Tejal Desai et al.

Patent Trials and Appeals BoardJul 9, 2020

14110549 - (D) (P.T.A.B. Jul. 9, 2020)

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. 14/110,549 12/19/2013 Tejal A. Desai UCSF-432 8779 24353 7590 07/09/2020 BOZICEVIC, FIELD & FRANCIS LLP BOZICEVIC, FIELD & FRANCIS 201 REDWOOD SHORES PARKWAY SUITE 200 REDWOOD CITY, CA 94065 EXAMINER BABSON, NICOLE PLOURDE ART UNIT PAPER NUMBER 1619 NOTIFICATION DATE DELIVERY MODE 07/09/2020 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): docket@bozpat.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte TEJAL A. DESAI, MARK RORY STEEDMAN, ROBERT BHISITKUL, DANIEL A. BERNARDS and KEVIN D. LANCE ____________ Appeal 2019-006401 Application 14/110,549 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and MICHAEL A. VALEK, Administrative Patent Judges. VALEK, Administrative Patent Judge. DECISION ON APPEAL Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving claims to a multilayer thin film medical device. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies The Regents of the University of California, as the real party in interest. Appeal Br. 3. Herein, we refer to the Final Action mailed July 24, 2018 (“Final Act.”); Appellant’s Appeal Brief filed February 5, 2019 (“Appeal Br.”); and Examiner’s Answer mailed May 24, 2019 (“Ans.”). Appeal 2019-006401 Application 14/110,549 2 STATEMENT OF THE CASE Appellant’s Specification discloses certain “[m]ultilayer thin film medical devices that include a plurality of thin film layers and a bioactive agent for use in the local delivery of the bioactive agent to a tissue of a subject in need thereof.” Spec. 7. At least “in certain embodiments . . . the releasing of the bioactive agent from the medical device is substantially zero order” this means that “the device provides for a substantially constant release of drug, e.g., a release profile where the fraction of bioactive agent eluted from the device is substantially linear with respect to time.” Id. at 22. Claims 138, 139, 141, 145–149, 155, 157–161, and 167–170 are on appeal and can be found in the Claims Appendix of the Appeal Brief. Claim 138 is illustrative. It reads as follows: 138. A multilayer thin film medical device, comprising: a first layer comprising a polymer, wherein the polymer is selected from the group consisting of poly(ε-caprolactone) (PCL), polylactide (PLA), polyglycolide (PGA), poly(DL- lactide-co-glycolide) (PLGA), and poly(DL-lactide-co-ε caprolactone) (DLPLCL), wherein the first layer does not include a water soluble polymer, wherein the first layer comprises a first surface and a second surface opposite the first surface; a layer of lyophilized bioactive agent in absence of a polymer; and a second layer comprising a polymer, wherein the polymer is selected from the group consisting of poly(ε-caprolactone) (PCL), polylactide (PLA), polyglycolide (PGA), poly(DL- lactide-co-glycolide) (PLGA), and poly(DL-lactide-co-ε- caprolactone) (DLPLCL), wherein the second layer does not include a water soluble polymer, wherein the second layer comprises a first surface and a second surface opposite the first surface; Appeal 2019-006401 Application 14/110,549 3 wherein the bioactive agent is positioned only between the second surface of the first layer and the first surface of the second layer, wherein the second surface of the first layer is in contact with the first surface of the second layer at the periphery of the multilayer thin film medical device and wherein the contact extends from the periphery of the device to a periphery of the location at which the bioactive agent is positioned thereby sealing the bioactive agent inside the multilayer thin film medical device, wherein the contact does not extend to regions in interior of the device, wherein the bioactive agent is not positioned between the first and the second layers at the periphery of the multilayer thin film medical device, wherein the device has an area between 1 mm2 and 36 mm2, wherein the device has a thickness between 10 μm and 500 μm, and wherein the device provides a zero order release of the bioactive agent over at least 10 days following administration. Appeal Br. 13. Claims 167 is also independent. Claim 167 recites a multilayer thin film device comprising “a layer of bioactive agent in a lyophilized form, wherein the layer does not include a gel matrix” between a first and second layer consisting of the same polymers as those recited in claim 138 and with the same thickness range and zero order release. Id. at 15–16. Appellant seeks review of the following rejections: Appeal 2019-006401 Application 14/110,549 4 I. Claims 138, 139, 141, 145–149, 155, 157–161, and 167–170 under 35 U.S.C. § 103 as unpatentable over Gould,2 Pitt,3 Arnold,4 and Cuddon;5 and II. Claims 162–166 under 35 U.S.C. § 103 as unpatentable over Gould, Pitt, Arnold, Cuddon, and Buevich.6 Analysis Both of the rejections turn on common issues relating to Examiner’s combination of Gould’s device with the polymers taught in Pitt. See Final Act. 7, 9. We consider the rejections together, focusing on claim 138 as illustrative. The same analysis, discussed below within the context of claim 138, also applies to the other rejected claims. Examiner finds that Gould teaches “zero-order release pharmaceutical devices” having a “thickness between 0.2-10 mm (i.e. 200-10,000 microns)”7 and comprising a “drug containing layer” between a “diffusion barrier” composed of polymers that are not the polymers recited in Appellant’s claims. Final Act. 4–5 (acknowledging that Gould does “not 2 US 3,641,237, issued Feb. 8, 1972 (“Gould”). 3 Colin G. Pitt et al., Sustained Drug Delivery Systems II: Factors Affecting Release Rates from Poly (ε-caprolactone) and Related Biodegradable Polyesters, 68 J. of Pharm. Sci. 1534–38 (1979) (“Pitt”). 4 US 3,961,628, issued June 8, 1976 (“Arnold”). 5 Pharmaceutical Freeze Drying, http://www.cuddonfreezedry.com/ pharmaceutical-freeze-drying, available Nov. 7, 2010 (“Cuddon”). 6 US 2008/0128315 A1, published June 5, 2008 (“Buevich”). 7 This finding is based on Gould’s disclosure that its films are “0.2–10 mils thick.” Gould, 1:64–65. In other words, Examiner interprets a “mil” to be a millimeter, whereas Appellant appears to interpret a mil as one thousandth of an inch. See Appeal Br. 9 (“Gould teaches a device made of thin films 0.2-10 mil (5-254 μm)”). This distinction does not affect the outcome of our analysis. Appeal 2019-006401 Application 14/110,549 5 teach the polymers as recited in Claims 138 and 167”). Examiner determines Pitt teaches “release rates of several steroids from films” comprising the polymers recited in Appellant’s claims. Id. at 5. In particular, Examiner points to Pitt’s teaching of an embodiment comprising a 3 μm progesterone-PLA (i.e., poly(DL-lactic acid)) layer sandwiched between two drug-free 3 μm layers of the same polymer that was shown to achieve a constant release rate over a period exceeding 10 days. Id. at 6 (citing Pitt, Fig. 4). In light of these teachings, Examiner concludes it “would have been obvious to one of ordinary skill in the art to select the polymer of Pitt et al. for use in the device of Gould . . . in order to provide steady drug release for up to 50 days.” Id. at 7. Appellant argues that one of ordinary skill in the art would lack a reasonable expectation that Gould’s device could be combined with Pitt’s polymers for at least two reasons. See Appeal Br. 6–9. First, Appellant argues that “the devices in Gould which are taught to provide zero order release required the drug to be present in a polymer layer,” while claim 138 requires “a layer of lyophilized bioactive agent in absence of a polymer.” See Appeal Br. 6–8. We are not persuaded by that argument. While Gould’s provides examples wherein the drug is incorporated into a polymer layer, Gould specifically teaches that “[z]ero order release of water soluble pharmaceutically active organic compounds alone or absorbed or incapsulated in hydrophilic polymers is obtained by providing a film diffusion barrier of an alkoxyethyl acrylate or methacrylate polymer.” Gould, Abstr. (emphasis added); see also id. 1:51–55 (describing “a diffusion barrier film around a drug alone or in a hydrophilic polymer”); Appeal 2019-006401 Application 14/110,549 6 2:27–31 (explaining that the drug-containing “layer can consist of the drug alone, or the drug in combination with various adjuvants”). Appellant also argues that one of ordinary skill in the art would not have “reasonably expect[ed] that [the] alkoxyethyl acrylate or methacrylate polymers . . . taught in Gould as required for providing zero order kinetics can be replaced with another polymer [specifically, those taught in Pitt] and . . . retain the zero order release kinetics.” Appeal Br. 8. As Appellant points out, the devices in Pitt made from PCL in Figures 1–2 and from PLA in Figure 3, i.e., the same polymers recited in claim 138, did not exhibit zero order release. Id. Those devices ranged in thickness from 100–300 μm and thus were similar in thickness the films taught in Gould’s examples. Compare Pitt, Figs. 1–3 (describing results for 100, 200, and 300 μm films) with Appeal Br. 8 (calculating “the overall thickness” of the devices in Gould’s examples as “203 μm to 355 μm”). In contrast, the sandwich embodiment Examiner relies on in Figure 4 of Pitt is thinner (9 μm) and comprises a drug-polymer layer, as opposed to the drug in the “absence of a polymer” as recited in claim 138. Pitt, 1535 (col. 2 ¶ 2). Thus, urges Appellant, “a person of ordinary skill in the art would have no reasonable expectation of success in modifying the device of Gould,” as articulated in the rejection. Appeal Br. 9. Based on the present record, we are persuaded by Appellant’s argument. Specifically, we determine that Examiner has not identified sufficient evidence to demonstrate that one of ordinary skill in the art would have reasonably expected to retain the zero order release kinetics of Gould’s device if Pitt’s polymers were substituted for those in Gould’s device. Gould specifically attributes the zero order release characteristic of its Appeal 2019-006401 Application 14/110,549 7 device to the use of a “film diffusion barrier of an alkoxyethyl acrylate or methacrylate polymer,” i.e., a diffusion barrier consisting of polymers other than those recited in claim 138. Gould, Abstr. In contrast, Pitt teaches that for devices made from the polymers recited in claim 138 “[r]elatively constant release rates . . . were obtained only under certain conditions” that differ from those taught in Gould. Pitt, Abstr. For example, the sandwich embodiment Examiner cites in Figure 4 of Pitt differs from Gould’s devices, as well as the device recited in claim 138, both in its thickness and because it contains polymer in the drug layer.8 Examiner has not pointed to sufficient evidence, nor articulated sufficient findings, to demonstrate a reasonable expectation of success on this record of producing a device with zero order release with the claimed layers. Examiner states that “[g]iven that Gould is directed to zero order release one of ordinary skill in the art would have varied the polymer choice and device parameters such that the release profile was achieved.” Ans. 6–7. However, Examiner has not pointed to evidence, nor provided a sufficient explanation based on scientific reasoning, to show that it would have been obvious to optimize the articulated combination of Gould and Pitt as Examiner supposes. See Ex parte Thomas J. Whalen II, Appeal 2007-4423, 14 (BPAI July 23, 2008) (noting that “Examiner has not pointed to any teaching in the cited references, or provided any explanation based on scientific reasoning, that would support the conclusion that those skilled in 8 Pitt also describes 100 μm PLGA films that exhibited “cumulative drug release[] . . . proportional to t1/2” for the first 20 days before having the release rate increase after 20 and 30 days. Pitt, 1536 (col. 2 ¶¶ 1–2, Fig. 5). However, these films mixed the polymer with the drug and did not have a sandwich configuration or diffusion barrier. Id. Appeal 2019-006401 Application 14/110,549 8 the art would have considered it obvious to ‘optimize’ the prior art compositions” in the manner proposed) (precedential). Indeed, if anything, the presence of a drug-polymer layer in Pitt’s sandwich and PLGA embodiments suggests a modification of Gould’s device that would seem to move away from the device in claim 138. Thus, while it may have been obvious to vary the polymer choice and device parameters to achieve zero release kinetics, Examiner has not, on the record before us, sufficiently articulated why a device with the characteristics recited in Appellant’s claims would be the obvious result of such optimization. For these reasons, we determine Examiner’s obviousness rejections are not supported by a preponderance of the evidence. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 138, 139, 141, 145– 149, 155, 157–161, 167–170 103 Gould, Pitt, Arnold, Cuddon 138, 139, 141, 145– 149, 155, 157–161, 167–170 162–166 103 Gould, Pitt, Arnold, Cuddon, Buevich 162–166 Overall Outcome 138, 139, 145, 145– 149, 155, 157–170 REVERSED