TARIS Biomedical LLCDownload PDFPatent Trials and Appeals BoardMay 19, 20202019005306 (P.T.A.B. May. 19, 2020) 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. 15/633,492 06/26/2017 Karen Danielle Daniel 29449-0366 4144 29052 7590 05/19/2020 EVERSHEDS SUTHERLAND (US) LLP 999 PEACHTREE STREET, N.E. SUITE 2300 ATLANTA, GA 30309 EXAMINER CABRAL, ROBERT S ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 05/19/2020 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): patentdocket@eversheds-sutherland.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte KAREN DANIELLE DANIEL, BURLEIGH M. HUTCHINS, CHERYL LARRIVEE-ELKINS, and HEEJIN LEE1 ____________ Appeal 2019-005306 Application 15/633,492 Technology Center 1600 ____________ Before DEBORAH KATZ, JOHN G. NEW, and RYAN H. FLAX, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies TARIS Biomedical LLC as the real party-in-interest. App. Br. 2. Oral argument was heard on May 6, 2020, and the transcript thereof is a part of the record on appeal. Appeal 2019-005306 Application 15/633,492 2 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1–20. Specifically, claims 1–7, 9–17, 19, and 20 stand rejected as unpatentable under 35 U.S.C. § 103 as being obvious over the combination of Politi et al. (US 2008/0111269 A1, May 15, 2008) (“Politi”), Peppas (US 2009/0317465 A1, December 24, 2009) (“Peppas”), A.L. Rosa et al., Clinical Effectiveness of Lidocaine and Benzocaine for Topical Anesthesia, 46 ANESTH. PROG. 97–99 (1999) (“Rosa”), Pich et al. (US 4,797,287, January 10, 1989) (“Pich), Pryce Lewis et al. (US 2003/0143268 A1, July 31, 2003) (“Pryce Lewis”), and Rothbard et al. (US 2005/0192210 A1, September 1, 2005) (“Rothbard”). Claims 8 and 18 stand rejected as unpatentable under 35 U.S.C. § 103 as being obvious over the combination of Politi, Peppas, Rosa, Pich, Pryce Lewis, Rothbard, and T. Rhines, Non-Chromatographic Methods to Support Stability Program, in HANDBOOK OF STABILITY TESTING IN PHARMACEUTICAL DEVELOPMENT, REGULATIONS, METHODOLOGIES, AND BEST PRACTICES (K. Huynh-Ba, ed.) 201, 215 (2009) (“Huynh-Ba”). Claims 1–20 also stand provisionally rejected under the nonstatutory doctrine of obviousness-type double patenting over claims 1–7 of copending US Appl. Ser. No. 13/729,974 (the “’974 application”).2 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 2 Appellant does not address this rejection in the Appeal Brief. We consequently summarily affirm this rejection. See 37 C.F.R. § 41.37(c)(iv) (“[A]ny arguments or authorities not included in the appeal brief will be refused consideration by the Board for purposes of the present appeal”). Appeal 2019-005306 Application 15/633,492 3 NATURE OF THE CLAIMED INVENTION Appellant’s invention is directed to “[a] drug dosage in the form of a solid tablet that is greater than 50% by weight of a local anesthetic agent.” Abstr. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A solid drug unit comprising: a drug in the form of a mini-tablet which is greater than 70% by weight [of] the drug, with the balance being at least one excipient, wherein the mini-tablet is cylindrical with flat end faces, the length of the tablet exceeding its diameter so that the mini- tablet has an aspect ratio of greater than 1:1, and wherein the mini-tablet has a diameter from 1.0 mm to 3.2 mm and a length from 1.7 mm to 4.8 mm, such that the mini- tablet is sized and shaped for insertion through the urethra of a patient. App. Br. 21. ISSUES AND ANALYSIS We agree with, and expressly adopt, the Examiner’s findings, reasoning, and conclusion that the claims are obvious over the combined cited prior art. We address below the arguments raised by Appellant. Appeal 2019-005306 Application 15/633,492 4 A. Independent claims 1 and 113 Issue Appellant argues that the Examiner erred by employing impermissible hindsight analysis in forming the rejection and by not providing any motivation to combine the references or establishing that a person of ordinary skill in the art would have had a reasonable expectation of success. App. Br. 6. Analysis The Examiner finds that Politi teaches “[a] granulate mass or tablet of the invention may comprise at a minimum 1, 5, or 10 percent (weight) and at a maximum 100, 95, 90, 80 or 70% of at least one active pharmaceutical ingredient” Final Act. 8 (quoting Politi ¶ 107; see also ¶¶ 94–95). The Examiner finds that Politi also teaches that “the method is applicable to a large variety of solid powder substances, e.g.[,] APIs and excipients.” Id. at 9 (quoting Politi ¶ 27). The Examiner finds that Pich teaches “cylindrical microtablets which have a convex upper face and a convex lower face and whose cylinder diameter and height independently of one another are each from 1.0 to 2.5 mm and the ratio of the said diameter to said height is from 1:0.5 to 1:1.5.” Final Act. 9 (citing Pich Abstr.). The Examiner finds that Pryce Lewis teaches uniaxially compressed dosage forms such that: 3 Appellant does not argue claims 2–5, 8, 10–15, 18, or 20. We therefore consider these claims as standing or falling with independent claims 1 and 11, from which they depend. Appeal 2019-005306 Application 15/633,492 5 Any dosage form would have a geometric center, and concentration of one or more components could be a function of distance from the geometric center of the dosage form, either by use of a dosage form having spherical symmetry or by use of a dosage form which lacks spherical symmetry but has a reasonably simple shape such as a circular cylinder or rectangular parallelepiped of not too extreme aspect ratio. Final Act.. 9 (quoting Pryce Lewis ¶ 89). In particular, the Examiner finds, Pryce Lewis teaches a dosage form having a cylindrical shape with flat ends. Id. (citing Pryce Lewis claim 24). The Examiner finds that Rothbard teaches compositions and methods for treating diseases and, specifically, that “drugs may be inserted into the urethra at the tip of the penis.” Final Act. 10 (citing Rothbard ¶ 100). The Examiner finds that Rothbard further teaches that: “[i]nserts into the urethra may be in the form of a tablet, suppository or other pill that may include biodegradable and/or nonbiodegradeable materials.” Id. (quoting Rothbard ¶ 140). The Examiner finds that Peppas teaches mini-tablets comprising local anesthetics, and discloses benzocaine as an example, and that Rosa teaches that lidocaine and benzocaine were equally efficient in reducing pain. Final Act. 9 (citing Peppas ¶¶ 67, 92; Rosa Abstr.). The Examiner concludes that Appellant’s claimed invention would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention. Final Act. 10. Specifically, the Examiner concludes that a skilled artisan would have been motivated to formulate a tablet small enough for insertion through the urethra with a high load of anesthetic agent, by the combined teaching and suggestions of Politi, Peppas, Rosa, and Rothbard. Id. The Examiner reasons that Politi teaches how to prepare Appeal 2019-005306 Application 15/633,492 6 high-load tablets, and Peppas and Rothbard teach that there would have been a reasonable expectation of success that such high-load mini-tablets of anesthetic agents, such as benzocaine were not only obtainable, but could be used, intended, or configured for insertion through the urethra. Id. The Examiner also reasons that a skilled artisan would have been motivated to modify the teachings of Politi and Peppas to incorporate lidocaine as a simple substitution for benzocaine to obtain a predictable result in view of Rosa’s teaching that benzocaine and lidocaine are functional equivalents. Id. Appellant acknowledges that Politi teaches that its oral dosage forms may contain from 1 to 100 weight percent drug. App. Br. 7 (citing Politi ¶ 107). However, argues Appellant, Politi provides no guidance regarding overcoming the known challenges with formulating drug compositions in the form of mini-tablets, let alone how one can achieve a mini-tablet containing greater than 70 percent by weight drug. Id. Turning to Peppas, Appellant argues that, contrary to the Examiner’s findings and prior to the present invention, it was believed in the art that to achieve a mini-tablet form, the composition can contain at most 42.8 to 50 weight percent drug. App. Br. 7 (citing Peppas ¶ 41). According to Appellant, Peppas teaches that, to formulate its mini-tablets, the excipient content must be at least 50 weight percent. Id. As such, Appellant contends, a person of ordinary skill in the art, reading Politi and Peppas as a whole, would have understood that a mini-tablet formulation should contain at most 50 weight percent drug to achieve desired structural and drug release profile characteristics of the mini-tablet. Id. Therefore, Appellant alleges, absent improper hindsight using Appellant’s Specification and claims as a Appeal 2019-005306 Application 15/633,492 7 blueprint, a person of ordinary skill in the art would not have been motivated to disregard the teachings of Peppas and arrive at the claimed mini-tablets. Id. Appellant agrees with the Examiner’s finding that Peppas teaches various layers of various drug content levels; however, Appellant maintains, the maximum drug content of any individual layer (and therefore the maximum possible drug content of the overall tablet) is 42.8 to 50 weight percent. Id. at 8. Appellant asserts that, unlike Peppas’ tablets, which contain at most 50 percent drug: [T]he [claimed] drug tablets may constitute mostly drug and little or no excipients, so the drug tablets contain a large amount of drug considering the tablet size.… Instead, the excipients present in the drug tablets may be present primarily or completely to facilitate the tableting process. Thus, the device may provide a very high drug payload on a volume or weight basis, such as at least 50 wt % drug, in contrast to known intravesical devices. App. Br. 9 (quoting Spec. 6). Appellant points to Examples 5–7 of the Specification as demonstrating the unpredictability and difficulties associated with tableting high amounts drug into mini-tablets. Id. Appellant notes that the Examiner relies upon Pich and Pryce Lewis as teaching the claimed mini-tablet dimensions and geometry; however, Appellant argues, the Examiner’s rejection relies on a misinterpretation of Pryce Lewis and disregards an alleged teaching away from Appellant’s claimed tablets by Pich. App. Br. 9. Appellant argues that the Examiner relies upon Pryce Lewis as teaching an oral dosage form having a shape that is cylindrical with flat ends with “dimensions of 1.78 mm in height (or length) and 11.17 in diameter.” App. Br. 9 (citing Pryce Lewis ¶ 98). However, Appellant argues, the aspect Appeal 2019-005306 Application 15/633,492 8 ratio taught by Pryce Lewis is the opposite of the claimed aspect ratio; Appellant contends that Pryce Lewis teaches away from the claimed aspect ratio, and instead teaches aspect ratios significantly less than 1:1. Id. Appellant asserts that Pryce Lewis teaches tablets having a wafer shape in which the diameter is at least twice as large as the length: the examples cited by the Examiner, argues Appellant, teach a diameter that is over six times at large as the length (i.e., an aspect ratio of about 1:6). Id. at 9–10 (citing Pryce Lewis, Table 1, ¶¶ 98, 100). According to Appellant, not only does Pryce Lewis fail to teach or suggest the claimed tablet diameter of 1.0 mm to 3.2 mm, instead teaching that the diameter should be at least three times the claimed diameter, Pryce Lewis further teaches that the diameter must exceed the length of the tablet, contrary to the claimed drug units. Id. Appellant argues further that Pryce Lewis’ use of the phrase “not too extreme aspect ratio” refers to the opposite aspect ratio than what is claimed by Appellant. App. Br. 10. Therefore, Appellant argues, the Examiner’s reliance upon the Pryce Lewis is not appropriate because, Appellant contends, Pryce Lewis teaches away from the claimed aspect ratio. Id. According to Appellant, the passage cited by the Examiner that recites that the dosage form can be in the form of a circular cylinder or a “rectangular parallelepiped of not too extreme aspect ratio” means that the dosage form could have a face that is rectangular in shape with the length of the rectangle being similar to its width, i.e., the rectangle face is close in dimensions to a circle. Id. Appellant asserts that this passage has nothing to do with the relative height of a rectangular-faced tablet to the length or width dimensions of the face, as found by the Examiner. Id. Appellant asserts that the relatively large, wafer-shaped oral dosage forms of Lewis would not Appeal 2019-005306 Application 15/633,492 9 have provided any guidance to a person of ordinary skill in the art looking to design a tablet for insertion through the urethra. Id. Appellant next argues that Pich is cited by the Examiner as teaching “cylindrical microtablets which have a convex upper face and a convex lower face and whose cylinder diameter and height independently of one another are each from 1.0 to 2.5 mm and the ratio of the said diameter to height is from 1:0.5 to 1:1.15.” App. Br. 11 (citing Pich col. 2, ll. 8–14). Appellant contends that Pich teaches that the aspect ratio may be such that the diameter is greater than or less than the height, but requires that the tablets have convex faces with particular radii of curvature. Id. Appellant contends that Pich teaches this is necessary, because when “larger radii flat upper and lower faces (infinite radius of curvature) are approached, with the disadvantage that the edges present problems during coating and a susceptible to mechanical damage.” Id. (citing Pich col. 2, ll. 40–48). Appellant asserts that Pich therefore expressly teaches away from tablets having flat faces, as claimed by Appellant, and suggests, rather, that cylindrical tablets having flat faces should be avoided due to, problems with coating and susceptibility to mechanical damage. Id. Appellant points to paragraph [0037] of the Specification, which discloses that “the drug tablets are substantially smaller than conventional drug tablets, and unlike conventional tablets that tend to be squat in shape, the drug tablets may be tall and elongated and/or may have flat, rather than convex, end faces.” App. Br. 12. Appellant asserts that it has discovered that the difficulties discussed by Pich may be overcome by formulating tablets having the particular claimed dimensions and compositions. Id. Appeal 2019-005306 Application 15/633,492 10 Therefore, Appellant contends, a person of ordinary skill in the art, reading Pich, would have had no reason to modify the tablet geometry to have the claimed aspect ratio in combination with flat or non-convex faces, at least because Pich expressly teaches that such tablets would have manufacturing and stability issues. Id. Appellant disputes the Examiner’s reasoning that Appellant misunderstands Pich’s teaching of convex faces, and particularly the Examiner’s finding that “Pich is referring to upper and lower face being convex and not end faces.” App. Br. 12 (quoting Final Act. 4). Appellant disagrees, contending that Pich teaches cylindrical microtablets having a face at each end of the cylindrical body. Id. (citing Pich Fig.). Appellant contends that the “upper and lower faces” of the cylindrical microtablet of Pich are the “end faces” of its cylindrical body. Appellant contends that, contrary to the Examiner’s findings, Pich does not merely describe convex end faces in more favorable language or as one alternative; Pich expressly teaches the use of non-convex faces as disadvantageous during coating and use due to mechanical damage, as described above. App. Br. 13 (citing Pich col. 2, ll. 40–48). Appellant contends that Pich therefore expressly teaches away from flat end faces, as required by Appellant’s claims. Id. With respect to Rothbard, Appellant notes the Examiner’s findings that Rothbard teaches: (1) “drugs may be inserted into the urethra at the tip of the penis”; (2) “Inserts into the urethra may be in the form of a tablet, suppository or other pill that may include biodegradable and/or nonbiodegradable materials.” App. Br. 14 (quoting Final Act. 10 (citing Rothbard ¶¶ 10, 140). However, Appellant argues, Rothbard neither teaches Appeal 2019-005306 Application 15/633,492 11 nor suggests overcoming the known challenges associated with formulating drug compositions in the form of mini-tablets, let alone how one can achieve a mini-tablet containing an active agent at greater than 70% by weight. Id. Furthermore, Appellant argues, Rothbard fails to teach or suggest any reason why one would have been “motivated to prepare or formulate a tablet small enough for insertion through the urethra with a high load of anesthetic agent” which, Appellant argues, is the cornerstone of the Examiner’s obviousness rejection. Id. We are not persuaded by Appellant’s arguments. As an initial matter: “[O]ne cannot show non-obviousness by attacking references individually where … the rejections are based on combinations of references.” In re Keller, 642 F.2d 413, 426 (C.C.P.A. 1981). Rather: The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. Id. at 425. Specifically, Politi teaches that it is technically feasible to produce A granulate mass or tablet of the present invention […] typically compris[ing] at minimum 1, 5 … (weight) and at maximum 100, 95, 90, 80 or 70% of at least one active pharmaceutical ingredient. In some embodiments said powder contains an amount of active pharmaceutical ingredient of at least 60% e.g.[,] at least 80%. The granulate mass or tablet may further comprise at minimum 5, 10, 20 or 30% (weight) and at maximum 99, 95 or 90% of at least one excipient, e.g.[,] long-chain polymer e.g.[,] starch or cellulose. Appeal 2019-005306 Application 15/633,492 12 Politi ¶ 107. Politi further teaches, with respect to the active pharmaceutical ingredient (“API”) in its compositions: The method of the present invention may thus be applicable to producing granules and tablets of the invention from material comprising APIs of one or multiple classes of APIs, the classes including for example antipyretics, analgesics, … and other orally administered agents. APIs can be used singly or two or more of them can be used in combination. Id. at ¶ 121 (emphasis added). We acknowledge that Politi is directed, in this instance, to orally administered agents, but Politi nevertheless teaches that it is technically feasible to synthesize a granulate mass or tablet containing “greater than 70% by weight [of] the drug, with the balance being at least one excipient,” as recited in the claims. Thus, the formulation can be tailored to the intended application. Appellant repeatedly asserts that manufacturing such a composition poses problems that would have discouraged a skilled artisan. See, e.g., App. Br. 9 (citing Ex. 5–7). We do not find this argument persuasive. First, Appellant points to no objective evidence of record to demonstrate that such technical difficulties would have been encountered by a person of ordinary skill in the art, despite the express teachings of Politi. Furthermore, although Examples 5 and 6 demonstrate some difficulties in manufacturing a tablet comprising either 95 or 100 wt% lidocaine (see Spec. Table 2) or approximately 90% lidocaine (see id., Table 3), Appellant’s Examples do not teach that such difficulties were present across the claimed range of active agent, i.e., greater than 70%. Furthermore, Example 7 of the Specification discloses that: Mini-tablets were made from various different drugs. In a first test, mini-tablets were made from lidocaine (base).… Each Appeal 2019-005306 Application 15/633,492 13 tableting test produced mini-tablets successfully. The mini- tablets had a diameter of about 1.5 mm and a length of about 2 mm. No excipients were added to any of the tableted compositions. Spec. 64. Appellant’s Specification thus discloses that mini-tablets containing 100% lidocaine (i.e., greater than 70% drug) could be successfully manufactured. With respect to Peppas, we agree with the Examiner that the reference teaches mini-tablets that can contain local anesthetic agents, including, e.g., benzocaine. See Peppas ¶¶ 67, 92. Appellant argues that the reference teaches limits upon the active agent in a mini-tablet of 50%. We acknowledge that Peppas teaches such limits, for example, Peppas teaches that: FIG. 1 shows a pharmaceutical composition 2 with at least 7 layers. The first layer 4 at has a mass ratio of drug (D) to polymer (P) of D/P of between about 0.75 and about 1.00, which corresponds to about 42.8 to about 50 wt % of drug. The first layer 4 of this composition can further include any drug or other active agent that can be granulated with pharmaceutical excipients…. Peppas ¶ 41; see also ¶¶ 42–44. However, in an obviousness analysis, we are required to read prior art references as a whole. See In re Enhanced Sec. Research, LLC, 739 F.3d 1347, 1355 (Fed. Cir. 2014). We find that, when read in the context of Peppas’ invention, it is evident that the limits described for the layers of Peppas’ mini-tablets are not absolute limits for all mini-tablet formulations. Peppas is specifically directed to “compositions that deliver one or more active agents with a substantially constant or zero order release profile.” Peppas ¶ 11. Peppas teaches that these “tablets can be prepared with Appeal 2019-005306 Application 15/633,492 14 intermediate drug-free layers, thus achieving one or more intermittent release at substantially constant rates followed by no release.” Id. In other words, Peppas teaches that the layered structures of its compositions, and the component active ingredients of the layers, are directly related to the drug delivery profile of the claimed mini-tablets. Appellant’s claims do not expressly recite, or inherently claim, any such delivery profile, and we are therefore not persuaded by Appellant’s argument that Peppas teaches or suggests an upper limit on the amount of the drug that can be incorporated into the mini-tablet under any circumstances. Pryce Lewis teaches that: Any dosage form would have a geometric center, and concentration of one or more components could be a function of distance from the geometric center of the dosage form, either by use of a dosage form having spherical symmetry or by use of a dosage form which lacks spherical symmetry but has a reasonably simple shape such as a circular cylinder or rectangular parallelepiped of not too extreme aspect ratio. Pryce Lewis ¶ 89 (emphasis added). With respect to the circular cylinder mentioned in the quoted passage, Pryce Lewis teaches that: In general, a dosage form and corresponding article such as a 3DP printed article may be cylindrical with either flat or rounded top and bottom surfaces, or rectangular prismatic with either fiat or rounded surfaces, elliptical prismatic with either flat or rounded surfaces, ellipsoidal, spherical, or could have any general shape of cross-section and any general shape of end or cap. Id. at ¶ 33 (emphasis added); see also id. at claim 24 (“The dosage form of claim 20 wherein the dosage form has a shape selected from the group consisting of: cylindrical with flat ends….”). Appeal 2019-005306 Application 15/633,492 15 Appellant’s claim 1 further recites, in relevant part: “[T]he length of the tablet exceeding its diameter so that the mini-tablet has an aspect ratio of greater than 1:1.”4 Claim 1 also recites “wherein the mini-tablet has a diameter from 1.0 mm to 3.2 mm and a length from 1.7 mm to 4.8 mm, such that the mini-tablet is sized and shaped for insertion through the urethra of a patient.” Pich is directed to: Cylindrical microtablets which have a convex upper face and a convex lower face and whose cylinder diameter and height independently of one another are each from 1.0 to 2.5 mm and the ratio of the said diameter to said height is from 1:0.5 to 1:1.5, and a process for their preparation. Pich Abstr. Adopting Appellant’s definition5 of the term “aspect ratio,” Pich thus teaches cylindrical microtablets with an aspect ratio of 0.5:1 to 1.5:1, the latter falling within claimed range of aspect ratios and also teaches absolute dimensions of height and diameter that are within the claimed ranges. Although Pich teaches that its cylindrical microtablets are convex at 4 We note here that aspect ratio is conventionally expressed as the ratio of the width of an object to its height, i.e., width:height. See, e.g., Aspect Ratio, available at: https://techterms.com/definition/aspect_ratio (last visited May 6, 2020). Appellant’s Specification, however, defines the claim term “aspect ratio” thus: “[E]ach drug unit may have a length that exceeds its width, meaning an aspect ratio of height:width that is greater than 1:1.” Spec. 27. We therefore adopt Appellant’s definition for the purposes of this analysis. See Phillips v. AWH Corp., 415 F.3d 1303, 1319 (Fed. Cir. 2005) (holding that: “Appellants may act as their own lexicographers as long as they have clearly set forth an explicit definition of the term”). 5 See id. Appeal 2019-005306 Application 15/633,492 16 either end, Pryce Lewis teaches that capsules can be either convex or flat at either end. Appellant argues that Pich, by teaching only convex ends to its capsules, expressly teaches away from flat end faces, as required by Appellant’s claims. See App. Br. 11. Specifically, Appellant points to Pich’s teaching that “the edges present problems during coating and a susceptible to mechanical damage.” Id. (citing Pich col. 2, ll. 40–48). We disagree that this constitutes a teaching away from Appellant’s claimed invention. A “teaching away” requires a reference to actually criticize, discredit, or otherwise discourage the claimed solution, such that “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 Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004); In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). Pich teaches: The radius of curvature r of the convex upper and lower faces of the cylindrical microtablet is from 0.6 to 1.5 times, preferably from 0.7 to 0.9 times, the diameter of the cylinder. With smaller radii of curvature (a spherical shape), the tools do not withstand the pressure required, while with larger radii [of curvature] flat upper and lower faces (infinite radius of curvature) are approached, with the disadvantage that the edges present problems during coating and are susceptible to mechanical damage. Pich col. 2, ll. 40–48. However, Pich teaches that its microtablets are made via a specific, specialized and novel tableting presses, which is what presented issues in forming tablets without curved ends. Id. at 24–31. Pryce Lewis teaches alternative methods of making cylindrical capsules with flat ends i.e., three-dimensional printing. See Pryce Lewis ¶ 33. Appellant’s Appeal 2019-005306 Application 15/633,492 17 claims do not recite a specific method of synthesizing the claimed composition, and Appellant adduces no evidence that the methods of Pryce Lewis would not have been known or available to a skilled artisan to achieve the claimed invention. Finally, Rothbard teaches: Solid inserts for localized delivery (e.g., to the eye, vagina, rectum and penis) may also be employed. Such inserts will be in suitable form for the target area to be inserted.… Inserts into the urethra may be in the form of a tablet, suppository or other pill that may include biodegradeable and/or nonbiodegradeable materials. Rothbard ¶ 140. Rothbard also teaches that such inserts can include anesthetic agents. Id. at ¶ 123. To summarize, Politi teaches that solid drug tablet compositions can include 70% by weight or greater active of the active agent, and Peppas teaches solid drug compositions that are mini-tablets that can include anesthetic agents. Pryce Lewis teaches cylindrical mini-tablets with flat ends, and Pich teaches cylindrical mini-tablets of the dimensions claimed by Appellant. Rothbard teaches that solid drug compositions of appropriate size and design can be inserted in the urethra and may include anesthetic agents. We agree with the Examiner that, for the reasons we have explained, a person of ordinary skill in the art, designing a solid drug composition that could be inserted into the urethra for therapeutic reasons, would look to the teachings of the combined cited prior art to produce the claimed invention. We also agree that a skilled artisan would have had a reasonable expectation of success in combining the references, the teachings of which are complementary and overlapping. See KSR Int’l Co. v. Teleflex Inc., 550 Appeal 2019-005306 Application 15/633,492 18 U.S. 398, 416 (2007) (holding that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”); see also id. at 420 (“A person of ordinary skill is also a person of ordinary creativity, not an automaton”). Appellant also contends that the Examiner improperly relied upon hindsight analysis in establishing the prima facie case of obviousness. We disagree. Any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper. In re McLaughlin, 443 F.2d 1392, 1395 (C.C.P.A. 1971). Appellant adduces no objective evidence of record that the Examiner relied upon knowledge that could have been obtained only from Appellant’s Specification. We consequently affirm the Examiner’s rejection of the claims. B. Claims 6, 7, 16, and 17 Issue Appellant argues that the Examiner erred because the combined cited prior art does not teach the limitations of claims 6, 7, 16, and 17. App. Br. 15. Dependent claims 6 and 16 recite a solid drug unit in which the drug comprises lidocaine, whereas dependent claims 7 and 17 recite a solid drug unit in which the mini-tablet is between 85 weight percent and 95 weight percent lidocaine. Id. Appeal 2019-005306 Application 15/633,492 19 Analysis Appellant contends that Peppas does not provide any teaching regarding lidocaine-containing minitablets, and the Examiner therefore relies upon Rosa as teaching that lidocaine and benzocaine are “equally efficient in reducing pain.” App. Br. 15. However, argues Appellant, Rosa teaches topical anesthetics injected into a patient’s palate in solution form, and provides no teaching regarding orally administered solid drug tablets, such as those taught by Politi and Peppas. Id. Furthermore, argues Appellant, benzocaine and lidocaine are physico- chemically different molecules, and behave differently when granulated and compressed. App. Br. 15. According to Appellant, the fact that topical applications of lidocaine and benzocaine are “equally efficient in reducing pain” does not render the drugs equivalents or substitutes for use in drug tablets with any degree of predictability. Id. Therefore, Appellant asserts, a person of ordinary skill in the art would not have been led to derive a tablet of granulated lidocaine based upon the teachings of Peppas and Rosa. Id. We are not persuaded by Appellant’s arguments. As an initial matter, we disagree with Appellant’s description of the studies presented in Rosa. Contrary to Appellant’s assertion that “Rosa relates to topical anesthetics injected in a patient’s palate in solution form” (App. Br. 15), Rosa teaches: The subjects ….were topically treated with one of the above drugs in random order. A cotton swab was inserted into the paste and rotated clockwise 3 times to standardize the amount of drug applied. At each session, a 27-gauge needle was inserted into the palate next to the greater palatine foramens twice, once before (baseline) and the other after (test) drug application for 1 minute. Immediately after each insertion, subjects indicated on a VAS the pain intensity perceived. No anesthetic solution was injected, nor was any other type of procedure carried out. Appeal 2019-005306 Application 15/633,492 20 Rosa 98 (emphases added). In other words, the use of the needle inserted into the subjects’ palate was to present a painful stimulus against which the efficacy of the topical6 anesthetic could be measured. Furthermore, Rosa teaches that “[t]he results of this study showed that lidocaine and benzocaine were equally efficient in reducing pain caused by insertion of needles into the palate, and both were better than placebo.” Rosa 98. Peppas and Rothbard both teach solid drug compositions containing anesthetic agents: Peppas teaches that local anesthetics (including benzocaine) can be used, and Rothbard teaches that pills containing anesthetics can be inserted into the urethra. Peppas ¶ 92; Rothbard ¶ 123. Rosa teaches that lidocaine and benzocaine are equally effective as topical anesthetics. Rosa 98. We agree with the Examiner’s finding that Rosa teaches that benzocaine and lidocaine are therefore functionally equivalent. We find no merit in Appellant’s argument that benzocaine and lidocaine “behave very differently when granulated and compressed” (see App. Br. 15), because Appellant adduces no objective evidence of record to support this contention, and we accord such unsupported attorney argument little probative weight. See In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) 6 We also note that the medical definition of “topical” is “designed for or involving application to or action on the surface of a part of the body.” Topical, MERRIAM WEBSTER MEDICAL DICTIONARY, available at: https://www.merriam-webster.com/dictionary/topical#medicalDictionary (last visited April 6, 2020) (emphasis added). As such, topical does not apply to agents that are injected into the body. Appeal 2019-005306 Application 15/633,492 21 (holding that attorney arguments and conclusory statements that are unsupported by factual evidence are entitled to little probative value). Appellant also repeats the arguments presented supra that the combined cited prior art references do not teach or suggest a solid drug composition containing 85–95% by weight of an active agent. We have explained our reasoning as to why we are not persuaded by Appellant’s argument, and we incorporate that reasoning here by reference. We consequently affirm the Examiner’s rejection of the claims. C. Claims 9 and 19 Issue Dependent claim 9 is representative and recites: “The solid drug unit of claim 1, wherein the mini-tablet is sterilized.” App. Br. 22. Appellant argues that the Examiner erred because the cited prior art references neither teach nor suggest this limitation. App. Br. 17. Analysis The Examiner finds that sterilization is common feature of regulated pharmaceuticals. Final Act. 11. The Examiner reasons that such a feature would also be more desirable if the tablet is intended for introduction in to the urethra, where reducing the risk of infection would be a goal, as opposed to if the tablet were simply intended for oral administration. Id. Appellant points out that none of the cited references teach or suggest that its dosage forms be sterilized. App. Br. 17. Furthermore, Appellant argues, the Examiner has repeatedly failed to respond to Appellant’s submitted evidence, namely ISPE, Oral Solid Dosage Forms, Course Appeal 2019-005306 Application 15/633,492 22 Description 1–3 (undated) (“ISPE”), which illustrates that solid dosage forms are commonly produced in non-sterile environments. Id. Appellant also points to J.E. Martinez, Microbial Bioburden on Oral Solid Dosage Forms, PHARM. TECH. 58–70 (February 2002) (“Martinez”), which teaches that sterilization is not a common feature of regulated oral pharmaceuticals, and instead teaches that “this attitude [that food and oral drugs must be sterile] is not in the best interest of the consumer. Sterilization of food and drugs is expensive, and the extra cost, when it is not necessary, is paid by the consumer and is a waste of money.” Id. (citing Martinez 66). Appellant notes further that the Examiner finds that sterilization “would also be more desirable if the tablet is intended for introduction in to the urethra wherein reducing the risk of infection would be a goal as opposed to if tablet were simply intended for oral administration.” App. Br. 18 (quoting Final Act. 11). However, Appellant argues, the Examiner continues to fail to cite any support for this conclusory statement; Appellant contends, rather, that this rejection is based on improper hindsight reconstruction using Appellant’s Specification as a blueprint. Id. Appellant also notes that the Examiner finds that “it is an undeniable matter of common sense to the general population not to stick dirty unsterilized needles or medical devices in[to] the body, it would not be any different with injectable or insertable drug tablets.” App. Br. 19 (quoting Final Act. 6). Appellant argues that this finding is not commensurate with Appellant’s claims, as “unsterilized” is not synonymous with “dirty.” Id. Appellant asserts that the evidence presented demonstrates that drug tablets are commonly not sterilized, although nevertheless being recommended for insertion and administration to the body. Id. Appeal 2019-005306 Application 15/633,492 23 We are not persuaded by Appellant’s argument. The Examiner has taken notice that sterilization is a common, if not universal procedure for medical devices that are to be inserted into the body, so as to prevent infection. The Examiner has therefore concluded that it would have been obvious to a person of ordinary skill in the art to sterilize a solid drug composition that was intended to be inserted into the urethra, as claimed by Appellant. We do not see the flaw in this logic. Nor are we persuaded that Appellant’s rebuttal evidence is relevant to this analysis. First, we are unable to discern any express teaching in ISPE that either sterile or non-sterile procedures are used in the manufacture of oral drug compositions. Second, both ISPE and Martinez are directed to orally ingested medications, and not to solid drug compositions intended to be inserted into the urethra. See ISPE 1–3; Martinez 66. Absent any evidence to support the contention that solid drug compositions intended to be inserted into the urethra are generally or routinely not sterilized, we are not persuaded that Appellant’s arguments are sufficient to overcome the Examiner’s prima facie conclusion that claims 9 and 19 are obvious over the combined cited prior art and the knowledge of a person of ordinary skill in the art. We therefore affirm the Examiner’s rejection of the claims. Appeal 2019-005306 Application 15/633,492 24 CONCLUSION The rejection of claims 1–20 as unpatentable under 35 U.S.C. § 103 is affirmed. The rejection of claims 1–20 as unpatentable under the nonstatutory doctrine of obviousness-type double patenting is affirmed.7 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). AFFIRMED Claims Rejected 35 U.S.C. § Reference/Basis Affirmed Reversed 1–7, 9–17, 19, 20 103 Politi, Peppas, Pryce Lewis, Pich, Rosa, Rothbard 1–7, 9–17, 19, 20 8, 18 103 Politi, Peppas, Pryce Lewis, Pich, Rosa, Rothbard, Huynh-Ba 8, 18 1–20 Obviousness- type double patenting ’974 application 1–20 Overall Outcome 1–20 7 See fn.2 supra. Copy with citationCopy as parenthetical citation