2020003706 (P.T.A.B. Jan. 12, 2021)

LABORATORIOS DEL DR. ESTEVE S.A.

Patent Trials and Appeals BoardJan 12, 2021

2020003706 (P.T.A.B. Jan. 12, 2021)

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. 14/379,613 08/19/2014 Pratibha S. Pilgaonkar 16326.0018FPWO 6655 23552 7590 01/12/2021 MERCHANT & GOULD P.C. P.O. BOX 2903 MINNEAPOLIS, MN 55402-0903 EXAMINER BECKHARDT, LYNDSEY MARIE ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 01/12/2021 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): USPTO23552@merchantgould.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte PRATIBHA S. PILGAONKAR, MAHARUKH T. RUSTOMJEE, and ANILKUMAR S. GANDHI ____________ Appeal 2020-003706 Application 14/379,613 Technology Center 1600 ____________ Before ERIC B. GRIMES, JOHN E. SCHNEIDER, 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 compositions of two distinct types of particles and capsules containing the same, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE.2 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies Esteve Pharmaceuticals, S.A., as the real party in interest. Appeal Br. 1. Herein, we refer to Appellant’s Appeal Brief filed December 6, 2019 (“Appeal Br.”) and Examiner’s Answer mailed February 19, 2020 (“Ans.”). 2 An oral hearing was held on January 7, 2021. A transcript of the hearing will be made of record. Appeal 2020-003706 Application 14/379,613 2 STATEMENT OF THE CASE “Dabigatran is a potent, reversible, univalent direct thrombin inhibitor” that is “currently available as dabigatran etexilate mesylate (DEM) under the brand name Pradaxa®.” Spec. 2:6–17. The Specification explains that “the aqueous solubility of DEM is strongly pH dependent with rather high solubility in acidic media and very poor solubility in neutral and basic media.” Id. at 2:24–26. Moreover, while “DEM is stable in the solid state” it “undergoes degradation by hydrolytic pathways in the presence of moisture” and “is acid sensitive.” Id. at 2:29–31. The Specification explains that “[d]ue to these physicochemical and biopharmaceutical properties of DEM . . . attempts have been made to provide compositions of DEM that are stable and/or provide desirable in vitro release and bioavailability.” One such approach is described in Brauns,3 which, according to the Specification: describes pharmaceutical compositions of DEM for oral administration in the form of pellets comprising (a) substantially spherical core material comprised of one or more pharmaceutically acceptable organic acids . . . and (b) an active substance layer containing one or more binders and optionally a separating agent, that encloses said core material. The separating agent layer or insulating layer separates the acid core from the active substance containing layer. . . . Such layered pellets are later filled into hard capsules. Spec. 3:1–10. According to the Specification, Brauns’ “process of preparing layered pellets is cumbersome, time consuming and uneconomical” and, therefore, a need exists for “alternate compositions of dabigatran etexilate that are stable, 3 US 2006/0183779 A1, published Aug. 17, 2006 (“Brauns”). Appeal 2020-003706 Application 14/379,613 3 easy or convenient to prepare,” and which “provide the desired in vitro release and bioavailability.” Spec. 3:10–12, 3:24–26. The Specification purports to provide such an alternate composition in a form of “a mixture of at least two types of particles . . . wherein a) the first type of particles comprise the active ingredient; [and] b) the second type of particles comprise at least one pharmaceutically acceptable organic acid.” See id. at 3:28–35. Claims 21, 23, 26, 30, 32, and 40–48 are on appeal and can be found in the Claims Appendix of the Appeal Brief. Claim 21 is illustrative and reads as follows: 1. A composition comprising: a mixture of at least two distinct types of particles wherein a) the first type of particle comprise dabigatran etexilate in the form of the free base or in the form of a pharmaceutically acceptable salt or polymorph thereof, wherein the first type of particles is free from organic acids and inorganic acids: and b) the second type of particles comprise at least one pharmaceutically acceptable organic acid, wherein the second type of particles is coated with a protective coating layer and is free from dabigatran etexilate. Appeal Br. 13. Appellant seeks review of Examiner’s rejection of claims 21, 23, 26, 30, 32, and 40–48 under 35 U.S.C. § 103 as unpatentable over Brauns in view of Habib4 and PubChem.5 Appeal Br. 3–12. 4 US 2008/0069891 A1, published March 20, 2008 (“Habib”). 5 “Compound Summary for CID 9578572: Dabigatran Etexilate,” available at https://pubchem.ncbi.nlm.nih.gov (“PubChem”). Appeal 2020-003706 Application 14/379,613 4 The issue is: Does the preponderance of evidence of record support Examiner’s conclusion that the cited prior art renders obvious the claimed compositions? Analysis Examiner finds that Brauns “teaches dabigatran etexilate and organic acids provide[] a significantly improved formulation” and describes a particle containing an organic acid core surrounded by “a separating layer followed by a layer containing the active substance.”6 Ans. 4. Examiner acknowledges that Brauns does not teach the drug and organic acid “in two distinct types of particles,” as claimed. Id. at 8. For that limitation, Examiner relies on Habib. Examiner determines Habib teaches a pharmaceutical composition that “comprises two particles, the first type containing the pharmaceutical agent and the second comprising fat/wax material.” Ans. 8. According to Examiner, it would have been obvious to formulate the composition taught by Brauns “as two distinct particles as [Habib] teaches [a] pharmaceutical composition [that] comprise[s] two distinct types of particles, one of which includes a pharmaceutical agent” and Brauns “teaches the need for spatial separation of the organic acid and the active substance.” Id. Appellant argues that Examiner has not presented a sufficient prima facie showing because Brauns describes only a single, layered particle composition that achieves an acidic microenvironment through “immediate diffusion” of the acid layer into the active substance layer (see Appeal Br. 4– 7) and there is no motivation or suggestion in the cited references to change 6 Examiner relies on PubChem to establish that the active substance in Brauns is dabigatran etexilate. See Ans. 4. Appeal 2020-003706 Application 14/379,613 5 that composition to the “two distinct types of particles” recited in Appellant’s claims. See id. at 9. In particular, Appellant points out that Habib “is not related at all to, or concerned with, the necessity of a close proximity between an acid and active ingredient to obtain a desired result, i.e., an acidic environment that allows for diffusion.” Id. Thus, urges Appellant, “[o]ne of skill in the art could not reasonably predict that the single layered particles of [Brauns] could be separated to form a composition” of two distinct particles as recited in Appellant’s claims. Id. at 10. We are persuaded by Appellant’s argument and agree that Examiner has not articulated a sufficient rationale for combining the two particle composition taught in Habib to modify the single particle composition taught in Brauns. Habib is directed to an “abuse resistant drug formulation” (Habib, title) comprising “two particles” wherein “[t]he first particle comprises an API” and “[t]he second particle comprises a fat/wax material present in a an amount sufficient to inhibit administration abuse of the API from the first particle,” e.g., if a capsule containing those particles is crushed, dissolved or injected. Id. ¶¶ 8, 20. It is not clear why one of ordinary skill in the art would have considered Habib’s abuse resistant formulations to be relevant to the layered particle compositions taught in Brauns. Indeed, Brauns teaches that an advantage of the “spatial separation of the organic acid and active substance by the insulating layer” in its layered particle composition is that it increases bioavailability by facilitating the creation of “an acid microclimate in which the active substance can dissolve” when acid from the core diffuses into the drug layer. Brauns ¶ 11. In contrast, the second particle in Habib’s Appeal 2020-003706 Application 14/379,613 6 composition is intended to achieve the opposite result, i.e., to inhibit dissolution of the drug. See Habib ¶ 36 (“It is believed that the combination of particles according to the present invention produces a barrier relative to the active ingredient-containing particles against solvent access, thereby protecting and preserving the intended controlled release properties of the active particles.”). In view of these teachings, Examiner has not sufficiently explained why a skilled artisan would be motivated to combine Habib with Brauns to achieve a composition with the “two distinct types of particles” recited in Appellant’s claims. For this reason, Examiner has not met the burden to establish a prima facie showing of obviousness. Accordingly, the rejection is not supported by the preponderance of the evidence and we, therefore, reverse. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 21, 23, 26, 30, 32, 40– 48 103 Brauns, Habib, PubChem 21, 23, 26, 30, 32, 40– 48 REVERSED