Ex Parte Schlutermann et al

Patent Trials and Appeals BoardMar 22, 2019

11990100 - (D) (P.T.A.B. Mar. 22, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 11/990,100 04/11/2008 20999 7590 03/26/2019 HAUG PARTNERS LLP 745 FIFTH A VENUE - 10th FLOOR NEW YORK, NY 10151 FIRST NAMED INVENTOR Burkhard Schlutermann 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. 247004-203 2060 EXAMINER PURDY, KYLE A ART UNIT PAPER NUMBER 1611 NOTIFICATION DATE DELIVERY MODE 03/26/2019 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): docket@haugpartners.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte BURKHARD SCHLUTERMANN and MANFRED KOHLMEYER 1 Appeal2018-001473 Application 11/990, 100 Technology Center 1600 Before RICHARD M. LEBOVITZ, JOHN E. SCHNEIDER, and DAVID COTTA, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to a pharmaceutical pellet comprising a spherical core. The Examiner rejected the claims as obvious under 35 U.S.C. Â§ 103. Pursuant to 35 U.S.C. Â§ 134, Appellants appeal the Examiner's determination that the claims are unpatentable. We have jurisdiction under 35 U.S.C. Â§ 6(b ). The Examiner's decision is affirmed. STATEMENT OF THE CASE Claims 1--4, 6-10, 13-19, 24--33, and 37 stand rejected under 35 U.S.C. Â§ 103(a) as obvious in view of Bai (US 5,840,329, issued Nov. 24, 1 The Appeal Brief ("Br." entered Apr. 7, 2017) lists ADD Advanced Drug Delivery Technologies Ltd., as the real party in interest. Appeal Br. 1. Appeal2018-001473 Application 11/990, 100 1998), Khan (US 2005/0112115 Al, published May 26, 2005), and Shimizu et al. (WO 0006126, published Feb. 10, 2000) ("Shimizu"). Ans. 2. Independent claim 1 is illustrative of the rejected claims and reads as follows 1. A pharmaceutical pellet, comprising: a spherical core with a smooth surface, the spherical core comprising an active substance; and a coating, on the core, which controls pH-independent release of the active substance, and which does not comprise the active substance; wherein the core has a diameter in the range of from 0.2 to 2.0 mm; and wherein the surface of the core has a mean roughness of less than 10 Âµm and a relative mean roughness of less than 2%. DISCUSSION The Examiner found that Bai describes the claimed spherical core with a coating that controls pH-independent release of a drug. Final Act. 4-- 5. The Examiner found that Bai does not describe the core as having "a mean roughness of less than 10 Âµm and a relative mean roughness of less than 2%." To meet this limitation, the Examiner cited Khan as teaching that "a smooth surface is desirable to prevent the blistering of the film, orange peeling, uneven application of coating solutions or dispersion and mottling." Id. at 6-7. The Examiner further cited Shimizu as describing a core diameter overlapping with the diameter recited in the claims. Id. at 7 (i-f 20). Appellants argue that Khan relates to a method of quantifying surface roughness, and not of producing a product with a given surface roughness. Appeal Br. 11. Appellants state that "Khan teaches that beads and granules can be measured by the disclosed method, and not that beads and granules 2 Appeal2018-001473 Application 11/990, 100 can be manufactured by any disclosed method." Id. at 12. Appellants further argue: Id. The preparation of pellets or pellet cores is achieved by particular granulation processes which are able to from spherical pellets instead of relatively irregular granules. The compression of a tablet from a powder or from granules plus powder ( excipients, compression aids) or even from pellets plus powder is a completely different process. Therefore, pellet cores will not necessarily have the claimed values of surface roughness given the disclosure of Khan about surface roughness of tablets. Appellants also contend that "Khan does not teach that a smooth surface of a tablet was desirable." Appeal Br. 13. Rather, Appellants argue that "Khan merely teaches that it was desirable to quantitatively measure the surface roughness of tablets." Id. We first begin with claim interpretation. The claim is directed to a pellet comprising "a spherical core with a smooth surface, the spherical core comprising an active substance." The core has a coating "which controls pH-independent release of the active substance." The Specification describes a core "as meaning that the entire inner portion of the pellet [which] is enclosed beneath a coating that controls the pH-independent release of the active substance. Spec. 12. The Specification discloses examples of cores, including "seed cores coated with a layer of active substance, where the layer of active substance can contain one or more substance", "release-controlling coatings", and "protective coatings." Id. See also claim 9 ("said spherical core comprises: a seed core not containing the active substance; and a layer, on the seed core, which 3 Appeal2018-001473 Application 11/990, 100 comprises the active substance."). Thus, a core can be made of a seed core covered by a layer, including a layer comprising an active substance. As discussed by the Examiner (Ans. 8), Khan describes coating beads with a material comprising an active substance ("verapamil"). Khan ,r 68. Khan teaches: Initially the surface was rough and, at 4% weight gain, the beads attained a relatively smoother surface. No additional change in roughness was observed as a function of an increase in coating weight gain. The drug-loaded beads appeared to be porous and rough. However, coating reduced the surface roughness and consequently a uniform film was formed. Khan ,r 71. Paragraph 71 of Khan states that the coating weight is increased until a smoother surface was obtained, indicating the desirability of reducing roughness and attaining a smoother surface. For this reason, we do not agree with Appellants that Khan does not describe the manufacture of cores or that "Khan does not teach that a smooth surface of a tablet was desirable." Appeal Br. 13. Khan teaches it is desirable to have smooth and uniform coating to facilitate a uniform release of drug. For tablets, Khan teaches: The Figure clearly demonstrates that a uniform membrane was achieved at 10% wt. gain and that any further increase in coating thickness would decrease the uniformity, resulting in an unpredictable release pattern. For predictable membrane- controlled dosage formulations, not only the weight gain of the membrane matters but also the uniformity of the membrane. Khan ,r 4 7. There is no reason to believe drug release from beads would be any different than tablets with respect to diffusion through the surface coating. 4 Appeal2018-001473 Application 11/990, 100 While it may be true that, as asserted by Appellants (Appeal Br. 12), the process described in the Specification results in pellets with a smooth surface (Spec. 28-31 ), which differs from the tablet compression processes described by Khan, Khan explicitly discloses a process of coating pellets with a material to form a surface coating which is smooth and uniform. Khan ,r 71. The definition of "core" in the Specification includes cores having a coating. Spec. 12. Thus, while Khan's process differs from the process described in the Specification, the claims are not limited to cores made by a specific method. Khan, thus, describe a method of making spherical cores having a smooth and uniform surface. Appellants emphasize that "Khan is silent as to [ disclosing] any pellet cores with the claimed roughness." Appeal Br. 14. As explained above, the claims do not exclude the "spherical core" ( a pellet) from comprising a coating. Khan teaches coated beads. Khan ,r 68. The coated beads are described by Khan as having "relatively smoother surface." Khan ,r 71. Appellants did not provide evidence that such "smoother" surface does not have "a mean roughness of less than 10 Âµm and a relative mean roughness of less than 2%." This is discussed in more detail below in the section titled "Roughness measurements." The Examiner found it would have been obvious to have modified Bai to impart a smooth surface with the claimed mean roughness: Here, the modification of Bai such that the surface to receive a coating be made to have a surface roughness of 2.97 Âµm or 1.77 Âµm (see Table 3 of Khan) would have been obvious as applying a known technique to a known product ready for improvement to yield predictable results is indicative of prima facie obviousness. See MPEP 2143(1)(D). Ans. 7. 5 Appeal2018-001473 Application 11/990, 100 Thus, it would have been obvious to one of ordinary skill in the art to coat Bai' s seed as described in Khan to impart a smooth and uniform surface to the seed, e.g., to give it predictable drug release rate. Again, Appellants have not identified a deficiency in this reasoning. Size Appellants' argue that the diameter of the beads described in paragraphs 68-71 of Khan does not meet the claimed limitation of "core has a diameter in the range of from 0.2 to 2.0 mm." Reply Br. 11. While the Examiner states that Khan's particles fall within the claimed range (Ans. 9), the Examiner relied on paragraphs 68-71 of Khan to establish that Khan described coating beads and measuring their mean roughness. Ans. 8-9. The Examiner relied upon Shimizu as teaching spherical particles with sizes that overlap with the claimed range. Final Act. 7 (i-f 20). Appellants in the Appeal Brief did not dispute the Examiner's findings with regard to Shimizu and the obviousness of using its particles in Bai. Appellants merely stated that "Shimizu does not teach how to prepare pellet cores having the claimed smooth surface," ignoring the fact that the Examiner did not rely on Shimizu for such a teaching. Appeal Br. 1 7. Roughness measurements The claim requires the spherical core to have "a mean roughness of less than 10 Âµm and a relative mean roughness of less than 2%." The Examiner found the ranges to be met by Khan's disclosure in Table 3 (citing to the values listed in the table under the "Ra" roughness property). Final Act. 6-7 (i-f 17). In the Reply Brief, Appellants argue that the roughness 6 Appeal2018-001473 Application 11/990, 100 value of Ra pointed to by the Examiner in Table 3 is not the claimed roughness value, but rather it is Rz, listed in the last column of Table 3, which Appellants assert fall outside the claimed values for mean roughness. Reply Br. 18-19. First, we note that Appellants' response in the Reply Brief is a new argument because the Examiner relied upon Table 3 in the Final Office Action, and therefore Appellants' had the opportunity to respond to it in the Appeal Brief, but did not. The argument is therefore waived because it was first raised in the Reply Brief. 3 7 C.F .R. Â§ 41.41 ( a )(2 ). Even if we were to consider Appellants' improperly raised argument, we would not be persuaded that the Examiner erred. The claim is drawn to spherical cores having a "mean roughness of less than 10 Âµm." The Specification defines "mean roughness" as a "root-mean-square value." Spec. 15. Rz, cited by Appellants, is defined in Khan as "mean roughness depth of the R-profile" and "mean peak to valley height." Khan ,r,r 11, 60. It therefore does not appear that Rz is the same value as the "root-mean- square value." Accordingly, Appellants did not establish that the Rz value corresponds to the claimed "mean roughness." The Examiner found in the Final Office Action that the Ra value corresponded to the claimed "mean roughness."2 Final Act. 6-7 (i-f 17). Appellants did not dispute this in the Appeal Brief, but rather waited until the Reply Brief to address it. In the Reply Brief, Appellants made no reference to how mean roughness is defined in the Specification and why it would correspond to the Rz value, but not to the Ra value identified by the 2 The Examiner did not explicitly state "Ra," but pointed the Ra values in Table 3. 7 Appeal2018-001473 Application 11/990, 100 Examiner. Appellants simply made the assertion that Rz meets the claims "mean roughness" without objective evidence to support the assertion. Appellants also argue that no units for the R values are disclosed in paragraphs 68-71 and Figure 4 (Reply Br. 12) in which the beads with a smoother surface are manufactured. Figure 4 of Khan shows a graph of the roughness parameters plotted as a function of coating weight gain. Khan ,r 71. The Y-axis does not describe the values as being in Âµm units. However, the Examiner found that the units were in Âµm, which is consistent with the fact that the values in Table 3 and Figure 3 of Khan are in Âµm. Ans. 8-9. We agree with this finding, particularly given that the examples describe the same objective achieving a "decrease in roughness" (Kahn ,r 51) for the tablets and "a relatively smoother surface" for the beads (Kahn ,r 71 ). Applicants contend that Khan does not show values which meet the claimed mean roughness. However, Figure 4 of Khan shows all roughness values under 6 (including Ra and Rz) for the beads produced in paragraphs 68-71. Appellants have not adequately explained why these values do not meet the claim limitation regarding mean roughness, except to argue that that the units are not shown. In addition to this, as discussed above, the values in Table 3 for Ra also fall within the scope of claim 1. Appellants have not provide adequate evidence that this teaching would not have been extended to beads as a desired roughness value, Thus, Khan shows, as well as suggests, roughness values for coated beads within the claimed range and describes how to manufacture them to have a smooth and uniform surface. Appellants have not provided evidence that the claimed values are critical or any different from those in Khan. 8 Appeal2018-001473 Application 11/990, 100 While Appellants continued to dispute that Khan provides a reason to make a pharmaceutical dosage having a smooth surface, Khan repeatedly refers to achieving a smooth surface (i1i19, 37, 47, 49, 50, 52, 71) and reasons for doing so: to achieve predictable drug release (i-f 47) and to have a sufficient coating (i-f 37). For example, in addition to what has already been cited, Khan teaches: If the tablets are smooth initially, improper or insufficient coating will produce higher surface roughness values. Once the coating is complete, the surface roughness values should decrease. Khan ,r 37. The increase in compression pressure from 0.5 Ton to 1.25 Ton dramatically decreased the surface roughness (see Table 2). Nevertheless, a further increase in compression pressure did not decrease the roughness proportionately, perhaps because a decrease in roughness goes in parallel with an increase in the hardness of the tablet. There is a saturation point in the decrease in roughness, above which any additional compression pressure may not facilitate a reduction in smoothness Khan ,r 51. Even if the above disclosures are in reference to tablets, we have not been presented with an adequate reason why they would not be applicable to a spherical bead or pellet. The reasoning that a smooth uniform surface would lead to predictable drug release rates would be the same for a tablet and spherical bead because both have outer surfaces through which the drug must be released. Non-analogous art Appellants argue that Khan is non-analogous art because it is not within the inventor's field of endeavor. Appellants state: "The current 9 Appeal2018-001473 Application 11/990, 100 Application relates to producing a pellet as a dosage form for an active substance. In contrast, Khan relates to a method of measuring surface roughness of a dosage form. Khan, [0003]-[0011]." Appeal Br. 15. Appellants further argue that "Khan has nothing whatsoever to do with producing a pellet. Thus, it is clear that Khan is not within the field of the instant inventors' endeavors." Id. at 16. This argument is not persuasive because Khan describes coating pellets to achieve a smooth uniform surface and reduce mean roughness. Khan ,r,r 68-71. The claims are directed to pellets having a particular degree of mean roughness. Consequently, Khan's teaching of how to measure surface roughness is clearly pertinent to the claims. Appellants' arguments about the inventors endeavor relating to "addressing problems associated with providing a pharmaceutical pellet for which the release of the active substance can be controlled independently of the pH value and independently of the action of enzymes" (Appeal Br. 17) ignore the explicit language in the claim of spherical cores having "a mean roughness of less than 10 Âµm and a relative mean roughness of less than 2%", values addressed by Khan's disclosure. Claim 2 Claim 2, depends from claim 1, and further recites "wherein the core has a length-width ratio of less than about 1.4." The Examiner found that because particles described in Shimizu are spherical, it would be expected that the ratio between width and length would be 1.0. Final Act. 7. 10 Appeal2018-001473 Application 11/990, 100 Appellants argue that there is no teaching in Bai, Khan, or Shimizu about the sphericalness of any particles or granules. Appeal Br. 18. This argument does not persuade us that the Examiner erred. As found by the Examiner, Shimizu describes a "spherical product" having a size which overlaps with the claimed range. Shimizu 16-17 (Section "7)"). The spherical product is made of crystalline cellulose and lactose (a sugar). Id. Bai teaches that its seed is made or sugar/starch or cellulose. Bai 6:3. Shimizu's spherical product therefore contains the same components as in Bai, making it obvious to have used it in Bai's method for its equivalency to Bai's seed. Final Act. 7 (i-f 20). Since Shimizu characterizes its product as "spherical," and a "sphere" has the meaning of "an object that is completely round in shape like a ball" as defined in a general purpose dictionary, 3 one of ordinary skill in the art would reasonably expect the width and length to about the same and about 1. 0 as found by the Examiner. Appellants state the depending on the method used to make it, the resulting shape of the pellet core may be more irregular than a sugar sphere, but provide no objective evidence to support this argument. Appeal Br. 18- 19. Moreover, the issue in this rejection is the sphericalness of Shimizu 's product which the Examiner found could be utilized in Bai' s method. Appellants' have not provided evidence that such product which is characterized as "spherical" by Shimizu would not have core has a length- width ratio of less than about 1.4 and fall outside the scope of the claim. The teaching in Shimizu that the product is "spherical" was sufficient to 3 https://www.collinsdictionary.com/us/dictionary/english/sphere_l 11 Appeal2018-001473 Application 11/990, 100 shift the burden to Appellants to show that it did not meet the limitations of the claim. Summary For the foregoing reason, the obviousness rejection of claims 1 and 2 is affirmed. Claims 3, 4, 6-10, 13-18, 24--33, and 37 were not argued separately and fall with claim 1. 37 C.F.R. Â§ 4I.37(c)(l)(iv). Claim 19 Appellants make the same arguments for claim 19, that they do for claims 1 and 2. The rejection of claim 19 is affirmed for the same reasons. TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. Â§ 1.136(a)(l )(iv). AFFIRMED 12