Ex Parte Henwood et alDownload PDFPatent Trial and Appeal BoardDec 12, 201612781628 (P.T.A.B. Dec. 12, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 121781,628 05/1712010 99969 7590 12/12/2016 Pepper Hamilton LLP/Recro Pharma 400 Berwyn Park 899 Cassatt Road berwyn, PA 19312 FIRST NAMED INVENTOR Geraldine Anne Henwood 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. 137617.00101 3106 EXAMINER THOMAS, TIMOTHY P ART UNIT PAPER NUMBER 1628 MAILDATE DELIVERY MODE 12/12/2016 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 GERALDINE ANNE HENWOOD, RANDALL JEROME MACK, CHRISTOPHER T. SHARR, and JOHN KOLENG 1 Appeal2014-005564 Application 12/781,628 Technology Center 1600 Before ERIC B. GRIMES, ULRIKE W. JENKS, and RACHEL H. TOWNSEND, Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims directed to a method of treating or preventing pain by administering dexmedetomidine to the oral mucosa of a patient. The Examiner rejects the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We AFFIRM. 1 According to Appellants, the real party in interest is Recro Pharma, Inc. (App. Br. 2.) Appeal2014-005564 Application 12/781,628 STATEMENT OF THE CASE According to the Specification, "[d]exmedetomidine, 5-[(lS)-1-(2,3- dimethylphenyl)ethyl]-lH-imidazole, is a non-narcotic a2-adrenoceptor agonist with sedative and analgesic properties" (Spec. i-f 2). "'Analgesia' is the alleviation or elimination of the sensation of pain. As used herein, 'pain' encompasses a wide range of clinical manifestations, and it has a broad meaning" (id. i-f 25). The Specification provides several examples of physiological conditions that are associated with pain. One example includes"[ w ]ithdrawal from chemical dependence on alcohol or drugs of abuse is also often associated with pain symptoms. Accordingly, 'pain' is understood herein to have a very broad meaning and it's [sic] claimed uses should not be construed as being limited to any particular malady or condition" (id.). Claims 5, 7-9, 11-13, 16, 17, 27, and 28 are on appeal, and can be found in the Claims Appendix of the Appeal Brief. Claim 5 is representative of the claims on appeal, and reads as follows: 5. A method of treating or preventing pain in a mammal without significant sedation comprising administering to oral mucosa of the mammal a unit dose between 0.05 µg/kg and 1.50 µg/kg of dexmedetomidine or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable vehicle suitable for administration to the oral mucosa, wherein said dexmedetomidine or pharmaceutically acceptable salt thereof treats or prevents pain without significant sedation, wherein during the hour immediately after administration of said dexmedetomidine, said mammal without significant sedation is categorized at a level of sedation that is no greater than level 2 on the Ramsay Sedation Scale. (App. Br. 15, Claims Appendix.) 2 Appeal2014-005564 Application 12/781,628 Appellants request review of the Examiner's rejection of claims 5, 7- 9, 11-13, 16, 17, 27, and 28 under 35 U.S.C. § 103(a) over Kanazi2 in view of Anttila3 and Ebert. 4 As Appellants do not argue the claims separately, we focus our analysis on claim 5, and claims 7-9, 11-13, 16, 17, 27, and 28 stand or fall with that claim. 37 C.F.R. § 41.37 (c)(l)(iv). The issue is: Does the preponderance of evidence of record support the Examiner's conclusion that based on the combination of references it would have been obvious to one of ordinary skill in the art at the time the invention was made to arrive at the claimed method of administering to the oral mucosa a dexmedetomidine dose in the range of 0.05 to 1.50 µg/kg to achieve pain treatment without significant sedation? Findings of Fact FF 1. Kanazi teaches that "[ d]exmedetomidine is an a 2-adrenoreceptor agonist that is approved as an intravenous sedative and coanalgesic" (Kanazi 222). Kanazi teaches intrathecally administering a combination of "bupivacaine 12 mg+ dexmedetomidine 3 µg" (Kanazi 223, see 224 Table 1) and shows that this combination "significantly shortened the onset of motor block and prolonged both motor and sensory block" (id. at 225). 2 Kanazi et al., Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block, 50 Acta Anaesthesiol. Scand. 222-227 (2006) ("Kanazi"). 3 Anttila et al., Bioavailability of dexmedetomidine after extravascular doses in healthy subjects, 56 J. Clin. Pharmacol. 691---693 (2003) ("Anttila"). 4 Ebert et al., The Effects of Increasing Plasma Concentrations of Dexmedetomidine in Humans, 93 Anesthesiology 382-394 (2000) ("Ebert"). 3 Appeal2014-005564 Application 12/781,628 FF2. "Intrathecally administered a2-agonists have a dose-dependent sedative effect[]. The doses of clonidine and dexmedetomidine [used in the study of Kanazi] were at the lower end of the dosing spectrum. This explains the lack of sedative effects between the study groups" (Kanazi 226). FF3. The Examiner finds that "[t]he 3 µg dose, when administered to patients ranging from 68-91 kg (see [Kanazi] Table 1), corresponds to the [dose] range 0.033-0.044 µg/kg" (Final Act. 7). FF4. Ebert teaches that "[i]ncreasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory" (Ebert Abstract) Ebert suggests that "lower plasma concentrations of dexmedetomidine may be useful to provide sedation and mild analgesia while preserving memory and cardiovascular and respiratory functions" (Ebert 393). FF5. Ebert teaches that "[t]here was a 14% decrease in the pain score to the CP [cold pressor] test after the first incremental dose of dexmedetomidine, accompanied by a significant decrease in the MAP [ (mean arterial blood pressure)] response to the CP. Increasing doses lead to linearly decreasing pain sensation and MAP response to the CP" (Ebert 392). FF6. Anttila teaches measuring serum concentrations of dexmedetomidine after a single 2 µg kg-1 dose of dexmedetomidine was administered intravenously (over 5 min at a constant rate using an infusion pump), intramuscularly (by injection), perorally (drug solution ingested with 150 ml of water) or buccally (the drug solution retained in the mouth for 5 min without swallowing, then expelled into a tube for the 4 Appeal2014-005564 Application 12/781,628 measurement of remaining drug) (Anttila 691---692). FF7. Anttila teaches that "the actual buccal doses varied from 0.49 to 1.75 µg kg-1 (mean± s.d., 1.12 ± 0.33 µg kg-1), because not all drug was absorbed. After buccal administration, AUC was 1.29 ± 0.50 µg h 1-1, and the dose-corrected mean buccal bioavailability was 81.8% (72.6- 92.1 %). The peak concentration (0.29 ± 0.09µg1- 1) was attained at 1.5 ± 0.2 h after a short lag-time of 0.13 ± 0.04 hours" (Anttila 692). Principles of Law "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418. See also id. at 421 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton."). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955). Analysis The Examiner finds that "[ t ]he low intrathecal dose [ dexmedetomidine] (3 ug amount dosed) is taught [by Kanazi] to be effective to provide sensory block, preserve hemodynamic stability and lack of sedation" (Ans. 4). "Ebert teaches [that] doses in the 0.25-1 µg/kg range show decreases in BP (i.e., the same effect taught for low epidural dosing by Kanazi)" (Ans. 4). The Examiner finds that Anttila teaches buccal 5 Appeal2014-005564 Application 12/781,628 administration of dexmedetomidine and "that a 2 µg/kg 'unit dose' results in a smaller amount of 'actual buccal doses' from 0.49-1.75 µg/kg; the 82% bioavalability [sic] is based on the actual dosing" (Ans. 4 ). The Examiner concludes that it would have been obvious to one of ordinary skill in the art to administer via buccal or sublingual administration a dosage within the range of claim 5 and an amount within the range of claim 7. The motivation would have been for the purpose of blocking or treating pain associated with surgery, with a minimal level of sedation. Such low level of sedation would have minimized the recovery time; use of buccal administration would have been for the art-recognized purpose of an alternative drug route, which is minimally invasive. Additionally, the dosages required by claims 5 and 7 would have been prima facie obvious as a result of routine optimization within the lower dosage range taught by Kanazi to be effective as an analgesic/coanalgesic, where sedation is minimized. (Final Act. 12; Ans. 10 ("routine optimization would be used to determine an optimal dosage useful for analgesia (without the sedation and associated problems with sedation)"); Advisory Act. 2 mailed April 23, 2013.) Kanazi teaches that dexmedetomidine is a a2-adrenoreceptor agonist that is known to have coanalgesic properties when administered to patients (FF 1 ). Kanazi teaches administering 3 µg of dexmedetomidine intrathecally to patients in conjunction with bupivacaine (FF 1 ). Kanazi also teaches that a2-adrenoreceptor agonists are known to have an analgesic effect as well as a sedative effect (FF2). Ebert teaches that dexmedetomidine decreases the pain score in subjects and that increasing doses lead to decreasing pain sensation (FF5). Ebert also teaches that increasing concentrations of dexmedetomidine also 6 Appeal2014-005564 Application 12/781,628 leads to increased sedation (FF4), and concludes that "lower plasma concentrations of dexmedetomidine may be useful to provide sedation and mild analgesia while preserving memory and cardiovascular and respiratory functions" (FF4). Anttila teaches buccal administration of dexmedetomidine at a dose of 2 µg/kg (FF6) results in a peak plasma concentration of the 0.29 µg per liter (FF7). Anttila teaches administration of dexmedetomidine to the oral mucosa. Kanazi and Ebert both recognize a 2-adrenoreceptor agonists are known to have both sedative and analgesic properties and that administration at lower ranges reduces both of these effects. We agree with the Examiner that the administration of dexmedetomidine at lower doses was obvious at the time the invention was made because it was already recognized that lower dosing was "effective for purposes of analgesia with a coanalgesic agent, [thus,] use of dexmedetomidine can be administered with minimal sedation. This provides motivation to optimize dosing using the art- recognized buccal dosing route, to achieve ana[l]gesia, with minimal sedation" (Ans. 5). "Further optimization to achieve coana[l]gesia/analgesia efficacy, but without sedation, would also have been obvious, per In re Aller" (Ans. 6). "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d at 456. We have reviewed Appellants' contentions that the Examiner erred in rejecting claims 5, 7-9, 11-13, 16, 17, 27, and 28 as obvious over the cited art. (App. Br. 5-13.) We disagree with Appellants' contentions and adopt the findings concerning the scope and content of the prior art set forth in the 7 Appeal2014-005564 Application 12/781,628 Examiner's Answer, the Final Rejection dated October 12, 2012, the Advisory Action dated Jan. 24, 2013, and the Advisory Action of April 23, 2013. For emphasis, we highlight and address the following: Appellants contend that the "the Office cannot simply substitute the dose that is used in Kanazi for the dose that is used in Antilla [sic]" (App. Br. 9). "Put simply, dexmedetomidine is used to enhance the local anesthetic effects ofbupivacaine" and "not to treat or prevent pain" (App. Br. 10). We are not persuaded by Appellants' contention that enhancing a local anesthetic effect is not encompassed by the definition of treating or preventing pain as disclosed in the Specification. The Specification states that "pain includes any sensory experience that causes suffering and is associated with an unpleasant awareness of one's own body" and "is understood herein to have a very broad meaning and it's [sic] claimed uses should not be construed as being limited to any particular malady or condition" (Spec. i-f 25). We agree with the Examiner that, under the broadest reasonable interpretation in light of the Specification, "[ s ]ensory and motor block is blockage of pain, necessary to alleviate pain during a surgical procedure (the meaning of anesthesia includes insensitivity to pain; and blockage of passage of pain impulses)" (Ans. 11 ). Kanazi assessed the sensory level of the patients using a pinprick method (Kanazi 223 ("The sensory level was assessed by pinprick sensation using a blunt 25-gauge needle along the mid-clavicular line bilaterally")). Getting pricked with a needle is reasonably interpreted to encompass "pain" within the meaning as set out in the Specification. Kanazi shows that "the combination of 12 mg of intrathecal bupivacaine with a low dose of 3 µg of 8 Appeal2014-005564 Application 12/781,628 dexmedetomidine or 30 µg of clonidine significantly shortened the onset of motor block and prolonged both motor and sensory block when compared with bupivacaine alone" (Kanazi 225). Kanazi reasonably established that 3 µg of dexmedetomidine contributes to preventing pain in a mammal. "The teaching of Kanazi [further] establishes the blockage of pain occurs without sedation. This has clear benefits in a surgical type setting, and motivates further modification to alternative dosing routes, such as buccal administration, which does not require the invasive administration of intrathecal dosing" (Ans. 11 ). We agree with the Examiner that the low dose dexmedetomidine effect as shown in Kanazi would motivate the ordinarily skilled artisan to use this concentration "as a starting point for further optimization of dose, keeping in mind the observation that low doses, which do not result in significant sedation are effective for analgesic/coanalgesic activity" (Ans. 8). We agree with the Examiner's position that it is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR, 550 U.S. at 418. See also id. at 421 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton."). In this regard, the Examiner explains that the ordinarily skilled artisan would have started at a low dose as suggested by Kanazi and would have "increased the unit dose to account for lower bioavailability compared to injected dosing, and loss of dexmedetomidine not absorbed across the buccal mucosa in the first 5 minutes" (Ans. 13). Here, the substitution suggested by the Examiner (see Ans. 13) is merely a reasonable starting point from which to optimize the dosage unit based on the combination of references because 9 Appeal2014-005564 Application 12/781,628 Kanazi suggests dosages that are effective at treating pain but do not produce sedation. Appellants contend that "Antilla [sic] administers a unit dose that is significantly greater than the presently recited range. One of skill in the art would not interpret the term 'unit dose' to mean what is absorbed" (App. Br. 10). "The Office's interpretation of the administered unit dose is not correct. The amount of a drug that is absorbed or bioavailable is not the same as the unit dose that is administered to the 'oral mucosa of the mammal."' (App. Br. 10). We are not persuaded by Appellants' contentions. The Examiner explains that Anttila clearly compares four types of dexmedetomidine dosing routes, concluding that buccal dosing achieves 82 % bioavailability (compared to low (16%) bioavailability with oral dosing and 104% for intramuscular dosing). Anttila clearly indicates that a 2 µg/kg "unit dose" results in a smaller amount of "actual buccal doses" from 0 .49-1. 7 5 µg/kg; the 82% bioavalability [sic] is based on the actual dosing (Ans. 4; FF6 & FF7). We agree with the Examiner's position that the "actual buccal doses" absorbed by the patients as determined by Anttila show that those patients actually received dexmedetomidine doses that fall within the claimed dosage range. However, the Examiner does not rely on Anttila alone in formulating the rejections but instead points to Kanazi for teaching pain relief without sedation using low levels of dexmedetomidine. It is the combination that suggests it "would have been prima facie obvious as a result of routine optimization within the lower dosage range taught by Kanazi to be effective as an analgesic/coanalgesic, where sedation is minimize[ d]" (Ans. 5). 10 Appeal2014-005564 Application 12/781,628 The claimed treatment method is not limited to using dexmedetomidine alone and can encompass combination therapy to reduce pain so long as the treatment is "without significant sedation." We agree with the Examiner's position that it would have been obvious to one of ordinary skill in the art at the time the invention was made to take Anttila' s dosing of 2 µg/kg which is outside the claimed range and Kanazi's dosing which is below the claimed range (FF3) and use those dosages as bookends to optimize the buccal dosage form. Ebert, which is also part of the rejection, teaches that increasing the concentration of dexmedetomidine causes both sedation and analgesia (FF4 & FF5). We agree with the Examiner's conclusion that the combination of references would have led the ordinary artisan to optimize buccal doses of dexmedetomidine for their analgesic effect. The establishment of a prima facie case of obviousness, as the Examiner has done here based on the teaching of Kanazi, Anttila, and Ebert, shifts the burden of producing contrary evidence or arguments to Appellants. See In re Oetiker, 977 F.2d 1443, 1445--46 (Fed. Cir. 1992). Appellants present two references in an effort to rebut the Examiner's prima facie case. Appellants contend that "the doses [of a pain medication] are significantly increased when an intrathecal dose is converted to an oral dose" citing Cohen5 Table 1 in support (App. Br. 8). Appellants contend that the Examiner has not rebutted the teaching ofNatale6 or Cohen. Based 5 Cohen and Dragovich, Intrathecal Analgesia, 25 Anesthesiology Clin. 863-882 (2007) ("Cohen"). 6 Natale et al., Intrathecal baclofen therapy for severe spasticity: Analysis on a series of 112 consecutive patients and future prospectives, 114 Clin. Neuro. and Neurosurgery 321-325 (2012) ("Natale"). 11 Appeal2014-005564 Application 12/781,628 on those teachings, they argue, "it is clear that one skilled in the art would expect significantly different doses would be used when converting from intrathecal administration to administering to oral mucosa for dexmedetomidine" (Reply Br. 5). We are not persuaded by Appellants' contention that Natale and/or Cohen provides sufficient evidence to overcome the Examiner's prima facie case based on the totality of the evidence. "After a prima facie case of obviousness has been made and rebuttal evidence submitted, all the evidence must be considered anew." In re Eli Lilly & Co., 902 F.2d 943, 945 (Fed. Cir. 1990) (citing In re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir. 1984)). As explained by the Examiner: Perhaps the skilled artisan would have considered the conversion ratios, in the absence of closer prior art information (dosing data, blood levels, correlation to physical criteria, such as heart rate, etc.). However, because there is such closer prior art, the skilled artisan would not have applied generic conversion ratios from Natale or Cohen (based on compounds without structural similarity), which does not even consider a drug with the same mechanism of activity; but instead the skilled artisan would have preferred reliance on actual data with the compound of interest, and on correlations from one dosing route to another, and the effects (pain relief, reduction of heart rate, etc.) to estimate dosing conversions, as a starting point for further optimization of dose, keeping in mind the observation that low doses, which do not result in significant sedation are effective for analgesic I coanalgesic activity. (Ans. 8.) Instead, the Examiner relies on Dobrydnjov's 7 teaching that shows: 7 Dobrydnjov et al., Intrathecal and Oral Clonidine As Prophylaxis for Postoperative Alcohol Withdrawal Syndrome: A Randomized Double- Blinded Study, 98 Anesth. Analg. 738-744 (2004) ("Dobrydnjov"). 12 Appeal2014-005564 Application 12/781,628 Clonidine has a similar structure to dexmedetomidine, and has the same mechanism of action, an agonist of alpha2-adrenergic receptors. Thus, it is a much better comparative compound for the conversions that are argued. Dobrydnjov's use of the same 150 microgram clonidine doses via intrathecal and oral dosing demonstrate the skilled artisan at least initially presumes simple substituion [sic] will be effective. (Advisory Act. 2 mailed Jan. 24, 2013.) The Examiner finds that Dobrydnjov shows that it is reasonable to use Kanazi's teaching as "the initial starting point of simple substitution" for taking an intrathecal dose and applying it as the starting point for an oral or buccal administration route (Advisory Act. 2). We agree with the Examiner's position that Appellants' reliance on Natale or Cohen is inapt because "[t]he drugs discussed by Cohen are all opioid agonists. None of these drugs have the same mechanism of action, or are in the same class of drugs as dexmedetomidine. The structures are different. The references simply establish conversion ratios used for some alternate drugs with different activities" (Advisory Act. 2). Appellants contend that "Dobrydnjov teaches that oral administration of clonidine (a similar drug according to the Office) also leads to more pronounced sedation in comparison with intrathecal administration" (Reply Br. 6; App. Br. 12). Appellants contend that this would teach away from the claimed method (see App. Br. 13). We are not persuaded by Appellants' contention. A prior art reference is said to teach away "when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant." In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 13 Appeal2014-005564 Application 12/781,628 1994). Here, Dobrydnjov is not relied on to formulate the rejection but instead is used for the purpose of rebutting Appellants' Natale and Cohen references that show differences between intrathecal and oral doses, and that oral doses can be in excess of 300 fold greater (see Ans. 13). Dobrydnjov teaches that "prophylactic preoperative treatment with intrathecal or oral clonidine resulted in a significant reduction of postoperative A WS [(alcohol withdrawal)] symptoms in alcohol-dependent men" (Dobrydnjov 741 ). According to the Specification"[ w ]ithdrawal from chemical dependence on alcohol or drugs of abuse is also often associated with pain symptoms" (Spec. f 25). Thus, Dobrydnjov teaches that treatment with clonidine to prevent A WS symptoms would reasonably encompass treating pain as claimed. "[B]oth oral and intrathecal clonidine seem to have similar systemic effects, which may explain why the incidence of A WS did not differ significantly between the clonidine groups" (Dobrydnjov 742). We recognize, but are not persuaded by, Appellants' conclusion that Dobrydnjov's observation that "oral administration also leads to more pronounced sedation in comparison with intrathecal clonidine" (Dobrydnjov 743) would lead the ordinary artisan away from applying an a2- adrenoreceptor agonist for the purpose of treating pain. It is important to note that the claim does not recite no sedation but instead recites the limitation "without significant sedation [as] categorized at a level of sedation that is no greater than level 2 on the Ramsay Sedation Scale." Dobrydnjov teaches that only 5 out of 15 patients in the perorally (p/ o) administered clonidine group had a Ramsay score of 3, which means 10 patients had scores below 3 (Dobrydnjov 740 ("Five patients with a Ramsay score of3 were observed in the ClonP10G at 1 h")). So even if oral 14 Appeal2014-005564 Application 12/781,628 administration leads to more pronounced sedation, the sedation levels with clonidine for the majority of the patients does not fall outside the scope of the claims and thereby would not lead the ordinary artisan away from the use of an a2-adrenoreceptor agonist for the purpose of treating pain. To reiterate, Dobrydnjov was cited by the Examiner to rebut Appellants' evidentiary evidence of Natale and Cohen. We find that the teaching of Dobrydnjov supports the Examiner's rationale that using the 3 µg of dexmedetomidine intrathecal dose given to patients as taught in Kanazi (FF1-FF3) is a reasonable starting point to for applying routine optimization to Anttila's buccal dosage form to arrive at a dexmedetomidine dosage that does not provide significant sedation. After considering the totality of the evidence presented, including the evidentiary references of Natale, Cohen, and Dobrydnjov presented by the Appellants and the Examiner, we conclude that the preponderance of the evidence of record supports the Examiner's conclusion that the combination of Kanazi, Anttila, and Ebert renders obvious the method of treating or preventing pain by administering dexmedetomidine to the oral mucosa of patients as recited in claim 5. We thus affirm the rejection of claim 5 under 35 U.S.C. § 103(a) as being obvious and, as claims 7-9, 11-13, 16, 17, 27, and 28 fall with that claim, we affirm the rejection as to those claims as well. 37 C.F.R. § 41.37(c)(l)(iv). 15 Appeal2014-005564 Application 12/781,628 SUMMARY We affirm the rejection of all claims. 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 16 Copy with citationCopy as parenthetical citation