Ex Parte MullerDownload PDFBoard of Patent Appeals and InterferencesFeb 27, 201212116303 (B.P.A.I. Feb. 27, 2012) 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. 12/116,303 05/07/2008 Walter Muller 512100-2037.1 6809 20999 7590 02/27/2012 FROMMER LAWRENCE & HAUG 745 FIFTH AVENUE- 10TH FL. NEW YORK, NY 10151 EXAMINER LANDAU, SHARMILA GOLLAMUDI ART UNIT PAPER NUMBER 1611 MAIL DATE DELIVERY MODE 02/27/2012 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 BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte WALTER MULLER __________ Appeal 2012-000649 Application 12/116,303 Technology Center 1600 __________ Before DONALD E. ADAMS, STEPHEN WALSH, and JACQUELINE WRIGHT BONILLA, Administrative Patent Judges. BONILLA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to directed to a transdermal therapeutic system comprising a polyisobutylene active substance layer with microreservoirs dispersed within, where the drug sufentanyl is dissolved in the microreservoirs. The Examiner has rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Appeal 2012-000649 Application 12/116,303 2 STATEMENT OF THE CASE The present invention relates to a transdermal therapeutic system comprising: a) an impermeable backing layer; b) an active substance layer comprising polyisobutylene with microreservoirs dispersed within, where sufentanyl is dissolved in the microreservoirs; and c) a protective layer. Claims 1-4 and 8-20 are on appeal. Appellant argued claims 2 and 3 separately from other pending claims.1 Claim 1 is the only independent claim and reads as follows (emphasis added): 1. A transdermal therapeutic system (TTS) containing an active substance comprising: a) an active substance impermeable backing layer, b) an active substance layer, wherein the active substance is sufentanyl, where said active substance layer comprises a polymer or a polymer mixture with microreservoirs dispersed therein, wherein the active substance is dissolved in the microreservoirs, and c) a protective layer, which is removed before use wherein the polymer or polymer mixture is a pressure sensitive adhesive polymer which is a polyisobutylene. 1 Appellant states that “[c]laim 2 and 3 will be argued separately” but also that “[i]n order to expedite the Appeal, claims 3-20 will be considered to stand or fall with the rejection of claim 1.” (App. Br. 3.) For the purposes of our analysis, we assume that Appellant intended claims 4 and 8-20 to stand or fall with claim 1, and that we should consider claims 2 and 3 separately from other pending claims. Appeal 2012-000649 Application 12/116,303 3 Claim 2 depends on claim 1 and recites that “the concentration of the active substance in the active substance layer is between 2 and 5% by weight.” Claim 3, which also depends on claim 1, recites that “at least 50% by weight of the active substance in the TTS is contained within said microreservoirs.” The claims stand rejected as follows: • Claims 1, 3, 8-15, and 20 under 35 U.S.C. §103(a) as obvious over Müller (WO 01/01967, Jan. 11, 2001) in view of Levy et al. (U.S. Pat. No. 4,822,802, issued Apr. 18, 1989) and Xiong and Patel (WO 01/35883, May 25, 2001) (“Patel”). • Claims 2,16, and 18-19 under 35 U.S.C. §103(a) as obvious over Müller in view of Levy and Patel as applied to claims 1, 3, 8-15, and 20, and further in view of Gale et al. (U.S. Pat. No. 4,588,580, issued May 13, 1986) as evidenced by the instant Specification. • Claim 4 under 35 U.S.C. §103(a) as obvious over Müller in view of Levy and Patel as applied to claims 1, 3, 8-15, and 20, and further in view of Fischer et al. (U.S. Pat. No. 5,683,711, issued Nov. 4, 1997). • Claim 17 under 35 U.S.C. §103(a) as obvious over Müller in view of Levy and Patel as applied to claims 1, 3, 8-15, and 20, and further in view of Chang et al. (U.S. Pat. No. 4,849,224, issued Jul. 18, 1989). Findings of Fact 1. Appellant and Examiner agree that while Müller describes a transdermal therapeutic system, Müller does not teach the “use of sufentanyl as an active ingredient or the substitution of polyisobutylene for polysiloxane.” (App. Br. 5; Ans. 5.) Appeal 2012-000649 Application 12/116,303 4 2. According to the Examiner, Müller teaches that the active ingredient in the described transdermal therapeutic system is not limited, and may include “pain means” such as fentanyl. (Ans. 5, citing Müller, 4). Although Müller fails to teach sufentanyl, the Examiner finds that Levy cures this deficiency. (Ans. 5-6.) 3. Levy teaches transdermal delivery of “[f]entanyl and its analgetically effective derivatives such as sufentanyl ….” (Levy, col. 1, ll. 15-18; see also abstract.) 4. Müller also discloses a transdermal therapeutic system comprising an active substance layer comprising a polymer with microreservoirs dispersed therein, where the polymer is polysiloxane. (Müller, 1 (stating that the “Prefered Polymer for micro reservoir systems is polysiloxanes”).) 5. As noted by the Examiner, Patel teaches transdermal patches comprising a pressure sensitive adhesive that may be polyisobutylene or polysiloxane. (Ans. 7.) Specifically, Patel states that “[s]pecific examples of suitable rubber-based pressure sensitive adhesives include … polyisobutylene (PIB), … and polysiloxanes ….” (Patel, 23, 2nd full ¶.) 6. Gale teaches a transdermal therapeutic system for delivery of fentanyl and its analgetically effective derivatives, such as sufentanyl. (Gale, abstract, col. 1, ll. 1-15, col. 2, ll. 56-59, col. 3, Table 1, col. 5, ll. 1-9.) Gale’s system comprises “a pouch formed from an impermeable backing,” as well as a strippable protective backing. (Id. at col. 5, ll. 2-6.) The Appeal 2012-000649 Application 12/116,303 5 impermeable backing “is configured to provide a central volume which contains a drug reservoir 6 in the form of a gel having a dissolved and suspended drug therein.” (Id. at col. 5, ll. 6-9.) 7. Gale, in Table 2 (col. 5), presents a general formulation for a preferred gel reservoir composition, which includes a “broad range” of 0.1% to 10% (w/w %) of a drug. (Gale, col. 5, ll. 29-40.) 8. In relation to its transdermal therapeutic system, Müller states that the active ingredient is “mostly not in the polymere ingredients of the system, but in the liquid micro reservoirs, which are [embedded] into the polymeric layers ….” (Müller, 1.) The Examiner interprets “mostly” in this section of Müller to mean more than half of the active ingredient is contained within the liquid microreservoirs. (Ans. 7.) 9. Müller also teaches that at least 80% of the active ingredient is contained in the microreservoir. (Müller, 2; Ans. 16.) Principles of Law The ultimate question of obviousness is one of law, based upon factual inquiries set forth in the Graham case: (1) the scope and content of the prior art; (2) the differences between the prior art and the claims at issue; (3) the level of ordinary skill in the pertinent art; and (4) objective evidence of non-obviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966). “An examiner bears the initial burden of presenting a prima facie case of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). “Once the examiner establishes a prima facie case of obviousness, the burden shifts to the applicant to rebut that case.” Id. If the applicant Appeal 2012-000649 Application 12/116,303 6 presents rebuttal evidence, such as unexpected results or that the prior art teaches away from the claimed invention, the Examiner must consider the totality of the evidence to determine whether the obviousness rejection should stand. Id. I. Issues Issues regarding claim 1 are (1) whether it would have been prima facie obvious to one of skill in the art to combine the teachings of Müller with those of Levy and Patel to prepare the transdermal therapeutic system recited in pending claim 1, and if so, (2) whether the record presents evidence of secondary considerations, such as unexpected results or teaching away in the prior art, sufficient rebut the prima facie case. Analysis Our analysis in relation to Müller’s transdermal therapeutic system (TTS) relates to whether it would have been obvious to use sufentanyl (instead of fentanyl, as described in Müller) as the active substance, and polyisobutylene (instead of polysiloxane, as described in Müller) as the pressure sensitive adhesive polymer. As noted by the Examiner, Müller teaches a relevant transdermal therapeutic system (TTS) for administering a “pain means” active ingredient, such as fentanyl, which is listed as an example (FF 1, 2; Müller, 4). Levy teaches transdermal delivery of fentanyl “and its analgetically effective derivatives such as sufentanyl” (Levy, col. 1, ll. 15-19; abstract; FF 3). Thus, Levy establishes that sufentanyl was a well-known “analgetically effective derivative” of fentanyl, and those skilled in the art would have Appeal 2012-000649 Application 12/116,303 7 thought to administer fentanyl or sufentanyl via transdermal delivery for the purpose of providing pain relief. Likewise, Patel teaches that well-known pressure sensitive adhesives for use in transdermal drug delivery systems included polyisobutylene and polysiloxane. (FF 5.) Appellant asserts that “the delivery systems of Levy and Patel lack any teaching of the use of microreservoirs, or that sufentanyl is dissolved within the microreservoirs.” (App. Br. 7.) This assertion ignores the Müller disclosure, and, as noted by the Examiner, “Levy and Patel are not relied upon for their teaching of microreservoirs.” (Ans. 15.) Based on teachings in Levy, absent evidence to the contrary, it would have been obvious to those skilled in the art to use sufentanyl in place of fentanyl in the transdermal therapeutic system described in Müller. Based on teachings in Patel, absent evidence to the contrary, it would have been obvious to use polyisobutylene in place of polysiloxane as a pressure sensitive adhesive in the TTS described in Müller. Thus, we conclude that the Examiner has established a prima facie case that the TTS of claim 1 is obvious over Müller in view of Levy and Patel. The question therefore becomes whether Appellant provides sufficient evidence, such as evidence of secondary considerations of non- obviousness, to rebut the prima facie case. Appellant provides no evidence that one would have thought that known alternatives to fentanyl (such as its derivative sufentanyl) and known alternatives to the pressure sensitive adhesive polysiloxane (such as polyisobutylene) would not work in the Müller system. Likewise, Appellant provides no evidence that anyone might have thought it was necessary to use Appeal 2012-000649 Application 12/116,303 8 only the specific drugs and pressure sensitive adhesives described in Müller for any reason when using Müller’s system. Appellant asserts that the parent to the instant application issued as U.S. Pat. No. 7,390,500. (App. Br. 3.) Appellant then “speculates” that a different Examiner allowed claims in the ‘500 patent “in spite of consideration of the Müller reference because one of ordinary skill in the art would have been surprised that a TTS would have been capable of delivering a drug such as sufentanyl in sufficient amounts to not produce a lag time before showing analgesic effects while controlling the delivery of sufentanyl in sufficient amounts not to effect an overdose.” (Id. at 5.) Appellant then states that Levy and the instant Specification describe concerns relating to lag time, and Patel and the instant Specification describe concerns relating to overdosing. (Id. at 5-6.) In this context, Appellant asserts that Patel teaches away from Appellant’s TTS “by trying to reduce or even eliminate the need for using an opioid such as sufentanil by disclosing the use of the aconitum species of compounds.” (Id. at 6.) As an initial matter, we note that “speculation” does not constitute evidence. Moreover, we agree with the Examiner that “[n]o such unexpected results have been presented or argued in the instant case.” (Ans. 14.) Rather, Appellant asserts a “teaching away” based on the contention that Patel teaches the use of aconitum species as analgesic agents, and that aconitine and sufentanyl have “great differences in chemical structure.” (App. Br. 6, 7.) Appellant cites to “col. 1, lines 28-32” in Patel as describing the “concern regarding overdosing.” (App. Br. 5.) Patel is a published PCT Appeal 2012-000649 Application 12/116,303 9 document, WO 01/35883, and does not present columns. That said, we assume that Appellant refers to Patel, page 1, lines 28-32, which describes “for more severe pain, opioids such as morphine, …, oxycodone … fentanyl, and heroin” and states that “heavy use of opioids … leads to chemical dependence, or addiction.” Chemical dependence or addiction is not the same thing as overdosing, such as might occur via a leak of a transdermal system containing an opioid. (See App. Br. 4, describing disadvantages of a leak in a pouch of a reservoir system.) In the context of treating drug addition, Patel teaches that “[b]ecause extracts of Aconite roots have no affinity for opioid receptors, they may be used to expediently relieve drug addiction.” (Patel, page 2, ll. 27-32.) In other words, Patel does not teach away from therapeutic use of opioids, such as fentanyl and its derivatives, but rather discloses a composition that might be useful to treat addiction to opioids, as well as for amelioration of pain and inflammation, for example by administering via a transdermal formulation. Id.; see also id. at 3, ll. 1-2, at 12, ll. 10-14). Evidence of record (e.g., Müller, Levy, Gale) expressly taught the use of fentanyl and its derivatives for therapeutic uses by administering such drugs using a TTS. Patel did not teach otherwise by disclosing that aconitine may be administered transdermally as an analgesic agent. Thus, we find that no prior art of record teaches away from using sufentanyl as the active substance instead of fentanyl, or polyisobutylene as the pressure sensitive adhesive instead of polysiloxane, in the TTS of Müller. In addition, Appellant has provided no evidence of unexpected Appeal 2012-000649 Application 12/116,303 10 results, nor any other evidence of secondary considerations of non- obviousness, in relation to the TTS recited in claim 1. Conclusion of Law We agree with the Examiner that, based on the cited references, it would have been prima facie obvious to combine the teachings of Müller with those of Levy and Patel to prepare the transdermal therapeutic system recited in claim 1. Because claims 4 and 8-20 stand or fall with claim 1, we conclude that the Examiner has set forth a prima facie case of obviousness with regard to these claims as well. We also conclude that the record before us does not provide sufficient evidence of secondary considerations to rebut the prima facie case. II. Issues The issues regarding claim 2 are (1) whether it would have been prima facie obvious to one skilled in the art to combine the teachings of Müller, Levy and Patel, as applied to claim 1 above, with Gale to prepare the transdermal therapeutic system recited in claim 2, and if so, (2) whether the record presents evidence of secondary considerations sufficient rebut the prima facie case. Additional Principles of Law As stated by the Federal Circuit, a “prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003); Ormco Corp. v. Align Technology, Inc., 463 F.3d 1299, 1311 (Fed. Cir. 2006). Even a slight overlap in range establishes a prima facie case of Appeal 2012-000649 Application 12/116,303 11 obviousness. In re Peterson, 315 F.3d at 1329. A prima facie case of obviousness likewise exists when the claimed range and the prior art range do not overlap but are close enough such that one skilled in the art would have expected them to have the same properties. Id. (citing Titanium Metals Corp. v. Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). One “may overcome a prima facie case of obviousness by establishing ‘that the [claimed] range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range.’” Peterson, 315 F.3d at 1330 (quoting In re Geisler, 116 F.3d 1465, 1469-70 (Fed. Cir. 1997) (alteration in original). Alternatively, one “may rebut a prima facie case of obviousness by showing that the prior art teaches away from the claimed invention in any material respect.” In re Peterson, 315 F.3d at 1331 (citing In re Geisler, 116 F.3d at 1469). Analysis Claim 2 depends on claim 1. As noted above, the Examiner presents a prima facie case with regarding to claim 1. The question therefore becomes whether it would have been prima facie obvious to use sufentanyl in the TTS system of claim 1 in the amount recited in claim 2, i.e., between 2 and 5% by weight. Appellant asserts that “Gale teaches such a concentration level without the use of the microreservoirs of the invention and as such does not teach this element of appellants’ claim 2.” (App. Br. 8.) This assertion ignores the fact, however, that rejection is based on the combined teachings of references, including Müller, and that the Examiner does not cite Gale for its teaching of microreservoirs. See Ans. 15. Rather, as noted by the Appeal 2012-000649 Application 12/116,303 12 Examiner, because Müller does not teach a weight % range of the active agent, one would have been motivated to look to Gale, which teaches a weight % of fentanyl or sufentanyl in a transdermal delivery system. (Ans. 9.) Specifically, Gale teaches using a “broad range” of 0.1% to 10% w/w of fentanyl and its derivatives, such as sufentanyl, in a transdermal therapeutic system (Gale, col. 5, Table 2). This range disclosed in Gale encompasses the narrower claimed range of “between 2 and 5% by weight” recited in claim 2. As stated by the Federal Circuit: [W]hen, as here, the claimed ranges are completely encompassed by the prior art, the conclusion is even more compelling than in cases of mere overlap. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages. In re Peterson, 315 F.3d at 1330. Here, the fact that the range recited in claim 2 is “completely encompassed by the prior art” is sufficient to establish a prima facie case of obviousness. Id. As noted above, one may overcome a prima facie case of obviousness by establishing that the claimed range is critical, e.g. achieves unexpected results, or by showing that the prior art “teaches away from the claimed invention in any material respect.” In re Peterson, 315 F.3d at 1331. Here, however, the Examiner correctly finds that Appellant provides no evidence of unexpected results. (Ans. 14.) As noted the Examiner, “[t]he instant specification does not contain a single example using sufentanyl” and presents no “unexpected results over the prior art as relate to a lack of lag time.” (Id.) In other words, Appellant points no evidence (in the Appeal 2012-000649 Application 12/116,303 13 Specification or elsewhere) of any unexpected advantage of the TTS recited in claim 1 or 2 regarding a prior art “lag time” or any other alleged concern. Moreover, Appellant provides no evidence indicating that Gale, or any other cited reference, disparages or otherwise discourages the use of sufentanyl in the claimed system in the % weight range recited in claim 2. For example, in addition to teaching the 0.1% to 10% w/w range of fentanyl and its derivatives, Gale discloses that: [W]e have found that fentanyl or its derivatives may be administered to the human body via the transdermal route for the purpose of inducing analgesia, if administered through about 5-100 cm2 and preferably about 10-50 cm2 of intact skin over an extended period of time at a rate within the range of about 0.5 to 10 µg/cm2/hour and preferably at a rate within the range of approximately 1-5 µg/cm2/hour. When so delivered it is possible, by appropriate selection of the surface area of the drug delivery device to obtain total drug input rates which provide an adequate range of titration for individual patient needs while maintaining a safe and effective dosage form. Gale, col. 2, ll. 55-67 (emphasis added). Thus, Gale indicates that the use of the described % range of fentanyl or its derivatives can be delivered in a safe manner. Appellant provides no evidence that one of skill in the art would have believed that the same range of active substance would fail to work in Appellant’s claimed system. At most, Appellant refers to alleged disadvantages due to “leaking” and “lag time” with reservoir systems such as presented in Gale (App. Br. 4.). That said, Appellant does not point to any evidence, for example in the Specification or prior art, indicating that one would not use the range amounts of sufentanyl (as described in Gale) in the system presented in Müller based on such concerns. Assuming those skilled in the art would Appeal 2012-000649 Application 12/116,303 14 have worried about leaks and lag time, there is no evidence that a person of ordinary skill in the art would have considered them to teach away from using fentanyl or its derivatives in transdermal therapeutic systems in the first place. Multiple references of record, i.e., Gale, Levy, and Müller, however, clearly taught using fentanyl in transdermal therapeutic systems. Thus, skilled artisans were motivated to prepare such systems for administering fentanyl and its derivatives, even if users would have understood that they should be careful regarding leaks and lag time. Those skilled artisans would have looked to prior art transdermal therapeutic systems, such as the one disclosed in Gale, to determine the relevant amounts of fentanyl and its derivatives to use in the system described in Müller. Appellant does not provide sufficient rebutting evidence to the contrary. Appellant asserts that “appellant’s invention and Levy are actively trying to avoid being similar to Gale.” (App. Br. 8.) To the contrary, however, Levy does not teach away from using fentanyl in a transdermal system as suggested by Appellant. While it is correct that Levy teaches that a solution to “Gale’s disadvantage” of lag time is to apply “a fentanyl solution transdermal in conjunction with via intravenous administration,” it is not correct that Levy teaches “to dispense with the reservoir system” altogether. (App. Br. 4). Rather, Levy teaches that: When fentanyl is administered as described in U.S. Pat. No. 4,588,580 [Gale], certain patients exhibited a lag time of about 12 hours before analgetically effective serum drug levels were achieved. This was too long to achieve analgesia when recovering from anesthesia after short duration surgical procedures. Part of this lag time can be taken care of according to our invention by placing the Appeal 2012-000649 Application 12/116,303 15 transdermal system on the patient prior to anesthesia and surgery. This, coupled with a 100 to 300 µg dose of fentanyl given at the induction of anesthesia provides analgetically effective serum drug levels when pain relief is needed…. Levy, col. 2, ll. 24-40. In other words, Levy expressly teaches administering fentanyl as described in Gale, and overcoming the lag time problem by doing so before anesthesia and surgery, and then also administering fentanyl intravenously with anesthesia. Thus, Levy expressly teaches using Gale’s TTS to administer fentanyl or sufentanyl. Neither Levy nor any other cited prior reference teaches away from using sufentanyl in Gale’s system or any other TTS. Thus, we find that no prior art of record teaches away from using sufentanyl as the active substance instead of fentanyl, or from using sufentanyl in the Müller TTS at the % weight ranges taught in Müller. In addition, Appellant has provided no evidence of unexpected results, nor anyother evidence of secondary considerations of non-obviousness, in relation to the TTS recited in claim 2, i.e., one having sufentanyl in the active substance layer at a concentration between 2 and 5% by weight. Conclusion of Law We agree with the Examiner that, based on the cited references, it would have been prima facie obvious to one skilled in the art to combine the teachings of Müller, Levy and Patel, as applied to claim 1 above, with Gale to prepare the transdermal therapeutic system recited in claim 2. We also conclude that the record does not provide sufficient evidence of secondary considerations to rebut the prima facie case. Appeal 2012-000649 Application 12/116,303 16 III. Issues Issues regarding claim 3 are (1) whether it would have been prima facie obvious to one of skill in the art to combine the teachings of Müller with those of Levy and Patel to prepare the transdermal therapeutic system recited in pending claim 3, and if so, (2) whether the record presents evidence of secondary considerations, such as unexpected results or teaching away in the prior art, sufficient rebut the prima facie case. Analysis Claim 3 depends on claim 1. As noted above, the Examiner presents a prima facie case with regarding to claim 1. The question therefore becomes whether it would have been prima facie obvious to make and use the TTS system of claim 1 where at least 50% by weight of the active substance in the TTS was contained within the microreservoirs, as recited in claim 3. Once again, we point out that Müller is the primary reference in the obviousness analysis. As noted by the Examiner (Ans. 7), Müller teaches that the “active ingredient is … mostly … in the liquid micro reservoirs.” (Müller 1). We agree with the Examiner one of skill in the art would have understood “mostly” in Müller to mean at least more than half of the active ingredient was contained in the microreservoirs. (Ans. 7.) In addition, Müller teaches that “preferably” at least 80% of the active ingredient is contained in the microreservoirs. (Müller 2; Ans. 16). In other words, Müller itself teaches the element recited in claim 3. Appeal 2012-000649 Application 12/116,303 17 Thus, we are back to the original question addressed above regarding claim 1, i.e., whether, when making the TTS taught in Müller, it would have been obvious to use sufentanyl as described in Levy (instead of fentanyl), and polyisobutylene as described in Patel (instead of polysiloxane). For all the reasons already discussed, we conclude that both claims 1 and 3 are obvious over the cited references. Conclusion of Law We agree with the Examiner that, based on the cited references, it would have been prima facie obvious to combine the teachings of Müller with those of Levy and Patel to prepare the transdermal therapeutic system recited in claim 3. We also conclude that the record does not provide sufficient evidence of secondary considerations to rebut the prima facie case. SUMMARY We affirm the rejection of claims 1, 3, 4 and 8-20 under 35 U.S.C. §103(a) as unpatentable over Müller in view of Levy and Patel. We also affirm the rejection of claim 2 under 35 U.S.C. §103(a) as unpatentable over Müller in view of Levy, Patel, and Gale. 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)(1)(iv). AFFIRMED pgc Copy with citationCopy as parenthetical citation