 11 Appeal2017-000874 Application 14/628,248 nanotubes for the single-wall nanotubes used in Wu's compositions. Accordingly, because a preponderance of the evidence does not support the Examiner's conclusion that Wu, Shen, Rosca, Lowman, and Appellants' Specification teach or suggest a composition having all of the elements required by Appellants' independent claims 1 and 16, we reverse the Examiner's obviousness rejection of those claims, and their dependents, over the cited prior art. SUMMARY For the reasons discussed, we reverse each of the Examiner's rejections. REVERSED 12 Copy with citationCopy as parenthetical citation